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Intra-operative portal hemodynamics in pediatric LDLT: Doppler ultrasound surveillance. Doppler ultrasonography is useful in monitoring intra-operative PV flow in LDLT. A retrospective cohort study included 550 pediatric recipients (<18 years) who underwent LDLT from October 2006 to August 2016 in our hospital. A total of 33 recipients (incidence 6%) were found to have insufficient intra-operative PV flow after PV reperfusion. The treatments included intra-operative stent placement (n=25), anticoagulation (n=3), thrombectomy and re-anastomosis (n=2), graft repositioning (n=1), collateral ligation (n=1), and replaced PV (n=1). The peak PV velocity, HAPSV, HARI, and HV velocity before and after the interventions were significantly improved 0(0,5.5) cm/s vs. 37.36±15.30 cm/s, 38.68±8.92 cm/s vs. 62.30±16.97 cm/s, 0.55±0.08 vs. 0.76±0.10, and 32.37±10.33 cm/s vs. 40.94±15.01 cm/s, respectively (P<.01). Insufficient PV flow and decreased HARI are two significant criteria indicating need for intra-operative PV management. Dramatic changes in the hepatic hemodynamics were detected after proper treatment. Immediate resolution of PV flow is feasible in pediatric LDLT.

Meta-analysis of staged versus combined carotid endarterectomy and coronary artery bypass grafting. The multiple options in the management of patients with concomitant carotid and coronary artery disease (CAD) make it difficult to find a clear consensus regarding the ideal surgical strategy. We performed a meta-analysis of studies comparing early outcomes of synchronous and staged approach of carotid endarterectomy and coronary artery bypass grafting. All English language publications were searched using the terms "carotid artery disease," "coronary artery disease," "carotid endarterectomy," and "coronary artery bypass grafting" alone or in combination. The endpoints studied were early mortality, major stroke, and major postoperative morbidity; myocardial infarction (MI) and stroke, and combined early mortality or stroke. Early events were compared using pooled estimates of risk ratios (RR) (random effects model) utilizing the inverse-variance method. Twelve studies were identified with a total of 17,469 and 7,552 patients in the combined and staged group, respectively. The pooled analysis revealed no difference in the early mortality (RR 1.36 [0.78, 2.36]; p = 0.27), post operative stroke (RR 1.14 [0.99, 1.31], p = 0.07), combined early mortality or stroke (RR 1.08 [0.98, 1.20], p = 0.11) and combined endpoint of MI or stroke (RR 0.75 [0.48, 1.17; I(2) = 11%], p = 0.2) between the 2 surgical approaches. Our meta-analysis of observational studies suggests comparable outcomes in combined and staged approach for synchronous carotid and coronary artery disease. Hence, the 2 strategies can be used interchangeable in the clinical practice, with each having specific applications linked to specific clinical conditions. A randomized trial is warranted to answer this question definitively.

Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung. Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success.

Endoscopic missed rates of upper gastrointestinal cancers: parallels with colonoscopy. Recent publications assessing colonoscopy missed rates of colorectal cancer have generated efforts toward colonoscopy quality improvement. To date, esophagogastroduodenoscopy (EGD) has escaped similar scrutiny in Western populations. Raftopoulos et al. (1) report an upper gastrointestinal cancer missed rate of up to 6.7% in a cohort of 28,000 patients who underwent EGD at a hospital-based endoscopy unit in Perth, Western Australia. Of the missed esophageal and gastric cancers, approximately 80% of patients had alarm symptoms and 73% had abnormalities reported at the time of EGD. The missed cancers may not have been visualized, or were visualized and either not biopsied or biopsied inadequately, or interpreted incorrectly by pathologists. There was no difference in survival between the missed cancers and those detected at the index EGD.

Blood oxidative status and selectins plasma levels in healthy donors receiving granulocyte-colony stimulating factor. Recombinant human G-CSF (rHuG-CSF) is used for hematopoietic progenitor cells (HPC) mobilization and collection. Activation of polymorphonuclear leukocytes (PMN) is present during rHuG-CSF treatment and is associated with endothelial cell dysfunction and hypercoagulation. We evaluated whether PMN activation by rHuG-CSF may alter the blood oxidative status and subsequently affect the vascular cell function. Fourteen healthy individuals received rHuG-CSF for HPC harvesting. Blood was drawn before starting rHuG-CSF (T0), on the last day of rHuG-CSF (T1) and 1 week after stopping rHuG-CSF (T2). Levels of CD11b, myeloperoxidase (MPO), hydroperoxides, nitric oxide (NO), and soluble endothelium (sES), leukocyte (sLS), and platelet (sPS) selectins were measured. During rHuG-CSF, CD11b, MPO and hydroperoxides significantly increased, while NO levels significantly decreased, compared with T0. At T2 all these markers returned to baseline values. Significant increments of all selectins were observed during rHuG-CSF. At T2 sES and sEP significantly decreased back to pre-treatment values, whereas sLS remained significantly high. These data show that rHuG-CSF induces a transient inflammatory status characterized by circulating activated PMN, which release reactive oxygen species and intracellular proteases, promoting the onset of an abnormal oxidative status. This process may modify the hemostatic balance towards a pro-thrombotic state.

Ceramide kinase promotes Ca2+ signaling near IgG-opsonized targets and enhances phagolysosomal fusion in COS-1 cells. Ceramide-1-phosphate (C1P) is a novel bioactive sphingolipid formed by the phosphorylation of ceramide catalyzed by ceramide kinase (CERK). In this study, we evaluated the mechanism by which increased C1P during phagocytosis enhances phagocytosis and phagolysosome formation in COS-1 cells expressing hCERK. Stable transfectants of COS-1 cells expressing FcgammaRIIA or both FcgammaRIIA/hCERK expression vectors were created. Cell fractionation studies demonstrated that hCERK and the transient receptor potential channel (TRPC-1) were enriched in caveolae fractions. Our data establish that both CERK and TRPC-1 localize to the caveolar microdomains during phagocytosis and that CERK also colocalizes with EIgG in FcgammaRIIA/hCERK-bearing COS-1 cells. Using high-speed fluorescence microscopy, FcgammaRIIA/hCERK transfected cells displayed Ca2+ sparks around the phagosome. In contrast, cells expressing FcgammaRIIA under identical conditions displayed little periphagosomal Ca2+ signaling. The enhanced Ca2+ signals were accompanied by enhanced phagolysosome formation. However, the addition of pharmacological reagents that inhibit store-operated channels (SOCs) reduced the phagocytic index and phagolysosomal fusion in hCERK transfected cells. The higher Ca2+ signal observed in hCERK transfected cells as well as the fact that CERK colocalized with EIgG during phagocytosis support our hypothesis that Ca2+ signaling is an important factor for increasing phagocytosis and is regulated by CERK in a manner that involves SOCs/TRPCs.

[Capitate Non-Union: One of the Causes of Carpal Tunnel Syndrome]. We report on a carpal tunnel syndrome in a 50-year-old woman, presumably caused in part by a 35-year-old asymptomatic capitate non-union. The carpal tunnel was released and a large exostosis removed. 3 weeks after the operation the patient was free of symptoms.

Variation assessment of deformable registration in stereotactic radiosurgery. The regular functions of CT-MRI registration include delineation of targets and organs-at-risk (OARs) in radiosurgery planning. The question of whether deformable image registration (DIR) could be applied to stereotactic radiosurgery (SRS) in its place remains a subject of debate. This study collected data regarding 16 patients who had undergone single-fraction SRS treatment. All lesions were located close to the brainstem. CT and MRI two image sets were registered by both rigid image registration (RIR) and DIR algorithms. The contours of the OARs were drawn individually on the rigid and deformable CT-MRI image sets by qualified radiation oncologists and dosimetrists. The evaluation metrics included volume overlapping (VO), Dice similarity coefficient (DSC), and dose. The modified demons deformable algorithm (VARIAN SmartAdapt) was used for evaluation in this study. The mean range of VO for OARs was 0.84 ± 0.08, and DSC was 0.82 ± 0.07. The maximum average volume difference was at normal brain (17.18 ± 14.48 cm3) and the second highest was at brainstem (2.26 cm3 ± 1.18). Pearson correlation testing showed that all DIRs' OAR volumes were linearly and significantly correlated with RIRs' volume (0.679-0.992, two tailed, P << 0.001). The 100% dose was prescribed at gross tumor volume (GTV). The average maximum percent dose difference was observed in brainstem (26.54% ± 27.027), and the average mean dose difference has found at same organ (1.6% ± 1.66). The change in image-registration method definitely produces dose variance, and is significantly more what depending on the target location. The volume size of OARs, however, was not statistical significantly correlated with dose variance.

Clinical assessment of vascular calcification. Cardiovascular calcification poses an increased risk for cardiovascular events in advanced phases of chronic kidney disease. This evidence has brought many investigators to focus their attention on the importance of detection of calcification and avoidance of further development of it with appropriate therapeutic choices. Physicians can use a variety of noninvasive imaging tools to identify cardiovascular calcification, some with merely qualitative and others with both qualitative and quantitative capabilities. Plain x-rays and ultrasonography can be used to identify macroscopic calcification of aorta and peripheral arteries, echocardiography is helpful for assessment of valvular calcification, and computed tomography technologies constitute the gold standard for quantification of cardiovascular calcification. The latter is also useful to monitor calcification progression and to assess the effect of different therapeutic strategies directed at modifying calcification progression. In this article, we review the clinical significance of vascular calcification and some of the evidence surrounding the most commonly employed noninvasive imaging techniques.

The effect of prostate volume, age, total prostate specific antigen level and acute inflammation on the percentage of free serum prostate specific antigen levels in men without clinically detectable prostate cancer. We determine the influence of age, prostate volume, total serum prostate specific antigen (PSA) level and histological evidence of acute inflammation in biopsy specimens on the percent free serum PSA level in men without clinically detectable prostate cancer. We studied 70 men with total PSA levels of 2.6 to 9.9 ng./ml. who had undergone at least 3 sets of prostate biopsies that were negative for cancer as part of our PSA based prostate cancer screening program. Total and free PSA levels were measured using Hybritech immunoassays. Prostate volume and the presence of acute inflammation were determined from the most recent transrectal ultrasonography and prostate needle biopsy. Percent free PSA levels correlated significantly with age (r = 0.48, p = 0.0001) and prostate volume (r = 0.44, p = 0.0002) but not with total PSA (r = 0.04, p = 0.7). The mean percent free PSA did not differ for those with or without acute inflammation. Multivariate regression models demonstrated that age and prostate volume were significant predictors of percent free PSA. Among men without detectable prostate cancer and a total PSA level between 2.6 and 9.9 ng./ml. percent free serum PSA was higher in older men and in men with a larger prostate gland but was not influenced by total PSA level or the presence of acute inflammation in the prostatic biopsy specimen.

Children's housing and their health and physical development. The housing conditions of children in the National Child Development Study were related to their health and their height at the age of 16. Although children in crowded homes missed more school for medical reasons, the only illness they reported more often than children in better conditions was bronchitis. Those with inadequate amenities did not miss more school, although they also reported more bronchitis, as well as bilious attacks. Children in council houses were shorter than those in owner-occupied homes, but the only difference in height related to the conditions of the home was that crowded boys were slightly shorter than those who were not crowded. There was therefore little evidence of an association between poor housing and either ill-health or retarded growth among Britain's 16-year-olds in the 1970s, and this was still the case for children who had spent longer periods of their childhood in unsatisfactory housing.

Assessing the Safety and Efficacy of Regional Anesthesia for Lower Extremity Microvascular Reconstruction: Enhancing Recovery. Perioperative pain, increased sympathetic tone, and peripheral vasospasm may be safely managed with regional nerve blockade during microvascular reconstruction in the lower extremity. Limited reports exist in this setting; therefore, we evaluated our use of peripheral nerve catheters (PNCs) during microvascular limb salvage to determine safety and efficacy for both patient and flap. A single-institution, retrospective review of a prospectively maintained database on all patients with lower extremity free tissue transfers between 2012 and 2017 was completed. Patients were matched into groups based on PNC utilization. The use of intravenous narcotics including patient-controlled analgesia (PCA), oral narcotics, antiemetics, length of stay (LOS), associated pain scores, flap-related performance, and patient morbidity was recorded. Of 48 patients who underwent lower extremity free tissue transfer, 35 satisfied criteria for comparison. Of these, PNC was utilized in 83%. The mean pain score in the immediate postoperative period was 3.84 ± 2.47 (10-point Likert scale). PCA and narcotic use were decreased in the PNC group, and no adverse effects of the catheter were identified. Microsurgical outcomes were not adversely affected in comparison. PNC utilization for lower extremity free flap transfer significantly reduced concurrent narcotic use and attained a shorter LOS. The technique provided for safe analgesia during lower extremity free flap reconstructions satisfying the microsurgeon and the anesthesiologist.

Inflammatory biomarkers, disease activity index, and self-reported disability may be predictors of chronic arthritis after chikungunya infection: brief report. The chikungunya virus (ChikV) is a reemerging mosquito-borne pathogen that causes disabling chronic arthritis. The relationship between clinical evolution and inflammatory biomarkers in patients with ChikV-induced arthritis has not been fully described. We performed a prospective case series to evaluate the association among joint involvement, self-reported disability, and inflammatory biomarkers. Patients with ChikV infection were followed for 1 year. Joint involvement and self-reported disability were evaluated with disease activity index 28 (DAS-28) and World Health Organization Disablement Assessment Schedule II (WHODAS-II). Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were used as biomarkers. Ten patients with mean age 48 ±15.04 years were included. Symptoms at diagnosis were fever, arthralgias, myalgias, rash, arthritis, nausea, vomiting, and back pain. Polyarticular involvement was present in seven cases. At diagnosis, measures were as follows: DAS-28, 5.08±1.11; WHODAS-II score, 72.3±10.3 %; CRP, 5.09±7.23 mg/dL; ESR, 33.5±17.5 mm/h; RF, 64±21.7 IU/mL; and IL-6, 17.6±10.3 pg/mL. Six patients developed subacute and chronic symptoms. During follow-up, DAS-28 index, WHODAS-II score, ESR, and IL-6 were statistically different in patients with subacute and chronic symptoms compared to those who resolved in the acute phase (p < 0.05). DAS-28 index, WHODAS-II score, and IL-6 were related to chronicity of articular symptoms and could be used as predictors of ChikV-induced arthritis.

Temporal and spatial resolution in foveal vision of multiple sclerosis patients. Deficits of spatial and temporal resolution were compared in a group of 49 definite multiple sclerosis(MS) patients showing no major evidence of previous optic neuritis attack but representative of the population of the Belgian National MS Centre as to age and the most important disease variables. Resolution in the two domains was measured foveally with forced-choice staircase psychophysical procedures using Landoldt C and double flash stimuli, respectively. The two measurements were equally sensitive to MS-induced deficits and did not exhibit cross-sensitivity. Since discrete deficits of either kind were equally prevalent and outnumbered combined deficits, this suggests a nonselective but nonuniform destruction of M and P visual pathway function in these patients.

Aloe spp.--plants with vertebrate-like telomeric sequences. Chromosome termini of most eukaryotes end in tracks of short tandemly repeated GC-rich sequences, the composition of which varies among different groups of organisms. Plant species predominantly contain (TTTAGGG)n repeats at their telomeres. However, a few plant species, including members of Alliaceae and Aloe spp. (Asphodelaceae) were found to lack such Arabidopsis-type (T3AG3)n telomeric repeats. Recently, it has been proposed that the lack of T3AG3 telomeric repeat sequences extends to all species forming the Asparagales clade. Here, we analysed the composition of Aloe telomeres by single-primer PCR and fluorescence in-situ hybridization (FISH) with directly labelled Arabidopsis-type (TTTAGGG)28-43 DNA probe, and with vertebrate-type (TTAGGG)33-50 DNA and a (C3TA2)3 peptide nucleic acid (PNA) probe. It was found that Nicotiana tabacum contained Arabidopsis-type telomeric repeats, while Aloe telomeres lacked the corresponding FISH signals. Surprisingly, FISH with the highly specific vertebrate-type (C3TA2)3 PNA probe resulted in strong T2AG3-specific FISH signals at the ends of chromosomes of both Aloe and Nicotiana tabacum, suggesting the presence of T2AG3 telomeric repeats in these species. FISH with a long (TTAGGG)33-50 DNA probe also highlighted Aloe chromosome ends, while this probe failed to reveal FISH signals on tobacco chromosomes. These results indicate the presence of vertebrate-like telomeric sequences at the telomeres of Aloe spp. chromosomes. However, single-primer PCR with (TAG3)5 primers failed to amplify such sequences in Aloe, which could indicate a low copy number of T2AG3 repeats at the chromosome ends and/or their co-orientation and interspersion with other repeat types. Our results suggest that telomeres of plant species, which were thought to lack GC-rich repeats, may in fact contain variant repeat types.

[Effect of blastolysin on the ultrastructure and functional activity of mast cells and eosinophils]. Blastolysin is shown to cause degranulation of mast cells, resulting in a reduction of their histamine content and in their release of mediators that activate eosinophilic leukocytes (EL). These accelerate the deamination of the histamine released by mast cells to the extracellular medium. It is possible that blastolysin acts directly on EL granules which are largely responsible for histamine inactivation.

Effects of pulsed light and sanitizer wash combination on inactivation of Escherichia coli O157:H7, microbial loads and apparent quality of spinach leaves. The purpose of this study was to investigate the efficacy of pulsed light (PL), a new formula of sanitizer (HEN) consisting of hydrogen peroxide, EDTA and Nisin, as well as synergy of PL and HEN sanitizer (PL-HEN) wash in inactivating E. coli O157:H7 on spinach. The treatment effect on microbial loads and apparent quality during 13 days storage at 4 °C was also determined. A bacterial cocktail containing three strains of E. coli O157:H7 was used as inoculum based on their association with produce-related outbreaks. Spinach leaves were spot inoculated on surface before treating with PL (1-63J/cm2), HEN sanitizer wash (2 min) or their combinations. PL inactivation was influenced significantly at low doses. Treatment dose of 15.75 J/cm2, equivalent to 15 s intense PL treatment, was found optimal above which adverse quality effect was evident. The optimal PL dose resulted 2.7 log CFU/g reduction of E. coli O157:H7 while a rapid 2 min wash in sanitizer formulation HEN, provided comparatively low, 1.8 log CFU/g, reduction of the pathogen. Two different sequences of PL and HEN treatment combinations were tested. In PL-HEN treatment, inoculated leaves were first treated at optimal PL dose (15.75 J/cm2) followed by 2 min immersion in HEN whereas in HEN-PL treatment, leaves were first washed in HEN before PL exposure. HEN-PL treatment indicated a compound inactivation activity (4.6 logs reduction) while PL-HEN treatment indicated a strong synergistic inactivation as E. coli cells were not detectable after treatment indicating >5 log reduction. The PL-HEN treatment not only significantly reduced spoilage microbial populations on spinach but also slowed their growth during storage. Furthermore, the visual and firmness quality of spinach were not significantly affected by the PL-HEN treatment. Overall, our results demonstrate that integrated PL-HEN technology can be used to enhance microbial safety of spinach.

[Expression of Mycobacterium tuberculosis early secretory antigenic target-6 protein and its application in detection of Mycobacterium tuberculosis antigen-specific interferon-gamma response]. To obtain the purified early secretory antigenic target-6 (ESAT-6) protein and to evaluate its application in detection of Mycobacterium tuberculosis antigen-specific interferon-gamma (IFN-gamma) response. ESAT-6 protein was expressed by genetic engineering. The antigen specificity and reactivity of ESAT-6 were evaluated by Western blot. Using ESAT-6 as the antigen, the antigen-specific IFN-gamma response in patients with tuberculosis, healthy medical workers, and village residents was detected by the Elispot method. The results were also compared with those obtained by a commercial kit (QuantiFERON-TB-GOLD, QFT-G). ESAT-6 protein was successfully expressed and purified, and the antigen specificity of ESAT-6 was confirmed by its recognition by the antigen-specific antibody (anti-ESAT-6). The specificity and sensitivity of the Elispot assay using ESAT-6 as the antigen in detecting the IFN-gamma response was comparable with those of the commercial kit (QFT-G). The positive rates of the Elispot assay for patients with tuberculosis, healthy medical workers and villagers were 36/49 (73.5%), 11/62 (17.7%), and 17/194 (8.8%), respectively, while the rates of the OFT-G method for patients with tuberculosis and healthy medical workers were 38/49 (77.6%) and 14/58 (24.1%), respectively. The sensitivity (73.5%, 77.6%; chi2 = 0.381, P > 0.05) and specificity (82.3%, 75.9%; chi2 = 0.406, P > 0.05) of these two methods did not differ significantly. Recombinant ESAT-6 protein was expressed and purified. Elispot using recombinant ESAT-6 protein as antigen showed high sensitivity and specificity for detection of Mycobacterium tuberculosis antigen-specific IFN-gamma response. The purified ESAT-6 can be used for diagnosis of Mycobacterium tuberculosis infection.

Asymmetric copper-catalyzed propargylic substitution reaction of propargylic acetates with enamines. Enamines served as carbon-nucleophiles for the first time in the Cu-catalyzed asymmetric propargylic substitution reaction of propargylic acetates, providing corresponding chiral beta-ethynyl-substituted ketones in high yields and in good to high enantioselectivity.

No predictive value of beta-hCG in patients with stage I seminoma--results of a long-term follow-up study after adjuvant radiotherapy. Radical inguinal orchiectomy followed by adjuvant para-aortic radiotherapy has been the standard treatment in stage I seminoma. We have reviewed our experience with reduced total doses (less than 26 Gy) in stage I seminoma to investigate if patients with an elevated beta-human chorionic gonadotropin (beta-hCG) level before orchiectomy possibly require higher total doses of adjuvant radiotherapy (RT). Two hundred and sixty-seven consecutive patients, with newly diagnosed pure seminoma of the testis, were treated with adjuvant RT between 1992 and 2000. All patients had stage I disease. Serum AFP and beta-hCG levels were analyzed prior to and after orchiectomy in case of an elevated beta-hCG level. The measurements were repeated after RT in routine follow-up at regular intervals. Serum beta-hCG was considered as elevated if the values exceeded the normal range (up to 5 U/L). A median total dose of 25.2 Gy (range, 19.8 to 26.0 Gy) was applied to the para-aortic region. Fourteen patients were excluded from this analysis because beta-hCG measurement was not available. Nineteen of the remaining 253 patients (7.5%) had an elevated serum beta-hCG, which returned to normal post-operatively by the start of adjuvant radiotherapy. Median serum beta-hCG level before orchiectomy was 27.7 U/L (range, 5.1 to 420 U/L) in the group of patients with initial elevation of serum beta-hCG. This did not correlate with tumor size or rete testis invasion. After a median follow-up of 6.1 years (range, 3.0 to 11.2 years), 11 out of 267 (4.1%) patients had developed lymph node recurrence, resulting in an actuarial 5-year relapse-free survival of 96%. Median time to relapse was 19 months (range, 11 to 47 months) after RT. Only one relapsing patient initially had an elevated serum beta-hCG level of 34.1 U/L. This patient had nodal relapse within the mediastinum without renewed elevation of the serum beta-hCG level. An elevated pre-treatment beta-hCG level appears to have neither importance nor a predictive value in stage I seminoma. Therefore, we recommend the current adjuvant standard treatment without any modification for all beta-hCG-positive stage I seminoma.

GP referral letters to a community mental health team: an analysis of the quality and quantity of information. Presents the results of a study which investigated whether the quality of information provided by GP referral letters to a community mental health team (CMHT) was sufficient to determine an appropriate response and the allocation of professional resources. A random sample of GP referral letters received over a six month period was analysed. The presenting problem, diagnosis and the indication of severity of symptoms were rated. Perusal of the CMHT members' replies to the GP's allowed a rough analysis of the extent of agreement with the GP's diagnoses, description of presenting problems and severity of symptoms. Discusses the results of the study with regard to the implications of GP fundholding and the employment of GP-based counsellors.

[Splenic Infarctions Caused by Acute Cytomegalovirus Infection: A Case Report]. We report a 48-year-old healthy man who presented with a 1-week history of fever and epigastric pain. He had traveled to Indonesia and had been in sexual contact with a local woman 4 weeks prior to admission. His peripheral blood film showed atypical reactive lymphocytes. A serological test for cytomegalovirus IgM was positive and the quantitative cytomegalovirus DNA level was 1.1×102 copies/mL, whereas Epstein-Barr virus IgM, HIV antigen and antibody tests were negative. He was diagnosed as having an acute cytomegalovirus infection and was treated with acetaminophen. However, his clinical symptoms deteriorated on the 4th day after admission and a computed tomography examination showed splenomegaly with wedge-shaped splenic infarctions. Blood culture, antinuclear antibodies, antineutrophilic cytoplasmic antibodies, anti-cardiolipin antibodies, and lupus anticoagulant tests were negative. The protein C and protein S activities were normal. He was diagnosed as having a splenic infarction caused by an acute cytomegalovirus infection, and intravenous heparin administration was performed. On day 12, his symptoms had improved and he was discharged. Splenic infarctions caused by acute cytomegalovirus infection can develop in immunocompetent patients without any coagulation disorder. The possibility of splenic infarctions should be considered in patients with acute cytomegalovirus infection, especially those experiencing a worsening of abdominal pain.

Catching Up on New Medications: New FDA Approvals. Despite all efforts of the Federal Drug Administration to release timely and accurate information about new drug approvals, marketing and media announcements about new drugs may be incomplete, misinterpreted, or misunderstood. Informed and knowledgeable nurses are able to educate patients about new medications: they can clarify misunderstandings or misconceptions and significantly reduce the potential for harm. In this article, selected examples of new brand name drugs and first-time generics approved this year are discussed.

Comparison of the efficacy between paclitaxel/carboplatin and doxorubicin/cisplatin for concurrent chemoradiation in intermediate- or high-risk endometrioid endometrial cancer: a single institution experience. We sought to compare survival and toxicity between paclitaxel/carboplatin (TC) and doxorubicin/cisplatin (AP) for concurrent chemoradiation (CCR) in intermediate- or high-risk endometrioid endometrial cancer. The clinical data of 40 patients with intermediate- (FIGO stage IC-IIB, n = 12) or high-risk endometrioid endometrial cancer (FIGO stage IIIA-IVA, n = 28) were reviewed retrospectively between March 2000 and December 2007, who were treated with TC (n = 23, group 1) or AP (n = 17, group 2) for CCR after surgery. Progression-free survival (PFS) and overall survival (OS) were not different between groups 1 and 2 (median PFS and OS; 35 vs 24 and 76 vs 39 months, respectively, P > 0.05). However, >or=6 cycles of chemotherapy improved PFS compared with 3-5 cycles of chemotherapy (51 vs 21 months, P = 0.04), suggesting that >or=6 cycles of chemotherapy was an independent prognostic factor improving PFS (adjusted HR, 0.27; 95% CI, 0.08 to 0.91; P = 0.04). Grade 3 or 4 hematological and non-hematological, especially, gastrointestinal, toxicities related with chemotherapy during CCR were more common in group 2 than in group 1, whereas there was no difference in grade 3 or 4 late complication by CCR between the 2 groups. These findings suggest that TC may have comparable efficacy to AP for CCR with lesser toxicity, and >or=6 cycles of chemotherapy may be more beneficial than 3-5 cycles of chemotherapy in intermediate- or high-risk endometrioid endometrial cancer. However, large-scale randomized controlled trials are needed to support these results.

Determining trigger values of suspended sediment for behavioral changes in a coral reef fish. Sediment from land use increases water turbidity and threatens the health of inshore coral reefs. This study performed experiments with a damselfish, Pomacentrus moluccensis, in four sediment treatments, control (0 mg l⁻¹), 10 mg l⁻¹ (∼1.7 NTU), 20 mg l⁻¹ (∼3.3 NTU) and 30 mg l⁻¹ (∼5 NTU), to determine when sediment triggers a change in habitat use and movement. We reviewed the literature to assess how frequently P. moluccensis would experience sub-optimal sediment conditions on the reef. Preference for live coral declined from 49.4% to 23.3% and movement between habitats declined from 2.1 to 0.4 times between 20 mg l⁻¹ and 30 mg l⁻¹, suggesting a sediment threshold for behavioral changes. Inshore areas of the Great Barrier Reef, P. moluccensis may encounter sub-optimal conditions between 8% and 53% of the time. Changes in these vital processes may have long-term effects on the persistence of populations, particularly as habitat loss on coral reefs increases.

Myocardial gene expression of matched hibernating and control tissue from patients with ischemic left ventricular dysfunction. Limited data are available in humans regarding the molecular biology of hibernating myocardium (HM). The aim of this study was to identify gene expression patterns distinctive for human HM. We compared in patients with ischemic left ventricular dysfunction the gene expression profile of myocardial biopsies from HM (n = 5), as identified by positron emission tomography, with expression profiles of matched biopsies from normally perfused myocardium by using cDNA array analysis. Gene-specific polymerase chain reaction of selected genes and immunohistochemical staining of desmoplakin were used to validate our technical approach. Of 4171 transcripts examined, we identified 86 to be differentially expressed. Compared to normally perfused myocardium, 21 genes showed an increased expression and 65 genes a decreased expression in HM. Functional clustering revealed changes in the expression of genes associated with transcription, protein modification and phosphorylation, regulation of apoptosis, and intercellular communication. Besides the reported upregulation of beta-adrenergic receptor kinase-1 in heart failure, we observed new gene expression patterns, such as the upregulation of fas-activated serine/threonine kinase (FAST) or reduced expression of desmoplakin. Downregulation of desmoplakin in cardiomyocytes from HM was also seen on the protein level. Gene expression analysis provided novel insights into the pathophysiological changes of HM. Impaired intercellular communication as suggested by decreased expression of desmoplakin may be an important feature of contractile dysfunction in HM.

Influence of S9788, a new modulator of multidrug resistance, on the cellular accumulation and subcellular distribution of daunorubicin in P-glycoprotein-expressing MCF7 human breast adenocarcinoma cells. A triazinoaminopiperidine derivative synthesized as a modulator of multidrug resistance, S9788, was investigated in the human breast adenocarcinoma MCF7DXR cell line expressing P-glycoprotein. In addition to being less sensitive to daunorubicin, the resistant cell line showed dramatic alterations in the subcellular distribution of daunorubicin, as observed via fluorescence microscopy and quantified via tritiated daunorubicin nuclear distribution analysis. Compared to verapamil and cyclosporin A at 2 and 5 mumol/liter, S9788 proved to be more potent in restoring the cellular accumulation and the subcellular distribution of daunorubicin in the resistant cells. Significant activity of S9788 was observed at 2 mumol/liter, which is clinically achievable, and S9788 restored the nuclear distribution of the drug to the level observed in the parental sensitive cell line. Consequently, the restoration of the cytotoxicity of daunorubicin by S9788 was nearly complete (> 90%) at 2 mumol/liter, wheras cyclosporin A reached this level of activity at 5 mumol/liter, and verapamil was always less active at both concentrations. These results suggest that the modulation of multidrug resistance by S9788 is not only related to the enhancement of the cellular accumulation but also especially by the restoration of the subcellular distribution of the drugs to their nuclear sites of action.

The critical amino acids of a nephritogenic epitope on human Goodpasture autoantigen for binding to HLA-DRB1*1501. Anti-GBM disease is caused by autoimmunity to Goodpasture antigen on α3(IV)NC1 and had strong associations with HLA-DRB1*1501. Previous studies identified α3127-148 (P14: TDIPPCPHGWISLWKGFSFIMF) as a T cell epitope. The present study was aimed to investigate the binding capacity of P14 to HLA-DRB1*1501 and the critical amino acids for this binding. A line of EBV-transformed human B cells homozygous for HLA-DRB1*1501 was used to detect the binding capacity of peptides to HLA-DRB1*1501 using flow cytometry analysis. P14 was sequentially truncated into 8 peptides with 15 amino acids to identify the core binding motif. A set of alanine substituted peptides of P14-2 was then synthesized to identify its critical residues for binding to HLA-DRB1*1501. The structure of HLA-DR2b-Peptide-TCR complex was constructed by modeling to analyze the interaction of each amino acids of P14-2 with the HLA-DR2b molecule. P14 could bind to HLA-DRB1*1501 expressed on B cell surface. The N-terminus of P14 was the core binding motif and the truncated peptide P14-2 (DIPPCPHGWISLWKG) 128-142 had the strongest binding capacity. After sequential amino acid substitution, we found the binding capacity of P14-2 was completely lost by the substitution of cysteine (C) 132 and significantly decreased by the substitution of tryptophan (W) 136, lysine (K) 141, or glycine (G) 142, but still at a high level. The modeling showed that (C) 132 had a strong interaction with pocket 4 on the β chain of DR2b. Thus, C132, W 136, K141, and G142 were defined as the critical amino acid residues for the binding capacity of P14 to HLA-DRB1*1501. We identified α3128-142 (DIPPCPHGWISLWKG) as the core binding motif of P14 to HLA-DRB1*1501 molecule. And the critical amino acid residues for this binding were further defined as C132, W 136, K 141, and G 142.

Deception by manipulating the clock calibration influences cycle ergometer endurance time in males. It is common for athletes striving to achieve maximal effort to exercise in the presence of a visible clock. It is implicitly assumed that calibration of the clock is normal (i.e. accurate). This study was designed to test the effect of secretly manipulating the clock calibration on maximal effort as measured by endurance times in cycle ergometry. Twelve subjects (6 male and 6 female) each undertook three identical rides to exhaustion on a cycle ergometer. In one the clock was normally calibrated, in another it was calibrated 10% faster, and in the third 10% slower. Tests were conducted double blind and in fully counterbalanced orders within gender. Clocked endurance times were recorded, and later converted to real times. Analysis of clocked times revealed no significant effects. Over all subjects, real endurance times showed a significant calibration effect, being on average 18.3% (73.4s) longer when the clock ran slow, compared to normal, and 20.5% (80.8s) longer when compared to fast. Because males exercised significantly longer than females, separate analyses reveal that the calibration effect was only significant in males, 27.7% (143.2s) and 29.7% (151.2s), respectively, and present but not significant in females, 1.3% (3.6s) and 3.8% (10.5s), respectively. These results suggest that, when deceived by a visible clock running slower than normal, times to exhaustion on the cycle ergometer were significantly longer in male subjects.

Dental amalgam and antibiotic- and/or mercury-resistant bacteria. Mercury emitted from dental amalgam may select for increased numbers of antibiotic- or mercury-resistant commensal bacteria in patients and increase their risk for bacterial diseases that are resistant to common therapies. We hypothesized that the presence of dental amalgams would increase the level of mercury-, tetracycline-, ampicillin-, erythromycin-, or chloramphenicol-resistant oral and urinary bacteria as compared with levels in children receiving composite fillings. Samples were collected at baseline, 3-6 months after the initial dental treatment, and annually for 7 years of follow-up. There were no statistically significant differences between treatment groups in the numbers of bacteria growing on antibiotic- or mercury-supplemented plates. This study provided no evidence that amalgam fillings on posterior teeth influenced the level of antibiotic- or mercury-resistant oral or urinary bacteria as detected by culture.

Iron deficiency after bariatric surgery: what is the real problem? The growing prevalence of obesity explains the rising interest in bariatric surgery. Compared with non-surgical treatment options, bariatric surgery results in greater and sustained improvements in weight loss, obesity associated complications, all-cause mortality and quality of life. These encouraging metabolic and weight effects come with a downside, namely the risk of nutritional deficiencies. Particularly striking is the risk to develop iron deficiency. Postoperatively, the prevalence of iron deficiency varies between 18 and 53 % after Roux-en-Y gastric bypass and between 1 and 54 % after sleeve gastrectomy. Therefore, preventive strategies and effective treatment options for iron deficiency are crucial to successfully manage the iron status of patients after bariatric surgery. With this review, we discuss the risks and the contributing factors of developing iron deficiency after bariatric surgery. Furthermore, we highlight the discrepancy in the diagnosis of iron deficiency, iron deficiency anaemia and anaemia and highlight the evidence supporting the current nutritional recommendations in the field of bariatric research. In conclusion, we advocate for more nutrition-related research in patient populations in order to provide strong evidence-based guidelines after bariatric surgery.

The role of multidrug transporters in drug availability, metabolism and toxicity. Multidrug resistance is frequently observed when treating cancer patients with chemotherapeutic agents. A variety of ATP binding cassette (ABC) transporters, localized in the cell membrane, cause this phenomenon by extruding a variety of chemotherapeutic agents from the tumor cells. However, the major physiological role of the multidrug transporters is the protection of our cells and tissues against xenobiotics, and these transporters play a key role in drug availability, metabolism and toxicity. Three major groups of ABC transporters are involved in multidrug resistance: the classical P-glycoprotein MDR1, the multidrug resistance associated proteins (MRP1, MRP2, and probably MRP3, MRP4 and MRP5), and the ABCG2 protein, an ABC half-transporter. All these proteins were shown to catalyze an ATP-dependent active transport of chemically unrelated compounds. MDR1 (P-glycoprotein) and ABCG2 preferentially extrude large hydrophobic, positively charged molecules, while the members of the MRP family can extrude both hydrophobic uncharged molecules and water-soluble anionic compounds. By examining the interactions of the multidrug transporters with pharmacological and toxic agents, a prediction for the cellular and tissue distribution of these compounds can be achieved. Oral bioavailability, entering the blood-brain and blood-CSF barrier, reaching the fetus through the placenta, liver and kidney secretion, cellular entry for affecting intracellular targets, are all questions, which can be addressed by basic in vitro studies on the multidrug resistance proteins. Investigation of the substrate interactions and modulation of multidrug transporters may pave the way for predictive toxicology and pharmacogenomics. Here we show that by using in vitro assay systems it is possible to measure the interactions of multidrug transporters with various drugs and toxic agents. We focus on the characterisation of the MRP1 and MRP3 proteins, their relevance in chemoresistance of cancer and in drug metabolism and toxicity.

Ultrastructural features of diffuse malignant mesotheliomas. The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.

[Cardiovascular complications of cancers and anti-cancer therapy]. In our aging population the incidence of cancer is increasing in the elderly. We are thus facing a new challenge especially considering incidence of cardiovascular diseases (CVD) in this patients population. Overall survival of cancer patients has significantly improved therefore cancer has become in many cases a chronic disease. We are about to be treating patients who either may develop a new CVD or their current CVD may deteriorate. Cancer can cause various cardiovascular conditions locally (pressure in mediastinum, effusions) or systemically (increased risk of pulmonary embolism, arrhythmias, carcinoid heart disease). Medical cancer therapy can lead to congestive heart failure (CHF) per se, by anthracycline or antiHER2 therapy direct cardiac toxicity or by number of other cardiac conditions medical treatment can cause, such as accelerated arterial hypertension due to anti-angiogenic therapy (tyrosine-kinase inhibitors, bevacizumab) or even standard chemotherapy (alkylating agents, cisplatin) or overusing steroids in cancer patients. Atrial fibrillation (AFib) also contributes to CHF development. AFib in cancer patients may develop secondary to ischaemia in anaemic patients, metabolic disorders caused by cancer or treatment, pulmonary embolism, sepsis or even as a result of direct impact of cytotoxic treatment (cisplatin, ifosfamide, gemcitabine, 5-fluorouracil, etoposide). One of major risk factors for CHF is coronary artery disease (CAD), which is a very serious late sequel of cancer therapy mainly in long time cancer survivors (testicular cancer, childhood cancer, hematologic malignancies, breast cancer). CAD may develop secondary to thoracic irradiation, dyslipidemia caused by hormonal treatment or simply as results of endothelial dysfunction caused by alkylating agents. In summary, long time cancer survivors represent a subgroup of patients at great risk of developing CVD in any form. It is crucial to mention that these patients can develop typical CVD much earlier compared to standard population and therefore require special follow-up with active surveillance.Key words: anthracycline - atrial fibrillation - cardiac toxicity - heart failure - pulmonary embolism.

Severe pretibial myxedema. Although pretibial myxedema (PTM) occurs in 4.3% of patients with Graves's disease, the most severe variant, elephantiasis nostras verrucosa, is found in less than 1% of cases. The most frequent location of infiltration is the lower extremities, especially the pretibial areas and on the dorsum of the foot. The authors report one of the most severe cases of elephantiasis nostras verrucosa, following radioactive iodine therapy.

[A case of pilocytic astrocytoma in an adult]. Pilocytic astrocytoma is the most common glioma in children, in whom the majority arise in the cerebellum. In contrast, pilocytic astrocytomas are less common in adults. The most frequent locations involved are the basal ganglia, cerebellum, optic chiasm, and hypothalamus. Overall survival rates are good. The case presented involved a pilocytic astrocytoma of the right parietal lobe in a 36-year-old man. Cranial magnetic resonance imaging (MRI) revealed a small mural nodule in the wall of the cyst, with no edema around the tumor. This nodule showed a hyperintense signal on gadolinium-enhanced MRI. Computed tomography (CT) scanning revealed a hypodense right parietal lobe mass with calcification. At surgery, the cyst contents were aspirated, and the mural nodule was excised. Postoperative radiotherapy was not given. Neuropathological examination revealed a pilocytic astrocytoma (Grade I). The MIB-index was 3.3%. There has been no recurrence after 1 year of postoperative follow-up.

Evaluation of the health benefits of consumption of extruded tannin sorghum with unfermented probiotic milk in individuals with chronic kidney disease. This study investigated the chemical and nutritional composition of breakfast cereal based on whole sorghum, and the effect of its association with unfermented probiotic milk on the inflammation and oxidative stress of individuals with chronic kidney disease. Extruded sorghum breakfast meal presented higher carbohydrate concentration (approximately 71%), followed by protein (approximately 11%) and lipid (approximately 0.4%). When compared to extruded maize breakfast meal, it presented higher percentage of dietary fiber (p < 0.05), and higher content of phenolic compounds and tannin, consequently higher antioxidant activity (p < 0.05). Extruded sorghum breakfast cereal combined with unfermented probiotic milk decreased the C-reactive protein (p < 0.05) and malondialdehyde (p < 0.05) serum levels and increased the total antioxidant capacity and superoxide dismutase (p < 0.05) in patients with chronic kidney disease. Therefore, the extruded sorghum, source of tannin, anthocyanin, and dietary fiber, when consumed with unfermented probiotic milk alleviates the inflammation and oxidative stress in patients with chronic kidney disease.

[Synthesis of protein, RNA and DNA and alkylation of macromolecules in the cells of sensitive and resistant strains of ascites hepatoma 22a induced by N-methyl-N-nitrosourea]. It was shown that both in vivo and in cell suspension cultures of N-methyl-N-nitrosourea (MNM)-sensitive and resistant strains of hepatoma 22a the alkylation of macromolecules by [14C]MNM and radioactivity in the acid-soluble cell fraction and ascite fluid at different time intervals after the label injection are practically the same. The synthesis of protein, RNA and DNA in the resistant strain cells is either not impaired at all or is rapidly restored after MNM injection in vivo. The mechanism of resistance is discussed in terms of cell ability to restore DNA damage and of the lack of cell sensitivity to target cell damage due to alkylation.

Simulated internal defibrillation in humans using an anatomically realistic three-dimensional finite element model of the thorax. Determination of the optimal electrode configuration during implantable cardioverter defibrillator (ICD) implantation remains largely an empirical process. This study investigated the feasibility of using a finite element model of the thorax to predict clinical defibrillation metrics for internal defibrillation in humans. Computed defibrillation metrics from simulations of three common electrode configurations with a monophasic waveform were compared to pooled metrics for similar electrode and waveform configurations reported in humans. A three-dimensional finite element model was constructed from CT cross-sections of a human thorax. Myocardial current density distributions for three electrode configurations (epicardial patches, right ventricular [RV] coil/superior vena cava [SVC] coil, RV coil/SVC coil/subcutaneous patch) and a truncated monophasic pulse with a 65% tilt were simulated. Assuming an inexcitability threshold of 25 mA/cm2 (10 V/cm) and a 75% critical mass criterion for successful defibrillation, defibrillation metrics (interelectrode impedance, defibrillation threshold current, voltage, and energy) were calculated for each electrode simulation. Values of these metrics were within 1 SD of sample-size weighted means for the corresponding metrics determined for similar electrode configurations and waveforms reported in human clinical studies. Simulated myocardial current density distributions suggest that variations in current distribution and uniformity partially explain differences in defibrillation energy requirements between electrode configurations. Anatomically realistic three-dimensional finite element modeling can closely simulate internal defibrillation in humans. This may prove useful for characterizing patient-specific factors that influence clinically relevant properties of current density distributions and defibrillation energy requirements of various ICD electrode configurations.

Cancer cachexia, a clinical challenge. The aim of this article is to review the metabolic background of the cachectic syndrome and to analyze the recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia. The main changes associated with the development of this multiorganic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. Among the most promising approaches for the treatment of cachexia include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and antimyostatin peptides. The multitargeted approach seems essential in these treatments, which should include the combination of both nutritional support, drugs and a suitable program of physical exercise, in order to ameliorate both anorexia and the metabolic changes associated with cachexia. In addition, another very important aspect for the design of clinical trials for the treatment of cancer cachexia is to staging cancer patients in relation with the degree of cachexia, in order to start as early as possible, this triple approach in the course of the disease, even before weight loss can be detected. Cancer cachexia has two main components: anorexia and metabolic alterations and both have to be taken into consideration for the treatment of the syndrome.

Effect of total food deprivation on the proteoglycans of rat hyaline cartilage and bone. Existing hypotheses suggest that the effect of food deprivation on bone occurs via alterations in the synthesis of the organic matrix. Thus, this work was carried out to characterize the modifications of the physico-chemical properties of the proteoglycans (PG) of rat hyaline cartilage and femur. Male Wistar rats were assigned at random to a control group which was fed a standard pellet diet or to an experimental group which was given water "ad libitum" and starved over the experimental period. On day 4 or 8 the animals were administered a dose of 35S, weighed and killed. PG and glycosaminoglycans (GAG) were isolated from femurs and xyphoid cartilages. Uptake of 35S, GAG distribution patterns, PG molecular weight, molecular size of the side chains and the PG density gradient were determined. The aforementioned parameters decreased significantly after 4 and 8 days of total starvation. The GAG distribution pattern only exhibited a reduction of the Chondroitin-4-Sulphate fraction. These changes could alter the binding properties of PG to other macromolecules such as collagen which plays an important role in the ossification process.

Neutrophil-to-Lymphocyte Ratio and Platelet Count Predict Long-Term Outcome of Stage IIIC Epithelial Ovarian Cancer. Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet count (PC) in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) is controversial. A total of 370 stage IIIC EOC patients who underwent primary debulking surgery (PDS) at the Department of Gynecology of Liaoning Cancer Hospital and Institute between January 2003 and August 2016 and had full information were involved. Patients were stratified into a high NLR (H-NLR) group versus a low NLR (L-NLR) group and a high PC (H-PC) group versus a low PC (L-PC) group according to cutoff values calculated through receiver operating characteristic (ROC) curves. Prognostic values of NLR and PC for progression-free survival (PFS) and overall survival (OS) were assessed. We identified the optimal cut-off value of 3.08 for NLR and 289.5*109/L for PC. The median PFS and OS of the patients with H-NLR were shorter than L-NLR (PFS: 16.9 months vs. 19.5 months, hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.03-1.63, P = 0.022; OS: 33.5 months vs. 46.8 months, HR 1.3, 95% CI 1.01-1.66, P = 0.001). The median PFS and OS of the patients with H-PC were shorter than L-PC (PFS: 15.3 months vs. 21.6 months, HR 1.3, 95% CI 1.04-1.63, P < 0.001; OS: 37.3 months vs. 46.1 months, HR 1.14, 95% CI 0.89-1.46, P = 0.306). H-NLR and H-PC could predict poor long-term outcome of patients with FIGO stage III EOC.

Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats. Although the mechanisms are not understood, evidence suggests that 17beta-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We have reported that E2 decreases angiotensin type 1 receptors (AT1Rs) in different tissues and hypothesize that E2 exerts tonic inhibition on AT1Rs, reducing effects of ANG II. This study determined the effects of E2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular AT1R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or orchidectomy (Cas) and were treated (Ovx +/- E2; Cas +/- DHT) for 3 wk. Cortical ERalpha protein was 2.5 times greater, and ERbeta was 80% less in females vs. males (P < 0.01). Glomerular AT1R binding was lower in females than males [4,657 +/- 838 vs. 7,457 +/- 467 counts per minute (cpm), P < 0.01]. Ovx reduced ERalpha protein by 50%, whereas E2 increased ERalpha expression after Ovx. The decrease in cortical ERalpha in Ovx rats was associated with a significant increase in AT1R binding (6,908 +/- 609 cpm), and E2 prevented this increase. There was no change in ERalpha or AT1R binding following Cas +/- DHT (25 mg) treatment, although Cas did elevate cortical ERbeta (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ERalpha 150% above intact levels and profoundly decreased AT1R binding (1,824 +/- 705 cpm, P < 0.001 vs. intact male). This indicates that under normal conditions, glomerular AT1R binding is significantly greater in male than female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E2 regulates ERalpha and is inversely associated with glomerular AT1R binding, supporting our hypothesis that E2 tonically suppresses AT1Rs and suggesting a potential mechanism for the protective effects of estrogen.

Prevention of experimental diabetic cataract by Indian Ayurvedic plant extracts. The efficacy of Momordica charantia (MC), Eugenia jambolana (EJ), Tinospora cordifolia (TC) and Mucuna pruriens (MP) was assessed in the prevention of murine alloxan dibetic cataract. Alloxan (120 mg/kg) was used as the diabetogenic agent. While controls and diabetic controls did not receive any plant extract, treated rats received lyophilized aqueous extract of MC and EJ (200 mg/kg p.o.), alcohol extract of TC (400 mg/kg) and MP (200 mg/kg p.o.) every day until 4 months. Serum glucose concentration was assessed and cataracts examined with both the naked eye and through a slit lamp. Of the eight animals in the diabetic control group, four developed cortical cataract (stage IV) by day 90 while the remaining four developed it by day 100. The incidence rate of cataract in MC, EJ, TC and MP treated groups at 120 days was only 0, 0, 1 and 2. Oral feeding of MC, EJ, TC and MP extracts for 1 month produced a fall of 64.33%, 55.62%, 38.01% and 40.17%, respectively, in the serum glucose levels in comparison with the 48 h level. After 2 months of treatment, the respective values were 66.96%, 59.85%, 40.41% and 45.63%. MC and EJ prevented the development of cataract while the protective effect was less with TC and MP along with a significant reduction of plasma glucose levels (p < 0.001).

[Hypertension. New French recommendations]. The field of hypertensive medicine is constantly and rapidly changing, especially with regards to treatment. In view of its high incidence and its complications, it is a major public health concern. This explains the periodic publication of national or international recommendations with the object of informing practitioners of the latest publications in a form applicable to clinical medicine. In France, the "Agence Nationale d'Accréditation et d'Evaluation en Santé" (ANAES) has recently published its recommendations for the management of hypertension. The dominant issues are the recognition of validated electronic sphygmomanometers for measuring the blood pressure in the out-patient setting, the evaluation of individual cardiovascular risk for treatment choice, the value of non-pharmacological interventions, the tailoring of antihypertensive treatment and the abandon of the concept of equal benefit of comparable blood pressure lowering irrespective of the molecule used.

Identification and Application of Antitarget Activity Hotspots to Guide Compound Optimization. The optimization of a lead structure to a development candidate often requires removal of undesirable antitarget activities. To this end, we have developed an approach to extract antitarget activity hotspots from larger databases and to transfer this knowledge onto novel chemical series. These antitarget activity hotspots will be captured as pairs of informative molecules, which are chemically closely related, but differ significantly in biological activity. We illustrate the application of antitarget activity hotspots as informative compound pairs for the optimization of side effects in lead structures for relevant antitargets in pharmaceutical research. The use for prospective design requires establishing a structural link between known antitarget hotspot pairs and a new lead structure: we employ 3D-based similarity comparison for this task. The entire workflow serves as idea generator in early optimization. The feasibility of this approach is demonstrated in several optimization problems related to hERG inhibition, and CYP3A4 inhibition. Several structural examples demonstrate the ability of the 3D-shape searching to identify related scaffolds and the usefulness of the antitarget hotspot information to guide optimization by modulating the undesirable antitarget activity. Such a concept based on the analysis of local similarities and the transfer to 3D-related series is especially promising in those cases, where the construction of antitarget QSAR models fails to detect local SAR trends for guiding the next optimization cycle.

[Cost-effectiveness analysis of samario-153 (Quadramet) for the treatment of patients with prostate cancer and bone metastases]. To evaluate the cost-effectiveness of samarium [153Sm-EDTMP] (Quadramet) compared to conventional therapy in the treatment of pain in patients with prostate cancer and bone metastases. A decision tree model for the treatment of bone pain due to metastases was adapted to the Spanish context. The model represents the standard treatment patterns in Spain for the study population. The time-course of the model is 4 months and it computes an estimate for the cost of pain control per patient. The effectiveness data for the model derive from a randomised trial. The current treatment patterns have been established according to the consensus opinions of a group of medical experts. The cost of pain control per patient is euro 12,515.39 for conventional therapy and euro 5,595.52 for samarium-153 (Quadramet) therapy. The incremental cost-effectiveness analysis shows that samarium-153 (Quadramet) is a dominant therapy. It presents lower costs and higher efficacy than the conventional strategy. The sensitivity analyses showed these results to be robust. Samarium-153 (Quadramet) is cost-effective in treating pain in patients with prostate cancer and bone metastases.

Repeatability of measurements with a double-pass system. To evaluate the repeatability of measurements with a double-pass system. Rothschild Foundation, Paris, France. Eyes were separated into 2 control groups (<30 years old and >40 years), a post-refractive surgery group, and a cataract group. Measurements were performed using the Optical Quality Analysis System. The main outcome measures were the objective scattering index (OSI), the cutoff frequency of the modulation transfer function (MTF), and the Strehl ratio. The repeatability limit was obtained from the individual standard deviations. Forty-two eyes were evaluated. The mean OSI value was 0.47 +/- 0.11 (SD) in the younger control group, 1.73 +/- 0.26 in the older control group, 1.34 +/- 0.16 in the post-refractive surgery group, and 6.15 +/- 0.50 in the cataract group. The mean cutoff MTF value was 39.44 +/- 3.93 cycles per degree (cpd), 26.07 +/- 3.89 cpd, 28.34 +/- 2.84 cpd, and 13.3 +/- 1.69 cpd, respectively, and the mean Strehl ratio, 0.234 +/- 0.023, 0.146 +/- 0.021, 0.169 +/- 0.023, and 0.098 +/- 0.010, respectively. The repeatability limit for the whole population was 0.841 (33.5%) for the OSI, 8.499 (31.1%) for the cutoff MTF, and 0.051 (31%) for the Strehl ratio. The repeatability limit was good and equivalent for the OSI, the MTF, and the Strehl ratio values. There was a wide interval between the normal and pathologic threshold for OSI measurements, indicating that the reliability of the double-pass device complies with the requirements for quantitative assessment of scattering. No author has a financial or proprietary interest in any material or method mentioned.

Activation of endoproteolytic processing of insulin-like growth factor-II in fetal, early postnatal, and pregnant rats and persistence of circulating levels in postnatal life. The process of posttranslational modifications of IGF-II likely has important physiological consequences. In addition to mature IGF-II, glycosylated proIGF-II(156-amino acid peptide) and two glycosylated big IGF-II forms, IGF-II(1-104) and IGF-II(1-87), have been identified in the human circulation. Due to lack of an appropriate methodology, different IGF-II isoforms have not been demonstrated and characterized in the rat circulation, thus preventing a better understanding of the physiological and pathological roles of IGF-II. In the present study, we characterized each IGF-II form and assessed its content in the rat circulation throughout life time by using a highly sensitive Western blot analysis, which is void of the IGF binding protein interference and distinguished all IGF-II forms. For the first time, we demonstrated the presence of IGF-II variants, including proIGF-II, IGF-II(1-87), and mature IGF-II, in the rat circulation during postnatal life, challenging the current impression that IGF-II is absent from sera of adult rats. ProIGF-II is glycosylated and is the predominant form in the rat circulation. Endoproteolytic processing of proIGF-II was clearly activated in fetal, neonatal, and pregnant rats, likely reflecting its involvement in fetal development through the generation of specific forms of IGF-II (e.g. mature IGF-II) that are required for their distinct biological functions. Taken together, our data also suggest that serum IGF-II profiles may reflect underlying physiological conditions.

Systematic qualitative and quantitative assessment of anthocyanins, flavones and flavonols in the petals of 108 lotus (Nelumbo nucifera) cultivars. Petal colour is one of the major characteristics that determine the ornamental value of lotus. To assess the contribution of different flavonoids to this character, composition and content of anthocyanins, flavones and flavonols were analysed through high performance liquid chromatography coupled with photodiode array detection tandem electrospray ionisation triple quad mass spectrometry in 108 lotus cultivars with red, pink, yellow, white and red/white pied petal colours. Totally, five anthocyanins and fourteen flavones and flavonols were detected and quantified. In general, the yellow, white and pied species hardly contained any anthocyanins; red cultivars contain more than pink cultivars. Among the five anthocyanins, malvidin 3-O-glucoside was the most abundant one in all the cultivars that contain anthocyanin. The fourteen flavones and flavonols belonged to four groups based on their aglycones. Except for the yellow cultivars, kaempferol-derivatives were the most abundant one. These data might be helpful in lotus breeding for different colours.

Performance of female college students and sexual abuse survivors on the Brief Symptom Inventory. The relation between childhood molestation and current adjustment, as measured by the Brief Symptom Inventory (BSI), was examined among women college students. Results suggest that the normative data available for the BSI are inappropriate for interpreting the performance of women college students and, particularly, students who have survived sexual abuse.

Layer-by-layer assembly of silica nanoparticles on 3D fibrous scaffolds: enhancement of osteoblast cell adhesion, proliferation, and differentiation. Silica nanoparticles were applied onto the fiber surface of an interbonded three-dimensional polycaprolactone fibrous tissue scaffold by an electrostatic layer-by-layer self-assembly technique. The nanoparticle layer was found to improve the fiber wettability and surface roughness. Osteoblast cells were cultured on the fibrous scaffolds to evaluate the biological compatibility. The silica nanoparticle coated scaffold showed enhanced cell attachment, proliferation, and alkaline phosphatase activities. The overall results suggested that interbonded fibrous scaffold with silica nanoparticulate coating could be a promising scaffolding candidate for various applications in bone repair and regeneration.

Attenuation of doxorubicin-induced cardiotoxicity in a human in vitro cardiac model by the induction of the NRF-2 pathway. Dose-dependent cardiotoxicity is the leading adverse reaction seen in cancer patients treated with doxorubicin. Currently, dexrazoxane is the only approved drug that can partially protect against this toxicity in patients, however, its administration is restricted to those patients receiving a high cumulative dose of anthracyclines. Investigations into the mechanisms of cardiotoxicity and efforts to improve cardioprotective strategies have been hindered by the limited availability of a phenotypically relevant in vitro adult human cardiac model system. Here, we adapted a readily reproducible, functional 3D human multi-cell type cardiac system to emulate patient responses seen with doxorubicin and dexrazoxane. We show that administration of two NRF2 gene inducers namely the semi-synthetic triterpenoid Bardoxolone methyl, and the isothiocyanate sulfurophane, result in cardioprotection against doxorubicin toxicity comparable to dexrazoxane as evidenced by an increase in cell viability and a decrease in the production of reactive oxygen species. We further show a synergistic attenuation of cardiotoxicity when the NRF2 inducers and dexrazoxane are used in tandem. Taken together, our data indicate that the 3D spheroid is a suitable model to investigate drug induced cardiotoxicity and we reveal an essential role of the NRF2 pathway in cardioprotection providing a novel pharmacological mechanism and intervention route towards the alleviation of doxorubicin-induced toxicity.

Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period. To evaluate thin-section computed tomography findings of patients with severe acute respiratory syndrome (SARS) in the convalescent period and to correlate the results with clinical parameters and lung function tests. Ninety-nine severe acute respiratory syndrome patients with persistent changes on follow-up chest radiography were included. One hundred seventy computed tomography examinations at baseline (n=70), 3 months (n=56), and 6 months (n=44) were retrospectively evaluated to determine the extent of ground-glass opacification, reticulation, and total parenchymal involvement. Patients' demographic information, clinical information during treatment, and results of lung function tests at 3 and 6 months were correlated with computed tomography findings. A significant serial improvement in the extent of overall ground-glass opacification, overall reticulation, and total parenchymal involvement was observed (P <0.01). Advanced age, previous intensive care unit admission, mechanical ventilation, alternative treatment, higher peak lactate dehydrogenase, and peak radiographic involvement during treatment showed a positive correlation with overall reticulation and total parenchymal involvement at 6 months. There was a significant negative correlation between overall reticulation and total parenchymal involvement with diffusion capacity adjusted for hemoglobin at 3 and 6 months (P <0.01). Lung changes on thin-section computed tomography of severe acute respiratory syndrome patients improved with time during the convalescent period and showed a significant correlation with advanced age, parameters indicating severe illness, and diffusion capacity adjusted for hemoglobin on follow-up.

Posaconazole. Posaconazole is a novel second-generation Triazole oral antifungal agent. It is highly effective in the prophylaxis of invasive fungal infections in immunocompromised patients. It is used as a first-line agent as well as for salvage therapy in invasive fungal infections including aspergillosis, oropharyngeal and esophageal candidiasis. It has a good adverse effect profile. With the rising incidence of invasive fungal infections due to the HIV pandemic and medical advancements in transplantation and cancer therapy, these features make posaconazole a valuable addition in the family of antifungal agents.

Down-Regulation of MiR-150 Alleviates Inflammatory Injury Induced by Interleukin 1 via Targeting Kruppel-Like Factor 2 in Human Chondrogenic Cells. Interleukin-1 (IL-1) is known to be involved in cartilage degeneration following joint injury or due to osteoarthritis. In the present study, we explored the effects of miR-150 on IL-1-stimulated human chondrogenic cells ATDC5. ATDC5 cells were transfected with the mimic, inhibitor or negative controls specific for miR-150, and subsequently treated by IL-1. CCK8 assay, PI and FITC-conjugated Annexin V double-staining, Western blot, qRT-PCR and ELISA assay were performed to determine the changes of cell viability, apoptosis, and the release of pro-inflammatory cytokines. Targeting relationship between miR-150 and KLF2 was detected by dual luciferase activity assay. IL-1 reduced cell viability, induced apoptosis, and enhanced the expression and release of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) in ATDC5 cells. IL-1 also increased the expression of miR-150. Suppression of miR-150 alleviated IL-1-induced cell damage in ATDC5 cells, while overexpression of miR-150 resulted in an opposite impact. KLF2 was negatively regulated by miR-150, and it was proved as a target gene of miR-150. KLF2 overexpression exhibited protective actions in IL-1-injured ATDC5 cells, even if miR-150 was suppressed in cell. Moreover, IL-1-induced activation of NF-kB and Notch pathways was alleviated by KLF2 overexpression. Suppression of miR-150 led to up-regulation of KLF2, which in turn protected ATDC5 cells against IL-1-induced injury.

Full-Endoscopic Lumbar Foraminoplasty for Symptomatic Cement Leakage with Exiting Nerve Root Impingement. Foraminal stenosis, a common disorder occurring in elderly patients, is often caused by narrowing of the foramen, resulting in the confinement of neural structures by the tissue and vertebrae. Full-endoscopic lumbar foraminoplasty (FELF) is an effective treatment option for patients with foraminal stenosis. However, to the best of our knowledge, no previous study has reported the treatment of symptomatic cement leakage. We report a case of symptomatic cement leakage treated with FELF with the patient under local anesthesia. An 85-year-old woman was admitted to our spine unit because of lower back pain. The patient had presented with lower back pain and new-onset left thigh pain after vertebroplasty performed 3 months previously. The patient was not able to walk and was bedridden. To overcome this problem, T12 percutaneous vertebroplasty and left transforaminal L3-L4 foraminoplasty was performed with the patient under local anesthesia. After surgery, the patient was able to walk and was discharged 4 days postoperatively. The present report has shown that FELF can successfully remove symptomatic cement leakage, resulting in pain relief.

Incidence and Phenotype at Diagnosis of Very-early-onset Compared with Later-onset Paediatric Inflammatory Bowel Disease: A Population-based Study [1988-2011]. Very-early-onset inflammatory bowel disease [VEO-IBD] is a form of IBD that is distinct from that of children with an older onset. We compared changes over time in the incidence and phenotype at diagnosis between two groups according to age at IBD diagnosis: VEO-IBD diagnosed before the age of 6 years, and early-onset IBD [EO-IBD] diagnosed between 6 and 16 years of age. Data were obtained from a cohort enrolled in a prospective French population-based registry from 1988 to 2011. Among the 1412 paediatric cases [< 17 years], 42 [3%] were VEO-IBD. In the VEO-IBD group, the incidence remained stable over the study period. In contrast, the incidence of EO-IBD increased from 4.4/105 in 1988-1990 to 9.5/105 in 2009-2011 [+116%; p < 10-4]. Crohn's disease [CD] was the most common IBD, regardless of age, but ulcerative colitis [UC] and unclassified IBD were more common in VEO-IBD cases [40% vs 26%; p = 0.04]. VEO-IBD diagnosis was most often performed in hospital [69% vs 43%; p < 10-3]. Rectal bleeding and mucous stools were more common in patients with VEO-IBD, whereas weight loss and abdominal pain were more frequent in those with EO-IBD. Regarding CD, isolated colonic disease was more common in the VEO-IBD group [39% vs 14%; p = 0.003]. In this large population-based cohort, the incidence of VEO-IBD was low and stable from 1988 to 2011, with a specific clinical presentation. These results suggest a probable genetic origin for VEO-IBD, whereas the increase in EO-IBD might be linked to environmental factors.

Site-Specific Labelling of Native Mammalian Proteins for Single-Molecule FRET Measurements. Human cells are complex entities in which molecular recognition and selection are critical for cellular processes often driven by structural changes and dynamic interactions. Biomolecules appear in different chemical states, and modifications, such as phosphorylation, affect their function. Hence, using proteins in their chemically native state in biochemical and biophysical assays is essential. Single-molecule FRET measurements allow exploration of the structure, function and dynamics of biomolecules but cannot be fully exploited for the human proteome, as a method for the site-specific coupling of organic dyes into native, non-recombinant mammalian proteins is lacking. We address this issue showing the site-specific engineering of fluorescent dyes into human proteins on the basis of bioorthogonal reactions. We show the applicability of the method to study functional and post-translationally modified proteins on the single-molecule level, among them the hitherto inaccessible human Argonaute 2.

4-oxo retinoic acid for refractory acute promyelocytic leukemia in children with all-trans retinoic acid therapy. Therapy with all-trans retinoic acid (ATRA) achieves complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), but the efficacy is reported to relate to plasma ATRA level after oral administration. The pharmacokinetics of ATRA and 4-oxo all-trans retinoic acid (4-oxo ATRA), a metabolite of ATRA, were studied in four children with APL at the time of initial oral administration. After administration of ATRA at a dose of 30 mg/m2, the peak plasma ATRA level was 20-741 ng/ml and was reached at 60-120 min. The patient with the lowest peak plasma level did not achieve complete remission and had a very high 4-oxo ATRA level compared to the patients with complete remission. These findings suggest that accelerated metabolism of ATRA plays a role in the failure of this agent in the patients without remission.

Trichinellosis surveillance--United States, 1997-2001. Trichinellosis is a parasitic disease caused by tissue-dwelling roundworms of the species Trichinella spiralis. The organism is acquired by eating Trichinella-infected meat products. The disease has variable clinical manifestations, ranging from asymptomatic to fatal. In the United States, trichinellosis has caused hundreds of preventable cases of illness and occasional deaths. The national trichinellosis surveillance system has documented a steady decline in the reported incidence of this disease, as well as a change in its epidemiology. This report summarizes surveillance data for trichinellosis in the United States for 1997-2001. Trichinellosis became a nationally reportable disease in 1966, but statistics have been kept on the disease since 1947. The national trichinellosis surveillance system is a passive system that relies on existing resources at the local, state, and federal levels. Cases are diagnosed based on clinical history with laboratory confirmation. Cases are reported weekly to CDC through the National Electronic Telecommunications System for Surveillance (NETSS). Detailed data regarding signs and symptoms, diagnostic tests, and food consumption are gathered by using a supplementary standardized surveillance form and are reported to CDC by fax or mail. This information is compared with NETSS data several times a year by CDC staff. Discrepancies are reviewed with the state health departments. The purpose of the surveillance system is to determine the incidence of trichinellosis, to maintain awareness of the disease, to monitor epidemiologic changes, to identify outbreaks, to guide prevention efforts, and to measure the effectiveness of those efforts. Although trichinellosis was associated historically with eating Trichinella-infected pork from domesticated sources, wild game meat was the most common source of infection during 1997-2001. During this 5-year period, 72 cases were reported to CDC. Of these, 31 (43%) cases were associated with eating wild game: 29 with bear meat, one with cougar meat, and one with wild boar meat. In comparison, only 12 (17%) cases were associated with eating commercial pork products, including four cases traced to a foreign source. Nine (13%) cases were associated with eating noncommercial pork from home-raised or direct-from-farm swine where U.S. commercial pork production industry standards and Regulations do not apply. The majority of the decline in reported trichinellosis cases is a result of improved observance of standards and regulations in the U.S. commercial pork industry, which has altered animal husbandry practices resulting in reduced Trichinella prevalence among swine. Because of the change in epidemiology of trichinellosis and the continued occurrence of cases among consumers of wild game meat and noncommercial pork, more targeted public education is needed to further reduce the incidence of this disease.

Surface oxidation of UHMWPE for orthopedic use increases apoptosis and necrosis in human granulocytes. Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis is often sterilized with gamma-rays and the subsequent oxidation was suggested to favor the in vivo wear. UHMWPE debries produced by wearing trigger an inflammatory response that can led to the implant failure. To explore direct effects of UHMWPE oxidation on immunocompetent cells and their possible role in the prosthesis failure, peripheral blood cells (PBCs) have been grown for 24 and 48 h onto plastic (Ct), UHMWPE (PE) and heat oxidized UHMWPE (PEOx) discs. PBCs necrosis and apoptosis were assessed in flow cytometry using propidium iodide staining. After 24 h, no statistically significant differences were observed in the amount of apoptotic and necrotic cells between Ct, PE and PEOx samples while, after 48 h, both necrotic and apoptotic cells were strongly increased in PEOx samples where also the granulocytes population appeared strongly reduced (6.3+/-1.1%) compared to PE (10.5+/-1.5%) and Ct (15.1+/-0.9%) samples. We conclude that surface oxidation may interfere with prosthetic failure and/or integration via granulocytes modulation.

Gerdy's tubercle osteotomy for the treatment of coronal fractures of the lateral femoral condyle. Coronal fractures of the femoral condyle (Hoffa fractures) are intraarticular fractures that are commonly treated surgically by open reduction and internal fixation. Surgical fixation is demanding because anatomic reduction is mandatory and adequate exposure is often difficult. Herein we describe a new technique that permits excellent visualization and fixation of lateral Hoffa fractures based on osteotomy of Gerdy's tubercle and reflection of the attached iliotibial band.

Descriptive sensory analysis and free sugar contents of chestnut cultivars grown in North America. Various chestnut (Castanea) species and cultivars are currently produced and marketed in North America including Peach, Qing, AU-Homestead, Eaton, Marrone di Castel del Rio, and Colossal. In spite of their availability in the marketplace, similarities in sensory characteristics of chestnuts, as well as their unique attributes, have not been explored. Therefore, the objectives of this study were to evaluate texture and flavor attributes of commonly grown chestnut cultivars using descriptive sensory analysis and to quantify their free sugar content by gas-liquid chromatography. Twenty-three sensory terms were used for descriptive analysis of roasted chestnuts. All but two attributes (raw impression and fermented) were common to all chestnut cultivars. Peelability, initial firmness, dissolvability, and mustard, sweet, and sour flavors varied among cultivars. Sucrose, the predominant free sugar in chestnuts, was greatest in Colossal chestnuts from California, while those of Peach had the lowest content. Glucose, fructose and maltose were also present in chestnuts. This study demonstrated that cultivars of various chestnut species share several common sensory attributes, but differ in intensity ratings of six descriptors. Of these attributes, sweetness has been associated with consumer acceptance and can be promoted in the marketplace.

Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels. Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

Time-of-day corrections in measures of aircraft noise exposure. Results of a socio-acoustic study of human reaction to aircraft noise around Australian airports are described. The relative importance of night, evening, and daytime operations in determining overall reaction is assessed using a correlation analysis procedure. The results indicate that night-time weightings used in most existing noise exposure indices including NEF and DNL, are too large. However, other evidence suggests that both night and evening weightings should be greater than 0 dB. The optimal weightings found were about 3 dB for night-time operations and 9 dB for evening operations. However, other considerations indicate that in a practical noise index it may be more reasonable to apply a weighting of about 6 dB during both night and evening hours.

Downregulation of γ-catenin inhibits CML cell growth and potentiates the response of CML cells to imatinib through β-catenin inhibition. γ-catenin plays different roles in different types of tumors, and its role in chronic myeloid leukemia (CML) cells has yet to be identified. In our study, two CML cell lines (K562, KU812) had higher γ-catenin expression levels compared to five types of BCR-ABL-negative leukemia cells. Knockdown of the expression of BCR-ABL resulted in downregulation of γ-catenin. Furthermore, downregulation of γ-catenin by siRNA inhibited the proliferation and colony formation of CML cells and the expression of the c-Myc and cyclin D1 genes; downregulation of γ-catenin also potentiated the effects of imatinib (inhibiting CML cell proliferation and inducing apoptosis) and suppressed the anti-apoptotic genes Bcl-xL and survivin. We also showed that downregulation of γ-catenin suppressed the phosphorylation of STAT5, promoted the phosphorylation of β-catenin and reduced the translocation of β-catenin into the nucleus, although there were no effects on the total level of β-catenin expression in the whole cells. Furthermore, downregulation of γ-catenin was found to promote glycogen synthase kinase-3β (GSK3β) and inhibit its phosphorylation. Collectively, our results suggest that γ-catenin is an oncogene protein in CML that can be regulated by BCR-ABL and that suppression of γ-catenin inhibits CML cell growth and potentiates the effects of imatinib on CML cells through inhibition of the activation of STAT5 and suppression of β-catenin by activating GSK3β.

[Psychological stress in oncology: the role of glucocorticoids]. During the last years, the correlations between biological processes, psychological adjustment and stress disorders have received increasing attention and a growing body of research results has been published in the general literature. In the realm of psycho-oncology, however, conceptual models on this topic and studies aimed at their validation have remained relatively scanty. On the basis of our observations and available literature in the field of post-traumatic and depressive stress disorders in oncology, we have proposed to apply the concept of allostatic load to the study and understanding of the psychological experience of cancer. This strategy has led us to the formulation of a novel classification of adjustment disorders in oncology and the creation of the clinical entity named "cancer-specific stress syndrome". Depending on clinical presentation of the syndrome, one distinguishes three subtypes, namely the depressive, post-traumatic and "dysallostatic" (mixed) forms. In the present paper, we examine the role of glucocorticoids and their relationships with one of the basic components of allostatic load--a failure to counter-regulate the immune system by the hypothalamic-pituitary-adrenal axis--in the physiopathology of stress disorders in oncology. Conflicting theories are presented--glucocorticoid cascade versus insufficient glucocorticoid signal transmission--and studies measuring potential correlations between stress and cortisol in oncology are critically reviewed. The results of this process provide substantial support for the application of the allostatic load model and post-traumatic phenomenology, but important advances have yet to be achieved before definitive conclusions can be established in this field. Such advances could lead to profound changes in the way we understand and treat psychological distress in patients with cancer, both pharmacologically and psychotherapeutically.

Surface areas of the cerebral cortex of mammals determined by stereological methods. The surface areas of the cerebral cortex excluding archipallium of 20 human, 11 cetacean, 6 carnivore, and 5 marsupial brains were determined by stereological methods. There exist rather strict relationships between volume, length of superficially exposed gyri, and cortical surface area.

Charge current driven by spin dynamics in disordered Rashba spin-orbit system. Pumping of charge current by spin dynamics in the presence of the Rashba spin-orbit interaction is theoretically studied. Considering a disordered electron, the exchange coupling and spin-orbit interactions are treated perturbatively. It is found that the dominant current induced by spin dynamics is interpreted as a consequence of the conversion from spin current via the inverse spin Hall effect. We also find that the current has an additional component from a fictitious conservative field. The results are applied to the case of a moving domain wall.

CONE: Convex-Optimized-Synaptic Efficacies for Temporally Precise Spike Mapping. Spiking neural networks are well suited to perform time-dependent pattern recognition problems by encoding the temporal dimension in precise spike times. With an appropriate set of weights, a spiking neuron can emit precisely timed action potentials in response to spatiotemporal input spikes. However, deriving supervised learning rules for spike mapping is nontrivial due to the increased complexity. Existing methods rely on heuristic approaches that do not guarantee a convex objective function and, therefore, may not converge to a global minimum. In this paper, we present a novel technique to obtain the weights of spiking neurons by formulating the problem in a convex optimization framework, rendering it be compatible with the established methods. We introduce techniques to influence the weight distribution and membrane trajectory, and then study how these factors affect robustness in the presence of noise. In addition, we show how the existence of a solution can be determined and assess memory capacity limits of a neuron model using synthetic examples. The practical utility of our technique is further assessed by its application to gait-event detection using the experimental data.

Liposuction and the platysma muscle. Adequate correction of an obtuse cervicomental contour frequently requires not only fat removal but tightening of the platysma muscle as well. The introduction of liposuction as a safe and effective technique for removing subcutaneous fat and sculpturing the neck has created some confusion as to the need, if any, to manipulate the platysma muscle.

Chemokine receptors in gastric MALT lymphoma: loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma. Chemokine receptors have a crucial role in the development and progression of lymphoid neoplasms. To determine the chemokine receptor expression profile in gastric mucosa-associated lymphoid tissue (MALT) lymphoma, we performed an expression analysis of 19 chemokine receptors at mRNA levels by using real-time RT-PCR, as well as of five chemokine receptors--CCR8, CCR9, CXCR4, CXCR6 and CXCR7--by immunohistochemistry on human tissue samples of Helicobacter pylori-associated gastritis, gastric MALT lymphoma and gastric extranodal diffuse large B-cell lymphoma originating from MALT lymphoma (transformed MALT lymphoma). Following malignant transformation from H. pylori-associated gastritis to MALT lymphoma, an upregulation of CCR7, CXCR3 and CXCR7, and a loss of CXCR4 were detected. The transformation of gastric MALT lymphomas to gastric extranodal diffuse large B-cell lymphoma was accompanied by upregulation of CCR1, CCR5, CCR7, CCR8, CCR9, CXCR3, CXCR6, CXCR7 and XCR1. Remarkably, CXCR4 expression was exclusively found in nodal marginal B-cell lymphomas and nodal diffuse large B-cell lymphomas but not at extranodal manifestation sites, ie, in gastric MALT lymphomas or gastric extranodal diffuse large B-cell lymphomas. Furthermore, the incidence of bone marrow infiltration (16/51 with bone marrow involvement vs 35/51 with bone marrow involvement; Spearman ρ=0467 P<0.001) positively correlated with CXCR4 expression. CXCL12, the ligand of CXCR4 and CXCR7, was expressed by epithelial, endothelial and inflammatory cells, MALT lymphoma cells and was most strongly expressed by extranodal diffuse large B-cell lymphoma cells, suggesting at least in part an autocrine signaling pathway. Our data indicate that CXCR4 expression is associated with nodal manifestation and a more advanced stage of lymphomas and hence, might serve as useful clinical prognostic marker.

Expression of proliferative markers in ameloblastomas and malignant odontogenic tumors. To compare the proliferative activity in ameloblastoma and malignant odontogenic tumors, as assessed by Ki-67 immunostaining and determine whether expression of substance P (SP) and NK-1 receptor (NK-1R) is related to cell proliferation in these tumors. Immunohistochemistry was used to evaluate protein expression in 44 benign and malignant odontogenic tumors from 39 patients. Immunohistochemistry was performed with anti-SP, anti-NK-1R, and anti-Ki-67 monoclonal antibodies, and the clinical and pathological data of the patients with odontogenic tumor were evaluated. Expression of Ki-67 in malignant odontogenic tumors was significantly higher than in ameloblastomas (P < 0.001), and the expression level was associated with higher expression of NK-1R. Among the ameloblastomas, there was significantly higher expression of Ki-67 in peripheral ameloblastic-like cells (3.3 ± 4.1) than in stellate reticulum-like cells (2.6 ± 3.7) (P = 0.04). In the majority of tissue locations of the malignant tumors, expression of SP and NK-1R was positively correlated with higher expression of Ki-67. These findings show that the expression level of Ki-67 in ameloblastomas was positively correlated with the rate of growth of odontogenic tumors. Overexpression of NK-1R complex in malignant odontogenic tumors could be part of the trigger stimulus that results in higher proliferative activity of the tumor.

Production of active mouse DNA polymerase delta in bacteria. The entire cDNA encoding the large subunit of mouse DNA polymerase delta (mPol delta; EC 2.7.7.7) has been cloned and expressed in various bacterial expression systems. A soluble protein could only be obtained when mPol delta was produced as a glutathione S-transferase (GST) fusion protein and the incubation temperature of the expression strain was reduced to 30 degrees C. After purification over a glutathione-Sepharose column, the fractions containing the recombinant (re-) fusion protein showed both DNA Pol and 3'-->5' Exo activities. In situ activity gel analysis indicated that the Pol activity resides in the re-protein. This activity, however, was not stimulated by proliferating cell nuclear antigen (PCNA). Our data are discussed in the view of the findings of Goulian et al. [J. Biol. Chem., 265 (1990) 16402-16411] that the second mPol delta subunit, the 48-kDa protein, might play an important role in DNA Pol delta-PCNA interaction.

Polymorphisms of the DNA repair gene EXO1 modulate cognitive aging in old adults in a Taiwanese population. Evidence indicates that the age-related neuropathological mechanisms associated with DNA repair genes may contribute to cognitive aging and Alzheimer's disease. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within 155 DNA repair genes may be linked to cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 3,730 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) was administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that out of 1,652 SNPs, the rs1776181 (P = 1.47 × 10-5), rs1776177 (P = 8.42 × 10-7), rs1635510 (P = 7.97 × 10-6), and rs2526698 (P = 7.06 × 10-6) SNPs in the EXO1 gene were associated with cognitive aging. The association with these SNP remained significant after performing Bonferroni correction. Additionally, we found that interactions between the EXO1 and RAD51C genes influenced cognitive aging (P = 0.002). Finally, we pinpointed the influence of interactions between EXO1 and physical activity (P < 0.001) as well as between DCLRE1C and physical activity (P < 0.001). Our study indicated that DNA repair genes may contribute to susceptibility in cognitive aging independently as well as through gene-gene and gene-physical interactions.

Monitoring of cyclic GMP during cerebellar microdialysis in freely-moving rats as an index of nitric oxide synthase activity. The nitric oxide synthase/cyclic GMP pathway has been studied in vivo in the adult rat cerebellum by monitoring the levels of extracellular cyclic GMP during microdialysis in conscious unrestrained animals. The basal cyclic GMP efflux was concentration-dependently reduced upon local infusion of the nitric oxide synthase inhibitor NG-nitro-L-arginine (10 microM-1 mM). The nitric oxide donor S-nitroso-N-penicillamine, perfused through the dialysis probe at 1 mM, increased by about 200% the extracellular levels of cyclic GMP. The glutamate receptor agonist N-methyl-D-aspartate (500 microM) produced a cyclic GMP response which was abolished by the selective receptor antagonist D-2-amino-5-phosphonovaleric acid (500 microM) or by NG-nitro-L-arginine (10 microM). The elevation of cyclic GMP levels caused by local infusion of 500 microM N-methyl-D-aspartate was also abolished by parenteral administration of the N-methyl-D-aspartate channel blocker dizocilpine (0.4 mg/kg, i.p.). Local perfusion of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (1 mM) increased by about 150% the extracellular levels of cyclic GMP. It is concluded that cyclic GMP collected during in vivo microdialysis reflects nitric oxide synthase activity in the rat cerebellum. The technique may be utilized to investigate the pathophysiology and the pharmacology of the nitric oxide/cyclic GMP pathway in the cerebellum of living animals.

[Prospective study of gracilis muscle repair of complex rectovaginal fistula and rectourethral fistula]. To assess the efficacy and experience of gracilis muscle transposition for complex rectovaginal fistula (RVF) and rectourethral fistula (RUF). Nineteen patients underwent gracilis muscle transposition for complex RVF and RUF from May 2009 to November 2011 in the Beijing Shijitan Hospital and the clinical data were prospectively collected. The success rate and complications were recorded. SF-36 quality of life score, Wexner fecal incontinence score, and female sexual function score before surgery and 6 months after surgery were recorded. In 19 patients, there were 8 males (RUF) and 11 females (RUF). The times of failed attempt repair preoperatively ranged from 0-3 (mean, 1.0). The diameter of the fistula ranged from 0.5-3.0 cm (mean, 1.6), and all fistulas located above the sphincter. The operative time ranged from 145-400 minutes (median, 240). The postoperative hospital stay ranged from 10-39 days (median 21). Early postoperative complications included thigh pain and numbness in 2 cases, leg numbness in 2 cases. No long-term complications were noticed. The follow-up period ranged from 6-35 months (median, 18). The gracilis muscle transposition had a healing rate of 94.7% (18/19). As compared with the preoperative level, Wexner score decreased from 10.0±8.8 to 2.9±5.8, and the continence function improved significantly (P=0.002). Sexual function score of 11 female patients increased from 1.0±1.8 to 4.0±4.0, and the sexual function had a significant improvement after surgery (P=0.022). SF-36 quality of life scores improved significantly (P<0.001). Gracilis muscle transposition for complex rectovaginal fistula and rectourethral fistula has high success rate with mild and rare complications.

The prognostic value of 2D strain in assessment of the right ventricle in patients with dilated cardiomyopathy. Several studies have been reported using right ventricular (RV) strain as a method for evaluating RV function in patients with various cardiovascular diseases; however, the clinical relevance of RV strain in dilated cardiomyopathy (DCM) patients with sinus rhythm is unknown. The aim of this study was to investigate the relationship between RV strain and adverse events in DCM patients with sinus rhythm. We enrolled 143 DCM patients with sinus rhythm who had been first diagnosed, evaluated, and followed at Sanggye Paik Hospital between March 2013 and August 2017. We performed echocardiography and measured RV strain values using the apical four-chamber view. The mean age was 64.6 years. During the median follow-up period of 40.0 months, adverse cardiovascular events developed in 21 patients (14.7%). By Cox proportional hazards multivariate analysis, only RV free wall longitudinal strain (RV-FWLS) independently predicted the primary outcome. Receiver-operating characteristic curve analysis showed that the optimal RV-FWLS cut-off value to identify patients with an event was -16.5% (area under the curve = 0.703, P = 0.003). When we divided the subjects into two groups based on the RV-FWLS of -16.5%, patients with RV-FWLS <-16.5% showed more favourable clinical outcomes than that in those with RV-FWLS ≥-16.5% (log-rank test, P < 0.001). RV-FWLS was associated with a significant prognostic impact in DCM patients with sinus rhythm.

Factors associated with clinical and structural outcomes after arthroscopic rotator cuff repair with a suture bridge technique in medium, large, and massive tears. This study was conducted to evaluate clinical outcomes, maintenance of repair integrity, and retear rate after arthroscopic rotator cuff repair by a suture bridge technique among patients with medium, large, and massive rotator cuff tears. We evaluated 147 patients who had undergone arthroscopic rotator cuff repair. Clinical and functional evaluations were performed with the Constant and University of California-Los Angeles scores. All patients were confirmed to have magnetic resonance imaging evidence of tendon healing at least 12 months postoperatively. The average postoperative time to follow-up magnetic resonance imaging was 23.4 months (range, 12-48 months). A total of 25 (17.0%) retears were observed. All clinical outcome scores were improved significantly at follow-up. Larger intraoperative tear sizes were correlated with higher retear rates. The incidence of retear was also higher in cases in which the preoperative fatty degeneration grade was higher. The incidence of retear increased with age and in the heavy worker group (e.g., farmers, carriers, car mechanics) but was not statistically significant. Arthroscopic rotator cuff repair by a suture bridge technique yields improvements in clinical outcome measures and a relatively high degree of patient satisfaction despite the fact that repair integrity is not maintained in many cases.

[Basal blood level of adrenocorticotropic hormone in diabetes mellitus patients]. A study was carried out on the basal blood level of adrenocorticotropic hormone (ACTH) in 355 patients with diabetes mellitus by a radioimmunologic method. A significant though quantitatively slight elevation of its average value was established versus that of the healthy controls. The changes established reveal a light dependence on sex, age, duration of the disease, type of diabetes, kind of medicamentosus treatment and blood sugar level. No correlation was also established between the hormonal changes and the vasculardegenerative complications with the exception of its insignificantly higher average value in the patients with proliferative retinopathy. The compensation of diabetes leads to normalization of the hormonal level.

Brain responses to changes in speech sound durations differ between infants with and without familial risk for dyslexia. A specific learning disability, developmental dyslexia, is a language-based disorder that is shown to be strongly familial. Therefore, infants born to families with a history of the disorder are at an elevated risk for the disorder. However, little is known of the potential early markers of dyslexia. Here we report differences between 6-month-old infants with and without high risk of familial dyslexia in brain electrical activation generated by changes in the temporal structure of speech sounds, a critical cueing feature in speech. We measured event-related brain responses to consonant duration changes embedded in ata pseudowords applying an oddball paradigm, in which pseudoword tokens with varying /t/ duration were presented as frequent standard (80%) or as rare deviant stimuli (each 10%) with an interval of 610 msec between the stimuli. The infants at risk differ from control infants in both their initial responsiveness to sounds per se and in their change-detection responses dependent on the stimulus context. These results show that infants at risk due to a familial background of reading problems process auditory temporal cues of speech sounds differently from infants without such a risk even before they learn to speak.

The cold shock response of Lactobacillus casei: relation between HPr phosphorylation and resistance to freeze/thaw cycles. When carrying out a proteome analysis with a ptsH3 mutant of Lactobacillus casei, we found that the cold shock protein CspA was significantly overproduced compared to the wild-type strain. We also noticed that CspA and CspB of L. casei and CSPs from other organisms exhibit significant sequence similarity to the C-terminal part of EIIA(Glc), a glucose-specific component of the phosphoenolpyruvate:sugar phosphotransferase system. This similarity suggested a direct interaction of HPr with CSPs, as histidyl-phosphorylated HPr has been shown to phosphorylate EIIA(Glc) in its C-terminal part. We therefore compared the cold shock response of several carbon catabolite repression mutants to that of the wild-type strain. Following a shift from 37 degrees C to lower temperatures (20, 15 or 10 degrees C), all mutants showed significantly reduced growth rates. Moreover, glucose-grown mutants unable to form P-Ser-HPr (ptsH1, hprK) exhibited drastically increased sensitivity to freeze/thaw cycles. However, when the same mutants were grown on ribose or maltose, they were similarly resistant to freezing and thawing as the wild-type strain. Although subsequent biochemical and genetic studies did not allow to identify the form of HPr implicated in the resistance to cold and freezing conditions, they strongly suggested a direct interaction of HPr or one of its phospho-derivatives with CspA and/or another, hitherto undetected cold shock protein in L. casei.

Relapsing Painful Ophthalmoplegic Neuropathy: No longer a "Migraine," but Still a Headache. Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. This review discusses the clinical presentation, current understanding of the pathophysiology, key differential diagnoses, and evaluation and treatment of RPON. The literature is limited due to the rarity of the disorder. Recent case reports and series continue to suggest the age of first attack is most often during childhood or adolescence as well as a female predominance. Multiple recent case reports and series demonstrate focal enhancement of the affected cranial nerve, as the nerve root exits the brainstem. This finding contributed to the current classification of the disorder as a neuropathy, with the present understanding that it is due to a relapsing-remitting inflammatory or demyelinating process. The link to migraine remains a cause of disagreement in the literature. RPON is a complex disorder with features of inflammatory neuropathy and an unclear association with migraine. Regardless, the overall prognosis is good for individual episodes, but permanent nerve damage may accumulate with repeated attacks. A better understanding of the pathogenesis is needed to clarify whether it truly represents a single disorder and to guide its treatment. Until that time, a combined approach with acute and preventive therapies can mitigate acute symptoms as well as attempt to limit recurrence of this disabling syndrome.

[Multicentric reticulo-histiocytosis; review of recent literature (since 1969)]. The review of recent literature (since 1969) shows 35 cases of multicentric reticulo-histiocytosis. This entity was first described as a dermatological disease, then as a dermatoarthritis. It is in fact a systemic disease which can involve many organs but is sometimes monosymptomatic. Its fatal outcome is, sometimes, the result of a disseminated neoplasia or a lymphoma. Its clinical and microscopic features allow to distinguish it from solitary reticulo-histiocytoma, generalized eruptive histiocytoma, congenital reticulo-histiocytosis of Hashimoto and Pritzker and familial histiocytic dermato-arthritis of Zayid.

The role of eosinophils and eosinophil cationic protein in oral cancer: a review. Eosinophils are multifunctional leukocytes implicated in the pathogenesis of numerous inflammatory processes, such as allergies and parasitic infections. Increased number of these cells has been described in many human cancers, including oral squamous cell carcinoma, and its presence related to favourable as well as unfavourable prognosis. Although the exact role of eosinophils in tumours is not yet defined, the anti-tumour activity of these rare granulocytes has been associated with the release of their cytotoxic proteins, especially the eosinophil cationic protein, a single polypeptide chain with a molecular mass ranging from 15 to 22kDa encoded by the RNSE3 gene located on chromosome 14q11.2. Functional studies have implicated ECP in numerous processes, such as tissue remodelling in allergic inflammation; however its most striking function is the cytotoxic activity. The aim of this review is to summarise the role and functions of eosinophils and their granule-derived products in oral malignant tumours and the clinical value of the tumour-associated tissue eosinophilia for patients' prognosis.

Effects of gonadotropins on bovine oocytes matured in TCM-199. The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during in vitro maturation of bovine oocytes in TCM-199 without serum were evaluated. Bovine oocytes with compact cumulus cells were collected from slaughterhouse-derived ovaries and cultured in Hepes-buffered TCM-199 supplemented with 5 mg/mL BSA, 1 microg/mL estradiol-17beta, FSH (0, 0.015, 0.05, 0.15, 1.5 or 15 ng/mL; Experiment 1), LH (0, 0.14, 1, 7 or 49 microg/mL; Experiment 2) and combinations of 1 or 10 ng/mL FSH and 1 or 10 microg/mL LH (Experiment 3) at 39 degrees C in 5% CO2 in air. After 22 h of maturation, cumulus expansion was estimated by scoring from 0 (no expansion) to 4 (full expansion of cumulus mass). In vitro fertilization was done with Percoll (45/90%) separated bull sperm at 1 x 10(6) sperm/mL in fert-TALP with 5 U/mL heparin. At 18 to 20 h post-insemination, presumptive zygotes were transferred to a chemically defined medium (CDM-1) supplemented with 0.5% BSA and nonessential amino acids for 72 h and then moved to CDM-2, additionally supplemented with essential amino acids. Zygotes were cultured at 39 degrees C in 5% CO2, 5% O2 and 90% N2 for 8 days. During Experiments 1 and 2, cumulus expansion increased in proportion to concentrations of FSH and LH. Cleavage rates and development to blastocysts were not significantly different among FSH and LH treatments. In Experiment 3, cumulus expansion of bovine oocytes was maximal when 1 ng/mL FSH and 1 microg/mL LH were added to IVM medium, but cumulus expansion again was not related to developmental ability, although cleavage rates were improved slightly (P<0.05) by the combination of LH and FSH. Blastocyst quality, estimated by the size of inner cell mass, was not different between combinations of FSH and LH, and the numbers of nuclei were not different. Although expansion of cumulus cells surrounding bovine oocytes was altered in response to FSH and/or LH in semi-defined medium, cumulus expansion was not related to rates of cleavage or subsequent embryonic development in vitro. The effects of LH on cumulus expansion can be explained by as little as 1 part per 10, 000 contamination with FSH.

Directed ortho-metalation-nucleophilic acyl substitution strategies in deep eutectic solvents: the organolithium base dictates the chemoselectivity. Directed ortho metalation (DoM) or nucleophilic acyl substitution (SNAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki-Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents.

Conceptual analysis of validation therapy. The present article examines the conceptual aspects of Validation Therapy. Validation Therapy is a humanistic approach used to give disoriented old-old people, eighty years and older, an opportunity to resolve their life's unfinished conflicts by encouraging them to express their feelings. This approach emphasizes the relationship between the old-old person and the caregiver by focusing on empathy, acceptance, and acknowledgment. Four stages of disorientation, ranging from mild to severe, are described on the basis of emotional and physical characteristics. The theoretical assumptions and underlying principals of Validation Therapy are discussed. Finally, research studies are outlined to evaluate the effectiveness of Validation Therapy. It is concluded that although Validation Therapy is a well-formulated, alternative approach to helping disoriented individuals, further research is needed to determine its validity.

Seroepidemiology of Hantavirus in the Philippines. This study was undertaken to determine the seroepidemiology of Hantavirus infection in the Philippines. This is a cross-sectional study done in asymptomatic volunteers from various communities in the Philippines selected by a stratified multistage sampling design. Antibody to Hantavirus was detected by particle agglutination (PA) test using Hantadia high-density particle agglutination (HDPA) reagent kit. The prevalence of positive Hantavirus antibody among 461 subjects was the same in both males (6.1%) and females (6.1%) in rural (7.6%), urban (5.6%), and urban poor (5.1%) populations. The prevalence of Hantavirus infection in the Filipino population is comparable to that seen in other developing countries. The HDPA can be conveniently used as a rapid tool to detect the Hantavirus antibody for seroepidemiologic and diagnostic purposes.

Retroclival arachnoid cyst presenting with haemorrhage: a brief report of a special case. Retroclival arachnoid cysts are rarely reported. A 40-year-old woman had a sudden onset of occipitocervical pain. Magnetic resonance imaging (MRI) revealed a cystic mass lesion located in the retroclival region and complicated with intracystic haemorrhage. At operation, by a right lateral suboccipital approach, an old, intracystic haemorrhage was aspirated and the cyst wall removed totally. This report demonstrated the second case of retroclival cyst presenting with symptomatic spontaneous intracystic haemorrhage.

Subjective socioeconomic status and health in cross-national comparison. Research has established a robust association between subjective socioeconomic status (SES) and health outcomes, which holds over and above the associations between objective markers of SES and health. Furthermore, comparative research on health inequalities has shown considerable variation in the relationship between different objective markers of SES and health across countries. Drawing on data from 29 countries, we present the first cross-national study on the subjective SES-health relationship. For two health outcomes, namely self-rated health (SRH) and psychological wellbeing, we are able to confirm that subjective SES is related to health in all countries under study, even when income, education, and occupational prestige are accounted for. Furthermore, we document considerable variation in the strength of the subjective SES-health association across countries. This variation however is largely independent of country differences in income inequality and country affluence. The health benefits of a high subjective SES appear to be slightly larger in more affluent countries, but only for SRH, not for psychological wellbeing.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy were assessed in patients with type 2 diabetes and inadequate glycemic control (glycosylated hemoglobin [HbA(1c)] > or =7% and < or =10%) while receiving a stable dose of pioglitazone. This was a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients aged > or =18 years (ClinicalTrials. gov NCT00086502). At screening, all patients began a diet/exercise program that continued throughout the study period. Patients taking antihyperglycemic therapy other than pioglitazone underwent a washout of this therapy and entered an 8- to 14-week open-label pioglitazone dose-titration/stabilization period. Patients with an HbA(1c) > or =7% and < or =10% at the end of this period entered a 2-week, single-blind, placebo run-in period (total duration of run-in period, up to 21 weeks). Patients who had been receiving pioglitazone monotherapy (30 or 45 mg/d) and had an HbA(1c) > or =7% and < or =10% entered the 2-week, single-blind, placebo run-in period directly. Thus, at the time of randomization, all patients were receiving ongoing pioglitazone (30 or 45 mg/d). Patients were randomized in a 1:1 ratio to receive sitagliptin 100 mg once daily or placebo for 24 weeks. The primary efficacy end point was the change from baseline in HbA(1c) at week 24. Secondary efficacy end points included the change from baseline in fasting plasma glucose (FPG), insulin, and proinsulin; the Homeostasis Model Assessment beta-cell function and insulin-resistance indexes; the proinsulin/ insulin ratio; the Quantitative Insulin Sensitivity Check Index; the percent changes from baseline in selected lipid parameters; the proportion of patients meeting the American Diabetes Association HbA(1c), goal of <7.0%; the proportion of patients requiring metformin rescue therapy; and the time to the initiation of rescue therapy. One hundred seventy-five patients were randomized to receive sitagliptin, and 178 were randomized to receive placebo. The mean (SD) baseline HbAlc value was 8.1% (0.8) in the sitagliptin group and 8.0% (0.8) in the placebo group. After 24 weeks, sitagliptin added to pioglitazone therapy was associated with significant reductions compared with placebo in HbA(1c) (between-treatment difference in least squares [LS] mean change from baseline. -0.70 %; 95 % CI, -0.85 to -0.54; P < 0.001) and FPG (-17.7 mg/dL; 95% CI, -24.3 to -11.0; P < 0.001). Mean HbA(1c) values at end point were 7.2% (0.9) and 7.8% (1.1) in the respective treatment groups, and the proportions of patients reaching a target HbA(1c) of <7.0% were 45.4% and 23.0% (P < 0.001). Significant reductions in fasting serum proinsulin levels and the proinsulin/insulin ratio were seen with sitagliptin treatment compared with placebo (both, P < 0.01). Sitagliptin was generally well tolerated, with no increased risk of hypoglycemia compared with placebo (2 vs 0 patients, respectively).

Neuromodulatory treatments for post-traumatic stress disorder (PTSD). Electroconvulsive therapy has been used successfully in some individuals with posttraumatic stress disorder (PTSD) whose symptoms have not improved with other treatments. But there are only a few reports. Meanwhile, an array of new neuromodulation strategies, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, trigeminal nerve stimulation, and deep brain stimulation have been developed and applied experimentally in the treatment of other psychiatric disorders. This article will review the clinical evidence and mechanistic basis for their use in PTSD.

Novel procedure with improved resolution and specificity for amplification and differentiation of variants of the gene encoding carboxylesterase 1. Carboxylesterase 1 (CES1) is implicated in the metabolism of several commonly used drugs and other xenobiotics. The gene encoding this enzyme, CES1, is duplicated in some individuals. The original gene copy is called CES1A1. The duplicated version, CES1A2, is a hybrid of CES1A1 and the CES1-related pseudogene, CES1P1. Variants of CES1A2 with a weak and a strong promoter, respectively, have been reported. In addition, there are chimeric subtypes of CES1A1 that contain a segment of CES1P1. Collectively, this represents challenges to the genotyping of CES1 that previous procedures have had difficulties in solving, frequently leading to loss of specificity and inaccurate genotyping. Here, we report a novel and specific procedure that can selectively amplify CES1A1 and CES1A2 and accurately determine their variants. This procedure may be useful for personalization of treatments with drugs metabolized by CES1.

The utilization of intravenously infused pyridoxine in humans. The utilization of a usual dose of intravenously infused pyridoxine (100 mg pyridoxine hydrochloride) was investigated in ten healthy males. Blood plasma and erythrocytes were investigated by means of high-performance liquid chromatography. Detectable metabolites in blood plasma were pyridoxine, pyridoxal 5'-phosphate, pyridoxal and 4-pyridoxic acid. In erythrocytes pyridoxine, pyridoxal 5'-phosphate, pyridoxal, and pyridoxamine 5'-phosphate were found. From their concentration-time curves rate constants of elimination and invasion, volume of distribution (pyridoxine) and the areas under the curves were calculated. Values for concmax and tmax are reported. A comparison with earlier results of oral pyridoxine administration revealed a better utilization after intravenous than after oral application, i.e. a greater build-up of coenzyme forms. A regulatory phenomenon in erythrocytes caused by high doses of pyridoxine is described. In view of the potential toxicity of pyridoxine the doses used in parenteral nutrition are called into question.

A population-based analysis of distinguishers of bipolar disorder from major depressive disorder. Many people with bipolar disorder (BD) in the community are misdiagnosed with major depressive disorder (MDD). A probabilistic model has been proposed to assist in the identification of BD among patients with depressive symptoms, however there are limited population-based data on the key distinguishers of BD from MDD. The objective of this study was to identify distinguishers of BD from MDD in a population-based sample. Population-based data were extracted from the Canadian Community Health Survey: Mental Health and Well-Being. Sociodemographic variables, clinical variables, and depressive symptomatology were compared between subjects with BD (N=467) and MDD (N=4145). Logistic regression analysis was used to identify significant correlates of BD, and areas under the receiver operating characteristic curves (AUCs) were determined for each model. BD and MDD subjects differed across a number of characteristics. Clinical variables significantly associated with BD included greater number of lifetime depressive episodes, earlier age of first depressive episode, lifetime anxiety disorder, problematic substance use, and lifetime suicide attempt. Symptoms significantly more common during a major depressive episode among BD subjects included agitation, suicidal ideation, anxious symptoms, and irritability. AUCs for these models ranged from 0.72 to 0.81. Data were not available for all potential distinguishers; subgroups of BD could not be determined; cross-sectional data. These population-based results reinforce the effort to establish a generalizable probabilistic model that incorporates clinical and symptom variables in order to assist clinicians in the diagnostic assessment of BD.

Environmental risks outweigh dopaminergic genetic risks for alcohol use and abuse from adolescence through early adulthood. Alcohol use is a primary public health concern, particularly among adolescents and young adults. Based on the rapidly growing field of gene-environment models, this study assessed the combined role of environmental and dopamine-related genetic correlates of early alcohol use and abuse. Multilevel growth models assessed trajectories of alcohol use and intoxication and ordered logistic regressions assessed alcohol use disorder among a sample of 12,437 youth from the nationally representative Add Health study who were followed from mid-adolescence through early adulthood. Endogenous and exogenous stressful life events and social norms supportive of alcohol use from parents and peers were significant predictors of alcohol use, intoxication, and alcohol use disorder, with consistent patterns across males and females. In contrast, a dopamine-system genetic risk score (GRS) was not associated with alcohol use trajectories nor alcohol use disorder in early adulthood, although weak connections emerged between the GRS and growth trajectories of intoxication, indicating that higher GRS predicted more frequent episodes of intoxication during the transition to adulthood but not during adolescence or later 20s. No evidence of gene-environment interactions emerged. Results extend a substantial body of prior research primarily assessing single genetic polymorphisms in the dopamine system, suggesting that dopaminergic GRSs may be associated with more problematic alcohol behaviors at some developmental periods, but further, that social norms and stressful life experiences are more consistent correlates of early and problematic alcohol use among youth. These environmental factors present potential targets for research manipulating contexts to identify causal pathways.

Elimination of urogenital schistosomiasis in Iran: past history and the current situation. In recent years, through a national programme for schistosomiasis control, this infection has been eliminated from Iran. The aim of this study was to report the process of significant decrease of urogenital schistosomiasis in southwestern Iran. During national programme surveillance for urogenital schistosomiasis control which was implemented by Centres for Disease Control and Prevention (CDC) of Khuzestan province from 1975 to 2013, more than 1·3 million urine samples were taken from inhabitants of high risk foci. All urine samples were gathered between 10:00 a.m and 02:00 p.m and, after centrifuging, specimens were tested under optical microscope in order to detect Schistosoma haematobium eggs. Data analysis was performed using SPSS 18 software. In this retrospective study significant reduction was seen in number of infections between 1975 and 2013. During the years 1975-1980, 1981-1990 and 1991-2000 there were 1582, 761 and 79 cases of S. haematobium, respectively. In 2001 only one case was reported from Ahvaz and indeed this was the last case of urogenital schistosomiasis in Khuzestan and of course, in Iran. Prevalence from 1·064% between 1975 and 1980 slumped to 0% in 2012-2013. During several projects for surveillance of urogenital schistosomiasis, selective population chemotherapy, snail control, population education, environmental improvement, etc were carried out throughout the surveillance period. According to elimination of S. haematobium in Khuzestan province, the only endemic region of Iran, control of disease, especially the campaign with intermediate host snails should be continued. Iran can be a successful model for countries suffering from this disease.

Energetic aspects of anaerobic growth of Aerobacter aerogenes in complex medium. Molar growth yields for anaerobic growth of Aerobacter aerogenes in complex medium were much higher than for growth in minimal medium. In batch cultures the molar growth yield for glucose varied from 44 to 50 and YATP from 17.1 to 18.8. For glucose-limited chemostat cultures a value of 17.5 g/mole was found for Y max ATP and a value of 2.3 mmoles ATP/g dry weight h for the maintenance coeficient. Growth-dependent pH changes were used to control the addition of fresh medium, containing excess of glucose to a continuous culture. The specific growth rate and the population density were dependent on the pH difference between the inflowing medium and the culture. At a mu value of 1.44 h-1 the molar growth yield for glucose was about 70 and Y ATP about 28.5. An equation is presented, which gives the relation between theoretical and experimental Y max ATP values.