Comorbidity and prognosis in head and neck cancers: Differences by subsite, stage, and human papillomavirus status.
The prognostic utility of comorbidity on head and neck cancer may differ by subsite, stage, and human papillomavirus (HPV) status. We reviewed the medical records of 4953 patients with head and neck cancer for comorbidity (Charlson Comorbidity Index [CCI]), smoking, and alcohol history. Multivariate proportional hazards assessed the association of CCI with survival. HPV status was determined using p16 immunohistochemistry. After accounting for stage, higher CCI was associated with worse overall survival (OS) in nasopharyngeal (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.53-5.62), oropharyngeal (HR, 1.99; 95% CI, 1.63-2.43), and oral cavity cancers (HR, 1.54; 95% CI, 1.27-1.86). These associations were most prominent in the early stage oral cavity (HR, 2.11; 95% CI, 1.50-2.96) and laryngeal (HR, 1.87; 95% CI, 1.35-2.58) cancers, and in advanced stage oropharyngeal (HR, 2.23; 95% CI, 1.81-2.74) and nasopharyngeal (HR, 3.50; 95% CI, 1.76-6.97) cancers. CCI was independently prognostic even in the HPV-adjusted oropharyngeal cancers. Comorbidity was prognostic in subsets of nasopharyngeal, oropharyngeal, oral cavity, and laryngeal cancers. Comorbidity may be a partial surrogate for age and social habits.


WF11605, an antagonist of leukotriene B4 produced by a fungus. I. Producing strain, fermentation, isolation and biological activity.
WF11605, a new antagonist of leukotriene B4 (LTB4) was isolated as a product of fungal strain F11605. The molecular formula of WF11605 was determined to be C38H60O11. WF11605 inhibited LTB4-induced chemotaxis of rabbit polymorphonuclear leukocytes (PMNLs) with an IC50 value of 1.7 x 10(-7) M and blocked 3H-LTB4 binding to PMNL membranes at 5.6 x 10(-6) M (IC50). WF11605 also inhibited LTB4-induced degranulation of rabbit PMNLs at 3.0 x 10(-6) M (IC50). However, WF11605 did not show any inhibitory effect on platelet activating factor (PAF)- and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced degranulation at concentrations up to 10(-4) M. These results suggest that WF11605 is a specific antagonist of LTB4.


Canine Comprehensive Mobility Assessment.
A comprehensive mobility assessment goes beyond the orthopedic or neurologic examination for the localization of pathology. This assessment involves attention to the dog's posture and stance, a hands-on examination with special attention to soft tissue structures, and the performance of functional assessments. A comprehensive mobility assessment can guide advanced diagnostic testing as well as providing a foundation in the formulation of a successful treatment plan.


Haematotoxicity of integrated textile mill effluent to an air-breathing fish Heteropneustes fossilis (Bloch).
The effect of integrated textile mill effluent on the haematological characteristic of the fish Heteropneustes fossilis was studied. LC50 values were found to be 34%-38% on 96-24 h duration. Four sub-lethal concentrations were selected for this study. Exposure to effluent caused an increase in large lymphocytes, monocytes, neutrophils and basiphil granulocytes and decrease in small lymphocytes in H.fossilis.


Emerging immunotherapeutic strategies for the treatment of breast cancer.
Immunotherapy has resulted in unprecedented gains in long-term outcomes for many cancer types and has revolutionized the treatment landscape of solid tumor oncology. Checkpoint inhibition in combination with chemotherapy has proven to be effective for the treatment of a subset of advanced triple-negative breast cancer in the first-line setting. This initial success is likely just the tip of the iceberg as there is much that remains unknown about how to best harness the immune system as a therapeutic strategy in all breast cancer subtypes. Therefore, numerous ongoing studies are currently underway to evaluate the safety and efficacy of immunotherapy in breast cancer. In this review, we will discuss emerging immunotherapeutic strategies for breast cancer treatment including the following: (1) Intratumoral therapies, (2) Anti-tumor vaccines, (3) B-specific T-cell engagers, and (4) Chimeric antigen receptor T-cell therapy, and (5) Emerging systemic immunotherapy strategies. For each topic, we will review the existing preclinical and clinical literature, discuss ongoing clinical trials, and highlight future directions in the field.


Impact of individual microvascular disease on the risks of macrovascular complications in type 2 diabetes: a nationwide population-based cohort study.
This study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases. We identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality. Patients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03-1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1-1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03-1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3-1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71-0.87). T2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.


Vascular endothelial growth factor system in the cow oviduct: a possible involvement in the regulation of oviductal motility and embryo transport.
Vascular endothelial growth factor (VEGF) is a potent angiogenic and permeability enhancing factor, which shows the highest activity in the oviduct during the periovulatory period of the estrous cycle in cattle. It has also been shown that the contraction activity of oviduct is highest during the periovulatory period. The present study therefore focused on the possible involvement of VEGF in the regulation of biosynthesis and secretion of contraction-relaxation-related substances in the cow oviduct. Possible autonomous VEGF system in the oviduct as well as its endocrine control was also studied. Bovine oviductal epithelial cells (BOEC) in the second passage were cultured with VEGF (1 ng/ml) alone or with luteinizing hormone (LH; 10 ng/ml), estradiol 17-beta (E2; 1 ng/ml), and/or progesterone (P4; 1 ng/ml). The levels of prostaglandins (PGs), endothelin-1 (ET-1), and angiotensin II (Ang II) in the medium were measured using second antibody enzymeimmunoassay (EIA). The mRNA expressions for cycloxygenase-2 (Cox-2), prostaglandin F synthase (PGFS), prostaglandin E synthase (PGES), prepro-ET-1, endothelin converting enzyme-1 (Ece-1), angiotensin converting enzyme-1 (Ace-1), VEGF and its receptors were investigated using real-time RT-PCR. The results indicate that, (1) VEGF dose-dependently stimulated the release of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), and ET-1, but not Ang II. VEGF and VEGF with LH, E2, and P4 upregulated mRNA expression for biosynthesis cascade of PG, ET-1 as well as their release. However, only the combination of VEGF with LH, E2, and P4 upregulated mRNA for Ace-1 and Ang II release, but not VEGF alone. (2) Treatments of LH, with E2 and/or P4 increased the mRNA expression for VEGF, Flk-1 and Flt-1, and (3) VEGF itself downregulated the expression of mRNA for VEGF, and LH, E2, and P4 enhanced this downregulatory effect. The results of the present study provide the first evidence that (1) VEGF directly stimulates the biosynthesis and release of PGE2, PGF2alpha, and ET-1 in the bovine oviduct, (2) LH stimulates the oviductal VEGF system, and (3) VEGF downregulates the oviductal VEGF system and this downregulation was further intensified in the presence of LH. The data suggest that the preovulatory LH-surge, together with increasing E2 secretion from the Graffian follicle and basal P4 levels from the regressing corpus luteum (CL), upregulates the oviductal VEGF system, inducing the maximum oviductal production of contraction-relaxation-related substances for active oviduct contraction and rapid transport of gametes to the fertilization site. However, the oviductal VEGF elevation caused by the LH-surge, appears to downregulate the oviductal VEGF system immediately after ovulation thereby may contribute to suppress oviductal contraction to secure slow transport of the embryo to the uterus at the optimal time.


Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.
Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required.


Propagation path loss prediction modelling in enclosed environments for 5G networks: A review.
Millimeter wave path loss modeling is essential for reliable system design and accurate link budget calculations. The motivation for this research is that channel modeling in 5G millimeter wave propagation in an indoor environment is a current research topic in which capacity differences have been noticed as a result of different models being utilized. Existing models for future millimeter wave propagation must be tested and improved in order to aid link design. The improvements in the path loss models will allow engineers and researchers to budget for 5G wireless networks with better quality in an indoor environment. In this paper, we discuss the survey of indoor environment undertaking for both line of sight (LOS) and non-line of sight (NLOS) scenarios as well as the comparison of path loss performance analysis of the three commonly used models: Close-In (CI) free space reference model, Floating Intercept (FI), and Alpha-Beta-Gamma (ABG) models at some selected frequencies. The review looked at how to determine efficient path loss models which is a major challenge in millimeter wave propagation. The paper also focuses on the measurement work done in millimeter wave research in interior environments. The analysis of path loss and shadow fading in different frequency bands are presented. The researchers whose publications were examined for this study used a range of methodologies to forecast path loss models and propagation parameters of millimeter wave communication channel. This will help design engineers and researchers calculate budgets for a suitable 5G and even forecasted 6G wireless network in an inside environment. Another purpose of this paper is to get a thorough understanding of the best route loss model, especially for interior situations, and to improve it in future research to provide a better line of fit and simplicity among the three fundamental path loss models: CI, ABG, and FI. In both LOS and NLOS scenarios, the study found that the CI free space reference model and the FI path loss models are the best path loss models for indoor millimeter wave propagation. Future research will focus on how to improve the appropriate model for path loss model estimate in both LOS and NLOS situations in an indoor environment with the best line of fit and the easiest implementation.


Molecular design of environment-friendly chlorophenol (CP) derivatives based on 3D-QSAR assisted with a comprehensive evaluation method combining bioaccumulation and degradation.
In this study, a chlorophenol (CP) 3D-QSAR model with a double activity (bioaccumulation and degradation) combination was established. 19 CPs were divided into a training set and test set according to the ratio of 4:1. The cross-validation coefficient (q2) and non-cross-validation coefficient (R2) of the model were 0.803 (> 0.5) and 0.925 (> 0.9), respectively, indicating a good stability and predictive ability of the 3D-QSAR. 2,4,6-trichlorophenol (2,4,6-TCP) was used as a target molecule, and 46 derivatives with low comprehensive effects were designed. Out of the 46 derivatives, 11 derivatives were screened to have the good insecticidal and preservative properties. From the perspective of the toxicity of zebrafish, 4 out of the 11 derivatives were found to have lower aquatic toxicity effects. Through the food chain simulation of cyanobacteria-daphnia-swamp-mandarin fish, it was found that the bioaccumulation effect of the four derivatives was lower than that of 2,4, 6-TCP. Finally, molecular dynamics simulation was conducted using 2-CH2NH2 substituted derivatives, and it was found that the degradation effect by laccase (white rot fungi) was significantly improved in the presence of violuric acid, hydroxybenzotriazole, and syringaldehyde. This study can provide theoretical support for the development of environment-friendly technology for emerging pollutants.


Arteriovenous malformation of the mandible--a case report.
Both arteriovenous malformations (AVMs) and solitary bone cysts of the mandible are uncommon lesions. The latter can be considered fairly innocuous but AVMs require careful management. The following is a description of a case where an arteriovenous malformation of the mandible presented with mental nerve paraesthesia. However, radiographically the features appeared to be consistent with a solitary bone cyst. It is important for clinicians in both a primary and secondary care setting to be aware that this type of lesion can have life threatening complications.


The human distribution of some barbiturate sedatives in combination with miscellaneous CNS-active drugs.
This paper presents 14 cases in which the distribution of barbiturates and the hydroxylated metabolites in combination with miscellaneous CNS-active drugs was studied. In 7 of these cases the other drug present was methadone, and in the remainder dihydrocodeine, morphine, propoxyphene, amitriptyline, meprobamate, cyclizine and dipipanone, diphenhydramine and methaqualine. Amitriptyline, methadone, cyclizine and dipipanone, methaqualone and diphenhydramine appeared to modify the distribution of amylorbarbitone and quinalbarbitone. Likewise, the barbituates seemed to alter the distribution of amitriptyline, propoxyphene and, in one instance, methadone.


Adjuvant treatment of colorectal adenocarcinoma.
Colorectal adenocarcinoma is diagnosed in 150,000 Americans yearly, and more than 50,000 die of this disease each year. Recently, as a result of well-controlled, randomized, cooperative group trials, it has been demonstrated that adjuvant therapy of node-positive colon cancer (stage III) and node-positive or negative rectal cancer (stage II or stage III) can reduce recurrence and mortality and significantly improve overall survival. It is now the standard of care to provide adjuvant chemotherapy with 5-fluorouracil and levamisole for patients with node-positive colon cancer and provide adjuvant chemoradiotherapy with both 5-fluorouracil and high-dose radiotherapy for patients with stage II or stage III rectal cancer. It is estimated that these interventions, which are readily tolerated, will reduce the incidence of recurrence by more than 30% in both patient groups at a reasonable economic and health cost. Although the ideal method of therapy for this type of disease is not yet firmly established, it appears that adjuvant therapy for node-negative stage III colon cancer may be effective as well. Recently completed and ongoing cooperative group trials are investigating different combinations of chemotherapy and radiotherapy, including 5-fluorouracil with the biomodulator leucovorin or continuous-infusion 5-fluorouracil with radiotherapy, and comparing different durations of therapy. Other trials are investigating combined modality therapy for the neoadjuvant treatment of locally advanced rectal cancer. New findings in the genetics of colon cancer are being studied as prognostic information or markers to determine whether there are subsets of patients who might benefit from more or less therapy. Randomized placebo-controlled trials have been initiated to study the use of aspirin as a means of colon cancer prevention in high-risk populations. Taken together, the recent advances in our treatment and understanding of colorectal adenocarcinoma have resulted in a major--albeit silent--revolution in therapy and give firm promise for further progress.


Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential.
The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemia has a consistently poor outcome. One of the most common translocation partners is AF9 (MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites and present the nuclear magnetic resonance (NMR) solution structure of a DOT1L-AF9 complex. We generate structure-guided point mutations and find that they have graded effects on recruitment of DOT1L to MLL-AF9. Chromatin immunoprecipitation sequencing (ChIP-seq) analyses of H3K79me2 and H3K79me3 show that graded reduction of the DOT1L interaction with MLL-AF9 results in differential loss of H3K79me2 and me3 at MLL-AF9 target genes. Furthermore, the degree of DOT1L recruitment is linked to the level of MLL-AF9 hematopoietic transformation.


Is the strain pattern of conventional stems negatively affected by a previously short stem THA? An experimental study in cadavaric bone.
A short stem hip arthroplasty can be revised in many cases using a conventional stem. Furthermore, in some cases the implantation of a short stem is intended, but intraoperatively reasons may lead to the decision to implant a conventional stem after previous preparation of a short stem. In both cases it is questionable if the anchorage of a conventional stem is negatively affected by the previous preparation of a short stem. In clinical practice mid- or long-term follow up for these special cases hardly exist. The strain patterns for the conventional Bicontact stem in primary implantation and after preparation of the proximal femur for a METHA short stem were tested biomechanically in three pairs of cadaveric femora. The strain patterns for the conventional Bicontact after preparation of the METHA short stem were similar to conditions after testing the conventional stem in primary conditions. These data lead to the consequence that in clinical practise the implantation of a conventional stem after preparation of a short stem and even after revision of a short stem is possible without increased risk of loosening or long-term stress-shielding.


Bone turnover in patients on home parenteral nutrition: a longitudinal observation by biochemical markers.
In order to characterize biochemical markers of bone turnover in home parenteral nutrition(HPN) patients, 8 adult patients on HPN for benign intestinal failure were studied at 0, 6 and 12 months by evaluating serum osteocalcin (bone formation marker), urinary hydroxylysyl pyridinoline, lysyl pyridinoline and beta-galactosyl hydroxylysine (bone resorption markers), serum PTH, Calcitonin, 25 vitD, 1-25vitD, serum and urinary minerals, body weight, rehabilitation degree and HPN characteristics. Three patients entered the study 2-3 months after the beginning of HPN. Their features of bone turnover were homogeneous, characterized by increased resorption associated with normal or increased formation, at baseline, and normalization of resorption associated with an increase or a parallel decrease of formation, at 6 months. At 12 months, the patterns were similar to those observed at 6 months. The patients were not of the same sex and age and had different underlying diseases and types of intestinal failure, HPN composition and serum vitamin D levels. They had weight gain that was already present at baseline and the positive outcomes of the rehabilitation and clinical status in common. Five patients entered the study more than 1 year after the beginning of HPN. They showed heterogeneous features of bone turnover that were stable throughout the study, characterized by increased resorption associated with low or normal formation in two cases, low normal resorption associated with low or normal formation in three. In one patient, who had increased resorption and low formation, the bone turnover appeared to be explained by the nutritional and clinical outcomes, which were negative. These results appeared consistent with those obtained in previous studies by bone histomorphometry, indicating that bone turnover of short-term HPN patients differed from that of long-term patients, and suggesting that the early months of HPN were associated with increased bone resorption.


A comparison of the borate-celite column screening technique with other extraction methods in forensic toxicology.
The comparison of five different extraction techniques from postmortem tissues was reported. The borate/celite column chromatography technique generally gave the best yields and its use as a screening method in forensic toxicology was discussed.


Feature description with SIFT, SURF, BRIEF, BRISK, or FREAK? A general question answered for bone age assessment.
Solving problems in medical image processing is either generic (being applicable to many problems) or specific (optimized for a certain task). For example, bone age assessment (BAA) on hand radiographs is a frequent but cumbersome task for radiologists. For this problem, many specific solutions have been proposed. However, general-purpose feature descriptors are used in many computer vision applications. Hence, the aim of this study is (i) to compare the five leading keypoint descriptors on BAA, and, in doing so, (ii) presenting a generic approach for a specific task. Two methods for keypoint selection were applied: sparse and dense feature points. For each type, SIFT, SURF, BRIEF, BRISK, and FREAK feature descriptors were extracted within the epiphyseal regions of interest (eROI). Classification was performed using a support vector machine. Reference data (1101 radiographs) of the University of Southern California was used for 5-fold cross-validation. The data was grouped into 30 classes representing the bone age range of 0-18 years. With a mean error of 0.605 years, dense SIFT gave best results and outperforms all published methods. The accuracy was 98.36% within the range of 2 years. Dense SIFT represents a generic method for a specific question.


miR-871-5p/PGC1α Regulates Aging-Induced Lipid Deposition in Hepatocytes Through Fatty Acid β-Oxidation.
This study investigated the role of the miR-871-5p/proliferator-activated receptor α (PGC1α) pathway in ameliorating hepatic steatosis. We examined miR-871-5p expression in liver tissues of aging mice and AML12 senescent cells co-induced by low serum and palmitic acid (PA). Bioinformatics and multiple experiments were employed to validate the expression level of the target gene PGC1α for miR-871-5p. In this study, we aimed to investigate the potential role of miR-871-5p in regulating hepatic lipid deposition associated with aging. To do so, we performed in vitro transfection of both miR-871-5p mimic and inhibitor into senescent hepatocytes. Our results showed that miR-871-5p could inhibit PGC1α expression and cause lipid deposition in the liver due to aging. miR-871-5p controls this process by regulating PGC1α/fatty acid β-oxidation. H&E staining displayed the appearance of fat vacuoles in the livers of aging mice, and fatty acid β-oxidation-related genes (acyl-coenzyme A oxidase 1 carnitine palmitoyl transferase 1α and peroxisome proliferator-activated receptor α) expression was significantly reduced. Lipogenic genes (sterol regulatory element binding protein 1C and fatty acid synthase) expression level was increased in the livers of aging mice. In AML12 cells co-induced by low serum and PA, miR-871-5p mimics decreased PGC1α expression and increased lipid droplet accumulation in senescent hepatocytes. Conversely, miR-871-5p inhibitor promoted PGC1α expression and reduced lipid deposition in senescent hepatocytes. Our findings suggest that inhibiting miR-871-5p could be crucial in ameliorating aging-associated hepatic steatosis. These findings offer valuable insights into the molecular mechanisms driving hepatic steatosis in aging.


Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis.
Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting. We searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF. From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; [95% confidence interval], 0.70; [0.63-0.78]), acute myocardial infarction (0.67; [0.57-0.79]), all-cause mortality (0.62; [0.56-0.69]), major bleeding (0.59; [0.50-0.69]), intracranial hemorrhage (0.50; [0.40-0.62]), gastrointestinal bleeding (0.66; [0.46-0.95]), and any bleeding (0.82; [0.73-0.92]) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (P interaction = 0.03) and acute myocardial infarction (P interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs. The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.


In vitro experiments on axon guidance demonstrating an anterior-posterior gradient on the tectum.
Axonal growth cones originating from explants of embryonic chick retina were simultaneously exposed to two different cell monolayers and their preference for particular monolayers as a substrate for growth was determined. These experiments show that: (1) nasal retinal axons can distinguish between retinal and tectal cells; (2) temporal retinal axons can distinguish between tectal cells that originated from different positions within the tectum along the antero-posterior axis; (3) axons originating from nasal parts of the retina have different recognizing capabilities from temporal axons; (4) the property of the tectal cells, which is attractive for temporal axons, has a graded distribution along the antero-posterior axis of the tectum; and (5) this gradient also exists in non-innervated tecta.


Role of team dynamics in the learning process: a mixed-methods evaluation of a modified team-based learning approach in a behavioral research methods course.
Health sciences education is increasingly focusing on building students' skills to work collaboratively. Therefore, instructors must intentionally incorporate team-based skill building into their courses, using teaching strategies like team-based learning (TBL). An assumption of TBL is that team dynamics facilitate learning; however, limited research has examined this connection. The primary purposes of this mixed-methods evaluation were: (a) to describe the characteristics of team dynamics in a graduate-level research methods course that employs a modified TBL approach, and (b) to examine the association between team dynamics and student grades. Given the importance of preparing health professional students to work collaboratively in their careers, a secondary aim was to examine how team skills developed through a team-based learning approach could be transferred to other courses and to future jobs. We conducted surveys on team dynamics at mid-semester (n = 64) and the end of the semester (n = 66), collected students' grades for the final paper and overall course, and conducted 4 focus groups with Master of Public Health students (n = 25). Paired t tests were used to examine change in team dynamics and correlations were conducted to assess the relationship between team dynamics and grades. Thematic analysis was used to identify themes related to team dynamics from the focus group data. Overall, students reported experiencing positive and beneficial team dynamics. The findings support two main underlying categories of team dynamics, interpersonal team processes and task orientation, and the linkages between the categories that allow teams to function. Team dynamics scores were not associated with student grades. However, students recognized the value of practicing team skills in preparation for future group work and jobs. These findings suggest that active learning approaches, such as TBL, can help to facilitate the acquisition of collaborative skills.


Investigation of micropollutants removal from landfill leachate in a full-scale advanced treatment plant in Istanbul city, Turkey.
Although the levels of micropollutants in landfill leachate and municipal wastewater are well-established, the individual removal mechanisms and the fate of micropollutants throughout a landfill leachate treatment plant (LTP) were seldom investigated. Therefore, the determination of the removal efficiencies and the fates of micropollutants in a full-scale leachate treatment plant located in the largest city of Turkey were aimed in this study. Some important processes, such as equalization pond, bioreactor, ultrafiltration (UF) and nanofiltration (NF), are being operated in the treatment plant. Landfill leachate was characterized as an intense pollution source of macro and micropollutants compared to other water types. Chemical oxygen demand (COD), NH3, suspended solids (SS) and electrical conductivity (EC) values of the landfill leachate (and their removal efficiencies in the treatment plant) were determined as 18,656 ± 12,098 mg/L (98%), 3090 ± 845 mg/L (99%), 4175 ± 1832 mg/L (95%) and 31 ± 2 mS/cm (51%), respectively. Within the scope of the study, the most frequently and abundantly detected micropollutants in the treatment plant were found as heavy metals (8 ± 1.7 mg/L), VOCs (38 ± 2 μg/L), alkylphenols (9 ± 3 μg/L) and phthalates (8 ± 3 μg/L) and the overall removal efficiencies of these micropollutants ranged from -11% to 100% in the treatment processes. The main removal mechanism of VOCs in the aerobic treatment process has been found as the volatilization due to Henry constants greater than 100 Pa·m3/mol. However, the molecular weight cut off restriction of UF membrane has caused to less or negative removal efficiencies for some VOCs. The biological treatment unit which consists of sequential anoxic and oxic units (A/O) was found effective on the removal of PAHs (62%) and alkylphenols (87%). It was inferred that both NO3 accumulation in anoxic reactor, high hydraulic retention time (HRT) and sludge retention time (SRT) in aerobic reactor provide higher biodegradation and volatilization efficiencies as compared to the literature. Membrane processes were more effective on the removal of alkylphenols (60-80%) and pesticides (59-74%) in terms of influent and effluent loads of each unit. Removal efficiencies for Cu, Ni and Cr, which were the dominant heavy metals, were determined as 92, 91 and 51%, respectively and the main removal mechanism for heavy metals has thought to be coprecipitation of suspended solids by microbial biopolymers in the bioreactor and the separation of colloids during membrane filtration. Total effluent loads of the LTP for VOCs, semi volatiles and heavy metals were 1.0 g/day, 5.2 g/day and 1.5 kg/day, respectively. It has been concluded that the LTP was effectively removing both conventional pollutants and micropollutants with the specific operation costs of 0.27 $/(kg of removed COD), 0.13 $/(g of removed VOCs), 0.35 $/(g of removed SVOCs) and 2.6 $/(kg of removed metals).


[14C]Pentachlorophenol mineralization in the rice rhizosphere with established oxidized and reduced soil layers.
Flooded soils with rooted aquatic macrophytes have adjacent aerobic and anaerobic zones at the soil-water interface and rhizosphere where many common soil constituents undergo sequential oxidation and reduction reactions. To investigate whether pentachlorophenol (PCP) mineralization would also be enhanced under these conditions, a laboratory study was conducted to determine the conversion of [14C]PCP to 14CO2, 14CH4 and [14C]humic substances in soil microcosms with established aerobic-anaerobic zones at the soil-water interface and rice (Oryza sativa) rhizosphere. Contrary to what was expected, PCP was least rapidly degraded in rhizosphere-soil microcosms that contained the most extensive amounts of aerobic-anaerobic interfaces (63% PCP loss in 82 d) and was most rapidly degraded in soil microcosms that lacked redox interfaces in the soil profile (94% PCP loss in 82 d). Decreased PCP mineralization in the presence of aerobic-anaerobic interfaces was explained by (i) lack of sufficient O2 for aerobic PCP mineralization, due to the oxidation of other soil constituents in aerobic zones, and (ii) lack of an adequate supply of electron equivalents for reductive dechlorination of PCP, due to the reduction of other alternate electron acceptors in anaerobic zones. It was concluded that PCP mineralization is inhibited in flooded soils that contain extensive amounts of aerobic-anaerobic interfaces, due to redox cycling of other soil constituents that occur in these zones.


Ultrastructure of unfixed plasma membranes in ultrathin frozen sections.
Ultrathin sections of unfixed kidney tubular cells were obtained by cryo-ultramicrotomy using the 'wet' method. The results showed that extremely thin sections permit high resolution studies on unfixed plasma membranes. Structural units on the inner surface of the plasma membrane could be detected.


[LSD score. A new classification system for peristomal skin lesions].
Peristomal skin lesions are frequent complications of ostomy; however, there is no generally accepted nomenclature and classification system. An interdisciplinary German expert panel (GESS) composed of ten members, developed an innovative semiquantitative classification system for peristomal skin lesions for further stratification of ostomy therapy. This score is based on criteria which can be assessed by stomal therapists and treating physicians. The new peristomal skin lesion score grades three categories: lesion (L), status of ostomy (S) and disease (D). The L category describes the integrity of the skin as normal (L0), lesion with sustained integrity of skin (L1), integrity destroyed (L2) and local infection (L3). The S category rates the complexity of ostomy therapy as normal (S0), increased (S1) and high but not sufficiently effective (S2). The additional letters for categorization O. R. P. H. E. US describe anatomical pathologies of the stoma itself: ostomy stenosis (O), retraction (R), prolapse (P), hernia (H), edema (E) and unfavorable site (US). A systemic disorder is either absent (D0), irrelevant (D1) or relevant (D2). The LSD score is the basis for a management algorithm. The LSD score is comprehensive, standardized and holistic. Its straightforward use by health professionals can improve the consistency of the description of skin lesions and enhance the quality of ostomy therapy.


Does complexity constrain organelle evolution?
The evolution of eukaryotes was punctuated by invasions of the bacteria that have evolved to mitochondria and plastids. These bacterial endosymbionts founded major eukaryotic lineages by enabling them to carry out aerobic respiration and oxygenic photosynthesis. Yet, having evolved as free-living organisms, they were at first poorly adapted organelles. Although mitochondria and plastids have integrated within the physiology of eukaryotic cells, this integration has probably been constrained by the high level of complexity of their bacterial ancestors and the inability of gradual evolutionary processes to drastically alter complex systems. Here, I review complex processes that directly involve translation of plastid mRNAs and how they could constrain transfer to the nucleus of the genes encoding them.


Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways.
Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types. Here we utilize Illumina Beadchip methylation array analysis to identify LRES across 800 kb of chromosome 5q31 in colorectal adenomas and carcinomas (n=34) relative to normal colonic epithelial DNA (n=6). This region encompasses 53 individual protocadherin (PCDH) genes divided among three gene clusters. Hypermethylation within these gene clusters is asynchronous; while most PCDH hypermethylation occurs early, and is apparent in adenomas, PCDHGC3 promoter methylation occurs later in the adenoma-carcinoma transition. PCDHGC3 was hypermethylated in 17/28 carcinomas (60.7%) according to methylation array analysis. Quantitative real-time reverse transcription-polymerase chain reaction showed that PCDHGC3 is the highest expressed PCDH in normal colonic epithelium, and that there was a strong reciprocal relationship between PCDHGC3 methylation and expression in carcinomas (R=-0.84). PCDH LRES patterns are reflected in colorectal tumour cell lines; adenoma cell lines are not methylated at PCDHGC3 and show abundant expression at the mRNA and protein level, while the expression is suppressed in hypermethylated carcinoma cell lines (R=-0.73). Short-interfering RNA-mediated reduction of PCDHGC3 led to a decrease of apoptosis in RG/C2 adenoma cells, and overexpression of PCDHGC3 in HCT116 cells resulted in the reduction of colony formation, consistent with tumour suppressor capabilities for PCDHGC3. Further functional analysis showed that PCDHGC3 can suppress Wnt and mammalian target of rapamycin signalling in colorectal cancer cell lines. Taken together, our data suggest that the PCDH LRES is an important tumour suppressor locus in colorectal cancer, and that PCDHGC3 may be a strong marker and driver for the adenoma-carcinoma transition.


Investigating the Primary Care Management of Low Back Pain: A Simulated Patient Study.
A limitation of existing studies of primary care for low back pain (LBP) is that they are not based on direct observation of the clinical encounter and so may underestimate or overestimate the extent of evidence-practice gaps. This was a cross-sectional observational study that observed the management recommendations for LBP provided in primary care using a simulated patient approach. Trained actors requested an over-the-counter medicine or asked for management advice for 1 of 2 simulated patient scenarios: nonspecific LBP (NSLBP) or vertebral compression fracture. Visits were audiorecorded to allow data capture, validation, and review. We evaluated concordance with key recommendations provided in evidence-based LBP guidelines on pain medicines, patient self-care advice, and referral. Visits were conducted across 534 pharmacies comprising 336 nonspecific scenarios and 198 fracture scenarios. Recommendations for pain medicines, but not patient self-care advice and referral, were typically consistent with guidelines. For the NSLBP scenario, the concerns were infrequent provision of reassurance of favorable outcome (8%), advice to stay active (5%), advice to avoid bed rest (0%), advice to use superficial heat (24%), and excessive endorsement of referral (57.4%) and imaging (22.7%). For the fracture scenario, the concerns were a low rate of prompt medical referrals (50.0%) and low endorsement of rest (1.0%). We observed primary care that aligned closely with some aspects, but was at odds with other aspects, of evidence-based LBP guidelines. Problems included inadequate self-care advice and failing to appropriately recommend imaging or prompt medical review when indicated. These results can inform implementation strategies to improve primary care management of LBP.


T Lymphocytes transduced with a lentiviral vector expressing F12-Vif are protected from HIV-1 infection in an APOBEC3G-independent manner.
The viral infectivity factor (Vif) is an essential component of the HIV-1 infectious cycle. Vif counteracts the action of the cytidine deaminase APOBEC3G (AP3G), which confers nonimmune antiviral defense against HIV-1 to T lymphocytes. Disabling or interfering with the function of Vif could represent an alternative therapeutic approach to AIDS. We have expressed a natural mutant of Vif, F12-Vif, in a VSV-G-pseudotyped lentiviral vector under the Tat-inducible control of the HIV-1 LTR. Conditional expression of F12-Vif prevents replication and spreading of both CXCR4 and CCR5 strains of HIV-1 in human primary T lymphocyte and T cell lines. T cells transduced with F12-Vif release few HIV-1 virions and with reduced infectivity. Several lines of evidence indicate that HIV-1 interference requires the presence of both wild-type and F12-Vif proteins, suggesting a dominant-negative feature of the F12-Vif mutant. Surprisingly, however, the F12-Vif-mediated inhibition does not depend on the reestablishment of the AP3G function.


Expression of hypoxia inducible factor-1alpha during liver regeneration induced by partial hepatectomy in rats.
It has been well established that hypoxia inducible factor-1alpha (HIF-1alpha) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF-1alpha expression during liver regeneration remains unknown. In this study, a role of HIF-1alpha was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration. Expression of HIF-1alpha was evaluated in the regenerating liver following 70% hepatectomy in rats. Expressions of nuclear HIF-1alpha, vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase-1 (flt-1) were measured by Western blot and liver blood flow by a laser Doppler. Sinusoidal endothelial cell area (SECA) and HIF-1alpha were localized by immunohistochemistry. HIF-1alpha mRNA was measured by reverse transcription-polymerase chain reaction. Liver blood flow and SECA were lowest 36 and 72 h following hepatectomy, respectively. Nuclear HIF-1alpha peaked at 24 h and continuously increased 72-120 h following hepatectomy. This transition was fully supported by histological HIF-1alpha expression and HIF-1alpha mRNA up-regulation. VEGF and flt-1 peaked at 120 and 12 h, respectively. A significant evaluation in HIF-1alpha expression was revealed in regenerating rat livers. HIF-1alpha expression was preceded by VEGF and flt-1 expression and thus may be related to sinusoidal endothelial reconstruction.


Investigating the key role of carrier transport mechanism in SnSe nanoflakes with enhanced thermoelectric power factor.
A novel SnSe nanoflake system is explored for its thermoelectric properties from both experiments andab initiostudy. The nanoflakes of the low temperature phase of SnSe (Pnma) are synthesized employing a fast and efficient refluxing method followed by spark plasma sintering at two different temperatures. We report an enhanced power factor (12-67μW mK-2in the temperature range 300-600 K) in our p-type samples. We find that the prime reason for a high PF in our samples is a significantly improved electrical conductivity (1050-2180 S m-1in the temperature range 300-600 K). From ourab initioband structure calculations accompanied with the models of temperature and surface dependent carrier scattering mechanisms, we reveal that an enhanced electrical conductivity is due to the reduced carrier-phonon scattering in our samples. The transport calculations are performed using the Boltzmann transport equation within relaxation time approximation. With our combined experimental and theoretical study, we demonstrate that the thermoelectric properties of p-type Pnma-SnSe could be improved by tuning the carrier scattering mechanisms with a control over the spark plasma sintering temperature.


Secretion of acid proteinases by different species of the genus Candida.
Strains of several Candida species that are isolated from humans aside of C. albicans have been screened for secretion of acid proteinases. A third of the strains of C. tropicalis was strongly proteolytic, other strains of this species were moderately or virtually nonproteolytic; the variety of activities resembled pattern found among strains of C. albicans (32). Strains of C. parapsilosis produced 24% of the proteolytic activity of strongly proteolytic strains of C. tropicalis. The proteolytic activity of C. pseudotropicalis, C. krusei, and C. glabrata accounted for 7.5, 2.0, and 0.8% respectively. Four strains of C. guilliermondii developed strain-specific proteolysis after prolonged cultivation only. Five proteinases from strains of C. tropicalis cross reacted immunologically as did five proteinases from C. albicans. Interspecific cross reaction, though, was not observed when certain sera from rabbits were employed.


Recent advances in in-situ transmission electron microscopy techniques for heterogeneous catalysis.
The process of heterogeneous catalytic reaction under working conditions has long been considered a "black box", which is mainly because of the difficulties in directly characterizing the structural changes of catalysts at the atomic level during catalytic reactions. The development of in situ transmission electron microscopy (TEM) techniques offers opportunities for introducing a realistic chemical reaction environment in TEM, making it possible to uncover the mystery of catalytic reactions. In this article, we present a comprehensive overview of the application of in situ TEM techniques in heterogeneous catalysis, highlighting its utility for observing gas-solid and liquid-solid reactions during thermal catalysis, electrocatalysis, and photocatalysis. in situ TEM has a unique advantage in revealing the complex structural changes of catalysts during chemical reactions. Revealing the real-time dynamic structure during reaction processes is crucial for understanding the intricate relationship between catalyst structure and its catalytic performance. Finally, we present a perspective on the future challenges and opportunities of in situ TEM in heterogeneous catalysis.


Dual task interference during gait in patients with unilateral vestibular disorders.
Vestibular patients show slower and unsteady gait; they have also been shown to need greater cognitive resources when carrying out balance and cognitive dual tasks (DT). This study investigated DT interference during gait in a middle-aged group of subjects with dizziness and unsteadiness after unilateral vestibular neuronitis and in a healthy control group. Fourteen individuals with subacute unilateral vestibular impairment after neuronitis and seventeen healthy subjects performed gait and cognitive tasks in single and DT conditions. A statistical gait analysis system was used and spatio-temporal parameters were considered. The cognitive task, consisting of backward counting by three, was tape recorded and the number of right figures was then calculated. Both patients and controls showed a more conservative gait during DT and between groups significant differences were not found. A significant decrease in cognitive performance during DT was found only in the vestibular group. Results suggest that less attentional resources are available during gait in vestibular patients compared to controls, and that a priority is given in keeping up the motor task to the detriment of a decrease of the cognitive performance during DT.


Expression of bone morphogenetic protein genes in the human dental pulp cells.
Dental pulp has a potential to induce ectopic bone formation, but little is known about its mechanism. We thought that bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are involved in the osteoinductive activity of dental pulp. In order to prove this assumption, we constructed a cDNA library from primary culture cells of human dental pulp (HDP cells), and screened the library with previously cloned cDNAs for mouse BMP-2 and -6 as probes. Three distinct cDNA clones encoding human BMP-2, -4 and -6 were isolated. By Northern blot analysis, specific transcripts of the genes of those BMPs were detected in the HDP cells. It was concluded that the BMPs were expressed in a certain population of dental pulp cells and might play some roles in ectopic bone formation by dental pulp.


Synthesis and reactivity of bis(imido) uranium(VI) cyclopentadienyl complexes.
The bis(imido) uranium(VI)-C(5)H(5) and -C(5)Me(5) complexes (C(5)H(5))(2)U(N(t)Bu)(2), (C(5)Me(5))(2)U(N(t)Bu)(2), (C(5)H(5))U(N(t)Bu)(2)(I)(dmpe), and (C(5)H(5))(2)U(N(t)Bu)(2)(dmpe) can be synthesized from reactions between U(N(t)Bu)(2)(I)(2)(L)(x) (L=THF, x=2; L=dmpe, x=1) and Na(C(5)R(5)) (R=H, Me); these complexes represent the first structurally characterized C(5)H(5)-compounds of uranium(VI) and they further highlight the differences between UO(2)(2+) and the bis(imido) fragment.


Seasonal variation in the form of iron in the liver of Spitsbergen reindeer: a Mössbauer spectroscopic study.
Mössbauer spectra have been obtained from samples of the liver of Spitsbergen reindeer at different times of the year. Most of the iron is in a very similar form to that of the iron storage materials ferritin and haemosiderin. The data reflect the large differences in the amount of iron found in the liver at different times of the year and also indicate that there are only relatively small differences in the chemical and physical form of the iron found in the liver at different times of the year.


Amelioration of Cadmium-Induced Nephropathy using Polyphenol-rich Extract of Vernonia amygdalina (Del.) Leaves in Rat Model.
To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA) in rats with Cd-induced nephropathy. Sixty five male Wistar rats were divided into five groups as follows; Group 1 received distilled water throughout the period of study. Group 2 received 5 mg/kg body weight of cadmium (Cd), in the form of CdSO4, for five consecutive days via intraperitoneal route. Groups 3, 4 and 5 were pretreated with Cd as group 2 and thereafter received oral treatment of PEVA for 4 weeks at 100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively. Exposure to Cd toxicity significantly induced deleterious alterations in plasma and urine levels of creatinine, urea and glucose as well as creatinine and urea clearance (p < 0.05) in the rat model. There was a significant disturbance in the antioxidant system as revealed by the levels of thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) (p < 0.05) in the kidney tissue of the rats. With marked improvements in renal histoarchitecture, PEVA treatment showed a duration and non dose-dependent ameliorative potential. PEVA treatment reversed the compromise of renal function that was induced by Cd toxicity in rat model.


The potential role of the X chromosome in the emergence of male-killing from mutualistic endosymbionts.
Endosymbionts infect most arthropods and cause a wide variety of phenotypes in their hosts, ranging from obligate mutualists to reproductive parasites. One of the most dramatic forms of reproductive parasitism is male-killing which involves the endosymbiont killing all of the sons of infected females. A phenotype with such a dramatic effect on host fitness is expected to provide strong selection for suppressors of male-killing, yet in many well-studied male-killer/arthropod systems, no suppressors have been found. Plausible explanations for a lack of resistance exist and include cryptic cytoplasmic incompatibility (males that survive male-killing are therefore infected and matings with uninfected females are incompatible) and deleterious pleiotropic effects of altering early embryonic development--the precise time when male-killing often occurs. Here I describe another possible scenario that sidesteps the problem: male killing may arise through an epistatic interaction between an endosymbiont and a paternally acting locus on the X chromosome. Since paternal X chromosomes never find themselves in sons, they never suffer from male-killing and instead enjoy any benefits (decreased sibling competition, inbreeding avoidance) caused by killing males. This scenario allows for the possibility that male-killing arose recently, even if there is no evidence for evolution in the endosymbiont genotype.


Multislice first-pass myocardial perfusion imaging on a conventional clinical scanner.
A technique is demonstrated for the acquisition and processing of multislice, first-pass contrast-enhanced perfusion images in the myocardium. The acquisition is a modification of "keyhole" imaging in which time series images are acquired by sampling a limited segment of k-space, corresponding to the low spatial frequencies. In the modification demonstrated here, keyhole samples are divided into two groups that are sampled on alternate cardiac cycles. The alternate "missing" k-space portions are synthesized by Fourier interpolation. Visualization of contrast agent accumulation by image subtraction is demonstrated. A motion artifact reduction process using time domain Fourier filtering is used to reduce artifacts from respiration. Studies were performed on 46 patients at 1.5 T using gadoteridol (0.05-0.1 mmol/kg) injected into the right antecubital vein in conjunction with radionuclide imaging. Fully concordant studies were noted in 27 of these patients. Remaining studies were either partially or completely discordant for reasons relating to the differing natures of radionuclide versus MR contrast agent characteristics.


Cell-free DNA as a potential biomarker for acute myocardial infarction: A systematic review and meta-analysis.
Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function. To explore the diagnostic role of cfDNA in acute myocardial infarction (AMI). This systematic review and meta-analysis included studies of cfDNA in patients with AMI and a comparator group without AMI. The quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used, with AMI determined from the criteria of the original study. Standardised mean differences (SMD) were obtained using a random-effects inverse variance model. Heterogeneity was reported as I2. Pooled sensitivity and specificity were computed using a bivariate model. The area under the curve (AUC) was estimated from a hierarchical summary receiver operating characteristics curve. Seventeen studies were identified involving 1804 patients (n = 819 in the AMI group, n = 985 in the comparator group). Circulating cfDNA concentrations were greater in the AMI group (SMD 3.47 (95%CI: 2.54-4.41, p < 0.001)). The studies were of variable methodological quality with substantial heterogeneity (I2 = 98%, p < 0.001), possibly due to the differences in cfDNA quantification methodologies (Chi2 25.16, p < 0.001, I2 = 92%). Diagnostic accuracy was determined using six studies (n = 804), which yielded a sensitivity of 87% (95%CI: 72%-95%) and specificity of 96% (95%CI: 92%-98%). The AUC was 0.96 (95%CI: 0.93-0.98). Two studies reported a relationship between peak cfDNA and peak troponin. No studies reported data for patients with pre-existing kidney impairment. Plasma cfDNA appears to be a reliable biomarker of myocardial injury. Inferences from existing results are limited owing to methodology heterogeneity.


Abdominal lymphography in thalassaemia major.
The appearances are described of abdominal lymphography in seven patients with thalassaemia major. All were severely and chronically anaemic. An abnormal course of lymphatic channels was seen in only one case. Nodal filling defects were found in all patients, lying centrally and peripherally, in para-aortic and iliac glands. The findings correlate well with the microscopic features of lymph nodes removed at therapeutic splenectomy. These show haemosiderin deposition and foci of extramedullary erythropoeisis.


Novel Lipidomic Signature Associated With Metabolic Risk in Women With and Without Polycystic Ovary Syndrome.
Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) and may augment metabolic dysfunction in this population. Using comprehensive lipidomic profiling and gold-standard metabolic measures, we examined whether distinct lipid biomarkers were associated with metabolic risk in women with and without PCOS. Using preexisting data and biobanked samples from 76 women (n = 42 with PCOS), we profiled > 700 lipid species by mass spectrometry. Lipids were compared between women with and without PCOS and correlated with direct measures of adiposity (dual x-ray absorptiometry and computed tomography) and insulin sensitivity (hyperinsulinemic-euglycemic clamp), as well as fasting insulin, HbA1c, and hormonal parameters (luteinizing and follicle-stimulating hormones; total and free testosterone; sex hormone-binding globulin [SHBG]; and free androgen index [FAI]). Multivariable linear regression was used with correction for multiple testing. Despite finding no differences by PCOS status, lysophosphatidylinositol (LPI) species esterified with an 18:0 fatty acid were the strongest lipid species associated with all the metabolic risk factors measured in women with and without PCOS. Across the cohort, higher concentrations of LPI(18:0) and lower concentrations of lipids containing docosahexaenoic acid (DHA, 22:6) n-3 polyunsaturated fatty acids were associated with higher adiposity, insulin resistance, fasting insulin, HbA1c and FAI, and lower SHBG. Our data indicate that a distinct lipidomic signature comprising high LPI(18:0) and low DHA-containing lipids are associated with key metabolic risk factors that cluster in PCOS, independent of PCOS status. Prospective studies are needed to corroborate these findings in larger cohorts of women with varying PCOS phenotypes.


The Neutrophil-to-Lymphocyte Ratio as a Marker of Lymph Node Status in Patients with Rectal Cancer.
The aim of the study was to investigate the role of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker of rectal cancers. We undertook a retrospective review of patients with rectal cancer. Pre-treatment NLR was assessed for association and predictive values against clinicopathological staging and post-treatment outcomes. A total of 140/180 cases were included in the final analysis [male:female 2:1; mean age 68 years (interquartile range 58-75)]. The pre-operative mean NLR was 5.4 ± 6.8. There was a strong positive correlation between NLR and C-reactive protein (Spearman's rho 64.3%, p < 0.001). A high NLR was associated with a positive nodal status on MRI (5.2 vs. 3.8, p = 0.03) and histopathological (4.8 vs. 3.8, p = 0.02) assessment. The NLR showed an average value for predicting MRI and pathological nodal status on receiver operating characteristic analysis [area under the curve = 0.72 (95% CI = 0.54-0.91), p = 0.031 and area under the curve = 0.64 (95% CI = 0.52-0.077), p = 0.021, respectively]. On multivariate analysis, the total lymph node retrieved at operation was the best predictor of pathological nodal involvement; NLR did not show any predictive value. Patients with an NLR >4 showed reduced recurrence-free (60 vs. 86 months, p = 0.52) and overall survival (57 vs. 84 months, p = 0.40) without statistical significance. Raised pre-treatment NLR may indicate nodal involvement in patients with rectal cancer.


Utility of (99m)Tc-MDP SPECT-CT for the diagnosis of sesamoiditis as cause of metatarsalgia.
Metatarsalgia is a general term for pain in the area of the metatarsophalangeal joints. Sesamoiditis is an uncommon cause of metatarsalgia. It is pain at the sesamoid bones beneath the head of the first metatarsal with inflammation or fracture. The diagnosis is usually clinical, with localized tenderness on palpation. Diagnosing the cause of metatarsalgia in patients without this classical sign is difficult. We present here such a case of a 37-year-old lady in whom sesamoiditis was diagnosed with technetium-99m ((99m)Tc)-methylene diphosphonate (MDP) single photon emission tomography-computed tomography (SPECT-CT).


Engineering of Methionine Adenosyltransferase Reveals Key Roles of Electrostatic Interactions in Enhanced Catalytic Activity.
As an important dietary supplement, S-adenosylmethionine (SAM) is currently synthesized by methionine adenosyltransferase (MAT) using ATP and methionine as substrates. However, the activity of MAT is severely inhibited by product inhibition, which limits the industrial production of SAM. Here, MAT from Bacteroides fragilis (BfMAT), exhibiting relatively low product inhibition and moderate specific activity, was identified by gene mining. Based on molecular docking, residues within 5 Å of ATP in BfMAT were subjected to mutagenesis for enhanced catalytic activity. Triple variants M3-1 (E42M/E55L/K290I), M3-2 (E42R/E55L/K290I), and M3-3 (E42C/E55L/K290I) with specific activities of 1.83, 1.81, and 1.94 U/mg were obtained, which were 110.5-125.6% higher than that of the wild type (WT). Furthermore, compared with WT, the Km values of M3-1 and M3-3 were decreased by 31.4% and 60.6%, leading to significant improvement in catalytic efficiency (kcat/Km) by 322.5% and 681.1%. All triple variants showed shifted optimal pH from 8.0 to 7.5. Moreover, interaction analysis suggests that the enhanced catalytic efficiency may be attributed to the decreased electrostatic interactions between ATP and the mutation sites (E42, E55, and K290). Based on MD simulation, coulomb energy and binding free energy analysis further reveal the importance of electrostatic interactions for catalytic activity of BfMAT, which could be an efficient strategy for improving catalytic performance of MATs.


Promoting rotational-invariance in object recognition despite experience with only a single view.
Different processes are assumed to underlie invariant object recognition across affine transformations, such as changes in size, and non-affine transformations, such as rotations in depth. From this perspective, promoting invariant object recognition across rotations in depth requires visual experience with the object from multiple viewpoints. One learning mechanism potentially contributing to invariant recognition is the error-driven learning of associations between relatively view-invariant visual properties and motor responses or object labels. This account uniquely predicts that experience with affine transformations of a single object view may also promote view-invariance, if view-invariant properties are also invariant across such affine transformations. We empirically confirmed this prediction in both people and pigeons, thereby suggesting that: (a) the hypothesized mechanism participates in view-invariance learning, (b) this mechanism is present across distantly-related vertebrates, and (c) the distinction between affine and non-affine transformations may not be fundamental for biological visual systems, as previously assumed.


Dynamics of underwater microparticle adhesion to soft hydrated surfaces: Modeling and analysis by time-dependent AFM force spectroscopy.
Understanding the attachment and detachment of microparticles and living cells to surfaces is crucial for developing antifouling strategies. Hydrogel coatings have shown promise in reducing fouling and particle adhesion due to their softness and high water content, yet the mechanisms involved are dynamic and complex, and relevant parameters are not easily accessible. AFM-based force spectroscopy (FS) experiments with colloidal probe particles is a direct way of evaluating adhesive and mechanical relaxational dynamics, yet their interpretation and modeling has been challenging. The present study proposes and examines several dynamic models, suitable for quantitative analysis of FS results with model probe particle on hydrogels surfaces. FS were performed using polyethylene glycol (PEG) hydrogels and polystyrene microspheres including particle attachement to the hydrogel surface (loading), holding the particle on the surface with a constant force for variable times (dwell) and pulling the particle away from the surface (unloading) FINDINGS: It was found that a viscoelastic extension of the classical JKR model with energy of adhesion unevenly distributed over the contact area and vanishing at its circumferences accurately described all FS experiments and yielded physically consistent viscoelastic and adhesive dynamic parameters, steadily changing with dwell time and applied force. The observed time evolution and force dependence were rationalized as combination of osmotic and osmo-mechnical relaxation in the contact region.


Interference of heavy metals on the photosynthetic response from a Cr(VI)-resistant Dictyosphaerium chlorelloides strain.
The successful selection of a particular type of bioelement and its association to the appropriate transducer determines the specificity of a biosensor. Therefore, from a strain of chloroficea Dictyosphaerium chlorelloides, modified in laboratory to tolerate high Cr(VI) concentrations, the possible interferences of other heavy metals on photosynthetic activity were studied. After exposing wild type and Cr(VI)-resistant cells to increasing Ag(+1), Co(+2), Hg(+2), Cr(+3), Cu(+2), Zn(+2), Fe(+3) and Cd(+2) concentrations, both photosynthetic quantum yields was compared. Photosynthetic electron transport rates were measured with a TOXY-PAM chlorophyll fluorometer, non-linear regression analysis of each of the toxicity tests was done, and means of both groups were compared using unpaired t test. The results show no significant differences between both cell types when they were exposed to Ag(+1), Co(+2), Hg(+2), Cr(+3), Cu(+2), Fe(+3) and Cd(+2) metal ions, and extremely significant differences (p < 0.0001) to Zn(+2) exposures. These results demonstrate the suitability of this Cr(VI)-resistant type D. chlorelloides strain as a suitable bioelement to be coupled to a biosensor based on dual-head microalgae strategy to detect and quantify Cr(VI) in water courses and waste water treatment plants. However, some disturbance may be expected, especially when certain analyte species such as zinc are present in water samples tested. The analysis of binary mixtures between Zn(+2) and other heavy metals showed a slight antagonistic phenomenon in all cases, which should not alter the potential Zn(+2) interference in the Cr(+6) detection process.


Assessment of arsenic levels in body samples and chronic exposure in people using water with a high concentration of arsenic: a field study in Kutahya.
This study aimed to evaluate the prevalence of skin lesions, which is a health effect of chronic arsenic (As) exposure, and determine the hair/blood arsenic concentrations of people living in Kutahya villages who are using and drinking tap water with a high concentration of arsenic. A total of 303 people were included in the present cross-sectional study. A prepared questionnaire form was used to collect the participants' information and environmental history. Skin examination was performed on all participants. Hair, blood and water samples were analyzed using atomic absorption spectroscopy. The cumulative arsenic index (CAI) was calculated for all participants. Villages were divided into two groups according to the arsenic level (<20 μg/L, Group I; >20 μg/L, Group II) in their water. The prevalence of skin lesions, hair and blood arsenic level, and CAI were found to be higher in the Group II participants. There was a positive association between body arsenic levels and CAI in the participants of each group. The number of skin lesions and arsenic concentrations in body samples were found to increase with the water arsenic level and exposure time. We hope that sharing this study's results with local administrators will help accelerate the rehabilitation of water sources in Kutahya.


Detection and characterisation of Yersinia enterocolitica strains in cold-stored carcasses of large game animals in Poland.
Yersinia enterocolitica is an important foodborne pathogen. The aim of the present study was to identify the bioserotypes and virulence markers of Y.enterocolitica strains isolated from three different anatomical regions of cold-stored carcasses of large game animals intended for human consumption. Y.enterocolitica strains were found in 12/20 (60%) of the roe deer carcasses examined, 7/16 (43.8%) of red deer carcasses and 11/20 (55%) of wild boar carcasses. Of the 52 Y.enterocolitica strains, 19 were isolated from the perineum, followed by 17 strains from the peritoneum of the longissimus dorsi muscle and 16 from the tonsils. Only one strain was isolated from warm culture. Bioserotype 1A/NI was the most commonly found and was detected in 29/52 isolates. All isolates contained amplicons corresponding to ystB gene fragments. The relatively high degree of carcass contamination with Y.enterocolitica is of concern due to the growing popularity of game meat with consumers.


Effects of acetylcholine and spermineNONOate on erythrocyte hemorheologic and oxygen carrying properties.
To determine the effects of acetylcholine and spermineNONOate--a NO donor--on RBC membrane and oxygen carrying properties. Aliquots of venous blood from eleven healthy subjects were incubated with ACh 10(-3) M, ACh 10(-5) M, spermineNONOate 10(-5) M and spermineNONOate 10(-4) M. The following parameters were determined: erythrocyte aggregation and deformability, hematocrit, plasma pH, osmolality, K(+), Na(+), Ca(2+) concentrations, hemoglobin, oxyhemoglobin, carboxyhemoglobin and methemoglobin concentrations, oxygen saturation of hemoglobin, oxygen and carbon dioxide partial pressures and p50. In presence of ACh there is an increase of erythrocyte deformability, decrease of erythrocyte aggregation, plasma pH, K(+) and Na(+) concentration, increase of Ca(2+) concentration and p50. In presence of spermineNONOate there is an increase of erythrocyte deformability, plasma pH, decrease of Na(+) and Ca(2+) concentration, increase of metHb concentration and decrease of p50. Acetylcholine and spermineNONOate are able to induce changes on RBC membrane and oxygen carrying properties.


Transcriptomic dataset of wild type and phoP mutant Pectobacterium versatile.
RNA-Seq transcriptome data for the wild type and phoP mutant strains of Pectobacterium versatile is described. P. versatile is a recently introduced name for a species of plant pathogenic bacteria that unites a group of strains previously embedded within the Pectobacterium carotovorum clade [1,2]. Little detail is available about how this pathogen adapts to changing environmental conditions, including those within its host plant. The PhoP/PhoQ two-component system is an important sensor responding to several stimuli and is present in most species of enteric bacteria. It usually controls large regulons, which vary greatly even between closely related species [3]. This dataset enables the discovery of the genes under direct or indirect transcriptional control by PhoP in P. versatile and should help to understand the physiology of this plant pathogen.


Sarcomatoid transitional cell carcinomas of the renal pelvis. An ultrastructural and immunohistochemical study.
Transitional cell carcinomas of the urinary tract may occasionally assume a partial or complete spindle cell pattern of growth, leading to the erroneous classification of some true carcinomas as sarcomas. We have recently observed two such tumors of the renal pelvis. In these cases, ultrastructural study showed that the spindle cells retained features of epithelial differentiation; this conclusion was further supported by positive results of several immunohistochemical stains, using biotinylated peanut agglutinin and soybean agglutinin, and a rabbit antiserum directed against keratin proteins. In addition, both tumors manifested immunoreactivity for blood-group antigens, using primary murine monoclonal antibodies. The results of these studies suggest that immunocytochemistry is a helpful diagnostic adjunct in the proper classification of sarcomatoid urothelial neoplasms.


Cell lineage analysis in ascidian embryos by intracellular injection of a tracer enzyme. III. Up to the tissue restricted stage.
Cell lineages during embryogenesis of the ascidian Halocynthia roretzi were analyzed up until the stage where each blastomere was fated to be only a single tissue type (i.e., the tissue restricted stage) by intracellular injection of horseradish peroxidase using the iontophoretic injection method. Initially, the developmental fates of all blastomeres of the 64-cell stage embryo were examined, and thereafter, only the fates of daughter blastomeres of those blastomeres that were not tissue restricted at the 64-cell stage were traced. The developmental fates of blastomeres were highly invariant except for two candidates for "equivalence groups" (J. Kimble, J. Sulston, and J. White (1979). In "Cell Lineage, Stem Cells and Cell Determination," pp. 59-68. Elsevier, Amsterdam/New York), in which cellular interaction is suggested to be involved in the specification of the fates. The right and left a8.25 cells gave rise to the otolith and ocellus, and the right and left b8.17 cells gave rise to the spinal cord and endodermal strand in a complementary manner. No fixed relationship existed between the position of the blastomere and its derivative. Most restrictions of cell fates occurred early in cleavage. The numbers of blastomeres which generated a single type of tissue were 44 at the 64-cell stage and 94 at the 110-cell stage. Eight pairs of blastomeres had not yet become tissue restricted by the 110-cell stage. Almost complete lineages of epidermis, nervous system, muscle, mesenchyme, notochord, and endodermal tissues were described, and a fate map was constructed for the blastula. For certain tissues, the primordial cells occupied two different regions. Supplementary investigations of the lineage of muscle cells were also performed on embryos of another species, Ciona intestinalis.


Early Pleistocene White-toothed Shrew Crocidura kornfeldi (Lipotyphla, Soricidae) from Crimea.
The remains of the white-toothed shrew Crocidura kornfeldi Kormos, 1934 (one skull fragment with almost complete dentition, the fragmental rostral part of a skull with the left upper incisor, a maxillary fragment, five mandibular fragments and an isolated upper incisor) from the Lower Pleistocene deposits of the Taurida cave in the central Crimea (Belogorsk district, Zuya village) are described. This earliest European species of the genus Crocidura was quite common in the Early Pleistocene of Central Europe and the Mediterranean; for the first time, it is described from Crimea and the entire Eastern Europe.


Induction of sister chromatid exchanges in xeroderma pigmentosum cells after exposure to ultraviolet light.
The role of DNA repair mechanisms in the induction of sister chromatid exchanges (SCE) after exposure to ultraviolet radiation was investigated in xeroderma pigmentosum cells. Cells from different excision-deficient XP strains, representing the 5 complementation groups in XP, A, B, C, D and E, and from excision-proficient XP variant strains were irradiated with low doses of UVR (0-3.5 J/m2). The number of SCE was counted after two cycles in the presence of BUdR. In cells of the complementation groups A, B, C and D the number of SCE was significantly higher than in UV-exposed control cells. The frequencies of SCE in group E cells and in XP varient cells were not different from those in control cells. Treatment with caffeine (0-200 microgram/ml) did not result in a different response of variant cells compared with normal cells. A simple correlation between SCE frequency and residual excision-repair activity was not observed. The response of the excision-repair deficient cells suggest that unrepaired damage, produced by UVR is involved in the production of SCE.


Childhood treatment with psychotropic medication and development of comorbid medical conditions in adolescent-onset bipolar disorder.
This study aims to investigate the association between early treatment with psychotropic medications and the development of medical comorbidities in pediatric patients who develop bipolar disorder (BD). Data from the South Carolina Medicaid program covering all medical services and medication prescriptions between January 1996 and December 2005 were used to determine the association between childhood exposure to psychotropic medications (i.e., psychostimulants, antidepressants, and antipsychotics) and the diagnosis of select comorbid medical conditions in 1841 children and adolescents diagnosed with Diagnostic and Statistical Manual IV defined BD. In separate regressions controlling for all psychotropic medications prescribed and all comorbid medical conditions diagnosed prior to the BD, hypertension and cardiovascular disorders were more likely in those prescribed second generation antipsychotics or psychostimulants, whereas obesity/overweight was more likely in those taking serotonin norepinephrine reuptake inhibitor/heterocyclic antidepressants, and asthma was more likely in those taking selective serotonin reuptake inhibitors. Childhood cardiometabolic events appear to be systematically associated with specific classes of psychotropic medications, but no innate, developmental sequencing of cardiometabolic abnormalities was apparent before early adolescence in patients subsequently diagnosed and treated for BD.


Is flow diversion the death of cerebral bypass and coiling/stent-assisted coiling for giant cavernous aneurysms? A critical review on comparative outcomes and ongoing clinical trials.
The classic surgical treatment for symptomatic giant aneurysms originating from the cavernous segment of the carotid artery has been either microsurgical direct clip-reconstruction or carotid occlusion followed by additional cerebral bypass for those patients who fail in a balloon test occlusion. Nevertheless the emergence of new endovascular techniques, especially flow-diverting devices, has promised to revolutionize the treatment of giant cavernous aneurysms, possibly avoiding major microsurgical operations. In this review the authors summarize the current "state-of-art" of treatment of giant cavernous aneurysms, comparing the overall outcomes, complications, morbidity and mortality rates of new flow-diverting devices in relation to traditional microsurgical series.


Parenting Practices of Mothers of Children with ADHD: The Role of Maternal and Child Factors.
We examined the relationships among child behavioural and demographic characteristics and parent characteristics in understanding the effectiveness of parenting practices used by mothers of children diagnosed with ADHD. One hundred and fifty Australian mothers of children diagnosed with ADHD were interviewed and asked to assess the severity of their child's disruptive behaviour, their own parenting sense of competence, perceptions of social isolation and parenting practices. The hypothesis was that severity of child disruptive behaviour, higher child age, 'only' child status, lower parental sense of competence and greater social isolation would be associated with the use of less effective parenting practices. The regression analysis indicated that the combination of these variables was significantly associated with parenting practices, accounting for 32% of the variance. Unique contributions were evident for severity of overall behavioural disturbance and parental sense of competence. Theoretical and clinical implications are discussed together with methodological limitations of the study.


In vivo methylation of an arginine in chicken myelin basic protein.
The amino acid sequence around the sole methylarginine residue in chicken myelin basic protein was determined and was found to be similar to that previously reported for mammalian myelin basic protein. The ratio NG, N'G-dimethylarginine: NG-monomethylarginine:arginine was approximately 1.3:0.9:1.0. No NG, NG-dimethylarginine was detected in the protein. The in vivo incorporation of methyl groups from [methyl-3H]methionine into methylarginines in myelin was found to occur readily in 2-day-old chickens. Radioactively labelled NG,N'G-dimethylarginine and NG-monomethylarginine in myelin were derived solely from myelin basic protein. Radioactivity was also incorporated into NG,NG-dimethylargnine, although this was not derived from myelin basic protein. As NG-monomethylarginine was easily separated from the dimethylarginines, and as it was derived from myelin basic protein, it may be a good marker for myelin basic protein turnover in vivo. A time course study of the incorporation showed that radioactivity was incorporated into NG-monomethylarginine up to 6 h after injection, and decayed slowly, with an apparent half-life of about 40 days.


Imaging pattern of previously in vitro sensitized and interleukin-2 expanded autologous lymphocytes in human cancer.
In vivo patterns of lymphocytes sensitized against autologous tumor (in vitro) were studied in seven patients with metastatic cancer as a potential candidate for an alternative method of radioimmunodetection and adoptive immunocytotherapy. Peripheral blood lymphocytes (PBL) were either activated in Interleukin-2 (IL-2) [lymphokine activated killer (LAK) cells] or sensitized against autologous tumor cells by in vitro co-culture (IVC) and expanded in IL-2 (educated cells); both were then labelled with 111In. Labelled autologous cells (1 x 10(7)-5 x 10(8)) were administered to patients and biodistribution studied by imaging under a gamma camera at various time intervals. In 4/7 cases, imaging with the educated cells showed concentrations of radioactivity at sites that correlated positively with clinically detectable metastatic tumor. By contrast, only one instance of positive uptake was seen with the LAK cells. Other than slight fever in three cases, infusions of labelled PBL were well tolerated. Educated lymphocytes were cytotoxic against autologous tumor cells and the cytotoxic reactivities of the educated cells were maintained in continuous culture in IL-2 for 4-6 weeks. Evidence of accumulation of radiolabelled educated autologous cells at a significantly higher frequency than that of the LAK cells suggests that in vitro expanded educated PBL might be better candidates for radioimmunodetection of human cancer, and continuous cultures of such educated autologous PBL might be sources for repeated administration of these effector cells.


DNA of Akodon (Rodentia, Cricetidae). I. Biophysical characterization.
Buoyant density in CsCl, melting temperature, and G + C base content of the DNA from four species of Akodon (Rodentia, Cricetidae) were determined. The buoyant density values of 1.699-1.701 g/cm3 were in accordance with the data reported for other cricetids. No satellite bands were seen in neutral CsCl. The Tm values determined in 1 x SSC ranged from 86.2 to 87.0 C, which corresponds to G + C contents of 41.2-43.2%. There was good agreement in DNA base composition of the four species, although values were slightly higher in A. obscurus, suggesting a certain degree of interspecies variability.


Current role for bone absorptiometry.
Bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA) is a key contributor to the management of bone fragility syndromes, most notably postmenopausal osteoporosis. Experimental studies of bone biomechanics have established that an accurate marker for mechanical strength is areal BMD (aBMD, g/cm2). Areal BMD contributes 70% of mechanical strength at the femur and 40% at the spine. Two decades after the T-score was first introduced (World Health Organization, 1994), changes have occurred in the indications of DXA and in the interpretation of its results for the diagnosis, prognosis, and treatment of osteoporosis.


Combination treatment with sofosbuvir and ribavirin for patients diagnosed with hepatitis C genotype 2: A real-world, single-center study.
The demand for treatments for viral hepatitis using direct antiviral agents (DAAs) has increased; however, few real-world clinical studies are available. The objective of this study was to evaluate the efficacy and safety of sofosbuvir combined with ribavirin for patients with chronic hepatitis C (CHC) genotype 2 (GT2). A total of 106 consecutive CHC GT2 patients treated with sofosbuvir plus ribavirin between May 2016 and August 2018 (median age: 52.5 years, male: 51 [48.1%], treatment-naïve patients: 98 [92.5%]) were analyzed. The primary endpoint was sustained virologic response at 12 weeks (SVR12). The secondary endpoint was the occurrence of side effects during treatment. Of a total of 106 patients with CHC GT2, 103 were genotype 2a (97.2%), and 3 were 2b (2.8%). SVR12 was confirmed in 105 of 106 patients (99.1%). The one patient with treatment failure had combined liver cirrhosis and hepatocellular carcinoma. Twenty-five patients had liver cirrhosis in addition to hepatitis C virus (HCV) (Child-Turcotte-Pugh (CTP)-A, n = 24; C, n = 1), and SVR12 was confirmed in 24 of these patients (96.0%). The mean HCV RNA titer was 2,629,159 IU/ml. Reductions in haemoglobin levels occurred in 23 patients during treatment (3.0 mg/dL, mean), and consequently, ribavirin dose reduction was required (365.2 mg, mean). Sofosbuvir plus ribavirin was highly effective for the treatment of patients with CHC GT2 and had no serious, treatment-related adverse effects.


Diminished insulin response in highly trained athletes.
Insulin secretion and glucose tolerance were examined in 6 highly conditioned athletes in comparison with a control group of 115 normal healthy persons. During glucose infusion the athletes showed low insulin secretion although there was no difference in the levels of blood glucose compared to the control group. It is concluded that under physiologic conditions the extent of insulin secretion is not dependent only upon the blood glucose levels. The results show that a lack of insulin response can occur as a consequence of adaption to physical training. A reduced insulin response, therefore, does not necessarily indicate a diabetic or prediabetic state.


Interaction between veralipride and the endogenous opioid system in the regulation of body temperature in postmenopausal women.
The influence of endogenous opioid peptides on body thermoregulation has been studied in untreated postmenopausal women and in the same subjects after chronic administration of the antidopaminergic drug veralipride (200 mg/day for 20 days). Subjects randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, both before and after veralipride treatment. In untreated subjects body core temperature, as evaluated by rectal temperature, did not vary during saline infusion, whereas a significant decrease was observed during naloxone infusion. Chronic administration of veralipride significantly increased the hypothermic response to naloxone. Therefore, veralipride seems to increase the activity of endogenous opioid peptides on mechanisms which regulate body temperature in postmenopausal women.


Expression of neuropeptide Y and cholecystokinin in the rat brain by chronic mild stress.
Neuropeptide Y (NPY) and cholecystokinin (CCK) are known to play important roles in the response to stress and the control of anxiety. In order to investigate the role of NPY and CCK in chronic mild stress (CMS), an animal model of depression, we examined the effects of CMS on sucrose intake as a measure of anhedonia, and expression of NPY and CCK in the rat brain utilizing immunohistochemistry. Sprague-Dawley rats were exposed to a variety of chronic unpredictable mild stressors for 8 weeks. CMS rats significantly reduced the consumption of sucrose intake and gained body weight more slowly, compared to control rats. CMS dramatically produced a decrease in NPY expression in several diencephalic regions including the parvocellular subregion of the paraventricular hypothalamic nucleus (PVN), the periventricular hypothalamic nucleus (PE), the paraventricular thalamic nucleus (PV) and the arcuate nucleus (ACN). In contrast, CCK-like immunoreactivity throughout these areas was substantially increased in chronic mild stressed rats. These results clearly demonstrated that exposure of chronic mild stress upregulated CCK synthesis and downregulated NPY synthesis within the hypothalamus. The present results demonstrated that there was an inverse relationship between NPY and CCK in mediating stress response in an animal model of depression. These findings suggest that CCK and NPY systems may play important roles in expressing the symptopathology of the chronic stress responses such as depression, abnormality of food intake or anxiety-related disorders.


Protistan and fungal diversity in soils and freshwater lakes are substantially different.
Freshwater and soil habitats hold rich microbial communities. Here we address commonalities and differences between both habitat types. While freshwater and soil habitats differ considerably in habitat characteristics organismic exchange may be high and microbial communities may even be inoculated by organisms from the respective other habitat. We analyze diversity pattern and the overlap of taxa of eukaryotic microbial communities in freshwater and soil based on Illumina HiSeq high-throughput sequencing of the amplicon V9 diversity. We analyzed corresponding freshwater and soil samples from 30 locations, i.e. samples from different lakes across Germany and soil samples from the respective catchment areas. Aside from principle differences in the community composition of soils and freshwater, in particular with respect to the relative contribution of fungi and algae, soil habitats have a higher richness. Nevertheless, community similarity between different soil sites is considerably lower as compared to the similarity between different freshwater sites. We show that the overlap of organisms co-occurring in freshwater and soil habitats is surprisingly low. Even though closely related taxa occur in both habitats distinct OTUs were mostly habitat-specific and most OTUs occur exclusively in either soil or freshwater. The distribution pattern of the few co-occurring lineages indicates that even most of these are presumably rather habitat-specific. Their presence in both habitat types seems to be based on a stochastic drift of particularly abundant but habitat-specific taxa rather than on established populations in both types of habitats.


The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus.
Endoscopic surveillance for Barrett's oesophagus (BO) is limited by sampling error and the subjectivity of diagnosing dysplasia. We aimed to compare a biomarker panel on minimal biopsies directed by autofluorescence imaging (AFI) with the standard surveillance protocol to derive an objective tool for dysplasia assessment. We performed a cross-sectional prospective study in three tertiary referral centres. Patients with BO underwent high-resolution endoscopy followed by AFI-targeted biopsies. 157 patients completed the biopsy protocol. Aneuploidy/tetraploidy; 9p and 17p loss of heterozygosity; RUNX3, HPP1 and p16 methylation; p53 and cyclin A immunohistochemistry were assessed. Bootstrap resampling was used to select the best diagnostic biomarker panel for high-grade dysplasia (HGD) and early cancer (EC). This panel was validated in an independent cohort of 46 patients. Aneuploidy, p53 immunohistochemistry and cyclin A had the strongest association with dysplasia in the per-biopsy analysis and, as a panel, had an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95 to 0.99) for diagnosing HGD/EC. The diagnostic accuracy for HGD/EC of the three-biomarker panel from AFI+ areas was superior to AFI- areas (p<0.001). Compared with the standard protocol, this panel had equal sensitivity for HGD/EC, with a 4.5-fold reduction in the number of biopsies. In an independent cohort of patients, the panel had a sensitivity and specificity for HGD/EC of 100% and 85%, respectively. A three-biomarker panel on a small number of AFI-targeted biopsies provides an accurate and objective diagnosis of dysplasia in BO. The clinical implications have to be studied further.


Acquisition of a brief behavioural experience in the rat is inhibited by the brain-specific monoclonal antibody, F3-87-8.
Intraventricular infusion of the brain-specific monoclonal antibody F3-87-8 is demonstrated to inhibit the acquisition of a passive-avoidance paradigm in a rat model. Antibody was infused prior to, and following, training of a step-down task and recall was assessed after 24 and 48 h. The antibody only inhibited recall when infused prior to training and no effect was seen when administered 6 h after acquisition of the task. No effect was found with absorbed antibody or in sham-operated animals and open field studies showed no alterations in locomotor activity. Results are discussed considering available information on the antigen and current memory/learning theories.


Transplantation of cultured astrocytes attenuates degenerative changes in rats with kainic acid-induced brain damage.
Viability of astrocyte grafts introduced into CA1 pyramidal layer of the left dorsal hippocampus after injection of kainic acid into this brain region and the effects of these grafts on the hippocampus and amygdala were studied on Wistar rats. In rats with astrocyte grafts the degree of destruction in fields CA1-CA2 of the dorsal and ventral hippocampus, fields CA3-CA4 of the ventral hippocampus, and central and basolateral amygdala was lower compared to animals with kainic acid-induced hippocampal damage and control rats; destructions in the dentate fascia were absent. Our results suggest that astrocyte grafts stimulate neurogenesis in the mature brain of recipient rats with kainic acid-induced brain damage.


Immunoglobulin heavy chain class switch from IgM to IgG in a hybridoma.
A subclone of an IgM-producing hybridoma has been identified which has switched to producing an IgG1 antibody. The parent hybridoma, PC-140, produces an antibody which binds phosphorylcholine and reacts with monoclonal antibodies that recognize myelomas of the T-15 idiotype. The IgG1 antibody binds phosphorylcholine with the same affinity as the parental IgM and also reacts with the anti-T-15 monoclonal antibodies. While the IgM-producing parent hybridoma does not express detectable surface IgM, the IgG1-producing subclone produces both membrane and secreted IgG1.