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We investigated carbohydrate residues on the epithelial surface, in the epithelial cells and in gland cells of the tongue of the mole rat using histochemical methods. We used horseradish peroxidase-conjugated lectins fromHelix pomatia(HPA),Arachishypogaea(PNA),Ulexeuropaeus(UEA I),Canavaliaensiformis(Con A). The most intense reactivity was observed in the keratin layer with HPA, UEA I and Con A, and in the epithelial cells with UEA I and Con A. In the glands, we found strong reactivity in serous cells with HPA and Con A, and in mucous cells with HPA and UEA I. PNA did not bind to epithelial or gland cells. Consequently, GlcNAc, fucose and α-D-mannose terminal glycoconjugates are distributed widely; GalNAc terminal glycoconjugates appeared in small amounts. [ABSTRACT FROM AUTHOR]

The distribution and relative frequency of external taste buds (TB) of Garra rufa were studied. TB of Garra rufa were observed on different body location (lips, lateral and ventral areas, forehead, operculum and dorsal–pelvic–pectoral–anal fins). TB are at the highest frequency in lips, forehead, pectoral and anal fins. These structures are moderate as a number in operculum, La2 (between pelvic and anal fins) areas, and then decreased a few in other areas. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy and safety of patient-controlled epidural analgesia of morphine or fentanyl in combination with bupivacaine for postoperative pain relief.Methods: Forty ASA I-II patients scheduled for major abdominal surgery were studied. After insertion of a lumbar epidural catheter, patients were given a non-opioid general anaesthetic. After surgery patients complaining of pain, received a loading dose of 2 mg morphine (Group I) or 50 micrograms fentanyl (Group II). For continuing pain, 1 mg morphine in 4 ml bupivacaine 0.125% (0.25 mg.ml-1 morphine and 1 mg.ml-1 bupivacaine, Group I) or 20 micrograms fentanyl in 4 ml bupivacaine 0.125% (5 micrograms.ml-1 fentanyl and 1 mg.ml-1 bupivacaine Group II) were administered. Blood pressure, heart rate, respiratory rate and SpO2 were monitored. Assessments of pain (VAS), nausea-vomiting, motor block, pruritus and sedation were recorded for 24 hr.Results: No difference in pain or sedation was observed between groups. The 24 hr postoperative opioid consumption was 15.50 +/- 7.53 mg morphine and 555.10 +/- 183.85 micrograms fentanyl. Total bupivacaine 0.125% consumption was 58.00 +/- 30.14 ml in Group I and 101.05 +/- 36.77 ml in Group II. One patient in Group II complained of motor weakness in one leg. The incidence of nausea (Group I 45%, Group II 10% P < 0.05) and pruritus (Group I 30%, Group II 5% P < 0.05) was less in patients receiving fentanyl.Conclusion: Both methods were effective in the prevention of pain but, because of fewer side effects, fentanyl may be preferable to morphine. [ABSTRACT FROM AUTHOR]

Current techniques of intelligent information access have surpassed the mere provision of static information. They attempt to overcome the limitations of traditional content delivery processes by exploiting information retrieval techniques. While the existing literature has extensively explored the adoption of these techniques, comparatively little notice has so far been taken of their application as ontology transformations. This paper aims to explore levels of intelligent information access from a practical perspective. Applying the theoretical framework of information retrieval techniques, we identify and define levels of information access and propose respective ontology transformations. For this purpose, we decided to use an ontology-editing tool for modeling, transforming and displaying information about the domain of Smart Homes.

This study investigated the relationship between parental psychological wellbeing, parenting, children's psychological difficulties, and prosocial behavior in Kahramanmaraş earthquake-affected families living in Türkiye in 2023. To this end, a mediation model was proposed for parental psychological distress that was hypothesized to exert an indirect effect on a child's psychological difficulties and prosocial behavior through parenting. Participants were 358 preschoolers between 4 and 6 years old and their one parent (father or mother) who completed a set of validated self-report surveys in a cross-sectional design study. Results showed positive associations between parental psychological distress and child's psychological difficulties but negative association with child's prosocial behavior. Furthermore, quality of parenting mediated the association between parental psychological distress and child's psychological difficulties and prosocial behavior. Our findings suggest that positive parenting may serve as a protective mechanism that mediates the association between parental psychological distress and a child's psychological difficulties and prosocial behaviors among families displaced by a natural disaster like an earthquake. These findings point to the need for supporting positive parent-child relationships in addition to decreasing the psychological distress of parents when exposed to potentially traumatizing events like this., (© 2024 The Author(s). Family Process published by Wiley Periodicals LLC on behalf of Family Process Institute.)

NOVA1, a neuronal RNA-binding protein expressed in the central nervous system, is essential for survival in mice and normal development in humans. A single amino acid change (I197V) in NOVA1's second RNA binding domain is unique to modern humans. To study its physiological effects, we generated mice carrying the human-specific I197V variant (Nova1 hu/hu ) and analyzed the molecular and behavioral consequences. While the I197V substitution had minimal impact on NOVA1's RNA binding capacity, it led to specific effects on alternative splicing, and CLIP revealed multiple binding peaks in mouse brain transcripts involved in vocalization. These molecular findings were associated with behavioral differences in vocalization patterns in Nova1 hu/hu mice as pups and adults. Our findings suggest that this human-specific NOVA1 substitution may have been part of an ancient evolutionary selective sweep in a common ancestral population of Homo sapiens, possibly contributing to the development of spoken language through differential RNA regulation during brain development., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Despite advancements in understanding the structure and functions of the Calcium Sensing Receptor (CaSR), gaps persist in our knowledge of the specific functions of its residues. In this study, we used phylogeny-based techniques to identify functionally equivalent orthologs of CaSR, predict residue significance, and compute specificity-determining position (SDP) scores to understand its evolutionary basis. The analysis revealed exceptional conservation of the CaSR subfamily, emphasizing the critical role of residues with high SDP scores in receptor activation and pathogenicity. To further enhance the findings, gradient-boosting trees were applied to differentiate between gain- and loss-of-function mutations responsible for hypocalcemia and hypercalcemia. Lastly, we investigated the importance of these mutations in the context of receptor activation dynamics. In summary, through comprehensive exploration of the evolutionary history of the CaSR subfamily, coupled with innovative phylogenetic methodologies, we identified activating and inactivating residues, providing valuable insights into the regulation of calcium homeostasis and its connections to associated disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bircan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper presents an evaluation of predictions submitted for the "HMBS" challenge, a component of the sixth round of the Critical Assessment of Genome Interpretation held in 2021. The challenge required participants to predict the effects of missense variants of the human HMBS gene on yeast growth. The HMBS enzyme, critical for the biosynthesis of heme in eukaryotic cells, is highly conserved among eukaryotes. Despite the application of a variety of algorithms and methods, the performance of predictors was relatively similar, with Kendall's tau correlation coefficients between predictions and experimental scores around 0.3 for a majority of submissions. Notably, the median correlation (≥ 0.34) observed among these predictors, especially the top predictions from different groups, was greater than the correlation observed between their predictions and the actual experimental results. Most predictors were moderately successful in distinguishing between deleterious and benign variants, as evidenced by an area under the receiver operating characteristic (ROC) curve (AUC) of approximately 0.7 respectively. Compared with the recent two rounds of CAGI competitions, we noticed more predictors outperformed the baseline predictor, which is solely based on the amino acid frequencies. Nevertheless, the overall accuracy of predictions is still far short of positive control, which is derived from experimental scores, indicating the necessity for considerable improvements in the field. The most inaccurately predicted variants in this round were associated with the insertion loop, which is absent in many orthologs, suggesting the predictors still heavily rely on the information from multiple sequence alignment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most algorithms that are used to predict the effects of variants rely on evolutionary conservation. However, a majority of such techniques compute evolutionary conservation by solely using the alignment of multiple sequences while overlooking the evolutionary context of substitution events. We had introduced PHACT, a scoring-based pathogenicity predictor for missense mutations that can leverage phylogenetic trees, in our previous study. By building on this foundation, we now propose PHACTboost, a gradient boosting tree-based classifier that combines PHACT scores with information from multiple sequence alignments, phylogenetic trees, and ancestral reconstruction. By learning from data, PHACTboost outperforms PHACT. Furthermore, the results of comprehensive experiments on carefully constructed sets of variants demonstrated that PHACTboost can outperform 40 prevalent pathogenicity predictors reported in the dbNSFP, including conventional tools, metapredictors, and deep learning-based approaches as well as more recent tools such as AlphaMissense, EVE, and CPT-1. The superiority of PHACTboost over these methods was particularly evident in case of hard variants for which different pathogenicity predictors offered conflicting results. We provide predictions of 215 million amino acid alterations over 20,191 proteins. PHACTboost is available at https://github.com/CompGenomeLab/PHACTboost. PHACTboost can improve our understanding of genetic diseases and facilitate more accurate diagnoses., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Organisms have evolved defense mechanisms to protect themselves from stressful conditions. The expression of heat shock proteins is considered a valid indication of protection from the adverse effects of hostile conditions. In this study, we used immunohistochemistry to investigate the seasonal effects of some abiotic factors on heat shock protein 70 and 90 (HSP70 and HSP90) expression in the liver, gills, and muscle tissues of 24 Common carp ( Cyprinus carpio ) caught in Karataş Lake (Burdur, Türkiye) using gillnets of various mesh sizes. We also measured some physicochemical parameters on-site at sampling time and took water samples for further analyses of other physicochemical parameters and heavy metals. Immunostaining for HSP90 was stronger than for HSP70 in both liver and gill samples. Liver and gill structures exhibited significant seasonal differences in HSP70 and HSP90 immunoreactivity, and the same was true for immunostaining for HSP70 and HSP90 in muscle samples. Some physicochemical properties seemed to vary considerably between seasons, with Fe, Mn, and Zn levels tending to exhibit changes throughout the seasons. However, these levels were considered acceptable for human health. In conclusion, this study suggests that substantial changes in HSP70 and HSP90 expression may be essential for seasonal adaptation and tolerance. Further research on fish HSPs would greatly contribute to aquaculture, which is essential for meeting food requirements., Competing Interests: Authors have no conflict of interest to declare., (© 2023 Urmia University. All rights reserved.)

Evolutionary conservation is a fundamental resource for predicting the substitutability of amino acids and the loss of function in proteins. The use of multiple sequence alignment alone-without considering the evolutionary relationships among sequences-results in the redundant counting of evolutionarily related alteration events, as if they were independent. Here, we propose a new method, PHACT, that predicts the pathogenicity of missense mutations directly from the phylogenetic tree of proteins. PHACT travels through the nodes of the phylogenetic tree and evaluates the deleteriousness of a substitution based on the probability differences of ancestral amino acids between neighboring nodes in the tree. Moreover, PHACT assigns weights to each node in the tree based on their distance to the query organism. For each potential amino acid substitution, the algorithm generates a score that is used to calculate the effect of substitution on protein function. To analyze the predictive performance of PHACT, we performed various experiments over the subsets of two datasets that include 3,023 proteins and 61,662 variants in total. The experiments demonstrated that our method outperformed the widely used pathogenicity prediction tools (i.e., SIFT and PolyPhen-2) and achieved a better predictive performance than other conventional statistical approaches presented in dbNSFP. The PHACT source code is available at https://github.com/CompGenomeLab/PHACT., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The qualification of a preschool teacher is one of the important factors that determine the quality of preschool education. To increase the quality in education, teachers should be equipped with the necessary knowledge starting from pre-service training, and in-service training should support the upgrading of their knowledge. Thus, the aim of this study was to develop an e-Mentoring-Based Education Program (e-MENTE:PT) for preschool teachers and to test its effectiveness on their professional development during the in-service support period. The study used a design-based research approach. First, focus group interviews were conducted with one-hundred-and-five preschool teachers to find out their needs. Then, an e-MENTE:PT Program was developed based on these needs and devised to be used on the Canvas learning management system (LMS), which involves all opportunities of e-learning and allows one-to-one e-mentoring. The e-MENTE:PT Program involved twelve modules related to the pedagogical content knowledge of the preschool education program. Each module included contents, goals, module materials, e-books, videos, pre- and post-module evaluation questions, discussion questions, live lessons and e-portfolios, all of which were integrated in the LMS. Next, eighteen full-time and nine substitute voluntary teachers from five different provinces were selected as mentees by means of criterion sampling. Nine academicians working in these provinces acted as mentors and implemented the application, each working with two mentees for two months. Qualitative data were analysed by means of descriptive analysis and quantitative data were analysed by means of the Wilcoxon signed rank test. The research concluded that the e-MENTE:PT program supported preschool teachers' professional knowledge, learning environments and classroom applications, and an e-mentoring based teaching management system was effective on professional development., Competing Interests: Conflicts of interest/Competing interestsThe authors have no financial or proprietary interests in any material discussed in this article., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Phylogenetic trees are useful tools to infer evolutionary relationships between genetic entities. Phylogenetics enables not only evolution-based gene clustering but also the assignment of gene duplication and deletion events to the nodes when coupled with statistical approaches such as bootstrapping. However, extensive gene duplication and deletion events bring along a challenge in interpreting phylogenetic trees and require manual inference. In particular, there has been no robust method of determining whether one of the paralog clades systematically shows higher divergence following the gene duplication event as a sign of functional divergence. Here, we provide Phylostat, a graphical user interface that enables clade divergence analysis, visually and statistically. Phylostat is a web-based tool built on phylo.io to allow comparative clade divergence analysis, which is available at https://phylostat.adebalilab.org under an MIT open-source licence., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

Aims: This multicenter phase II trial evaluates the efficacy of everolimus in poor prognosis grade 2 (G2) pancreatic neuroendocrine tumors (PNETs), defined by 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) avidity. FDG-PET avidity in NETs is associated with a significantly higher risk of death, outperforming Ki-67 index or liver metastases as a poor prognostic factor. We hypothesized that everolimus has efficacy in patients with FDG-PET-avid G2 PNETs and prospectively evaluated progression-free survival (PFS) and response in the first-line setting., Methods: Patients with FDG-PET-avid G2 advanced PNET received everolimus 10 mg daily until disease progression. Patients were staged every 12 weeks with CT/MRI and FDG-PET and every 24 weeks with Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE, GaTate) PET. The primary endpoint was PFS at 6 months. Overall survival rate, PET/structural imaging response and toxicity were also measured., Results: Nine patients were accrued from December 2012 to February 2015. Median treatment duration was 13.8 months. The estimated PFS rate at 6 months was 78%. The best response on CT/MRI was stable disease in nine patients (100%) and partial response on FDG-PET in five patients (55.5%). Treatment-related adverse effects were consistent with previous studies of everolimus., Conclusion: Everolimus is active with prolonged disease control in poor prognosis FDG-avid G2 PNETs. Treatment individualization based on functional imaging warrants further evaluation., (© 2020 John Wiley & Sons Australia, Ltd.)

Combination therapies that produce synergistic growth inhibition are widely sought after for the pharmacotherapy of many pathological conditions. Therapeutic selectivity, however, depends on the difference between potency on disease-causing cells and potency on non-target cell types that cause toxic side effects. Here, we examine a model system of antimicrobial compound combinations applied to two highly diverged yeast species. We find that even though the drug interactions correlate between the two species, cell-type-specific differences in drug interactions are common and can dramatically alter the selectivity of compounds when applied in combination vs. single-drug activity-enhancing, diminishing, or inverting therapeutic windows. This study identifies drug combinations with enhanced cell-type-selectivity with a range of interaction types, which we experimentally validate using multiplexed drug-interaction assays for heterogeneous cell cultures. This analysis presents a model framework for evaluating drug combinations with increased efficacy and selectivity against pathogens or tumors.

This study was conducted to reveal the morphometric and morphological features of foot pads in the Anatolian bobcat (Lynx lynx). To achieve this objective, dissection, histological, and radiography techniques were applied to two dead materials obtained from the Republic of Turkey Ministry of Forest and Water Works Sivas Branch Manager. Digit I is radiographically rudimentary in the forepaw. The paws of the forelimb of the Anatolian bobcat have a carpal, a metacarpal, and four digital pads, while the hind feet have a metatarsal pad and four digital pads. The metacarpal pad is cone-like, while the metatarsal pad resembles a butterfly. The digital pads in the paws of the forelimb are longer and thinner than in the paws in the hind feet. The paws in both feet are situated as binary. Through histological examination, it was determined that the skin of the foot pads consists of epidermis, dermis, and pad cushion. The epidermis is subdivided into basal, spinous, granular, lucidum, and corneum layers. The dermis of each pad consists of papillar and reticular strata containing sweat glands, elastin, collagen, and reticular fibers. Anat Rec, 301:932-938, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Aims and Objectives: To evaluate the effect of Laughter therapy on the quality of life of nursing home residents., Background: By improving the quality of life of residents living in nursing homes and allowing them to have a healthier existence, their lives can be extended. Therefore, interventions impacting the quality of life of older adults are of critical importance., Design: Quasi-experimental design., Method: The study was conducted between 2 March - 25 May 2015. The experimental group was composed of 32 nursing home residents from one nursing home, while the control group consisted of 33 nursing home residents from another nursing home in the capital city of Turkey. Laughter therapy was applied with nursing home residents of the experimental group two days per week (21 sessions in total). A socio-demographic form and the Short-Form Health Survey (SF-36) were used for data collection., Results: After the laughter therapy intervention, general and subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and spiritual health) quality-of-life scores of residents in the experimental group significantly increased in comparison with the pretest., Conclusion: Laughter therapy improved the quality of life of nursing home residents. Therefore, nursing home management should integrate laughter therapy into health care and laughter therapy should be provided as a routine nursing intervention., Relevance to Clinical Practice: The results indicated that the laughter therapy programme had a positive effect on the quality of life of nursing home residents. Nurses can use laughter therapy as an intervention to improve quality of life of nursing home residents., (© 2016 John Wiley & Sons Ltd.)

Combinations of three or more drugs are used to treat many diseases, including tuberculosis. Thus, it is important to understand how synergistic or antagonistic drug interactions affect the efficacy of combination therapies. However, our understanding of high-order drug interactions is limited because of the lack of both efficient measurement methods and theoretical framework for analysis and interpretation. We developed an efficient experimental sampling and scoring method [diagonal measurement of n -way drug interactions (DiaMOND)] to measure drug interactions for combinations of any number of drugs. DiaMOND provides an efficient alternative to checkerboard assays, which are commonly used to measure drug interactions. We established a geometric framework to factorize high-order drug interactions into lower-order components, thereby establishing a road map of how to use lower-order measurements to predict high-order interactions. Our framework is a generalized Loewe additivity model for high-order drug interactions. Using DiaMOND, we identified and analyzed synergistic and antagonistic antibiotic combinations against Mycobacterium tuberculosis . Efficient measurement and factorization of high-order drug interactions by DiaMOND are broadly applicable to other cell types and disease models.

Combination antibiotic therapies are clinically important in the fight against bacterial infections. However, the search space of drug combinations is large, making the identification of effective combinations a challenging task. Here, we present a computational framework that uses substructure profiles derived from the molecular structures of drugs and predicts antibiotic interactions. Using a previously published data set of 153 drug pairs, we showed that substructure profiles are useful in predicting synergy. We experimentally measured the interaction of 123 new drug pairs, as a prospective validation set for our approach, and identified 37 new synergistic pairs. Of the 12 pairs predicted to be synergistic, 10 were experimentally validated, corresponding to a 2.8-fold enrichment. Having thus validated our methodology, we produced a compendium of interaction predictions for all pairwise combinations among 100 antibiotics. Our methodology can make reliable antibiotic interaction predictions for any antibiotic pair within the applicability domain of the model since it solely requires chemical structures as an input.

Unlabelled: Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2)., Significance: We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses., (©2015 American Association for Cancer Research.)

Apoptosis of neurons in the maturing neocortex has been recorded in a wide variety of mammals, but very little is known about its effects on cortical differentiation. Recent research has implicated the RhoA GTPase subfamily in the control of apoptosis in the developing nervous system and in other tissue types. Rho GTPases are important components of the signaling pathways linking extracellular signals to the cytoskeleton. To investigate the role of the RhoA GTPase subfamily in neocortical apoptosis and differentiation, we have engineered a mouse line in which a dominant-negative RhoA mutant (N19-RhoA) is expressed from the Mapt locus, such that all neurons of the developing nervous system are expressing the N19-RhoA inhibitor. Postnatal expression of N19-RhoA led to no major changes in neocortical anatomy. Six layers of the neocortex developed and barrels (whisker-related neural modules) formed in layer IV. However, the density and absolute number of neurons in the somatosensory cortex increased by 12-26% compared with wild-type littermates. This was not explained by a change in the migration of neurons during the formation of cortical layers but rather by a large decrease in the amount of neuronal apoptosis at postnatal day 5, the developmental maximum of cortical apoptosis. In addition, overexpression of RhoA in cortical neurons was seen to cause high levels of apoptosis. These results demonstrate that RhoA-subfamily members play a major role in developmental apoptosis in postnatal neocortex of the mouse but that decreased apoptosis does not alter cortical cytoarchitecture and patterning.

A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, substituted at the 2-position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Attachment of the charged entity using an N-ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa.

A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with carbon-linked substituents, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Palladium-catalyzed cross-coupling methods were applied for the incorporation of aliphatic and aromatic substituents.

Objective: To examine serum leptin concentrations in obese and lean patients with polycystic ovary syndrome (PCOS) to assess whether the changes in leptin levels are due to obesity or hormonal alterations., Design: Controlled clinical study., Setting: Academic research environment., Patient(s): Obese and lean women with PCOS., Intervention(s): Blood samples were collected before and after food consumption., Main Outcome Measure(s): Serum leptin and insulin levels., Result(s): Serum leptin concentrations were significantly correlated with body mass index (r = 0.649) and also with HOMA (r = 0.535). However, after controlling for body mass index in a partial correlation analysis, no significant correlation was found between serum leptin levels and HOMA or hyperinsulinemia. While lean patients with PCOS had a significant correlation between leptin concentrations and obesity parameters, they did not show any significant correlation with insulin resistance parameters., Conclusion(s): Although leptin concentrations in women with PCOS correlate with insulin resistance/hyperinsulinemia, this is related only to obesity.

Exchange of the ethylene tether in a series of pyridopyrimidine-based MexAB-OprM specific efflux pump inhibitors to an amide bond stabilized the olefin of the acrylic acid moiety, preventing facile photoisomerization to the Z-isomer. Furthermore, the activity was drastically improved in the amide tether variants, providing extremely potent acrylic acid and vinyl tetrazole analogues.

While the best way to identify microalbuminuria is to determine albumin excretion rate (AER) in a 24 h urine sample. Published data have shown that calculation of an albumin/creatinine ratio (ACR) in a spot urine sample has reasonable rate of sensitivity and specificity. We aimed to evaluate the effect of daily exercise on ACR and estimate the best time for the examination of the ACR in a spot urine sample. Sixteen eligible patients with Type 1 diabetes mellitus were asked to perform varying degree of exercise periods. Urinary albumin and creatinine excretion rates during each period were determined. ACR and AER of timed urinary samples were compared with the 24 hour urinary AER. We found significant correlations between timed and 24 hour urinary AER. According to diagnostic performance tests, ACR and AER of timed urine samples were both found to be significantly more sensitive during resting period when compared with mild or moderate active periods. It is concluded that ACR and AER of a timed urine sample are sensitive and specific methods for determining microalbuminuria, while overnight resting samples give the impression of being more diagnostic. Key PointsTimed urine samples can predict microalbuminuria but because of the erroneous urine collections, microalbuminuria measurement should be calculated with creatiniuria measurement.With increasing physical activity during urine collection diagnostic performances of the cut-off values go downhill.For detecting microalbuminuria best results are reached with the early-morning urine samples.

The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the 2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency.

The aim of this study was to prevent the complications of gastrocystoplasty by using reversed seromuscular gastrocystoplasty for bladder augmentation. Healthy mongrel dogs were used in the study. A diamond shaped segment was separated from the remainder of the stomach preserving the right gastroepiploic artery in 11 dogs. The gastric mucosa was removed. A reversed seromuscular gastrocystoplasty was performed. The animals were observed for a mean of 7.7 months. Thereafter, relaparotomy was performed in all animals. A bladder stone was found in 1 dog. In the histopathological evaluation of the urinary bladder, it was seen that the gastric serosal surface was covered with the urothelium in all dogs. Transitional epithelial hyperplasia in 1 dog (12.5%) and squamous metaplasia in 2 dogs (25%) were identified. There were no statistical differences between preoperative and postoperative values of urine and blood pH and serum sodium, potassium, chloride, and bicarbonate levels. Complications of gastrocystoplasty such as hypochloremic metabolic alkalosis and hematuria and dysuria syndrome, are prevented by this procedure. The shrinkage of the gastric patch surface may also be prevented by facing the smooth gastric serosa to the internal surface of the urinary bladder.

The nonoperative treatment of intussusception is done by fluoroscopy, however, false-positive and negative images may lead to unnecessary operations. The aim of this study was to evaluate the feasibility of laparoscopy in pneumatic reduction. Surgical ileoileocolic intussusception was performed in 27 dogs. Sixteen dogs were observed for 3 days (group A), and 11 were observed for 5 days (group B). Laparoscopy was performed in the intussuscepted dogs during pneumatic reduction. Under general anesthesia, a 10-mm trocar was inserted supraumblically in the midline, and the laparoscope was introduced. The intussuscepted bowel was observed on the video monitor. A 5-mm trocar was inserted in the right upper quadrant. The mesentery of the terminal ileum was manipulated using grasping forceps to assist reduction. CO2 was insufflated into the rectum using a Foley catheter, and the reduction was observed on the video monitor. The success rate was 94% (mean reduction time, 2.5 minutes +/- 1.0) for group A and 100% (mean reduction time, 3.7 minutes +/- 0.8) for group B. Bowel perforation was observed in one dog, and recurrence of intussusception in another. The authors claim that observing the bowel on the video monitor may help in the differential diagnosis and reduction of difficult cases such as ileoileocolic and delayed intussusceptions. Therefore, unnecessary open surgery may be prevented.

In this study, we have tried to determine the age-specific seroprevalence of hepatitis B virus (HBV) infection and to make some conclusions about the mode of transmission and vaccination strategy which should be chosen in Turkey. Eight hundred and one patients between the ages of six months and 60 years of age were included in this study. According to the HBV serologic markers, (HBsAg, Anti-HBc and Anti-HBs), HBsAg positivity and HBV exposure rates were 6.5% and 32.8%, respectively. HBsAg positivity was 6.6% under one year of age. The highest rate of HBsAg positivity was in the 6-10 year age-group (p < 0.05). The prevalence of total hepatitis B virus seropositivity increased with age (p < 0.05). The HBV exposure rate was higher in males than in females (p < 0.05). It was concluded that HBV infection is an important infection in Turkey and is acquired very early in life. A mass hepatitis B vaccination strategy should be thus chosen in Turkey.

Seventy-eight infants born to HBsAg-positive women were randomly assigned to receive either the plasma-derived vaccine or 0.5 ml (10 micrograms HBsAg) yeast-derived recombinant hepatitis B vaccine within 24 hours of birth, simultaneously with hepatitis B hyperimmunoglobulin. In 67 infants who received the plasma-derived vaccine, one of the doses of 0.5 ml (25 micrograms HBsAg) was used randomly. In all of the infants, the second and third doses of both vaccines were given at one and two months of age, respectively. The booster doses were given at 12 month of age in all of the infants. These vaccinated infants were followed up until 13 months of age. There were differences in the seroconversion rates with different vaccines and doses. The recipients of the half-dose of plasma-derived vaccine showed lower seroconversion rates than the others, and the newborns in this group showed more seronegativity (13.2%) than the others (p < 0.05). The lowest anti-HBs geometric mean titers (GMTs) were obtained in newborns vaccinated with Hevac B 0.5 ml. Sixty percent of the anti-HBs GMTs in this group were under 100 mlU/ml. There were statistically significant differences between males and females in anti-HBs seronegativity rates, with males having lower anti-HBs GMTs than females. The difference was particularly significant among male newborns vaccinated with a half-dose of plasma-derived vaccine.