Do transvalvular pacemaker leads influence functional outcome after tricuspid ring annuloplasty?
The impact of permanent pacemaker (PPM) leads on functional outcome of tricuspid valve (TV) repair has not been clearly demonstrated. Therefore, controversy exists as to whether transvalvular PPM leads should be explanted and replaced by epicardial leads at the time of valve repair. This study evaluates the influence of PPM leads on functional outcome, TV-related reoperations and survival in patients undergoing TV repair for functional tricuspid regurgitation (TR). We retrospectively reviewed 415 consecutive patients who underwent TV ring annuloplasty at our institution from July 2007 to February 2013. In 112 patients (27%), a PPM was implanted either pre- or postoperatively. The follow-up is 94% complete (mean: 24.4 months; cumulative total 845 patient-years). The mean age was 70.2 ± 9.8 years and the mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 12.4%. Of note, 76.6% of the patients were in New York Heart Association class III or IV. Echocardiography documented moderate or severe TR in 96.4% of the patients, with a mean annulus diameter of 44.8 ± 5.4 mm. 95.4% of the patients underwent a combined procedure and 16.4% an urgent or emergent operation. The 30-day mortality was 7.5%. The preoperative TR grade was reduced from 2.47 ± 0.52 to 0.70 ± 0.54 (P < 0.001). At hospital discharge, residual ≥II TR was present in 7.1% of the patients. Freedom from recurrent ≥II TR at 5 years was 86.7 ± 3.2%. Upon uni- and multivariate analyses, the presence of a transvalvular PPM was not a risk factor for recurrent ≥II TR and late mortality. Freedom from TV-reoperations was 98.1 ± 0.8% at 5 years without significant difference between groups. The presence of a transvalvular PPM lead is not a risk factor for recurrent TR, TV-related reoperations and late mortality in patients undergoing ring annuloplasty for functional TR.


Vascular function in alcohol-treated pregnant and nonpregnant mice.
The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6-18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These studies provide novel information regarding the effects of alcohol on the maternal vascular system during pregnancy and thereby contribute to further understanding of the adverse effects associated with prenatal alcohol exposure.


Overexpression of leptin reduces the ratio of glycolytic to oxidative enzymatic activities without changing muscle fiber types in mouse skeletal muscle.
Increased spontaneous locomotive activity and oxygen consumption have been reported in transgenic mice overexpressing leptin in the liver. In the present study, we examined whether the overexpression of leptin altered glycolytic and oxidative metabolic enzymatic activities as well as the composition of myosin heavy chain (MHC) isoforms in skeletal muscle. Enzymatic activities of lactate dehydrogenase (LDH) and citrate synthase (CS) were quantified in gastrocnemius muscle (GAS) and the red portion of tibialis anterior muscle (TA) from leptin transgenic (Tg) mice and non-Tg mice. The composition of MHC isoforms was measured in soleus muscle (SOL) and extensor digitorum longus muscle (EDL) from the two groups. In red TA, LDH-to-CS ratio was significantly lower in Tg than in non-Tg (p=0.014), whereas no significant change was observed in GAS. The composition of MHC isoforms was not significantly different in SOL or EDL between Tg and non-Tg groups. Our data indicate that chronic overexpression of leptin reduces the ratio of glycolytic to oxidative capacity without changing muscle fiber types particularly in red muscles. This metabolic change may contribute to the increased spontaneous locomotive activity and oxygen consumption in Tg mice reported previously.


Galanin-like immunoreactivity is influenced by estrogen in peripubertal and adult rats.
Galanin gene expression in the anterior pituitary is potently stimulated by estrogen in adult rats. To evaluate the influence of estrogen on galanin during the peripubertal period 30- to 32-day-old female rats were treated with pregnant mare serum gonadotropin (PMSG, 10 IU s.c., 10.00 h). Galanin-like immunoreactivity (galanin-LI) in hypothalamic and pituitary tissues was evaluated 1, 2 or 3 days after PMSG treatment between 17.00 and 19.00 h. The PMSG treatment stimulated 17 beta-estradiol secretion, which induced a midafternoon LH surge 2 days after the PMSG treatment. Concentrations of galanin-LI at the time of this LH surge were elevated 82% in the anterior pituitary and 58% in the hypothalamus (without the median eminence) when compared to saline-treated female rats. On the 3rd day after the PMSG injection, galanin-LI was increased 236% in the anterior pituitary, 88% in the neurointermediate lobe and 39% in the median eminence compared to saline-treated female rats. These changes in galanin-LI were not observed in similarly aged male rats or ovariectomized rats treated with PMSG. In adult male rats, daily injections with 17 beta-estradiol valerate (10 micrograms/daily s.c.) for 1 week increased galanin-LI in the median eminence and neurointermediate lobe to an extent similar to that seen in juvenile female rats following PMSG treatment. In contrast, the high serum levels of 17 beta-estradiol achieved after 17 beta-estradiol valerate treatment increased galanin-LI in the anterior pituitary 65-fold. These studies indicate that galanin-LI is influenced by estrogen in peripubertal and adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Horizontal gene transfer of a Chlamydial tRNA-guanine transglycosylase gene to eukaryotic microbes.
tRNA-guanine transglycosylases are found in all domains of life and mediate the base exchange of guanine with queuine in the anticodon loop of tRNAs. They can also regulate virulence in bacteria such as Shigella flexneri, which has prompted the development of drugs that inhibit the function of these enzymes. Here we report a group of tRNA-guanine transglycosylases in eukaryotic microbes (algae and protozoa) which are more similar to their bacterial counterparts than previously characterized eukaryotic tRNA-guanine transglycosylases. We provide evidence demonstrating that the genes encoding these enzymes were acquired by these eukaryotic lineages via horizontal gene transfer from the Chlamydiae group of bacteria. Given that the S. flexneri tRNA-guanine transglycosylase can be targeted by drugs, we propose that the bacterial-like tRNA-guanine transglycosylases could potentially be targeted in a similar fashion in pathogenic amoebae that possess these enzymes such as Acanthamoeba castellanii. This work also presents ancient prokaryote-to-eukaryote horizontal gene transfer events as an untapped resource of potential drug target identification in pathogenic eukaryotes.


Osseo integrated finger prosthesis with a custom abutment.
One of the most regularly encountered forms of partial hand loss causing physical, psychosocial and financial burden to an individual is the finger amputation followed by trauma. The prosthetic rehabilitation of amputated finger is a good treatment option, when compared to all other means of complex and unaffordable options. Osseointegrated implant retained silicone finger prosthesis with innovative prosthetic designs can provide the patient a life changing experience.


Unusual antigenic composition of an Arizona strain.
The immunochemical analysis of Arizona strain 23:23:30:42 displayed a peculiar antigenic composition. Hyperimmune sera prepared in rabbits with formaldehyde-treated bacteria precipitated, in agar-gel, the proteins from numerous Salmonellae and E. coli by homogenous lines of apparent serological identity with the Arizona proteins. The reactions were unilateral. The proteins from Arizona did not react against the heterologous antibacterial sera tested; they precipitated, however against sera, rich in common antibodies, that were prepared with proteins from Salmonellae and E. coli. The genetic architecture of this Arizona's chromosome is, apparently, responsible for the unusual antigenic composition of the strain as exhibited by the immunochemical analysis of its hyperimmune serum.


Ageing in reptiles.
Like in fishes, the reptiles appear to show three types of senescence. The African skink, Mabuya buettneri, shows rapid senescence similar to death at mating observed in Salmon and marsupial mouse. Most of the lizards and snakes undergo gradual senescence comparable to the pattern exhibited by a majority of vertebrates. On the other hand, turtles, tortoises and crocodiles continue to grow throughout life and are thus credited with slow or negligible senescence. Evidences and mechanisms of rapid or negligible senescence in reptiles are still fragmentary and unclear. Findings in a few species of lizards (Calotes versicolor) and snakes (Natrix natrix) showing gradual senescence support the concept of commonalities in ageing phenomena in vertebrates. An age-related increase in the stability of collagen and accumulation of altered enzyme molecules, a decrease in metabolism and response to stress-enhanced anti-oxidative defence mechanisms and the nature of responses to hormones, restricted diet and lower environmental temperature corroborate the concept. On the other hand neither the increase in mortality rate and accumulation of lipofuscin nor the reproductive senility have been shown conclusively in ageing reptile populations. It is likely that there are multiple mechanisms of senescence in reptiles. Further studies on selected species from among the 6,000 living species are necessary to unravel the phenomena.


Olfactory neuroblastoma: results of combined therapy.
Olfactory neuroblastomas are seldom encountered in otolaryngologic practice. Eleven such patients were treated by combined therapy over a nine year period. Two cases who initially underwent surgery only required salvage for a local recurrence by a combined modality. Nine patients were disease-free at the end of two years, with four of them being so for five years. Adjuvant chemotherapy was used in four cases, one of whom developed distant cutaneous metastasis after two years. Craniofacial resection was performed on three patients. A combined therapy is recommended for all stages of olfactory neuroblastoma.


Premature satellite cell activation before injury accelerates myogenesis and disrupts neuromuscular junction maturation in regenerating muscle.
Satellite cell (SC) activation, mediated by nitric oxide (NO), is essential to myogenic repair, whereas myotube function requires innervation. Semaphorin (Sema) 3A, a neuro-chemorepellent, is thought to regulate axon guidance to neuromuscular junctions (NMJs) during myotube differentiation. We tested whether "premature" SC activation (SC activation before injury) by a NO donor (isosorbide dinitrate) would disrupt early myogenesis and/or NMJs. Adult muscle was examined during regeneration in two models of injury: myotoxic cardiotoxin (CTX) and traumatic crush (CR) (n = 4-5/group). Premature SC activation was confirmed by increased DNA synthesis by SCs immediately in pretreated mice after CTX injury. Myotubes grew faster after CTX than after CR; growth was accelerated by pretreatment. NMJ maturation, classified by silver histochemistry (neurites) and acetylcholinesterase (AchE), and α-bungarotoxin staining (Ach receptors, AchRs) were delayed by pretreatment, consistent with a day 6 rise in the denervation marker γ-AchR. With pretreatment, S100B from terminal Schwann cells (TSCs) increased 10- to 20-fold at days 0 and 10 after CTX and doubled 6 days after CR. Premature SC activation disrupted motoneuritogenesis 8-10 days post-CTX, as pretreatment reduced colocalization of pre- and postsynaptic NMJ features and increased Sema3A-65. Premature SC activation before injury both accelerated myogenic repair and disrupted NMJ remodeling and maturation, possibly by reducing Sema3A neuro-repulsion and altering S100B. This interpretation extends the model of Sema3A-mediated motoneuritogenesis during muscle regeneration. Manipulating the timing and type of Sema3A by brief NO effects on SCs suggests an important role for TSCs and Sema3A-65 processing in axon guidance and NMJ restoration during muscle repair.


T cell clones for antigen selection and lymphokine production in murine Schistosomiasis mansoni.
The role of T cells in immunity to murine schistosomiasis was examined through the use of T cell clones that recognize the live schistosomulum stage of Schistosoma mansoni. T cell clones of three different phenotypes were isolated and expanded into long term culture from lymph nodes of C57B1/6J mice vaccinated with irradiated S. mansoni larvae. They were characterized by surface markers, lymphokine production, and functional assays. The m.w. range of the Ag recognized by one clone was identified through nitrocellulose blotting and confirmed with a preparation of the putative protein made by immunoaffinity purification. All but one of the clones were CD4+, CD5+, Th cells. One clone, 35, produced Il-2 and IFN-gamma and was designated a TH1 clone. The others were designated TH2 clones because of Il-4 production. One clone was CD8+ and failed to show help. Clone 35 recognized live schistosomula and produced Il-2 when presented a 27-kDa protein from nitrocellulose. It proliferated in response to purified Ag. Clone 35 participated along with macrophages to induce up to 98% killing of live schistosomula in vitro. IFN-gamma and TNF-alpha were essential to the killing mechanism whereas Il-1, Il-2, and Il-4 were not required. This study has approached Ag identification for vaccine development from the point of view of T cells and showed that TH1 cells are essential to in vitro macrophage killing of schistosomula in murine schistosomiasis.


A simple method to retrospectively estimate patient dose-area product for chest tomosynthesis examinations performed using VolumeRAD.
The purpose of the present work was to develop and validate a method of retrospectively estimating the dose-area product (DAP) of a chest tomosynthesis examination performed using the VolumeRAD system (GE Healthcare, Chalfont St. Giles, UK) from digital imaging and communications in medicine (DICOM) data available in the scout image. DICOM data were retrieved for 20 patients undergoing chest tomosynthesis using VolumeRAD. Using information about how the exposure parameters for the tomosynthesis examination are determined by the scout image, a correction factor for the adjustment in field size with projection angle was determined. The correction factor was used to estimate the DAP for 20 additional chest tomosynthesis examinations from DICOM data available in the scout images, which was compared with the actual DAP registered for the projection radiographs acquired during the tomosynthesis examination. A field size correction factor of 0.935 was determined. Applying the developed method using this factor, the average difference between the estimated DAP and the actual DAP was 0.2%, with a standard deviation of 0.8%. However, the difference was not normally distributed and the maximum error was only 1.0%. The validity and reliability of the presented method were thus very high. A method to estimate the DAP of a chest tomosynthesis examination performed using the VolumeRAD system from DICOM data in the scout image was developed and validated. As the scout image normally is the only image connected to the tomosynthesis examination stored in the picture archiving and communication system (PACS) containing dose data, the method may be of value for retrospectively estimating patient dose in clinical use of chest tomosynthesis.


Effects of omega-3 polyunsaturated fatty acids on platelet function in healthy subjects and subjects with cardiovascular disease.
Hyperactivation and aggregation of platelets play a major role in thrombosis and hemostasis. The aims of this study were to investigate the effects of omega-3 polyunsaturated fatty acids (PUFAs) on platelet function. Light transmission aggregometry and flow cytometric analyses of platelet activation and platelet-leukocyte aggregates were determined at baseline and after 4 weeks of omega-3 (docosahexaenoic acid 520 mg and eicosapentaenoic acid 120 mg) supplementation. In total, 40 healthy subjects and 16 patients with a history of cardiovascular disease (CVD) completed the study. In healthy subjects, omega-3 PUFA significantly reduced adenosine diphosphate (ADP)-induced (maximum amplitude, 77.0% ± 3.2% vs. 71.6% ± 3.4%, p = 0.036; maximum slope, 86.3 ± 1.8 vs. 80.7 ± 2.1, p = 0.014) and adrenaline-induced platelet aggregation (maximum slope, 42.8 ± 2.7 vs. 37.4 ± 3.0, p = 0.013; lag time, 00:21 ± 00:02 vs. 00:31 ± 00:03 s, p = 0.002). Omega-3 PUFA also reduced P-selectin expression (40.5% ± 2.9% vs. 34.4% ± 2.4%, p = 0.049) on platelets and platelet-monocyte aggregates (38.5% ± 2.6% vs. 31.4% ± 2.5%, p = 0.022) after activation with ADP 0.5 µM. There were fewer changes in platelet aggregation and activation found in subjects with CVD. Nevertheless, there was a reduction in the slope of arachidonic acid-induced platelet aggregation (13.21 ± 6.41 vs. 4.88 ± 3.01, p = 0.009) and increased lag time for U46619 (00:16 ± 00:00 vs. 00:29 ± 00:07 s, p = 0.018) induced platelet aggregation. Thus, 4-week supplementation of 640 mg omega-3 PUFA reduced measures of platelet aggregation and activation in healthy subjects but effects were less evident in patients with existing CVD. Our findings support the recommendation that the omega-3 PUFA dose be higher in CVD than among healthy subjects.


Targeted Next-Generation Sequencing Newly Identifies Mutations in Exostosin-1 and Exostosin-2 Genes of Patients with Multiple Osteochondromas.
Multiple osteochondromas (MO) is one of the most common benign bone tumors in humans with an autosomal dominant hereditary mode. MO is a genetic heterogeneity disease with variable number and size of osteochondromas, as well as changeable number and location of diseased bones. Mutations in Exostosin-1/Exostosin-2 (EXT1/EXT2) genes are the main molecular basis of MO. EXT1 and EXT2 genes encode exostosin 1 and exostosin 2, respectively, both of which are transmembrane glycosyltransferases that elongate the chains of heparin sulfate (HS) at HS proteoglycans (HSPGs). HSPGs are considered to be involved in regulating the proliferation and differentiation of chondrocytes. Owing to large size of EXT1/EXT2 genes and lack of mutation hotspots, molecular diagnosis of MO is challenging. Here, we applied targeted next-generation sequencing (t-NGS) in mutation screening of EXT1/EXT2 genes for 10 MO patients. The results were compared and validated with Sanger sequencing. Overall, nine mutations identified by t-NGS were confirmed with Sanger sequencing, excluding two variants of false positive, suggesting the reliability of mutation screening by t-NGS. The nine mutations identified by t-NGS include two missense mutations (EXT1: c.1088G>A and c.2120C>T), one splicing mutation (EXT2: c.744-1G>T), and six nonsense mutations (EXT1: c.351C>G, c.1121G>A, and c.1843_1846dup; EXT2: c.67C>T, c.561delG, and c.575T>A). In summary, our paper provides the primary data of the application of t-NGS in MO molecular diagnosis, including six newly identified mutations (EXT1: c.1843_1846dup, c.1088G>A, c.351C>G, and c.2120C>T and EXT2: c.744-1G>T and c.575T>A), which further enrich the mutation database of MO from the Chinese population.


Health economic evaluation of preventive digital public health interventions using decision-analytic modelling: a systematized review.
Digital public health (DiPH) provides novel approaches for prevention, potentially leading to long-term health benefits in resource-limited health systems. However, cost-effectiveness of DiPH interventions is unclear. This systematized review investigates the use of decision-analytic modelling in health economic evaluations of DiPH primary prevention and health promotion interventions, focusing on intervention's design, methods used, results, and reporting quality. PubMed, CINAHL, and Web of Science were searched for studies of decision-analytic economic evaluations of digital interventions in primary prevention or health promotion, published up to June 2022. Intervention characteristics and selected items were extracted based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Incremental cost-effectiveness ratios (ICERs) were then extracted and price-adjusted to compare the economic evaluation results. Finally, the included studies' reporting quality was assessed by building a score using CHEERS. The database search (including search update) produced 2,273 hits. After removing duplicates, 1,434 titles and abstracts were screened. Of the 89 studies meeting the full-text search criteria, 14 were ultimately reviewed. The most common targets were physical activity (five studies) and weight loss (four). Digital applications include text messages, web-based inventions, app-based interventions, e-learning devices, and the promotion of smartphone apps. The mean ICER of the 12 studies using quality-adjusted life years (QALYs) is €20,955 per QALY (min. - €3,949; max. €114,211). The mean of reported CHEERS items per study is 81% (min. 59%; max. 91%). This review only includes primary prevention and health promotion, and thus excludes other DiPH fields (e.g. secondary prevention). It also focuses on decision-analytic models, excluding study-based economic evaluations. Standard methods of economic evaluation could be adapted more to the specifics of DiPH by measuring the effectiveness of more current technologies through alternative methods, incorporating a societal perspective, and more clearly defining comparators. Nevertheless, the review demonstrates using common thresholds that the new field of DiPH shows potential for cost-effective preventive interventions.


Bariatric Surgery Improves Outcomes After Lower Extremity Arthroplasty in the Morbidly Obese: A Propensity Score-Matched Analysis of a New York Statewide Database.
The purpose of this study was to compare risks for revision and short-term complications after total joint arthroplasty (TJA) in matched cohorts of morbidly obese patients, receiving and not receiving prior bariatric surgery. Patients undergoing elective TJA between 1997 and 2011 were identified in a New York Statewide database, analyzing total knee arthroplasty (TKA) and total hip arthroplasty (THA) separately. Propensity scores were used to match morbidly obese patients receiving and not receiving bariatric surgery prior to TJA. Cox proportional hazard modeling assessed revision risk. Logistic regression evaluated odds for complications. For TKA, 2636 bariatric surgery patients were matched to 2636 morbidly obese patients. For THA, 792 bariatric surgery patients were matched to 792 morbidly obese patients. Matching balanced all covariates. Bariatric surgery reduced co-morbidities prior to TJA (TKA P < .0001; THA P < .005). Risks for in-hospital complications were lower for THA and TKA patients receiving prior bariatric surgery (odds ratio [OR] 0.25, P < .001; and OR = 0.69, P = .021, respectively). Risks for 90-day complications were lower for TKA (OR 0.61, P = .002). Revision risks were not different for either THA (P = .634) or TKA (P = .431), nor was THA dislocation risk (P = 1.000). After accounting for relevant selection biases, bariatric surgery prior to TJA was associated with reduced co-morbidity burden at the time of TJA and with reduced post-TJA complications. However, bariatric surgery did not reduce the risk for revision surgery for either TKA or THA.


A simple model of a steady state differentiating cell system.
A simple theoretical model is hypothesized to describe the steady state behavior of a differentiating cell system as exemplified by blood cells. The cell system consists of several morphologically distinguishable cell classes which develop sequentially. Each cell class except the last one is mitotically capable. Mitosis is assumed to be either heteromorphogenic, homomorphogenic, or asymmetric. Some algebraic equations are derived which are conservation equations describing the flux of cells from one class to another. The theoretical considerations have been applied to some experimental observations in humans concerning neutrophil production, particularly in reference to relative cell numbers and mitotic fractions of the myeloblast, promyelocyte, and myelocyte cell classes. These observations are utilized to help determine the values of the parameters which characterize the model. Among these parameters are the generation times of the various cell classes, and the predicted values of the generation times are found to be in excellent agreement with observed grain-count halving times. However, the predicted mitotic times are in disagreement with their observed values.


Deep sequencing of amplified Prasinovirus and host green algal genes from an Indian Ocean transect reveals interacting trophic dependencies and new genotypes.
High-throughput sequencing of Prasinovirus DNA polymerase and host green algal (Mamiellophyceae) ribosomal RNA genes was used to analyse the diversity and distribution of these taxa over a ∼10 000 km latitudinal section of the Indian Ocean. New viral and host groups were identified among the different trophic conditions observed, and highlighted that although unknown prasinoviruses are diverse, the cosmopolitan algal genera Bathycoccus, Micromonas and Ostreococcus represent a large proportion of the host diversity. While Prasinovirus communities were correlated to both the geography and the environment, host communities were not, perhaps because the genetic marker used lacked sufficient resolution. Nevertheless, analysis of single environmental variables showed that eutrophic conditions strongly influence the distributions of both hosts and viruses. Moreover, these communities were not correlated, in their composition or specific richness. These observations could result from antagonistic dynamics, such as that illustrated in a prey-predator model, and/or because hosts might be under a complex set of selective pressures. Both of these reasons must be considered to interpret environmental surveys of viruses and hosts, because covariation does not always imply interaction.


Association between the EGF rs4444903 polymorphism and liver cancer susceptibility: a meta-analysis and meta-regression.
Emerging evidence suggests that a common functional polymorphism, rs4444903 (A>G), in the EGF gene might impact an individual's susceptibility to liver cancer; however, individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between the EGF rs4444903 polymorphism and liver cancer risk. A literature search was conducted in the PubMed, Embase, Web of Science, and CBM databases from inception through May 1st, 2013. Seven case-control studies were included with a total of 1408 liver cancer cases and 1343 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Our meta-analysis results indicated that the G variant of the rs4444903 polymorphism might be associated with an increased risk of liver cancer (G allele vs A allele: OR = 1.25, 95%CI = 1.01-1.56, P = 0.040; GG + AG vs AA: OR = 1.65, 95%CI = 1.27-2.15, P < 0.001; GG vs AA: OR = 1.77, 95%CI = 1.34-2.35, P < 0.001). Further subgroup analysis by ethnicity also showed significant associations between the G variant of the rs4444903 polymorphism and an increased risk of liver cancer among Asian, Caucasian, and African populations. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis suggests that the G variant of the rs4444903 polymorphism may increase the risk of liver cancer. The EGF rs4444903 (A>G) polymorphism can be useful as a biomarker in predicting the development of liver cancer.


Targeting of Apoptotic Cells Using Functionalized Fe₂O₃ Nanoparticles.
Fe₂O₃ nanoparticles (NPs) have been synthesized and functionalized with SiO₂ and -NH₂ group, respectively. Conjugation to fluorescently-labeled poly-caspase inhibitor (SR-FLIVO) has been carried out for better cellular uptake studies of apoptosis arising from brain focal cerebral ischemia. Highest conjugation affinity to SR-FLIVO was found to be ca. 80% for Fe₂O₃-SiO-NH₂ functionalized nanoparticles (FNPs). Tracking of SR-FLIVO conjugated functionalized nanoparticles (SR-FLIVO-FNPs) in vivo and in vitro has been carried out and detected using microscopic techniques after histochemical staining methods. Experimental results revealed that SR-FLIVO-FNPs probe could passively cross the blood brain barrier (BBB) and accumulated within the apoptotic cell. Optimization of SR-FLIVO-FNPs probe can effectively promise to open a new era for intracellular drug delivery and brain diagnosis.


Cadmium-Induced Oxidative Stress Impairs Glycemic Control in Adolescents.
Experimental evidence suggests that cadmium (Cd) boosts oxidative stress that may result in toxicity on the endocrine system also in humans. The aim of this study was to investigate the glycemic control and oxidative stress markers in male adolescents with increased urinary levels of cadmium. We investigated 111 males, aged 12-14 years, living in a polluted area of Sicily and a control age-matched population (n = 60) living 28-45 km far from the polluted site. Malondialdehyde (MDA), total antioxidant activity (TAC), metallothionein-1A (MT-1A) gene expression, insulin resistance by the homeostatic model assessment (HOMA-IR), and urinary cadmium were investigated. Cd levels were significantly higher in adolescents living in the polluted area than in control age-matched subjects. Adolescents with elevated Cd levels had a significant increase in MDA, MT-1A, and HOMA-IR and reduced TAC compared to the control group. A robust correlation was found between urinary cadmium and MT-1A, HOMA-IR, and MDA whereas an inverse correlation was identified between urinary cadmium and TAC. This study indicates that cadmium burden alters glycemic control in adolescents and suggests that oxidative stress plays a key role in cadmium-induced insulin resistance, increasing the risk of developing metabolic disorders.


[Influence of growing experience on non-heterosexual orientation among male college students in Nanjing].
Objective: To analyze the influence of growing experience on non-heterosexual orientation among male college students. Methods: From October to November in 2015, a total of 2 535 male students from 96 classes in 14 colleges/departments were recruited from two colleges that participated in the experimental work of AIDS prevention by cluster random sampling method. A structured questionnaire was administered in this study, including general demographic information, growing experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500 questionnaires distributed in this study, 2 332 effective copies were withdrew, with the effective rate at 93.3%. Chi square test was used to analyze the differences of non-heterosexual orientation among the individuals with different social demographic characteristics. Multivariate logistic regression model was used to analyze the influencing factors of non-heterosexual orientation. Results: Among the 2 332 individuals, the proportion of self-reported non-heterosexual was 6.2% (144).The proportions of male students who identify as non-heterosexual from freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and 4.7%(3/64), respectively (χ(2)=9.06,P=0.029). Compared with the individuals of very good relationship with parents, those with bad relationship (OR=3.3, 95%CI: 1.7-6.5) and general relationship (OR=1.7, 95%CI: 1.0-2.9) with parents had a higher risk of non-heterosexual orientation, respectively. Those encountered sexual assault had a higher risk of non-heterosexual orientation than those without encountered sexual assault (OR=5.9, 95%CI: 3.2-10.9). Conclusions: This study reported a high proportion of self-reported non-heterosexual among college male students in Nanjing, and highlighted the importance of targeting students with poor parental relationships and who subjected to sexually abused.


A patient with primary Burkitt's lymphoma of the postnasal space: case report.
Burkitt's lymphoma is a highly aggressive lymphoma. The endemic form is present with Epstein - Barr virus. The most common sites are the mandible, facial bones, kidneys, gastrointestinal tract, ovaries, breast and extra-nodal sites. We present the first reported case of a primary Burkitt's lymphoma of the postnasal space occurring in an elderly Caucasian male. A 72-year-old Caucasian male farmer presented with a 6-week history of a productive cough and a painless left sided cervical swelling. Examination of the neck revealed a 5 cm by 5 cm hard mass in the left anterior triangle. A CT scan of the head and neck showed a soft tissue swelling in the postnasal space. Histology of the postnasal space mass showed squamous mucosa infiltrated by a high grade lymphoma. Immunohistochemical staining and in situ hybridisation confirmed the tumour to be Epstein - Barr virus Ribonucleic acid negative suggesting this was a rare sporadic form of the tumour presenting in a location that is atypical for the clinical subtype and age of the patient. This is the first reported case of sporadic Burkitt's lymphoma of the postnasal space of an elderly Caucasian male in the absence of Epstein - Barr virus or human immunodeficiency virus infection and further serves to illustrate the diversity of histological subtypes of malignancies that may develop at this concealed site.


Spotlight on epigenetics as a missing link between obesity and type 2 diabetes.
Type 2 diabetes (T2D) is a complex disorder that is caused by a combination of genetic, epigenetic, and environmental factors. β-cell failure and insulin resistance in peripheral tissues that are induced by lipid overload are main hallmarks of T2D. The mechanisms that link obesity-driven alterations of lipid metabolism and T2D are still elusive, thereby impeding the development of effective prevention and treatment strategies. Although genetic variants that have been identified in high-throughput studies comprise an appreciable proportion of the genetic component of T2D, they explain < 20% of the estimated heritability of T2D. A growing body of evidence suggests an intrinsic role for epigenetic modifications in the pathogenesis of T2D. The epigenetic regulation of gene expression in tissues that play a key role in the obesity-related development of T2D has been demonstrated, including PDX1 in pancreatic islets, PPARGC1A in skeletal muscles, ADIPOQ in adipose tissue, and TXNIP in the liver. The present review summarizes our current knowledge of crosstalk between the epigenetic control of gene expression, particularly via DNA methylation, toxic lipid mediators, and the pathogenesis of obesity-related T2D.


Seroprevalence and risk factors of hepatitis E virus infection among the Korean, Manchu, Mongol, and Han ethnic groups in Eastern and Northeastern China.
Hepatitis E virus (HEV) infection is a serious public health concern in developing countries. China is regarded as an HEV-endemic area, but epidemiological data for HEV among different nationalities is limited. This study was conducted to estimate the seroprevalence and risk factors of HEV infection in Koreans (n = 520), Manchus (n = 303), Mongols (n = 217), and Hans (n = 802) in Eastern and Northeastern China between 2013 and 2015. A total of 366 (19.87%) out of 1842 samples were seropositive for IgG or IgM HEV-antibodies detected by enzyme-linked immunoassays. Among these groups, the Mongols had the highest seroprevalence of HEV infection (25.35%, 55/217), followed by the Koreans (23.65%, 123/520), the Manchus (19.80%, 60/303), and the Hans (15.96%, 128/802). Multiple analysis showed that the gender, consumption of raw/undercooked meat, source of drinking water, residence area, and age were significantly associated with HEV infection in four ethnic groups. The present results indicated that HEV infection was prevalent in Mongols, Koreans, Manchus, and Hans in the surveyed regions, which demonstrated the higher risk of transmitting HEV in multiple nationalities in Eastern and Northeastern China.


Predictors of active cancer thromboembolic outcomes: mortality associated with calf deep vein thrombosis.
Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer. Outcomes, including mortality data, in the cancer population are limited in those with calf deep vein thrombosis (CDVT) compared to individuals with proximal deep vein thrombosis. The aim of this study was to assess the prognosis among patients with active cancer and CDVT. Single institution inception cohort of cancer-associated CDVT patients who presented with thrombosis distal to popliteal level confirmed objectively by ultrasound. We defined active cancer as metastatic disease or use of chemotherapy at diagnosis. Clinical and laboratory data were extracted from the electronic health records. The Khorana Risk Score (KRS) was extracted based on data at entry. Institutional review board approval was obtained prior to the analysis. Categorical variables are expressed as percentages and continuous variables as median (interquartile range). Kaplan-Meier method, Pearson's χ2, Mann-Whitney U and Cox proportional hazard were applied. SPSS software version 22 was used for all statistics. One hundred nine patients (men=44 [40%], Age>65=89 [82%], BMI>30=25 [23%], Smoker=59 [54%]) were included. The majority had a low (30%) or intermediate KRS (64%) at diagnosis. Forty-seven percent died during a median follow-up time of 2.5 years (0.5-3.1). After multivariate analysis, the predictors of mortality were: smoking (hazard ratio [HR] 2.3; 95% CI: 1.2-4.7), metastasis (HR=5.8; 95% CI: 2.9-11.7), gastrointestinal cancer (HR=3.9; 95% CI: 1.8-8.5), and lung cancer (HR=4.1 95% CI: 1.7-10.3). VTE specific variables not associated with mortality included: bilateral CDVT, concomitant pulmonary embolism, multiple vein involvement, filter placement, or a surgery-associated event. The KRS was not predictive of death. Cancer-specific variables and smoking predicted mortality among CDVT patients in this cohort, rather than VTE characteristics at the time of CDVT diagnosis.


[Two centers with a native fistula prevalence higher than 90%: organization and activity].
Vascular access (AV) dysfunction is a major cause of morbidity and hospitalisation in hemodialysis population. Despite of guidelines statements which consider native arteriovenous fistula (nAVF) the gold standard, epidemiological studies still show a decline in their prevalence with an increase of central venous catheters (CVC). In this study we compared the activity of two Dialysis Units both characterized by a high prevalence (> 90%) of nAVF, in order to highlight the possible reasons. No collaboration existed between the two centres until the decision to design this work. The "policy" on creation and management of vascular access and organizational models of the two centres were assessed, in particular focusing on surgeons, presence of dedicated nephrologists, preoperatory ultrasound evaluation, follow-up and diagnosis of complications, resort to interventional radiology, complications management, in particular the timing of intervention after AVF thrombosis. Of the two dialysis populations were analysed: age, time on dialysis, coexistence of diabetes and the prevalence of various types of vascular access to 31 December 2007. It was evaluated the AV incidence in the last 4 years. The statistical analysis was performed by T student and Chi square tests. There were no substantial differences in the organizational models of the two centres, which had both a routine ECD use in preoperatory mapping and in monitoring of complications; in case of thrombosis both centres performed surgery within 12-24 hours; in case of stenosis both centres performed the correction, surgical or by angioplasty, within 15 days from the diagnosis. Another common element was the presence of a multidisciplinary team with a interventionist nephrologist, a vascular surgeon and a vascular interventional radiologist, where nephrologist has the coordination role. The data analysis showed a prevalence of nAVF in the two centres of 92.5% and 96.1%, Pescara and Lecce respectively, with a prevalence of forearm nAVF of more than 80% and 90% respectively. The analysis of incident interventions showed high percentage of forearm AVF in case of revisions for complications (stenosis, thrombosis), and a little recourse to proximal AVF and graft.


Statistical analysis of dose heterogeneity in circulating blood: implications for sequential methods of total body irradiation.
Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these "sequential" techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than +/- 10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times. However, the EUD was unaffected (within 10%) for perfusion periods of less than 150 s or treatment times of 20 min or greater. Treatment over six fractions improved the EUD per fraction such that all parametric combinations resulted in unaffected EUD. The stochastic models confirmed these results. Dose heterogeneity in circulating blood cells is clinically acceptable for typical treatment times, perfusion rates, and cell types. Development of conformal, sequential TBI treatment techniques should not be withheld based on concerns over circulating blood dose heterogeneity.


Transforming information use in preventive medicine: learning to balance technology with the art of caring.
CompuHx* is an Interactive Health Appraisal System (IHAPS) used in the examining room to record patient information, assist in diagnosis, and provide a legible summary of findings. This paper describes Phase I of a longitudinal study in which 22 examiners (five system users and 17 non-users) responded to detailed surveys and interviews about the system. Findings indicated that both users and non-users had mixed feelings about the system's ease of use and impact on their jobs, but agreed that it would have value for their practice. Underlying their acceptance of the system was a common concern for maintaining a caring relationship with patients and not allowing computer technology to depersonalize the examining room. Examiners also expressed concerns about the implementation process.


Full-dimensional quantum mechanics calculations for the spectroscopic characterization of the isomerization transition states of HOCO/DOCO systems.
Full-dimensional quantum mechanics calculations were performed to determine the vibrational energy levels of HOCO and DOCO based on an accurate potential energy surface. Almost all of the vibrational energy levels up to 3500 cm-1 from the vibrational ground state were assigned, and the calculated energy levels in this work are well in agreement with the reported results by Bowman. The corresponding full dimensional wavefunctions present some special features. When the energy level approaches the barrier height, the trans-HOCO and cis-HOCO states strongly couple through tunneling interactions, and the tunneling interaction and Fermi resonance were observed in the DOCO system. The energy level patterns of trans-HOCO, cis-HOCO and trans-DOCO provide a reasonable fitted barrier height using the fitting formula of Field et al., however, a discrepancy exists for the cis-DOCO species which is considered as a random event. Our full-dimensional calculations give positive evidence for the accuracy of the spectroscopic characterization model of the isomerization transition state reported by Field et al., which was developed from one-dimensional model systems. Furthermore, the special case of cis-DOCO in this work means that the isotopic substitution can solve the problem of the accidental failure of Field's spectroscopic characterization model.


Decompressive hemicraniectomy in patients with subarachnoid hemorrhage and intractable intracranial hypertension.
To evaluate the outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) developing intractable intracranial hypertension and treated by decompressive hemicraniectomy (DHC). Of 193 patients with aSAH 38 patients were treated with DHC after early aneurysm clipping. Indications for DHC were 1. Signs of brain swelling during aneurysm surgery (group 1: primary DHC). 2. Intracranial pressure- (ICP)-elevation and epidural, subdural or intracerebral hematoma after aneurysm surgery (group 2: secondary DHC due to hematoma) 3. Brain edema and elevated ICP without radiological signs of infarction (group 3: secondary DHC without infarction). 4. Brain edema and elevated ICP with radiological signs of infarction (group 4: secondary DHC with infarction). Thirty-one patients (81.6%) suffered from high grade aSAH Hunt & Hess 4-5. 21 belonged to group 1, five to group 2, six to group 3 and six to group 4. Of a total of 38 patients a good functional outcome according to Glasgow Outcome Score (GOS 4 & 5) could be reached in 52.6% of the cases. 26.3% survived severely disabled (GOS 3), no case suffered from a vegetative state (GOS 2) but 21.1% died (GOS 1). After 12 months good functional outcome could be achieved in 52.4% of the cases in group 1, in 60% in group 2, in 83.3% in group 3 and in 16.7% in group 4. In more than half of the patients with intractable intracranial hypertension after aSAH a good functional outcome could be achieved after DHC. Patients with progressive brain edema without radiological signs of infarction and those with hematoma may benefit most. The indication for DHC should be set restrictively if secondary infarcts are manifest.


HDAC3 Is Required for the Downregulation of RORγt during Thymocyte Positive Selection.
To generate functional peripheral T cells, proper gene regulation during T cell development is critical. In this study, we found that histone deacetylase (HDAC) 3 is required for T cell development. T cell development in CD2-icre HDAC3 conditional knockout (cKO) mice (HDAC3-cKO) was blocked at positive selection, resulting in few CD4 and CD8 T cells, and it could not be rescued by a TCR transgene. These single-positive thymocytes failed to upregulate Bcl-2, leading to increased apoptosis. HDAC3-cKO mice failed to downregulate retinoic acid-related orphan receptor (ROR) γt during positive selection, similar to the block in positive selection in RORγt transgenic mice. In the absence of HDAC3, the RORC promoter was hyperacetylated. In the periphery, the few CD4 T cells present were skewed toward RORγt(+) IL-17-producing Th17 cells, leading to inflammatory bowel disease. Positive selection of CD8 single-positive thymocytes was restored in RORγt-KO Bcl-xL transgenic HDAC3-cKO mice, demonstrating that HDAC3 is required at positive selection to downregulate RORγt.


Health care as a right, fairness and medical resources.
Our intention in the following is to use the WHO declaration as a basis for considering the allocation of resources in health care. We shall first argue that most of the criteria suggested as grounds for fair allocation of scarce medical resources have their difficulties if one tries to apply them one by one to medical practices. We shall then go on to claim that, if we take the right of all human beings to health or health care even moderately seriously, increasing the resources would in most cases be more ethical than attempting to allocate them 'fairly'.


"An epoch in the annals of national sport": football in Sheffield and the creation of modern soccer and rugby.
By the 1860s the two most prominent football cultures in Britain were in London and Sheffield. In 1863 the football culture in London created the Football Association, but within weeks a coup by those members who opposed a game that incorporated elements from that played at Rugby School led to the latter's supporters leaving. The fragmented FA continued to loose both members and influence and by 1867 was on the point of dissolving. By contrast, in terms of both rules and organization, the football culture of Sheffield was remarkably uniform and was the dominant centre of the game. The example set by Sheffield, coupled with the immense support that it provided to the ailing FA, enabled the London-based organization to survive and prosper.


Striatal specificity of gene expression dysregulation in Huntington's disease.
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expanded CAG repeat region in exon 1 of the HD gene. This mutation results in the presence of an abnormally long polyglutamine tract in the encoded protein, huntingtin (htt). A major question in this field is how the mutant htt protein, which is expressed ubiquitously throughout the brain and body, causes severe neuropathologic changes predominantly in the striatum. The mechanisms accounting for this specificity are unknown. The role of transcriptional dysregulation in the pathophysiology of HD has gained much attention in recent years, however, this theory has been unable to explain the specificity of dysfunction and degeneration in HD. Microarray studies have showed hundreds of gene expression changes in mouse models of HD and in post-mortem brain samples from HD subjects. Among the genes whose expression levels are preferentially altered are those that exhibit enriched expression in the striatum, which we have argued are the most relevant to disease pathology. These "striatal-enriched" genes are associated with several systems previously implicated in HD pathology, especially disturbances in transcriptional processes and calcium homeostasis. Large-scale changes in striatal gene expression in this manner would likely have particularly devastating effects to normal striatal function and could explain the specificity of striatal dysfunction and ultimate neurodegeneration observed in HD.


Role of Val289 residue in the alpha-amylase of Bacillus amyloliquefaciens MTCC 610: an analysis by site directed mutagenesis.
The Val289 residue in the alpha-amylase of Bacillus amyloliquefaciens, which is equivalent to the Ala289 and Val286 residues in the alpha-amylases of B. stearothermophilus and B. licheniformis, respectively, was studied by site-directed mutagenesis. This residue was substituted with 10 different amino acids by random substitution of the Val codon. In these mutant alpha-amylases, Val289 was substituted with Ile, Tyr, Phe, Leu, Gly, Pro, Ser, Arg, Glu, and Asp. Compared with the wild-type alpha-amylase, the mutant alpha-amylase Val289Ile showed 20% more hydrolytic activity, whereas Val289Phe and Val289Leu showed 50% lesser activity. On the other hand, the mutant alpha-amylases Val289Gly, Val289Tyr, Val289Ser, and Val289Pro showed less than 15% activity. The substitution of Val289 with Arg, Asp, or Glu resulted in complete loss of the alpha-amylase activity. Interestingly, the mutant alpha-amylase Val289Tyr had acquired a transglycosylation activity, which resulted in the change of product profile of the reaction, giving a longer oligosaccharide.


Superior clinical pregnancy rates after microsurgical epididymal sperm aspiration.
To assess normal fertilization, clinical pregnancy, and live birth rates after the use of microscopic epididymal sperm aspiration (MESA). One-hundred-and-sixty azoospermic participants who underwent MESA were evaluated. The MESA was performed by using a micropuncture method with a micropipette. In cases in which motile sperm were not obtained after the MESA, conventional or micro-testicular sperm extraction (TESE) was completed. Adequate motile sperm were retrieved in 71 participants by using MESA and in 59 out of 89 participants by using TESE. Of the total number of patients, 123 underwent intracytoplasmic sperm injection. After MESA, the normal fertilization rate was 73.5% and the clinical pregnancy rate per case was 95.7%. Healthy deliveries resulted after MESA in 65 (92.9%) cases and after TESE in 38 (71.7%) cases. The MESA specimen collection does not have any special requirements, such as mincing tissue disposition. The MESA also can reduce the amount of laboratory work that is needed for cryopreservation. In the authors' experience, MESA is a beneficial procedure and should be given priority over TESE.


Cytoplasmic processing events in the polyadenylate region of Physarum messenger RNA.
Cytoplasmic processing events in the poly(A) region of mRNA from Physarum polycephalum are reviewed. Two classes of poly-containing RNA [poly(A)+ RNA] exist in the cytoplasm. One contains very short poly(A) sequences, averaging about 15 adenylate residues, while the other contains relatively long poly(A) sequences, averaging about 60 residues. Molecules with short poly(A) sequences are found exclusively in the polysomes while those with long poly(A) sequences are restricted to the free cytoplasmic mRNP. Since proteins are associated with only the long poly(A) sequences the poly(A) . protein complex is also restricted to the free mRNP. The long poly(A) sequences are relatively short-lived. They are degraded by two distinct processes, a shortening process in which 15-20 residues are gradually removed and a turnover process in which long poly(A) tracts are rapidly converted to the short sequences. This process, along with the dissociation of the poly(A) . protein complex, occurs when poly(A)+ RNA molecules located in free mRNP are transferred to the polysomes. Poly(A) . protein complex dissociation appears to precede poly(A) turnover during translational selection. The significance of these processing events in relation to mRNA maturation is discussed.


Modeling the Correlation between Z and B in an X-ray Crystal Structure Refinement.
We have examined how the refined B-factor changes as a function of Z (the atomic number of a scatterer) at the sulfur site of the [4Fe:4S] cluster of the nitrogenase iron protein by refinement. A simple model is developed that quantitatively captures the observed relationship between Z and B, based on a Gaussian electron density distribution with a constant electron density at the position of the scatterer. From this analysis, the fractional changes in B and Z are found to be similar. The utility of B-factor refinement to potentially distinguish atom types reflects the Z dependence of X-ray atomic scattering factors; the weaker dependence of electron atomic scattering factors on Z implies that distinctions between refined values of B in an electron scattering structure will be less sensitive to the atomic identity of a scatterer than for the case with X-ray-diffraction. This behavior provides an example of the complementary information that can be extracted from different types of scattering studies.


Opposite central cardiovascular effects of various morphine-like drugs and opiate peptides in the rat.
Opiate agonists were administered into the cisterna magna of normotensive urethane-anaesthetized artificially-ventilated rats. Increases in blood pressure and heart rate were produced by fentanyl (0.3-3.0 nmol). [D-ala]2-met-enkephalinamide (17 nmol), and beta-endorphin (2.9 nmol). On the contrary, ethylketocyclazocine (78.7 nmol) and dynorphin (1-13) (62.3 nmol) produced decreases in blood pressure and heart rate. The cardiovascular effects of ethylketocyclazocine and dynorphin (1-13) were antagonized by higher doses of naloxone than that required to counteract the effects of fentanyl. These results suggest that opposite central cardiovascular effects could be induced by activation of various opiate receptors.


[Pharmacokinetic and clinical studies of ceftizoxime in the perinatal period. The Chemotherapy Research Group for Mothers and Children].
Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.


[Possible routes of infection in hip replacement].
To evaluate the probability of direct inoculation of pathogens into the bone bed by surgical instruments and implants. The study included 22 patients who underwent surgery at the Vreden National Medical Research Center of Traumatology and Orthopedics. Mean age was 73.3±3.7 years. These patients underwent total hip replacement. Intraoperative skin scrapings within the wound edge were made. Pressure on the scalpel was applied in two fashions. In 10 cases, scraping was performed by minimally pressure on the skin (superficial contact). In 12 cases, scalpel was pressed with force (skin deformation to a depth of 3-4 mm). Next, microbiological analysis of scrapings was performed. There was no growth of microorganisms in samples obtained by minimal pressure on the scalpel. Analysis of 12 scrapings in the second group (tight contact simulating damage to the skin with surgical instruments) revealed growth of microflora in all cases. Contact of cutters, rasps and implants with skin can be a mechanism for direct inoculation of pathogens into the bone tissue and potentially cause periprosthetic infection.


Awareness of dental disorders and discrepancy between "objective" and "subjective" dental treatment needs.
A dental health survey including an interview, a questionnaire and a clinical examination was conducted among adults aged 25, 35, 50, and 65 yr in Ostrobothnia, Finland. A total of 1275 subjects, 80% of the sample, participated in the clinical examination. 40% of the subjects with at least one dentate sextant had noticed gingival bleeding, 16% gingival inflammation, 20% "gum disease", and 70% at least one decayed tooth. When objectively assessed, a total of 98% had a maximum CPITN code 1-4, 38% a maximum CPITN code 3-4 and 76% were deemed to be in need of fillings. Dentures were objectively non-acceptable in 64% of wearers and subjectively so in 42%. A need for replacing missing teeth was expressed by 14% of the total sample, whereas according to "objective" assessment, 23% had such a need. It is concluded that people tend to underestimate their dental treatment needs, the discrepancy being most distinct in the field of periodontology. Sufficient emphasis should thus be given to improving people's awareness and knowledge of their own dental disorders.


Effectiveness of betahistine (48 mg/day) in patients with vestibular vertigo during routine practice: The VIRTUOSO study.
Vestibular vertigo is associated with substantially reduced quality of life. Betahistine is effective in improving vertigo-associated symptoms, with longer treatment periods leading to greater improvements; however, it is not known whether these effects persist after treatment cessation. VIRTUOSO was a prospective, multinational, non-comparative, post-marketing observational programme investigating the effectiveness of betahistine (48 mg/day) and the course of vertigo after the discontinuation of treatment. Patients with vestibular vertigo who were prescribed 48 mg/day betahistine were enrolled in Russia and Ukraine. Treatment duration was up to 2 months, and patients were followed up for 2 months after discontinuation of betahistine. Efficacy endpoints included clinical response (assessed by change in vertigo severity), monthly attack frequency, and physician and patient grading of overall clinical response and improvement of vertigo-associated symptoms. Overall, 309 patients were enrolled and 305 completed the study. Clinical response was rated as good, very good or excellent in 74.1% of patients at end of treatment, with vertigo severity significantly decreased from baseline (p < 0.001). Monthly vertigo attack frequency decreased significantly during the 2 months of treatment (p < 0.001 from baseline) and further decreased during the 2-month follow-up (p < 0.001 from end of treatment). Overall, clinical response was graded as good or excellent by 94.4% of physicians and 95.4% of patients. Clinical improvement was considered either good or excellent by 82.6-90.5% of physicians and patients for nausea, vomiting and faintness. Only one adverse event was reported, with no serious adverse events. Our findings suggest that betahistine (48 mg/day) therapy is effective in treating vertigo in routine clinical settings. The observed effects persisted for 2 months after treatment cessation, suggesting that betahistine may facilitate lasting vestibular compensation.


Chromatographic separation, determination and identification of ecdysteroids: Focus on Maral root (Rhaponticum carthamoides, Leuzea carthamoides).
The review presents general principles for choosing optimal conditions for ecdysteroid separation, identification, and isolation using HPLC/TLC techniques in RP, NP-HILIC or NP modes. Analytics of ecdyteroids pose a still insufficiently resolved problem. Plant-derived ecdysteroids are a point of interest of pharmaceutical industry and sport medicine due to their postulated adaptogenic and anabolic properties. In insects, ecdysteroids regulate larval transformation. Maral root (Rhaponticum carthamoides, Leuzea carthamoides), traditional Siberian folk-medicine plant used as stimulant to boost overall health and fitness, is a particularly rich source of a wide variety of phytoecdysteroids. The similarity of molecular structures of ecdysteroids present in its extracts together with high content of unrelated compounds of similar chromatographic characteristics makes optimization of separation, identification and isolation of ecdysteroids a difficult analytical task. In that respect, two-dimensional separations, two-dimensional separations, 2D HPLC or 2D TLC, could be of use. For identification, the hyphenated techniques are particularly important. Thus, comprehensive overview of MS spectral parameters of ecdysteroids is provided. Described principles could easily be applied for separation of ecdysteroids in extracts from other sources. They are also useful for development of separation procedures for isolation of ecysteroids in preparative-scale applications.


Identification of Enterococcus faecalis in a patient with urinary-tract infection based on metagenomic next-generation sequencing: a case report.
Urinary tract infection (UTI) caused by various pathogenic microorganisms is ubiquitous in the parts of the urinary system such as kidney, ureter, bladder, and urethra. Currently, clinical detection of UTI is mainly focused on urine culture; however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate, especially in patients who have used antibiotics. Generally, treatment for UTI relies on empirical medication rather than pathogen diagnosis, which leads to the inappropriate use of antimicrobial agents and a significant increase in resistant strains. Comparatively, metagenomic next-generation sequencing (mNGS) is capable of overcoming the disadvantages of clinical culture, and identifying pathogens for further treatment. A 33-year-old male patient was admitted to hospital with a high fever and chills. None of his autoimmune disease or thyroid function related indicators were positive, and he had no risk of endocarditis. His white blood cell count, C-reactive protein, procalcitonin, interleukin 6, and neutrophil proportion were markedly elevated. He was initially diagnosed as having an infection of unknown etiology. Since empirical treatment of Sulperazon and Metronidazole did not relieve his symptoms, both the blood and urine specimens were examined using traditional culture, serological testing, and mNGS assay. Traditional culture and serological testing produced negative results, while the mNGS assay revealed the presence of a potential pathogen, Enterococcus faecalis, in the urine specimen, which was further confirmed by both Sanger sequencing and qPCR analysis. A CT scan of the patient's whole abdomen showed stones in the right kidney. Once targeted antibiotic therapy was administered, the patient recovered quickly. Our case illustrated that mNGS, as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. Furthermore, this technology provides strong support for guiding clinicians to determine appropriate treatment.


Reviewing the regulatory barriers for nanomedicine: global questions and challenges.
Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine.


Effect of the reversible monoamine oxidase-A inhibitor befloxatone on the rat 5-hydroxytryptamine neurotransmission.
The aim of the present study was to assess, using in vivo electrophysiological paradigms, the effect of sustained administration of the selective and reversible monoamine oxidase-A inhibitor beflotaxone on serotonin (5-hydroxytryptamine, 5-HT) neurotransmission. In male Sprague-Dawley rats with the osmotic minipumps in place, a treatment with befloxatone (0.75 mg/kg per day, s.c.) for 2 days decreased the spontaneous firing activity of dorsal raphe 5-HT neurons. The combination of befloxatone and the 5-HT1A/1B receptor antagonist (-)-pindolol (15 mg/kg per day, s.c.) for 2 days slightly increased the firing activity of 5-HT neurons, whereas a treatment with (-)-pindolol alone for 2 days did not modify this parameter. The suppressant effects on the firing activity of 5-HT neurons of the 5-HT autoreceptor agonist lysergic acid diethylamide (LSD), injected intravenously, and of both 5-HT and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), applied by microiontophoresis, were attenuated in rats treated with befloxatone for 2 days, suggesting an early desensitization of the somatodendritic 5-HT1A receptors. The firing activity of 5-HT neurons was back to normal after a treatment for 21 days with befloxatone but the suppressant effects of LSD, 5-HT or 8-OH-DPAT was the same as in controls. In contrast, the suppressant effect of the alpha2-adrenoceptor agonist clonidine on the firing activity of 5-HT neurons was significantly attenuated after the treatment with befloxatone for 21 days. At the postsynaptic level, the administration of the selective 5-HT1A receptor antagonist (N-[2-[4(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide trihydroxychloride (WAY 100635, 100 microg/kg, i.v.) did not modify the firing activity of quisqualate-activated dorsal hippocampus CA3 pyramidal neurons in control rats. In contrast, in rats treated with befloxatone in combination with (-)-pindolol for 2 days as well as with befloxatone alone for 21 days, WAY 100635 significantly increased the firing of CA3 pyramidal neurons. In conclusion, these data suggest that when the firing activity of 5-HT neurons is normal in the presence of befloxatone, either after a two-day treatment together with (-)-pindolol or alone for 21 days, the tonic activation of postsynaptic 5-HT1A receptors is enhanced.


A 14-Year Italian Experience in DM2 Genetic Testing: Frequency and Distribution of Normal and Premutated CNBP Alleles.
Myotonic dystrophy type 2 (DM2) is a multisystemic disorder caused by a (CCTG) n in intron 1 of the CNBP gene. The CCTG repeat tract is part of a complex (TG) v (TCTG) w (CCTG) x (NCTG) y (CCTG) z motif generally interrupted in CNBP healthy range alleles. Here we report our 14-year experience of DM2 postnatal genetic testing in a total of 570 individuals. The DM2 locus has been analyzed by a combination of SR-PCR, TP-PCR, LR-PCR, and Sanger sequencing of CNBP alleles. DM2 molecular diagnosis has been confirmed in 187/570 samples analyzed (32.8%) and is mainly associated with the presence of myotonia in patients. This set of CNBP alleles showed unimodal distribution with 25 different alleles ranging from 108 to 168 bp, in accordance with previous studies on European populations. The most frequent CNBP alleles consisted of 138, 134, 140, and 136 bps with an overall locus heterozygosity of 90%. Sequencing of 103 unexpanded CNBP alleles in DM2-positive patients revealed that (CCTG)5(NCTG)3(CCTG)7 and (CCTG)6(NCTG)3(CCTG)7 are the most common interruption motifs. We also characterized five CNBP premutated alleles with (CCTG) n repetitions from n = 36 to n = 53. However, the molecular and clinical consequences in our cohort of samples are not unequivocal. Data that emerged from this study are representative of the Italian population and are useful tools for National and European centers offering DM2 genetic testing and counseling.


[Diagnosis and treatment of prostatic abscess: Report of 11 cases and review of the literature].
To analyze the clinical features, imaging characteristics, treatment options and prognosis of prostatic abscess (PA), and provide some new ideas for the diagnosis and treatment of the disease. This retrospective study included 11 cases of confirmed PA treated in the Fifth Medical Center of PLA General Hospital. We analyzed the clinical data obtained from the electronic medical records, including basic demographic statistics, risk factors, clinical symptoms, laboratory results, imaging findings, treatment methods, treatment-related complications and outcomes. The 11 patients diagnosed with PA between May 2016 and August 2022 were aged (64.18 ± 7.19) years and all had at least 1 comorbidity, including 5 cases of diabetes mellitus (45.5%) and 8 cases of dysuria (72.8%). PA was confirmed in 3 cases by CT and in 8 cases by MRI, 6 (54.5%) multifocal and 10 (90.9%) >2 cm in diameter, with a median size of 3.84 cm. After admission, positive urine culture was found in 3 cases, positive blood culture in 1, Klebsiella pneumoniae in 2 and Enterococcus Faecalis in 1. Three of the patients were treated by intravenous administration of antibiotics alone, and the other 8 by transurethral PA unroofing in addition. Antibiotics medication lasted for a median of (12.9 ± 3.88) d and hospital stay averaged (19.18 ± 8.20) d. The patients were followed up for 3 months, which revealed the presence of PA in 2 of the cases treated with antibiotics alone, but not in any of the cases treated by surgery. PA is relatively rare and has no specific symptoms clinically. Imaging examination is very important for accurate diagnosis, and transurethral PA unroofing plus antibiotics administration could be considered as an optimal management of the disease.


Fenoterol in exercise-induced asthma. Effect of dose on efficacy and duration of action.
The effectiveness of inhaled fenoterol doses of 0.4 mg and 0.8 mg in preventing exercise-induced asthma was investigated in 12 patients. Exercise-induced asthma was prevented by both doses for two hours after administration, but the effect of neither dose was significantly different from that of placebo four hours after. There was no statistically significant difference between the effects of the two fenoterol doses; and only a few patients were protected for more than two hours by the higher dose.


[Technical features of intestinal ureteroplasty. Part 2: right-sided ileoureteroplasty].
To present the results of intestinal ureteroplasty and technical features of right-sided ileoureteroplasty. From 2001 to 2015, 78 patients underwent isolated reconstruction of the ureter using a segment of the ileum, of whom 57 (73%) and 21 (27%) patients had unilateral and bilateral operation, respectively. In total, isolated segments of the ileum were used to substitute 101 ureters including 45 (44.6%) right ureters. The follow-up period ranged from 3 months to 14 years (mean 8.3 +/- 0.8 years). Early postoperative complications occurred in 8 (10.2%) patients and 5 (6.4%) of them required reoperation. Long-term postoperative complications occurred in 7 (8.9%) patients and 4 required surgical treatment. All patients had good results of conservative treatment and reoperations. There were no deaths. All patients achieved restoration of urodynamics and normalization of kidney function. Right-sided, especially total, ileoureteroplasty is the most technically challenging among other possible options to substitute the ureter with a small bowel segment. To avoid mesenteric torsion when performing isoperistaltic ureteroplasty, the graft should be placed above and in front of the intestinal anastomosis.


Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization.
Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1' pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the µM range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new N-acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.


The role of individual, community and societal gender inequality in forming women's attitudes toward intimate-partner violence against women: a multilevel analysis.
Establishing risk factors for intimate partner violence against women (IPVAW) is crucial for addressing women's health and development. Acceptance of IPVAW has been suggested as one of the strongest predictors of IPVAWs. The aim of this study was to examine the independent contributions of individual, community, and societal measures of gender inequality in forming women's attitudes toward IPVAW. We applied multivariable multilevel logistic regression analysis to Demographic and Health Survey data for 120,467 women nested within 7463 communities from 17 countries in sub-Saharan Africa. We found that women whose husband had higher education (odds ratio [OR] =1.06; 95% confidence interval [CI] 1.02 to 1.10) and women whose husband had more than one wife (OR=1.14; 95% CI 1.09 to 1.19) were more likely to accept IPVAW than other women. Unemployed women with an unemployed partner were more likely to justify IPVAW than employed women with working partners (OR=1.32; 95% CI 1.08 to 1.61). Both community and societal measures of gender inequality were associated with women's attitudes toward IPVAW, even after controlling for gender inequality at the individual level. There was evidence of clustering of women's attitudes within communities and within countries. We provide evidence that community and societal forms of gender inequality influence women's attitudes toward IPVAW beyond individual factors. Choices women make are important, but community and society also impose restraints on women's attitudes toward IPVAW. Thus, policies and programs aimed at reducing or eliminating IPVAW must address people, the communities and societies in which they live in order to be successful.


Fetal and neonatal outcomes in women taking domperidone during pregnancy.
The safety of domperidone in pregnancy remains unknown. Therefore, the study aimed to prospectively evaluate the fetal outcomes of women who were taking domperidone during pregnancy. In a prospective cohort study design, 120 1st- trimester pregnant women who were taking domperidone for controlling gastrointestinal tract symptoms and 212 age-matched pregnant women not exposed to any potential teratogenic agent, were followed-up until delivery. In the case group, domperidone was indicated for control of functional gastrointestinal disorders in 59.2%, the maximum dose was 30 mg/day and exposure occurred between 2(+4) and 20 weeks' gestation. Fetal outcomes including gestational age at birth, birth weight and length, head circumference at birth, and 1- and 5-min Apgar score were similar in the two study groups. There were three babies born with malformations in each group (OR = 0.6; 95% CI 0.1, 2.8). In conclusion, domperidone does not appear to be a major human teratogen. However, our findings require further confirmation in larger studies.


A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'.
We have identified a putative signalling feature of the cytoplasmic domains of the tumour necrosis factor (TNF) family members based on available amino acid sequence data. A casein kinase I (CKI) consensus sequence is conserved in the cytoplasmic domain of six of 15 members of the type II integral membrane TNF ligand family. We examined the phosphorylation state of transmembrane tumour necrosis factor-alpha (mTNF) with [32P]orthophosphate labelling and in vitro kinase assays, in lipopolysaccharide-stimulated RAW264.7 cells. A dimeric form of the type I soluble TNF receptor (sTNFR) was found to dephosphorylate mTNF. This effect could be prevented by treatment with phosphatase inhibitors. Recombinant CKI was able to phosphorylate mTNF that had been dephosphorylated by sTNFR ligation in vivo, and this was less effective if phosphatase inhibitors had been used to prevent mTNF dephosphorylation. A mutated form of mTNF, lacking the CKI recognition site, cannot be phosphorylated by the enzyme. Binding of sTNFR to mTNF induced an increase in intracellular calcium levels in RAW264.7 cells, implying the presence of an associated signalling pathway. We predict that this CKI motif is phosphorylated in other TNF ligand members, and that it represents a new insight into the mechanism of 'reverse signalling' in this cytokine family.


Screening with Papanicolaou tests in Alberta: Are we Choosing Wisely?
To describe the prevalence and geographic distribution of cervical cancer screening, as well as the age groups of those undergoing screening, in Alberta, and to determine if screening practices conform to current guidelines and follow Choosing Wisely Canada recommendations. Descriptive study using data from the Alberta Ministry of Health Analytics and Performance Reporting Branch. Alberta. Women who had 1 or more Papanicolaou tests between 2011 and 2013. Number of women aged 15 to 20 and those aged 70 and older who had 1 or more Pap tests in a 3-year period; year-to-year trends in screening rates for women in these 2 age groups; trends in screening rates in various geographic regions (ie, cities and zones) in Alberta; and the discipline of clinicians who ordered the Pap tests. Between 2011 and 2013, 805 632 women in the province of Alberta had 1 or more Pap tests for cervical cancer screening. Overall, 25 511 (17.5%) women aged 15 to 20 and 16 818 (10.3%) aged 70 and older were screened contrary to most existing guidelines. Screening rates varied markedly in different geographic regions of the province. Most Pap tests were ordered by family physicians or general practitioners. Within the geographic regions of Alberta, provincial, national, and international guidelines for screening with Pap tests are inconsistently followed. This strongly echoes the need for clinicians and patients to consider the Choosing Wisely Canada recommendations and current guidelines for cervical cancer screening.


A second isoform of 3-ketoacyl-CoA thiolase found in Caenorhabditis elegans, which is similar to sterol carrier protein x but lacks the sequence of sterol carrier protein 2.
We cloned a full-length cDNA of the nematode Caenorhabditis elegans that encodes a 44-kDa protein (P-44, 412 residues) similar to sterol carrier protein x (SCPx). Mammalian SCPx is a bipartite protein: its 404-residue N-terminal and 143-residue C-terminal domains are similar to 3-ketoacyl-CoA thiolase and identical to the precursor of sterol carrier protein 2 (SCP2; also termed non-specific lipid-transfer protein), respectively. P-44 has 56% sequence identity to the thiolase domain of SCPx but lacks the SCP2 sequence. Northern blot analysis revealed only a single mRNA species of 1.4 kb, which agrees well with the length of the cDNA (1371 bp), making it improbable that alternative splicing produces an SCPx-like fusion protein. The sequence similarities of P-44 to conventional thiolases are lesser than that to SCPx. Purified recombinant P-44 cleaved long-chain 3-ketoacyl-CoAs (C(8-16)) in a thiolytic manner by the ping-pong bi-bi reaction mechanism. The inhibition of P-44 by acetyl-CoA was competitive with CoA and non-competitive with 3-ketooctanoyl-CoA. This pattern of inhibition is shared with SCPx but not with conventional 3-ketoacyl-CoA thiolase, which is inhibited uncompetitively with respect to 3-ketoacyl-CoA. From these results, we concluded that nematode P-44 and mammalian SCPx constitute a second isoform of thiolase, which we propose to term type-II 3-ketoacyl-CoA thiolase.


Reliability and acceptability of a five-station multiple mini-interview model for residency program recruitment.
Standard interviews are used by most residency programs in the United States for assessment of aptitude of the non-cognitive competencies, but variability of interviewer skill, interviewer bias, interviewer leniency or stringency, and context specificity limit reliability. To investigate reliability and acceptability of five-station multiple mini-interview (MMI) model for resident selection into an internal medicine residency program in the United States. One independent academic medical center. Two hundred and thirty-seven applicants and 17 faculty interviewers. Five, 10-min MMI stations with five different interviewers blinded to the candidate's records and one traditional 20-min interview with the program director. Candidates were rated on two items: interpersonal and communication skills, and overall performance. Generalizability data showed that the reliability of our process was high (>0.9). The results of anonymous surveys demonstrated that both applicants and interviewers consider the MMI as a fair and more effective tool to evaluate non-cognitive traits, and prefer the MMI to standard interviews. The MMI process for residency interviews can generate reliable interview results using only five stations, and it is acceptable and preferred over standard interview modalities by the applicants and faculty members of one US residency program.


Contamination of fox hair with eggs of Toxocara canis.
Eighty-seven red foxes were investigated for the presence of Toxocara eggs on a sample of their hair from the peri-anal region. The worm burden of Toxocara in each fox intestine was also assessed and the relationship between eggs on the hair and worms in the intestine explored. Twenty-eight per cent of the foxes were found to have Toxocara eggs on their hair, with an average of 1.31 +/- 3.21 eggs per gram of hair (+/- SD). Sixty-one per cent of foxes harboured Toxocara worms within their intestines, with a mean worm burden (+/- SD) of 4 +/- 8. Host age and sex did not significantly influence the observed eggs on the hair or the worm burden. No significant correlation was found between the numbers of eggs on the hair and the worm burden within the intestine. These data collected from foxes are explored in the context of data from stray dogs and the possible epidemiological differences are discussed.


Tissue androgen concentrations in golden hamsters with benign prostatic tumours.
Using gas chromatography-high resolution mass spectrometry with selected ion detection, the concentrations of testosterone, 5alpha-dihydrotestosterone, androsterone, 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17alpha-diol and 5alpha-androstane-3beta,17beta-diol were measured in the dorsal and ventral prostates of two strains of golden hamster (Mesocricetus auratus) at various ages from 60 to 250 days. The tissue concentrations from a control strain were compared with those of the BIO 87.2 strain of hamster, the latter developing benign hyperplasia of the prostate between 90 and 120 days of age. Marked increases in the concentration of total 5alpha-androstanediols in both prostatic lobes of the BIO 87.2 strain were detected, with the highest level of over 345 nmol/g protein being found at 200 days of age. In comparison, the control strain showed a less pronounced increase in concentration at 150 days. Increases in total 5alpha-androstanediols were mainly associated with increases in the concentration of 5alpha-androstane-3alpha,17beta-diol. Concentrations of testosterone in prostatic tissue were also found to increase in the BIO 87.2 animals with peak values being seen at 200 days. Increases in concentration of androsterone were observed by 150 days and these levels were maintained up to 250 days of age. Control animals showed no comparable increases in testosterone and androsterone during the time-course studied. Surprisingly, no significant variation in 5alpha-dihydrotestosterone concentration was detected in either strain from 60 to 250 days although levels were slightly but consistently higher in the BIO 87.2 strain. There were no significant fluctuations in any of the androgens assayed either before or during tumour development. The increases in 5alpha-androstane-3alpha,17beta-diol, testosterone and androsterone were detected only after tumours had become established.


Porcine epidemic diarrhea virus M protein blocks cell cycle progression at S-phase and its subcellular localization in the porcine intestinal epithelial cells.
Porcine epidemic diarrhea (PED) caused by virulent strains of porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric disease of swine characterized by severe enteritis, vomiting, and watery diarrhea. This study investigates the subcellular localization and function of PEDV M protein through examination of its effects on cell growth, cell cycle progression, and interleukin 8 (IL-8) expression. Our results revealed that the PEDV M protein is localized throughout the cytoplasm. The M protein altered swine intestinal epithelial cell line (IEC) growth and induced cell cycle arrest at the S-phase via the cyclin A pathway. The S-phase arrest is associated with a decrease in level of cyclin A. Furthermore, our results revealed that the M protein of PEDV does not induce endoplasmic reticulum (ER) stress and does not activate NF-κB which is responsible for IL-8 and Bcl-2 expression. This is the first report to demonstrate that the PEDV M protein is localized in the whole cell and induces cell cycle arrest at the S-phase. This study provides novel findings in the function of M proteins of PEDV.


Onco-Golgi: The Missed Target.
The Golgi apparatus or complex, a highly dynamic organelle, is a factory in which proteins are processed and sorted for transport to various target organelles.(1) It was first discovered by Camillo Golgi in 1898 and was described as an intracellular reticular apparatus stained by the 'black reaction' in neuronal cells.(1,2) Despite of several research works, this complex remains one of the most inexplicable structures of the cytoplasmic organelles.


Valeric Biofuel Production from γ-Valerolactone over Bifunctional Catalysts with Moderate Noble-Metal Loading.
SiO2 -Al2 O3 -supported Ru, Ir and Pt-based catalysts with moderate metal loading (1 %) were tested for the first time in the production of pentyl valerate (PV) in liquid phase from γ-valerolactone, pentanol (in excess) and H2 . The acidity of these bifunctional catalysts, plays a key role in the one-pot process comprising two consecutive acid-catalyzed reactions and a metal-catalyzed one. Metal dispersion also shown to be relevant for the conversion of the pentyl pentenoate intermediate into PV by hydrogenation over the metal sites. Pt/SA catalyst with the highest surface acidity and metal dispersion reached optimal GVL conversion with a PV yield of 90.0 % after 10 h, exhibiting a PV productivity of 300 mmol/gM .h, i. e. a value between three and four times higher than the best result reported until now (91.8 mmol/gM .h). These findings highlight the potential that noble metal-based catalyst with moderate metal loading have in the valorization of biomass-derived platform molecules such as γ-valerolactone.


Cinnamon products as a possible etiologic factor in orofacial granulomatosis.
It has been reported that clinical changes due to hypersensitivity reactions to various foods, preservatives, and oral hygiene products may be consistent with the characteristic signs of orofacial granulomatosis (OFG). The objective of this study was to examine 37 well-documented cases of cinnamon-induced contact stomatitis for clinical and histological features consistent with a diagnosis of OFG. We reviewed the records of the 37 cases to screen them for the clinical and histopathologic features of OFG. Twelve patients showed clinical characteristics of OFG. The most commonly affected site was the gingiva. Focal non-caseating, epitheloid granulomas were observed in four histologic specimens. Multinucleated giant cells were observed in an additional four cases. Although OFG may have multiple etiologies, it is clear that, in some instances, a hypersensitivity reaction to cinnamon products can elicit lesions consistent with OFG.


The rupture of periaortic infective aneurysm into the left atrium and the left ventricular outflow tract: preoperative diagnosis by transthoracic echocardiography.
We present a rare complication of infective endocarditis, perforated periaortic abscess with fistulous communication between the aortic root, the left atrium, and the left ventricular outflow tract. Preoperative transthoracic echocardiographic diagnosis was confirmed intraoperatively. The patient was treated successfully by aortic homograft implantation.


The Importance of the Pars Interarticularis as a Landmark for Safe Lumbar Pedicle Screw Placement: Technical Note.
The use of navigational adjuncts for pedicle screw placement has increased in popularity among surgeons with access to this technology. However, it remains important to have a comprehensive understanding of posterior bony element anatomy with respect to the location of the pedicle in order to ensure safe placement of pedicle screws. Proper exposure and identification of the pars interarticularis provide a helpful landmark during pedicle screw placement in order to confirm navigation accuracy and avoid misplaced instrumentation. In this technical note, we highlight the surgical anatomy of the pars interarticularis of the lumbar spine and its relationship to the lateral, inferior, and medial borders of the pedicle using diagrams and cadaveric dissections.


Point-of-care ultrasound for the acute abdomen in the primary health care.
Point-of-care ultrasound (POCUS) is a focused examination, which is performed and interpreted at the bedside by the treating physician answering a specific clinical question. It is currently utilized as an essential adjunct to physical examination in many medical specialties. Recent advances in technology have made POCUS machines portable, affordable, and could be used with minimal training even by nonradiologists. This review aims to cover the fundamental physics of POCUS and its applications for diagnosing the acute abdomen in the primary health care including the most common causes encountered by family physicians. These are acute appendicitis, acute cholecystitis, renal colic, ectopic pregnancy, acute diverticulitis, bowel obstruction, and abdominal aortic aneurysm. We hope to encourage primary care physicians to incorporate POCUS in their routine clinical practice. We also highlight challenges encountered when using POCUS in the primary health care including limited availability and the need for proper training. Furthermore, we review the POCUS results when performed by primary health-care physicians. Integrating POCUS in primary health care empowers primary health-care physicians to provide high-quality, safe, and cost-effective care to the patients.


Mespirenone and other 15,16-methylene-17-spirolactones, a new type of steroidal aldosterone antagonists.
The ability of a series of 15,16-methylene-spirolactones in comparison to known antimineralocorticoids to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The standard procedure involved continuous i.v. infusion with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 micrograms/(kg X h)] resulting in a long-lasting reduction of renal sodium excretion, increase of renal potassium excretion and hence decrease of the urinary Na/K-ratio. In some experiments sodium input was increased (0.2% NaCl + 4.3% glucose or 0.9% NaCl, respectively). The test drugs either were administered orally 1 h before start of the infusion or were added to the infused solution. With the exception of two steroids which could only be tested at single doses, all compounds were administered at three doses ranging from 2.2 to 40 mg/kg (p.o.) or from 0.83 to 6.7 mg/kg/h (i.v.). Spironolactone or spirorenone (oral administration) and potassium canrenoate (i.v. infusion) served as reference compounds. The antimineralocorticoid activity of the steroids was judged by the increase in the aldosterone-lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used as controls. To obtain preliminary information on potential antiandrogenic and progestogenic (side-)effects, binding of the test-compounds to androgen receptors (rat prostate cytosol) and progestogen receptors (rabbit uterus cytosol) was measured in vitro using 3H-dihydrotestosterone (DHT) and 3H-progesterone (prog.) as tracer and unlabelled DHT and prog. as references. All steroids tested exhibited antimineralocorticoid activity. For compounds tested at three doses levels the potency relative to the standard used was evaluated using regression analysis based on the Na/K-ratio or the log (Na X 100)/K-ratio. The relative potency of the other compounds was estimated by comparing the biological effect of single doses of test drug and standard drug, respectively, using nonparametric statistical tests.(ABSTRACT TRUNCATED AT 400 WORDS)