Hematology and serum biochemistry values of trapped, healthy, free-ranging rock hyraxes (Procavia capensis) and their association with age, sex, and gestational status.
The rock hyrax (Procavia capensis) is an herbivore prevalent from South Africa to Turkey, and a most common zoo animal. Although many studies of hyrax diseases and physiology are available, clinicopathologic data are limited. The purpose of this study was to establish comprehensive hematologic and biochemical reference intervals for trapped, apparently healthy, free-ranging rock hyraxes using modern laboratory methods and to assess differences related to sex, gestation, and age. Blood samples were obtained from 27 healthy, free-ranging hyraxes under anesthesia. Gender, body weight, and gestational status were recorded. Hematologic (n = 25) and serum biochemical (n = 22) analyses were performed using standard automated methodology. Data for male vs female, adult vs juvenile, and pregnant vs nonpregnant female hyraxes were compared using the Mann-Whitney U-test. Associations between variables were assessed using Pearson's or Spearman rank correlation tests. Significant age- and sex-related, but not gestation-related differences were observed in several variables. Serum alkaline phosphatase activity and phosphorus concentration were significantly higher in juveniles compared with adults. A unique type of monocyte comprised 1-3% of leukocytes in 4 hyraxes. Markedly high serum creatine kinase (CK) activity was observed in most hyraxes. The large number of animals and the availability of sex, age, and gestational data in this study will be useful to zoo and wildlife veterinarians working with rock hyraxes. High serum concentrations of betahydroxybutyric acid in the rock hyrax, compared with dogs, cats, and ruminants, may be related to its unique digestive system. High CK activity may have been the result of a capture myopathy-like syndrome. The unique monocytes in hyraxes resemble those of elephants and are a novel finding in this species.


[Nitroprusside ions as a liposome label].
It has been shown that nitroprusside ions incorporated into bilayer liposomes may be used as a label to form an opinion as to the liposome intactness in the blood and distribution in animal organ tissues in vivo.


The effects of sclerostin antibody plus parathyroid hormone (1-34) on bone formation in ovariectomized rats.
Previous studies have demonstrated the effects of sclerostin antibody (Scl-Ab) and parathyroid hormone (1-34, PTH) on healing in osteoporosis; however, reports about the combined effects of Scl-Ab plus PTH on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with Scl-Ab and PTH on osteoporosis healing in ovariectomized (OVX) rats. After bilateral ovariectomy, 12 weeks were allowed to pass for the establishment of standard conditions for osteoporosis in animal models. The rats then randomly received a vehicle (control), Scl-Ab (25 mg/kg body weight, twice weekly), PTH (60 μg/kg, three times per week) or PTH plus Scl-Ab until death at 12 weeks. The blood and distal femurs of the rats were harvested for evaluation. The results of treatment for osteoporosis were evaluated by serum analysis, histology, microcomputed tomography (micro-CT) and biomechanical tests. Results from this study indicated that PTH + Scl-Ab had stronger effects on the prevention and treatment of osteoporosis than either of the monotherapies in OVX rats. The PTH + Scl-Ab produced the strongest effects on bone volume fraction (BV/TV), bone trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular spacing (Tb.Sp), bone mineral density (BMD) and strength of distal femurs and increased the levels of procollagen type I N‑terminal propeptide (PINP) and osteocalcin. In contrast, monotherapy with PTH or Scl-Ab showed no differences between treated groups in the assessment of the metaphysis of contralateral femurs by histology, serum, biomechanical tests and micro-CT. These results seem to indicate that Scl-Ab plus PTH has an additive effect on osteoporosis in OVX rats.


An Update on Psychopharmacological Treatment of Autism Spectrum Disorder.
While behavioral interventions remain the mainstay of treatment of autism spectrum disorder (ASD), several potential targeted treatments addressing the underlying neurophysiology of ASD have emerged in the last few years. These are promising for the potential to, in future, become part of the mainstay treatment in addressing the core symptoms of ASD. Although it is likely that the development of future targeted treatments will be influenced by the underlying heterogeneity in etiology, associated genetic mechanisms influencing ASD are likely to be the first targets of treatments and even gene therapy in the future for ASD. In this article, we provide a review of current psychopharmacological treatment in ASD including those used to address common comorbidities of the condition and upcoming new targeted approaches in autism management. Medications including metformin, arbaclofen, cannabidiol, oxytocin, bumetanide, lovastatin, trofinetide, and dietary supplements including sulforophane and N-acetylcysteine are discussed. Commonly used medications to address the comorbidities associated with ASD including atypical antipsychotics, serotoninergic agents, alpha-2 agonists, and stimulant medications are also reviewed. Targeted treatments in Fragile X syndrome (FXS), the most common genetic disorder leading to ASD, provide a model for new treatments that may be helpful for other forms of ASD.


Thyroid hormone-regulated chromatin landscape and transcriptional sensitivity of the pituitary gland.
Thyroid hormone (3,5,3'-triiodothyronine, T3) is a key regulator of pituitary gland function. The response to T3 is thought to hinge crucially on interactions of nuclear T3 receptors with enhancers but these sites in pituitary chromatin remain surprisingly obscure. Here, we investigate genome-wide receptor binding in mice using tagged endogenous thyroid hormone receptor β (TRβ) and analyze T3-regulated open chromatin using an anterior pituitary-specific Cre driver (Thrbb2Cre). Strikingly, T3 regulates histone modifications and chromatin opening primarily at sites that maintain TRβ binding regardless of T3 levels rather than at sites where T3 abolishes or induces de novo binding. These sites associate more frequently with T3-activated than T3-suppressed genes. TRβ-deficiency blunts T3-regulated gene expression, indicating that TRβ confers transcriptional sensitivity. We propose a model of gene activation in which poised receptor-enhancer complexes facilitate adjustable responses to T3 fluctuations, suggesting a genomic basis for T3-dependent pituitary function or pituitary dysfunction in thyroid disorders.


Evidence for Right-Sided Horses Being More Optimistic than Left-Sided Horses.
An individual's positive or negative perspective when judging an ambiguous stimulus (cognitive bias) can be helpful when assessing animal welfare. Emotionality, as expressed in approach or withdrawal behaviour, is linked to brain asymmetry. The predisposition to process information in the left or right brain hemisphere is displayed in motor laterality. The quality of the information being processed is indicated by the sensory laterality. Consequently, it would be quicker and more repeatable to use motor or sensory laterality to evaluate cognitive bias than to perform the conventional judgment bias test. Therefore, the relationship between cognitive bias and motor or sensory laterality was tested. The horses (n = 17) were trained in a discrimination task involving a box that was placed in either a "positive" or "negative" location. To test for cognitive bias, the box was then placed in the middle, between the trained positive and negative location, in an ambiguous location, and the latency to approach the box was evaluated. Results indicated that horses that were more likely to use the right forelimb when moving off from a standing position were more likely to approach the ambiguous box with a shorter latency (generalized linear mixed model, p < 0.01), and therefore displayed a positive cognitive bias (optimistic).


Effects of edrophonium bromide on neuromuscular transmission in a healthy human subject.
Regional intravenous injections of different amounts (1-3 mg) of edrophonium were given to the hand of a healthy subject. The earliest change was a small negative deflection occurring at the end of the muscle response evoked by nerve stimulation, due to repetitive activity. It did not occur after a second stimulus at 30 ms or immediately after 10 s maximum voluntary contraction. Repetitive stimulation at 0.5 Hz reduced the repetitive activity. With a higher dose of edrophonium the response to a second shock (M2) at 30 ms was reduced in amplitude, but M2 at 80 ms was unaffected. An even larger dose caused depression of M2 at 80 ms also and a decremental response to 50 Hz stimulation. The amplitude of the response to a single shock was unchanged throughout.


Genetic counseling for early onset and familial dementia: Patient perspectives on exome sequencing.
Genetic testing has become routine for many inherited conditions; however, little is known about the unique issues that arise when offering genetic testing for inherited forms of dementia. To better understand the patient perspective, we surveyed study participants about their experiences as they underwent genetic counseling and genetic testing for dementia. We recruited 50 pairs of subjects. Each pair was comprised of one person with cognitive impairment and a cognitively intact co-participant. Study participants received pre- and post-test genetic counseling and comprehensive genetic testing for dementia. During the study, participant pairs completed four surveys which asked about their experience. Testing began with a 38 gene dementia panel. Participants with negative panel results or variants of uncertain significance (VUS) were reflexed to exome sequencing (ES). Twenty-nine participants (58%) reported that their primary motivation to join the study was for the benefit to their families. Fifty-two percent of participants initially planned to use their test results to make health and wellness changes, but, six months after disclosure, only 31% had done so. Six months after result disclosure, approximately 90% of participant pairs accurately recalled their genetic test results. Overall satisfaction with testing was high, and decision regret was negligible. This observational study describes the experiences of study participants undergoing genetic counseling and genetic testing for dementia and found that most participant pairs accurately recalled their results up to six months following disclosure while also maintaining high levels of satisfaction without decision regret. These findings suggest that, in the context of genetic counseling, genetic testing can be effectively used in this population.


A conserved RNA degradation complex required for spreading and epigenetic inheritance of heterochromatin.
Heterochromatic domains containing histone H3 lysine 9 methylation (H3K9me) can be epigenetically inherited independently of underlying DNA sequence. To gain insight into the mechanisms that mediate epigenetic inheritance, we used a Schizosaccharomyces pombe inducible heterochromatin formation system to perform a genetic screen for mutations that abolish heterochromatin inheritance without affecting its establishment. We identified mutations in several pathways, including the conserved and essential Rix1-associated complex (henceforth the rixosome), which contains RNA endonuclease and polynucleotide kinase activities with known roles in ribosomal RNA processing. We show that the rixosome is required for spreading and epigenetic inheritance of heterochromatin in fission yeast. Viable rixosome mutations that disrupt its association with Swi6/HP1 fail to localize to heterochromatin, lead to accumulation of heterochromatic RNAs, and block spreading of H3K9me and silencing into actively transcribed regions. These findings reveal a new pathway for degradation of heterochromatic RNAs with essential roles in heterochromatin spreading and inheritance.


Neural Correlates of Moral Evaluation and Psychopathic Traits in Male Multi-Problem Young Adults.
Multi-problem young adults (18-27 years) present with a plethora of problems, including varying degrees of psychopathic traits. The amygdala and ventromedial prefrontal cortex (vmPFC) have been implicated in moral dysfunction in psychopathy in adolescents and adults, but no studies have been performed in populations in the transitional period to adulthood. We tested in multi-problem young adults the hypothesis that psychopathic traits are related to amygdala and vmPFC activity during moral evaluation. Additionally, we explored the relation between psychopathic traits and other regions consistently implicated in moral evaluation. Our final sample consisted of 100 multi-problem young adults and 22 healthy controls. During fMRI scanning, participants judged whether pictures showed a moral violation on a 1-4 scale. Whole brain analysis revealed neural correlates of moral evaluation consistent with the literature. Region of interest analyses revealed positive associations between the affective callous-unemotional dimension of psychopathy and activation in the left vmPFC, left superior temporal gyrus, and left cingulate. Our results are consistent with altered vmPFC function during moral evaluation in psychopathy, but we did not find evidence for amygdala involvement. Our findings indicate the affective callous-unemotional trait of psychopathy may be related to widespread altered activation patterns during moral evaluation in multi-problem young adults.


[Distance orientation of the tick Ixodes persulcatus to the attractant factors of the prey].
The laboratory and field tests have shown that the odour is the main factor which activates ticks (Ixodes persulcatus) attraction to the host. Ticks have a sensation of a man on 15 metres distance; the number of activated ticks increases with the distance to the host and depends on the wind direction. The infrared radiation source excites only a short time activation of the ticks on 0.5-1.0 metres distance. Mechanic and sound stimulations were found to be uneffective for the ticks in the experiment.


[Activity of the inositol-containing phospholipid dimer analogues against human immunodeficiency virus].
For the purpose of finding effective inhibitors of virus adsorption the series of inositol-containing phospholipid dimer analogues were previously synthesized. In the present work, the antiretroviral activity of these compounds against HIV-1 was demonstrated on the model of cells infected with the virus. The highest effect was found in the case of dimer poliol 5, EC50 (50%-effective concentration) was 3.9 microg/ml. The development of new polyanionic compounds, which can interfere with early steps of the virus life cycle, is a promising addition to the antiretroviral therapy based on the virus enzyme inhibitors.


Infants' reasoning about hidden objects: evidence for event-general and event-specific expectations.
Research over the past 20 years has revealed that even very young infants possess expectations about physical events, and that these expectations undergo significant developments during the first year of life. In this article, I first review some of this research, focusing on infants' expectations about occlusion, containment, and covering events, all of which involve hidden objects. Next, I present an account of infants' physical reasoning that integrates these various findings, and describe new experiments that test predictions from this account. Finally, because all of the research I discuss uses the violation-of-expectation method, I address recent concerns about this method and summarize new findings that help alleviate these concerns.


Relationship between body mass index and asthma characteristics in a group of Italian children and adolescents.
The prevalence of asthma and obesity, two often associated conditions, is influenced not only by age and gender but also by lifestyle factors. This study aimed to determine whether, in a Mediterranean northern Italian region, Liguria, an increased prevalence of obesity could be detected in asthmatic children and adolescents and to evaluate the possible relationship between body mass index (BMI) and the characteristics and/or severity of asthma. BMI was determined in 554 asthmatic subjects (2.2-16.1 years) and 625 age-matched controls; BMI was expressed as a continuous variable in standard deviation score (SDS) units, determined as difference between the individual observed value and the reference mean for age and sex, divided by the corresponding standard deviation (BMI-SDS). Overweight/obesity was set at BMI-SDS of 2 or more. BMI-SDS was significantly higher in controls than in asthmatics (p = 0.04); however, the proportion of overweight/obesity subjects (BMI-SDS > or = 2) was similar in controls and in asthmatic patients (p = 0.08). Evaluation of the asthmatic group revealed that BMI-SDS was independent of gender (p = 0.57), atopic sensitization (p = 0.69), and comorbidity with other allergic symptoms (p = 0.60). By contrast, BMI-SDS was lower in preschool-age children than in school-age children and adolescents (p < 0.0001), in subjects with a high rate of acute respiratory tract infections (p = 0.04), and in those not treated with inhaled corticosteroids (IGCs) (p = 0.02). Although an increase in the prevalence of overweight/obesity was not detected in asthmatic children and adolescents, the results reported here suggest a preventive surveillance of calorie intake and a promotion of physical activity in children requiring long-term treatment with inhaled glucocorticosteroids.


Improving Social Isolation and Loneliness Among Adolescents With Physical Disabilities Through Group-Based Virtual Reality Gaming: Feasibility Pre-Post Trial Study.
Adolescents with disabilities experience alarmingly higher rates of depression and isolation than peers without disabilities. There is a need to identify interventions that can improve mental health and isolation among this underserved population. Innovations in virtual reality (VR) gaming "standalone" headsets allow greater access to immersive high-quality digital experiences, due to their relatively low cost. This study had three purposes, which were to (1) examine the preliminary effects of a low-cost, home-based VR multiplayer recreation and socialization on depression, socialization, and loneliness; (2) quantify the acceptability of the program as measured by participant adherence, total play time, and exercise time; and (3) identify and describe behavioral mechanisms that affected participant engagement. This was a single-group, pre- to postdesign trial. The intervention was conducted at home. Participants were recruited from a children's hospital. The intervention lasted 4 weeks and included 2×1-hour sessions per week of supervised peer-to-peer gaming. Participants used the Meta Quest 2 headset to meet peers and 2 coaches in a private party held digitally. Aim 1 was evaluated with the Children's Depression Inventory 2 Short Form and the University of California, Los Angeles Loneliness Scale 20 items, which are measures of social isolation and loneliness, respectively. Aim 2 was evaluated through the following metrics: participant adherence, the types of games played, friendship building and playtime, and program satisfaction and enjoyment. In total, 12 people enrolled (mean age 16.6, SD 1.8 years; male: n=9 and female: n=3), and 8 people completed the program. Mean attendance for the 8 participants was 77% (49 sessions of 64 total possible sessions; mean 6, SD 2 sessions). A trend was observed for improved Children's Depression Inventory 2 Short Form scores (mean preintervention score 7.25, SD 4.2; mean postintervention score 5.38, SD 4.1; P=.06; effect size=0.45, 95% CI -0.15 to 3.9), but this was not statistically significant; no difference was observed for University of California, Los Angeles Loneliness Scale 20 items scores. Most participants (7/8, 88%) stated that they became friends with a peer in class; 50% (4/8) reported that they played with other people. Participants reported high levels of enjoyment and satisfaction with how the program was implemented. Qualitative analysis resulted in 4 qualitative themes that explained behavioral mechanisms that determined engagement in the program. The study findings demonstrated that a brief VR group program could be valuable for potentially improving mental health among adolescents with physical disabilities. Participants built friendships with peers and other players on the web, using low-cost consumer equipment that provided easy access and strong scale-up potential. Study findings identified factors that can be addressed to enhance the program within a larger clinical trial. ClinicalTrials.gov NCT05259462; https://clinicaltrials.gov/study/NCT05259462. RR2-10.2196/42651.


Oesophagectomy for carcinoma of the oesophagus--early results.
Oesophagectomy for squamous cell carcinoma of the oesophagus was performed in 25 consecutive patients over a 3.5 years period, for an overall resection rate of 11 pc. It was an Ivor-Lewis in 19 and a left thoracotomy in six. The stage of the disease was II in two, III in six and IV in 17 cases. Seventeen patients had uneventful postoperative evolution. Complications occurred in eight patients: heart failure in three, anastomotic leak in three, massive chest wall infection in two and four of these patients died: a mortality rate of 16 pc. All the 21 patients who left the hospital were able to take normal diet. The mortality of oesophagectomy for cancer can be as high as 30 pc but decreases with better selection of patients and surgical experience. Cure is rarely achieved. Resective surgery, when successful, offers the best palliation for dysphagia. Resectability rate in all African series is very low. There is a need for a more aggressive surgery therapeutic attitude. Our series shows that it is possible in our environment to achieve an acceptable operative morbidity and mortality. With increasing experience, results can only improve.


Significance of Cuproptosis-related genes in immunological characterization, diagnosis and clusters classification in Parkinson's disease.
Parkinson's disease (PD) is a progressive neurological disorder that affects millions of people throughout the world. Cuproptosis is a newly discovered form of programmed cell death linked to several neurological disorders. Nevertheless, the precise mechanisms of Cuproptosis-related genes (CRGs) in PD remain unknown. This study investigated immune infiltration and CRG expression profiling in patients with Parkinson's disease and healthy controls. Subsequently, we construct a predictive model based on 5 significant CRGs. The performance of the predictive model was validated by nomograms and external datasets. Additionally, we classified PD patients into two clusters based on CRGs and three gene clusters based on differentially expressed genes (DEG) of CRGs clusters. We further evaluated immunological characterization between the different clusters and created the CRGs scores to quantify CRGs patterns. Finally, we investigate the prediction of CRGs drugs and the ceRNA network, providing new insights into the pathogenesis and management of PD.


Inflammatory macrophages switch to CCL17-expressing phenotype and promote peritoneal fibrosis.
Peritoneal fibrosis remains a problem in kidney failure patients treated with peritoneal dialysis. Severe peritoneal fibrosis with encapsulation or encapsulating peritoneal sclerosis is devastating and life-threatening. Although submesothelial fibroblasts as the major precursor of scar-producing myofibroblasts in animal models and M2 macrophage (Mϕ)-derived chemokines in peritoneal effluents of patients before diagnosis of encapsulating peritoneal sclerosis have been identified, attenuation of peritoneal fibrosis is an unmet medical need partly because the mechanism for cross talk between Mϕs and fibroblasts remains unclear. We use a sodium hypochlorite-induced mouse model akin to clinical encapsulated peritoneal sclerosis to study how the peritoneal Mϕs activate fibroblasts and fibrosis. Sodium hypochlorite induces the disappearance of CD11bhigh F4/80high resident Mϕs but accumulation of CD11bint F4/80int inflammatory Mϕs (InfMϕs) through recruiting blood monocytes and activating local cell proliferation. InfMϕs switch to express chemokine (C-C motif) ligand 17 (CCL17), CCL22, and arginase-1 from day 2 after hypochlorite injury. More than 75% of InfMϕs undergo genetic recombination by Csf1r-driven Cre recombinase, providing the possibility to reduce myofibroblasts and fibrosis by diphtheria toxin-induced Mϕ ablation from day 2 after injury. Furthermore, administration of antibody against CCL17 can reduce Mϕs, myofibroblasts, fibrosis, and improve peritoneal function after injury. Mechanistically, CCL17 stimulates migration and collagen production of submesothelial fibroblasts in culture. By breeding mice that are induced to express red fluorescent protein in Mϕs and green fluorescence protein (GFP) in Col1a1-expressing cells, we confirmed that Mϕs do not produce collagen in peritoneum before and after injury. However, small numbers of fibrocytes are found in fibrotic peritoneum of chimeric mice with bone marrow from Col1a1-GFP reporter mice, but they do not contribute to myofibroblasts. These data demonstrate that InfMϕs switch to pro-fibrotic phenotype and activate peritoneal fibroblasts through CCL17 after injury. CCL17 blockade in patients with peritoneal fibrosis may provide a novel therapy. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Comparison of symmetric and asymmetric double quantum well extended-cavity diode lasers for broadband passive mode-locking at 780 nm.
We present a compact, mode-locked diode laser system designed to emit a frequency comb in the wavelength range around 780 nm. We compare the mode-locking performance of symmetric and asymmetric double quantum well ridge-waveguide diode laser chips in an extended-cavity diode laser configuration. By reverse biasing a short section of the diode laser chip, passive mode-locking at 3.4 GHz is achieved. Employing an asymmetric double quantum well allows for generation of a mode-locked optical spectrum spanning more than 15 nm (full width at -20 dB) while the symmetric double quantum well device only provides a bandwidth of ∼2.7 nm (full width at -20 dB). Analysis of the RF noise characteristics of the pulse repetition rate shows an RF linewidth of about 7 kHz (full width at half-maximum) and of at most 530 Hz (full width at half-maximum) for the asymmetric and symmetric double quantum well devices, respectively. Investigation of the frequency noise power spectral density at the pulse repetition rate shows a white noise floor of approximately 2100 Hz2/Hz and of at most 170 Hz2/Hz for the diode laser employing the asymmetric and symmetric double quantum well structures, respectively. The pulse width is less than 10 ps for both devices.


[Age related morphological features of rat peripheral lymphoid organs at various levels of antigenic load].
Peripheral lymphoid organs from 2 different groups of laboratory rat's was studied (30 animals in each group). 1) Gnotobionts received from experimental - biological models Iffa-Credo laboratory (Lyon, France), 2) Ordinary conventional animals from the same laboratory, contained in standard conditions of vivarium microbial environment (control group). Animals from each group were subdivided into 2 aged categories (15 in each group): mature (8-12 month, 200,0 - 250,0 g) and aged (I period of old age 24-32 month; 300,0-450 g.) animals. Histological, electron-microscopic and morphmetric methods of studies were used. Correlations between morphological peculiarities and cellular composition of the rat's lymphoid tissue with antigenic load and age were determined. Namely, gnotobiont rat's lymphoid tissue contains less mature population, hence inactive lymphoid cells compared with conventional animals. However, with age this processes in both animal groups acquire a similar orientation.


Differential capacitance of the electric double layer: the interplay between ion finite size and dielectric decrement.
We study the electric double layer by combining the effects of ion finite size and dielectric decrement. At high surface potential, both mechanisms can cause saturation of the counter-ion concentration near a charged surface. The modified Grahame equation and differential capacitance are derived analytically for a general expression of a permittivity ε(n) that depends on the local ion concentration, n, and under the assumption that the co-ions are fully depleted from the surface. The concentration at counter-ion saturation is found for any ε(n), and a criterion predicting which of the two mechanisms (steric vs. dielectric decrement) is the dominant one is obtained. At low salinity, the differential capacitance as function of surface potential has two peaks (so-called camel-shape). Each of these two peaks is connected to a saturation of counter-ion concentration caused either by dielectric decrement or by their finite size. Because these effects depend mainly on the counter-ion concentration at the surface proximity, for opposite surface-potential polarity either the cations or anions play the role of counter-ions, resulting in an asymmetric camel-shape. At high salinity, we obtain and analyze the crossover in the differential capacitance from a double-peak shape to a uni-modal one. Finally, several nonlinear models of the permittivity decrement are considered, and we predict that the concentration at dielectrophoretic saturation shifts to higher concentration than those obtained by the linear decrement model.


Comparative effectiveness and impact on health-related quality of life of hysterectomy vs. levonorgestrel intra-uterine system for abnormal uterine bleeding.
To compare hysterectomy and levonorgestrel intra-uterine system (LNG-IUS) for the treatment of abnormal uterine bleeding (AUB) and iron deficiency anemia. Retrospective study evaluating quality of life, sexual function, satisfaction and blood hemoglobin concentration improvement in 60 pre-menopausal women treated with hysterectomy or LNG-IUS. All analysis was performed with statistical software SPSS 21.0 (SPSS Inc., Chicago, IL, USA). Despite superior control of bleeding and dysmenorrhea observed after hysterectomy, LNG-IUS showed similar impact on blood hemoglobin levels, quality of life, satisfaction and sexual function resulting more cost-effective. In the absence of contraindications, LNG-IUS should always be the first therapeutic choice for chronic AUB. Surgical treatment must be considered as an "extrema ratio".


[Detection and early treatment of subjects at high risk of clinical psychosis: Definitions and recommendations].
In children and adolescents, psychotic disorders already represent one of the leading causes of disability-adjusted life years. During the past two decades, early detection of risk for psychosis has been intensively investigated, and in particular, predictive power for early signs of risk has been initiated and translated into clinical practice. In particular, the attenuated and transient positive symptoms of the ultra-high risk criteria, and the basic symptom criterion "cognitive disturbances", open promising routes to an indicated prevention and have recently been considered by the European Psychiatric Association (EPA) as diagnostic criteria of a psychosis-risk syndrome. The EPA recently provided evidence-based recommendations on the early detection of clinical high risk (CHR) for psychosis in patients with mental distress. In 2015, experts in the field of early detection conducted a meta-analysis reporting on studies examining conversion rates to psychosis in non-overlapping samples meeting at least one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria, examining the effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates. In the 42 identified samples, comprising more than 4000 CHR patients who had been mainly identified by means of UHR criteria and/or the basic symptom criterion 'cognitive disturbances' (COGDIS), conversion rates showed considerable heterogeneity. While UHR and COGDIS criteria were related to comparable conversion rates until a 2-year follow-up, rates for COGDIS were significantly higher for follow-up periods beyond 2 years. Differences in onset and frequency requirements of symptomatic UHR criteria, or in their different consideration of functional decline, substance use and co-morbidity, did not seem to have an impact on conversion rates. The 'genetic risk and functional decline' UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for the early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states. The EPA guidance on early intervention aimed to provide evidence-based recommendations on early intervention in CHR states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were also made by experts in the field of early intervention in psychoses and derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. In addition to analyses of treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status. Overall, age-related specificities and developmental transitions in the early detection and intervention in psychoses should be better accounted for in future research.


Readmission to medical intensive care units: risk factors and prediction.
The objectives of this study were to find factors related to medical intensive care unit (ICU) readmission and to develop a prediction index for determining patients who are likely to be readmitted to medical ICUs. We performed a retrospective cohort study of 343 consecutive patients who were admitted to the medical ICU of a single medical center from January 1, 2008 to December 31, 2012. We analyzed a broad range of patients' characteristics on the day of admission, extubation, and discharge from the ICU. Of the 343 patients discharged from the ICU alive, 33 (9.6%) were readmitted to the ICU unexpectedly. Using logistic regression analysis, the verified factors associated with increased risk of ICU readmission were male sex [odds ratio (OR) 3.17, 95% confidence interval (CI) 1.29-8.48], history of diabetes mellitus (OR 3.03, 95% CI 1.29-7.09), application of continuous renal replacement therapy during ICU stay (OR 2.78, 95% CI 0.85-9.09), white blood cell count on the day of extubation (OR 1.13, 95% CI 1.07-1.21), and heart rate just before ICU discharge (OR 1.03, 95% CI 1.01-1.06). We established a prediction index for ICU readmission using the five verified risk factors (area under the curve, 0.76, 95% CI 0.66-0.86). By using specific risk factors associated with increased readmission to the ICU, a numerical index could be established as an estimation tool to predict the risk of ICU readmission.


Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.
Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid.


Optimizing antibody affinity and stability by the automated design of the variable light-heavy chain interfaces.
Antibodies developed for research and clinical applications may exhibit suboptimal stability, expressibility, or affinity. Existing optimization strategies focus on surface mutations, whereas natural affinity maturation also introduces mutations in the antibody core, simultaneously improving stability and affinity. To systematically map the mutational tolerance of an antibody variable fragment (Fv), we performed yeast display and applied deep mutational scanning to an anti-lysozyme antibody and found that many of the affinity-enhancing mutations clustered at the variable light-heavy chain interface, within the antibody core. Rosetta design combined enhancing mutations, yielding a variant with tenfold higher affinity and substantially improved stability. To make this approach broadly accessible, we developed AbLIFT, an automated web server that designs multipoint core mutations to improve contacts between specific Fv light and heavy chains (http://AbLIFT.weizmann.ac.il). We applied AbLIFT to two unrelated antibodies targeting the human antigens VEGF and QSOX1. Strikingly, the designs improved stability, affinity, and expression yields. The results provide proof-of-principle for bypassing laborious cycles of antibody engineering through automated computational affinity and stability design.


Augmented Reality Holographic Visualization System for Surgery Auxiliary Visualization: Proof of Concept for Surgical Training.
An Augmented Reality (AR) system based on the holographic projection of the relevant anatomic structures is proposed for auxiliary visualization during surgeries. The current two-dimensional visualization systems require the surgeons to mentally extract the associated three-dimensional information during the interventions, which entails risks and complications. This work shows an AR holographic projection system for real-time three-dimensional representation of the relevant surgical information, thus overcoming this problem. As an initial proof of concept, the system is experimentally assessed as potential surgery training tool.Clinical Relevance- This work explores the potential of AR holographic projection systems for intraoperative assistance to the surgical team, starting from its possible use as surgery training and planning tool.


[Initial phase of the left ventricular ejection (mesosystole) in coronary artery disease].
In patients with coronary artery disease (CAD), the ventricular ejection is altered specially the initial phase or the mid-systole. We studied such abnormalities through two-dimensional echocardiography and phonocardiography. We studied 40 patients with CAD and 11 normal subjects, we determined the times and volumes of total, initial and end of systole for to calculate the ejection fraction, integrated ejection and mean ejection rate. The measurements of total systole did not show important differences. In contrast, the initial ejection time (IET), the initial integrated ejection (IIE), the mid-systolic stroke volume (MSV), the mid-systolic ejection fraction (MEF) and the mean mid-systolic ejection rate (MMER) showed significant differences. The CAD group compared with normal subjects, had lower values of IET (P less than 0.05), MSV and MEF (P less than 0.01). The presence of myocardial infarction, the number of arteries with significant obstruction and the elevation of the left ventricular enddiastolic pressure had relationship with decrease in IIE (P less than 0.01) and with amount of MSV, MMER and MSV/end systolic stroke volume ratio (P less than 0.01). On the other hand, patients with angina, specially unstable and in those with ventricular aneurysm, the IIE showed higher values (P less than 0.01) and MSV, MMER, the percentage of mid-systolic ejection fraction and MSV/ESV ratio were lower (P less than 0.01). We conclude that in CAD, the mid-systolic changes are more sensitive than those of the whole systole. In presence of heart failure, the reduced stroke volume is ejected almost totally in the initial period or mid-systole. In patients with ventricular aneurysm or in those with unstable angina is the opposite behavior, the mid-systolic ejection is reduced and the small volume is ejected in the end last period or end systole. These observations could be useful to recognize the damage and the severity of it in CAD.


An unexpected complication of hypoglossal schwannoma surgery: Cerebrospinal fluid leakage-A case report and literature review.
Extracranial hypoglossal schwannoma is a rare tumor primarily treated with surgical excision. This article aims to highlight the potential for unexpected complications intraoperatively, such as cerebrospinal fluid leakage from skullbase to neck. A previously healthy 23-year-old male presented with tongue numbness. Magnetic resonance imaging revealed a 17 × 20 mm nodular lesion adjacent to the cervical segment of the internal carotid artery. Surgical excision was scheduled due to suspicion of a neurogenic tumor. Intraoperatively, despite careful handling, cerebrospinal fluid leakage was observed. Manipulation of the mass caused detachment of proximal nerve fibers, potentially indicating avulsion of the hypoglossal nerve from the brainstem or nearby. Clear fluid leakage from the skull base was also noted. Thorough preoperative evaluation and patient education regarding potential complications are crucial. This article presents an unexpected complication encountered during surgical excision of extracranial hypoglossal schwannoma, emphasizing the need for awareness and preparedness in such cases.


Vaccines against Theileria parva.
Bovine theileriosis caused by Theileria parva continues to be a major economic problem in many parts of Eastern, Southern, and Central Africa. Due to the unsustainable nature of the present control method--using toxic acaricides to kill ticks--alternative control methods are being sought. Live vaccines are being used in many countries in the region. These vaccines are based on the infective sporozoite stage of the parasite. Sporozoites are inoculated in cattle with simultaneous administration of a long-acting formulation of oxytetracycline. These vaccines are poorly adopted in the region, mainly because of problems associated with the use of live parasites. An experimental recombinant vaccine based on a sporozoite surface antigen (p67) has been developed. Immunization with this antigen induces neutralizing antibodies and, under laboratory conditions, this technique protects approximately 70% of the immunized cattle to a defined needle challenge. The efficacy of the vaccine is currently being evaluated under field challenge in Kenya. Since a vaccine based on a single antigen may not be sustainable under field conditions, a search for schizont antigens that induce protective cell-mediated immune responses continues. It is expected that the ultimate vaccine against theileriosis will incorporate a mixture of several antigens derived from both sporozoite and schizont stages, contributing to robust immunity.


Mucoepidermoid carcinoma of the penis: Case report and literature review.
We describe the fifth case of mucoepidermoid carcinoma. The patient had penile ulcer with bilateral inguinal and pelvic lymphadenopathy and underwent total penectomy. After antibiotic therapy, the patient began outpatient chemotherapy, but the treatment was discontinued due to his intolerance. The patient died due to infectious complications of the inguinal lymphatic fistula 7 months after the histological diagnosis. Notably, the periurethral area was involved in the anatomopathological evaluation of the excised penis. The penile mucoepidermoid carcinoma was aggressive and the perimeatal region was involved. This case helps demystify the origins and prognosis of this rare case. More reports documenting patient characteristics and their evolution with penile mucoepidermoid carcinoma are needed.


Synaptic and extrasynaptic location of the receptor tyrosine kinase met during postnatal development in the mouse neocortex and hippocampus.
MET, a replicated autism risk gene, encodes a pleiotropic receptor tyrosine kinase implicated in multiple cellular processes during development and following injury. Previous studies suggest that Met modulates excitatory synapse development in the neocortex and hippocampus, although the underlying mechanism is unknown. The peak of Met expression corresponds to the period of process outgrowth and synaptogenesis, with robust expression in hippocampal and neocortical neuropil. Resolving whether neuropil expression represents presynaptic, postsynaptic or glial localization provides insight into potential mechanisms of Met action. The subcellular distribution of Met was characterized using complementary ultrastructural, in situ proximity ligation assay (PLA), and biochemical approaches. At postnatal day (P) 7, immunoelectron microscopy revealed near-equivalent proportions of Met-immunoreactive pre- (axons and terminals) and postsynaptic (dendritic shafts and spines) profiles in the stratum radiatum in the hippocampal CA1 region. Staining was typically in elements in which the corresponding pre- or postsynaptic apposition was unlabeled. By P21, Met-immunoreactive presynaptic profiles predominated and ~20% of Met-expressing profiles were glial. A different distribution of Met-immunoreactive profiles was observed in layer V of somatosensory cortex: Met-labeled spines were rare and a smaller proportion of glial profiles expressed Met. Strikingly, Met-immunoreactive presynaptic profiles predominated over postsynaptic profiles as early as P7. PLA analysis of neurons in vitro and biochemical analysis of tissue subsynaptic fractions confirmed the localization of Met in specific synaptic subcompartments. The study demonstrates that Met is enriched at synapses during development and its activation may modulate synapse formation and stability through both pre- and postsynaptic mechanisms.


Cellular and Morphological Alterations in the Vastus Lateralis Muscle as the Result of ACL Injury and Reconstruction.
Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation. We performed diffusion tensor imaging-magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine fiber type and size, Pax-7-positive (satellite) cells, and extracellular matrix (via wheat germ agglutinin straining). Using the diffusion tensor imaging data, the fiber tract length, pennation angle, and muscle volume were determined, yielding the physiological cross-sectional area (PCSA). Paired t tests were used to compare the effects of the injury between injured and uninjured limbs and the effects of surgery and rehabilitation within the injured limb. We found significant reductions before surgery in type-IIA muscle cross-sectional area (CSA; p = 0.03), extracellular matrix (p < 0.01), satellite cells per fiber (p < 0.01), pennation angle (p = 0.03), muscle volume (p = 0.02), and PCSA (p = 0.03) in the injured limb compared with the uninjured limb. Following surgery, these alterations in the injured limb persisted and the frequency of the IIA fiber type decreased significantly (p < 0.01) and that of the IIA/X hybrid fiber type increased significantly (p < 0.01). Significant and prolonged differences in muscle quality and morphology occurred after ACL injury and persisted despite reconstruction and extensive physical therapy. These results suggest the need to develop more effective early interventions following an ACL tear to prevent deleterious alterations within the quadriceps.


Temporal properties of the short-range process in apparent motion.
A study is reported of the perception of random-dot two-frame apparent motion in which the durations of each exposure and the interstimulus interval between them were varied. The results are largely consistent with the rule that, for optimal motion detection, a portion of each exposure must fall within the same time interval of about 40 ms. In addition, motion perception is separably dependent on the displacement from one exposure to the next and on the time interval between those exposures, rather than on the 'velocity' implied by their ratio.


μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges.
Opioid misuse and opioid-involved overdose deaths are a massive public health problem involving the intertwined misuse of prescription opioids for pain management with the emergence of extremely potent fentanyl derivatives, sold as standalone products or adulterants in counterfeit prescription opioids or heroin. The incidence of repeated opioid overdose events indicates a problematic use pattern consistent with the development of the medical condition of opioid use disorder (OUD). Prescription and illicit opioids reduce pain perception by activating µ-opioid receptors (MOR) localized to the central nervous system (CNS). Dysregulation of meso-corticolimbic circuitry that subserves reward and adaptive behaviors is fundamentally involved in the progressive behavioral changes that promote and are consequent to OUD. Although opioid-induced analgesia and the rewarding effects of abused opioids are primarily mediated through MOR activation, serotonin (5-HT) is an important contributor to the pharmacology of opioid abused drugs (including heroin and prescription opioids) and OUD. There is a recent resurgence of interest into psychedelic compounds that act primarily through the 5-HT2A receptor (5-HT 2A R) as a new frontier in combatting such diseases (e.g., depression, anxiety, and substance use disorders). Emerging data suggest that the MOR and 5-HT2AR crosstalk at the cellular level and within key nodes of OUD circuitry, highlighting a major opportunity for novel pharmacological intervention for OUD. There is an important gap in the preclinical profiling of psychedelic 5-HT2AR agonists in OUD models. Further, as these molecules carry risks, additional analyses of the profiles of non-hallucinogenic 5-HT2AR agonists and/or 5-HT2AR positive allosteric modulators may provide a new pathway for 5-HT2AR therapeutics. In this review, we discuss the opportunities and challenges associated with utilizing 5-HT2AR agonists as therapeutics for OUD.


Oxidative stress and neutrophil function in cats with chronic renal failure.
Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. Twenty cats with previously diagnosed renal failure were compared with 10 age-matched control cats. A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2-tailed t-test) were reported as mean +/- standard deviation. The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 +/- 197, 61.7 +/- 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 +/- 0.21, 0.81 +/- 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 +/- 253, 524 +/- 54; P < .05). The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF.


Effect of aprindine, verapamil and nifedipine on ventricular fibrillation threshold in isolated rabbit hearts.
The effect of aprindine, verapamil and nifedipine on electrical stimulation threshold (EST) and ventricular fibrillation threshold (VFT) was studied in isolated rabbit hearts. Aprindine steeply raised EST and VFT in a dose-dependent manner. With the highest concentration of aprindine tested (0.56 mumol/l), protection against electrically-induced ventricular fibrillation was achieved in 4 out of 6 hearts after 60 min exposure to the drug. Perfusion with verapamil (0.1 and 0.2 mumol/l) and nifedipine (0.14 and 0.21 mumol/l) produced significant rise in both thresholds. When the hearts were perfused with higher concentration (0.3 mumol/l verapamil, 0.28 mumol/l nifedipine), EST and VFT did not continue to be increased in a dose-dependent manner but actually dropped below the control value in most hearts. These results suggest that the effect of aprindine on EST and VFT is different from that of verapamil and nifedipine and further indicate a limited effectiveness of these two slow channel blockers against ventricular fibrillation.


Physiologic changes associated with cerebellar dystonia.
Dystonia is a neurologic disorder characterized by sustained involuntary muscle contractions. Lesions responsible for unilateral secondary dystonia are confined to the putamen, caudate, globus pallidus, and thalamus. Dysfunction of these structures is suspected to play a role in both primary and secondary dystonia. Recent evidence has suggested that the cerebellum may play a role in the pathophysiology of dystonia. The role of the cerebellum in ataxia, a disorder of motor incoordination is well established. How may the cerebellum contribute to two apparently very different movement disorders? This review will discuss the idea of whether in some cases, ataxia and dystonia lie in the same clinical spectrum and whether graded perturbations in cerebellar function may explain a similar causative role for the cerebellum in these two different motor disorders. The review also proposes a model for cerebellar dystonia based on the available animal models of this disorder.


Autologous blood transfusions in children and young adults with low body weight undergoing spinal surgery.
The perioperative course of 118 patients weighing less than 45.5 kg (100.1 pounds) who participated in a predeposited autologous blood program from 1979-1984 is reviewed. Average age was 13 years 11 months (range 6 years 4 months to 20 years 4 months) and the average weight, 41 kg (range 30-45.4 kg). All underwent spinal surgery, 96% for scoliosis. The program involved preoperative donation of blood that was stored and subsequently retransfused to replace operative blood losses. Patients donated an average of 811 ml (range 208-1,320 ml) blood. Operation and hospitalization were completed by 63% without receiving any homologous blood, and the need for donor blood was reduced in the remaining 37%. Preoperative blood donation and retransfusion led to no significant complications. We describe an autologous blood transfusion program and show that autotransfusion is a safe and preferred method of blood replacement for children and young adults with low body weight undergoing elective surgery.


[Higher cortisol levels in frequently ill children as a factor increasing susceptibility to acute respiratory infections].
The authors have defined some specific features of performance of the immune and lipid-transporting systems in their association with serum cortisol levels in frequently ill children when the signs of an infectious process are absent. The possible links of a pathological process, which give rise to enhanced susceptibility to acute respiratory infections in this patient group, are described.


Histopathologic effects of meconium on human umbilical artery and vein: in vitro study.
To determine the histopathologic effects of meconium on human umbilical artery and vein. Umbilical cords from six patients with uncomplicated, singleton, term gestations were obtained immediately after delivery. One centimeter segments from each cord were flushed, isolated, placed in either modified Krebs solution alone or modified Krebs solution with various concentrations (1%, 10%, or 25%) of fresh meconium, and then incubated at pH 7.2, temperature 37 degrees C, PCO2 50-55 mmHg, PO2 40-45 mmHg for 1, 6, 12, or 24 h. The specimens were then fixed, stained, and examined under light microscopy. Umbilical arteries exhibited focal vacuolation of the endothelium after exposure of the cord to meconium. Umbilical veins revealed: 1) endothelial loss proportionate to the meconium concentration at all intervals (P < 0.05), 2) increased density or focal absence of the internal elastic lamina, and 3) focal loss of myocyte nuclei. Rare nonpigmented macrophages and increased mast cells were identified in the Wharton's jelly. Exposure to meconium in vitro results in histopathologic changes in the umbilical artery and vein.


Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion.
Desmosomes are unique intercellular junctions in that they invariably contain two types of transmembrane cadherin molecule, desmocollins and desmogleins. In addition they possess a distinct cytoplasmic plaque structure containing a few major proteins including desmoplakins and the armadillo family member plakoglobin. Desmosomal cadherins are putative cell-cell adhesion molecules and we have tested their adhesive capacity using a transfection approach in mouse L cells. We find that L cells expressing either one or both of the desmosomal cadherins desmocollin 2a or desmoglein 1 display weak cell-cell adhesion activity that is Ca2+-dependent. Both homophilic and heterophilic adhesion could be detected. However, co-expression of plakoglobin with both desmosomal cadherins, but not with desmoglein 1 alone, resulted in a dramatic potentiation of cell-cell aggregation and the accumulation of detergent-insoluble desmosomal proteins at points of cell-cell contact. The effect of plakoglobin seems to be due directly to its interaction with the desmosomal cadherins rather than to its signalling function. The data suggest that the desmosome may obligatorily contain two cadherins and is consistent with a model in which desmocollins and desmogleins may form side by side heterodimers in contrast to the classical cadherins that are homodimeric. Plakoglobin may function by potentiating dimer formation, accretion of dimers to cell-cell contact sites or desmosomal cadherin stability.


[How to optimize lipid-lowering therapy: do not forget patient's non-compliance].
The pharmacological treatment of dyslipidaemia, essentially by statins, should take place in a global strategy of prevention of cardiovascular diseases. Treating a risk factor, asymptomatic by definition, which imposes an early constraint for a potential late benefit, exposes to patient's noncompliance. Besides physician's clinical inertia to initiate and adjust the lipid-lowering therapy in at risk patients, such lack of patient's compliance is one of the key elements that may explain the failure to reach or maintain therapeutic targets, and represents a major pharmacoeconomical concern. This article analyses first the main reasons explaining the poor compliance to lipid-lowering therapy and, then, describes some approaches to improve patient's adherence to medications in order to better prevent cardiovascular diseases.


RepExplore: addressing technical replicate variance in proteomics and metabolomics data analysis.
High-throughput omics datasets often contain technical replicates included to account for technical sources of noise in the measurement process. Although summarizing these replicate measurements by using robust averages may help to reduce the influence of noise on downstream data analysis, the information on the variance across the replicate measurements is lost in the averaging process and therefore typically disregarded in subsequent statistical analyses.We introduce RepExplore, a web-service dedicated to exploit the information captured in the technical replicate variance to provide more reliable and informative differential expression and abundance statistics for omics datasets. The software builds on previously published statistical methods, which have been applied successfully to biomedical omics data but are difficult to use without prior experience in programming or scripting. RepExplore facilitates the analysis by providing a fully automated data processing and interactive ranking tables, whisker plot, heat map and principal component analysis visualizations to interpret omics data and derived statistics. Freely available at http://www.repexplore.tk email@example.com Supplementary data are available at Bioinformatics online.


Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis.
To investigate the impact of smoking on the response to treatment with a first tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) in a real-life cohort. Patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA in the Swiss Clinical Quality Management Cohort were included in this study. The potential association between smoking status and differential response to TNFi in terms of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) was analysed using multiple adjusted longitudinal mixed effect models. Binary response rates at 1 year were assessed with multiple adjusted logistic analyses. A first TNFi was initiated in 698 patients with axSpA with available smoking status and a baseline or follow-up BASDAI assessment, of which 490 (70%) had complete covariate data. In comparison to non-smokers, current smokers demonstrated significantly smaller reductions in BASDAI and ASDAS scores upon treatment with TNFi (0.75 BASDAI units and 0.69 ASDAS units less, p=0.005 and 0.001, respectively) for patients with elevated baseline C-reactive protein (CRP) level. This effect was numerically smaller in patients with normal CRP. The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after 1 year were significantly lower in current smokers than in non-smokers (0.54, 95% CI 0.31 to 0.95, p=0.03 and 0.43, 95% CI 0.24 to 0.76, p=0.004, respectively). Current smoking is associated with an impaired response to TNFi in axSpA.


Kinetics of the Ca(2+)-activated K+ channel in rat hippocampal neurons.
The kinetics of the large-conductance Ca(2+)-activated K+ channel (235 pS in symmetrical 150 mM K+) were examined in the inside-out mode of the patch clamp technique. The open probability of the channel increased when [Ca2+]i, [Sr2+]i, or [Ba2+]i was increased. The [Ca2+]i-response relation was fitted with a Hill coefficient of 2 and half-maximum concentrations of 185, 80, 14.5, and 5.5 microM at -40, -20, +20, and +40 mV, respectively. The channel was blocked by TEA or Ba2+. The open-time histogram showed a single exponential component and the closed-time histogram showed at least two exponential components at various [Ca2+]i. Increasing [Ca2+]i decreased the time constant of the slow component of the closed-time histogram. Cell-attached patch recording revealed activation of the large-conductance Ca(2+)-activated K+ channel (BK channel) during the action potential. The deactivation time course was consistent with the fast after-hyperpolarization. A minimum model of the channel, close(2)-close(1)-open, where the transition from close(2) to close(1) requires the binding of 2 Ca2+, reconstructed quick activation of the channel if [Ca2+]i of 40 microM was assumed.


[The rumen fermenter].
The two main pregastric compartments of ruminants (rumen and reticulum) can be compared to an anaerobic fermenter which allows them to use energetic and nitrogen substrates which are indigestible by monogastric animals. The aim of this bibliographic review is to describe the main features (characteristics) of this fermenter, focusing on the role of microbes (bacteria, protozoa and fungi), on the degradation of cell-wall carbohydrates (cellulose, hemicelluloses, pectic substances), on nitrogen digestion and finally on the utilisation of the major minerals and trace elements.


Effect of Phellius linteus water extract on benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is one of the most common diseases among elderly men. As the old-age population is increasing recently, it is to our interest to observe the growing BPH within them. In BPH, the dihydrotestosterone (DHT) acts as promotes prostate growth. It inhibits enzyme 5α-reductase that is involved in the conversion of testosterone to the DHT activity which reduces the excessive prostate growth. Through experiments, the effects of Phellius linteus water extract performed on the BPH rats were induced by testosterone treatments. For 12 weeks, Sprague-Dawley rats were treated with testosterone for the induction of BPH. Rats were divided into four experimental groups: the not treated group (N), the testosterone injection and D.W treatment group (TN), the testosterone injection and Phellinus linteus treatment group (TP) and testosterone injection and finasteride treatment group (TF). Prostate weight, volume and weight ratio in the TP group and the TF group were significantly lower than the TN group. Testosterone and DHT levels in the TN group were significantly higher than that of the N group. And the TP group was significantly decreased than that of the TN group. While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation; the TP and TF groups showed trophic symptoms and were lined by flattened epithelial cells, thus, the stromal proliferation is relatively low as compared to the TN group. These suggest that Phellinus linteus water extracts may be an useful remedy for treating the benign prostatic hyperplasia.


A multicellular model for differential regulation of circadian signals in the core and shell regions of the suprachiasmatic nucleus.
We developed a multicellular model of the mammalian circadian clock characterized by a high degree of heterogeneity with respect to single cell periodicity and behavior (intrinsic and driven oscillators), neurotransmitter release (VIP, GABA and glutamate synthesis) and spatial organization (core and shell regions), mimicking structural patterns within the suprachiasmatic nucleus (SCN) associated with distinct circadian functions. We simulated the SCN core and shell separately utilizing experimentally derived connectivity schemes for the two subdivisions as observed within the rat SCN. The core was modeled via a small world network characterized by VIP and GABA co-localization, whereas the shell was simulated as a nearest neighbor network promoting local GABAergic connections. To study the function of the axonal plexus extending from the densely innervated ventrolateral region to distal areas across the dorsomedial SCN, directed long range links from the core to the shell were gradually introduced via a probability p(cs) that ranged from 0 to 1. A probability value of 0 excluded core-shell interactions, whereas p(cs)=1 achieved maximal connectivity between the two regions. Our model exhibited a threshold in the number of core-to-shell links required for sufficient cell-to-cell coordination to maintain periodicity and rhythmic behavior across the entire model network (including both shell and core populations) in constant darkness as well as 12:12h light-dark cycles. By contrast, constant light was shown to increase phase synchronization across the shell while core populations remained poorly synchronized, suggesting differential light response across the two SCN compartments. We further simulated increasing percentages of intrinsic oscillators and demonstrated a negative correlation between the number of intrinsic oscillators distributed across the SCN and the ability of the system to produce synchronized signals. Simulations that differed with respect to the placement of intrinsic oscillators supported the hypothesis that improved synchronization is achieved with networks characterized by localized intrinsic oscillators placed exclusively within the shell versus networks containing uniformly distributed intrinsic oscillators in both SCN compartments. This study has successfully reproduced a number of spatiotemporal and behavioral attributes of the SCN, providing a useful computational tool to correlate observed circadian phenotypes with distinct chemoarchitectural properties of spatially localized neural populations.


Conformational Plasticity of HLA-B27 Molecules Correlates Inversely With Efficiency of Negative T Cell Selection.
The development of autoimmune disorders is incompletely understood. Inefficient thymic T cell selection against self-peptides presented by major histocompatibility antigens (HLA in humans) may contribute to the emergence of auto-reactive effector cells, and molecular mimicry between foreign and self-peptides could promote T cell cross-reactivity. A pair of class I subtypes, HLA-B2705 and HLA-B2709, have previously been intensely studied, because they are distinguished from each other only by a single amino acid exchange at the floor of the peptide-binding groove, yet are differentially associated with the autoinflammatory disorder ankylosing spondylitis. Using X-ray crystallography in combination with ensemble refinement, we find that the non-disease-associated subtype HLA-B2709, when presenting the self-peptide pGR (RRRWHRWRL), exhibits elevated conformational dynamics, and the complex can also be recognized by T cells. Both features are not observed in case of the sequence-related self-peptide pVIPR (RRKWRRWHL) in complex with this subtype, and T cell cross-reactivity between pGR, pVIPR, and the viral peptide pLMP2 (RRRWRRLTV) is only rarely observed. The disease-associated subtype HLA-B2705, however, exhibits extensive conformational flexibility in case of the three complexes, all of which are also recognized by frequently occurring cross-reactive T cells. A comparison of the structural and dynamic properties of the six HLA-B27 complexes, together with their individual ability to interact with T cells, permits us to correlate the flexibility of HLA-B27 complexes with effector cell reactivity. The results suggest the existence of an inverse relationship between conformational plasticity of peptide-HLA-B27 complexes and the efficiency of negative selection of self-reactive cells within the thymus.


Primary structure of the Escherichia coli thyA gene and its thymidylate synthase product.
The nucleotide sequence of a 1,163-base-pair fragment that encodes the entire thyA gene of Escherichia coli K-12 was determined. The strategy involved sequence determination of both DNA strands by using overlapping deletions that had been generated in vitro from the two ends of the fragment with BAL-31 nuclease. The amino-terminal sequence of thymidylate synthase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 18.104.22.168), the product of the thyA gene, located the 792-base-pair open reading frame, which codes for the 264 amino acid residues of this enzyme. The amino acid sequence deduced from the nucleotide data was confirmed to the extent of 40% by partial sequence analysis of the enzyme purified from extracts of the amplified cloned gene. Transcriptional and translational control areas were apparent in the regions flanking the structural gene. The 5-fluorodeoxyuridylate-binding residue of the active site was identified as cysteine-146. Comparison of the E. coli and Lactobacillus casei synthase sequences reveals consistent homology (62%) over extensive regions. This homology is particularly striking in a very hydrophobic region bordering cysteine-146. In the two enzymes, this region, which probably defines the active site, is 82% homologous. However, a dramatic difference between the two sequences is reflected by the surprising finding that a 51-amino-acid stretch, present midway through the L. casei sequence, is completely absent from the E. coli enzyme.


Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer patients.
Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3' untranslated region (UTR) 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407). Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL) compared to the control group (median 10.1 U/mL, P<0.001). The area under the receiver operating characteristic curve (AU-ROC) values of sHLA-G for differentiating breast cancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.


P53, apoptosis, and breast cancer.
Wild-type p53 is a tumor suppressor gene that plays a central role in maintaining the genetic integrity of the cell by preventing cells with damaged DNA from further proliferation. Mutation and deletion of p53 are the most common genetic defects seen in clinical cancer. About 40% of breast carcinomas show high levels of stabilized, often mutant, p53 protein in their cells as detected by immunohistochemistry. p53-related defects in tumor cells correlate with a poor prognosis and may also indicate a poor response to chemotherapy. In experimental systems, the p53 status of cells is important in determining their sensitivity to radiation and chemotherapeutic drugs. Cells with functional p53 die by apoptosis, whilst similar cells lacking p53 function continue to proliferate, perpetuating potentially oncogenic mutations. Not only may p53 status be a marker of the biological aggressiveness of individual tumors and of their likely response to therapy, but restoration of normal p53 function is itself already a goal of cancer therapy.


(E)-9-(But-2-en-1-yl)-6-chloro-9H-purine.
The asymmetric unit of the title compound, C9H9ClN4, contains two mol-ecules. In the crystal, the mol-ecules are ordered in a chain-like fashion along the a axis, and form layers offset relative to the C plane by approximately 30°. This ordering does not, however, appear to be directed by classical hydrogen bonding.The allylic side chains of both independent mol-ecules are disordered, with occupancies of 0.870 (4) and 0.934 (3) for the major components. The disorder components represent two possible spatial orientations of the atoms around the C=C double bond.


Transient hyperglycosylation of rhodopsin with galactose.
Rhodopsin's oligosaccharide chains contain predominantly two types of sugar residues: mannose and N-acetylglucosamine. In the present work, bovine and rat rhodopsin were analysed biochemically for the presence of a third sugar, galactose. Treatment of bovine rod outer segments (ROS) with galactose oxidase followed by reduction with tritium-labeled sodium borohydride revealed the presence of existing molecules of galactose on rhodopsin. Rats injected intravitreally with [3H]galactose and [14C]leucine and maintained in darkness were killed 1 hr, 6 hr, 1, 3 or 5 days following the injection. Retinas were collected for subcellular fractionation and rhodopsin from each of the fractions was purified by ConA sepharose chromatography and SDS-PAGE. During the first 6 hr, galactose selectively labeled rhodopsin in the Golgi-enriched fraction resulting in increased [3H]/[14C] ratios in both Golgi and ROS. The data suggested that trimming was occurring at the transition from Golgi to ROS. Furthermore, a decrease in isotope ratio in the ROS between 6 hr and 1 day suggested further trimming of rhodopsin after membrane assembly in the ROS. Additional in vivo experiments demonstrated existing molecules of galactose on rhodopsin's oligosaccharide chain using lectin affinity chromatography. Rats injected intravitreally with [35S]methionine were dark-adapted for 2 hr. Following subcellular fractionation of retinas, ConA purified rhodopsin from ROS was applied to one of two additional lectin columns: Ricinus communis agglutinin (RCA) or Griffonia simplicifolia I (GSA). Eight to nine percent of the labeled rhodopsin was bound to and eluted from RCA, whereas none bound to GSA, indicating the presence of a beta-galactoside. The RCA agarose eluted protein co-electrophoresed with a rhodopsin standard and was light sensitive. Galactose was shown to be the terminal sugar on this subset of rhodopsin and was not capped by neuraminic acid. Binding of rhodopsin's oligosaccharide to RCA was abolished by pre-treatment with beta-galactosidase. Decreased binding of rhodopsin to RCA was observed following intravitreal injection of castanospermine but not swainsonine. Of those two inhibitors of glycoprotein trimming, only castanospermine would be expected to prevent the addition of galactose to the oligosaccharide. The association of galactose with rat rhodopsin appeared to be a transient one. At 2 hr, 8-9% of rhodopsin contained galactose, at 6 hr only 2.2% had galactose and by 24 hr less than 1% did. The galactose was trimmed from rhodopsin's oligosaccharide presumably after its role was complete. Separation of rhodopsin of the plasma membranes from rhodopsin of discs indicated that 75% of the galactose-containing rhodopsin was in the plasma membrane and only 25% was in the discs. These findings suggested a possible role for galactose in new disc formation with subsequent removal after the discs are sealed.


Coordination chemistry of silanedithiolato ligands derived from cyclotrisilathiane: synthesis and structures of complexes of iron(II), cobalt(II), palladium(II), copper(I), and silver(I).
The coordination chemistry of chelating silanedithiolato ligands has been investigated on Fe(II), Co(II), Pd(II), Cu(I), and Ag(I). Treatment of M(OAc)(2) (M = Fe, Co, Pd) with cyclotrisilathiane (SSiMe(2))(3) in the presence of Lewis bases resulted in formation of Fe(S(2)SiMe(2))(PMDETA) (1), Fe(S(2)SiMe(2))(Me(3)TACN) (2), Co(S(2)SiMe(2))(PMDETA) (3), and Pd(S(2)SiMe(2))(PEt(3))(2) (4) (PMDETA = N,N,N',N',N' '-pentamethyldiethylenetriamine; Me(3)TACN = 1,4,7-trimethyl-1,4,7-triazacyclononane). The analogous reactions of M(OAc) (M = Cu, Ag) in the presence of PEt(3) gave rise to the dinuclear complexes M(2)[(SSiMe(2))(2)S](PEt(3))(3) [M = Cu (5), Ag (6)]. Complexes were characterized in solution by (1)H, (31)P[(1)H], and (29)Si[(1)H] NMR and in the solid state by single-crystal X-ray diffraction. Mononuclear complexes 1-3 have a four-membered MS(2)Si ring, and these five-coordinate complexes adopt trigonal-bipyramidal (for the PMDETA adducts) or square-pyramidal (for the Me(3)TACN adduct) geometries. In dimer 6, the (SSiMe(2))(2)S(2)(-) silanedithiolato ligand bridges two metal centers, one of which is three-coordinate and the other four-coordinate. The chelating effect of silanedithiolato ligands leads to an increase in the stability of silylated thiolato complexes.


[The prenatal development of nephrological abnormalities detected during pregnancy].
The objective of the present study was to evaluate the conformity between the pathological prenatal ultrasound findings of the kidney and urinary tract during fetal life and in the neonatal period. In a period of four years (1991-1994) 14,938 pregnant woman were controlled in our hospital by performing at least one prenatal ultrasound during the third trimester of their pregnancy to detect alterations of the kidneys and fetal urinary tract. In those newborns with a positive fetal ultrasound, a renal ultrasonography study was performed in the first week of life. Anomalous fetal images at the level of the kidney and/or urinary tract were found in 71 cases (0.5% of all fetuses studied), with sonography during the neonatal period confirming 46.5% of them. The most common fetal images found were pyelocaliceal dilatation in 58 cases (82% of the total) and amongst these mild cases (with renal pelvis diameter less than 10 mm) with 39 cases (55%) none of which malformation of the urinary tract could be diagnosed. In the extreme opposite, the images of severe pyelocaliceal dilatation (pelvic diameter greater than 15 mm), renal cystic images and images of agenesis or renal hypoplasia were interrelated very well (100%, 75% and 100%, respectively) with the neonatal ultrasound findings. We want to indicate the great help that fetal ultrasound provides in the precocious diagnosis of nephrourological malformations in the newborn.


Promoting transfer in memory training for older adults.
Many studies have focused on memory training in aging, showing that older adults can improve their performance. Unfortunately, the benefits of training can rarely be generalized to other tasks for which adults were not specifically trained. We investigated the benefits of instruction-based training in promoting transfer effects in older adults. In Experiment 1, we evaluated transfer effects in a training group who practiced using standard mnemonics to learn paired associates and word lists, and this group was given instructions about how the mnemonics could be used for two of the four transfer tasks (text learning, name-face learning, grocery list learning, place learning). In Experiment 2, we compared transfer effects for two different training groups: one practiced the strategies with the two trained tasks and did not receive instructions, and the other had the same practice but also received instructions on all the transfer tasks. Transfer in text learning occurred in both experiments. This transfer is particularly interesting, as text learning was the most dissimilar task in terms of both the nature of the materials and the underlying processes that support performance. The transfer was reliably greater when training involved instructions about applicability than when it did not. Instructions to use practiced strategies on new materials may be a useful technique in promoting transfer in older adults. It seems that the lack of transfer does not necessarily arise from older adults' inabilities, but because they do not realize that trained strategies can (or should) be applied to new materials.


Expression Profiling of Castanea Genes during Resistant and Susceptible Interactions with the Oomycete Pathogen Phytophthora cinnamomi Reveal Possible Mechanisms of Immunity.
The most dangerous pathogen affecting the production of chestnuts is Phytophthora cinnamomi a hemibiotrophic that causes root rot, also known as ink disease. Little information has been acquired in chestnut on the molecular defense strategies against this pathogen. The expression of eight candidate genes potentially involved in the defense to P. cinnamomi was quantified by digital PCR in Castanea genotypes showing different susceptibility to the pathogen. Seven of the eight candidate genes displayed differentially expressed levels depending on genotype and time-point after inoculation. Cast_Gnk2-like revealed to be the most expressed gene across all experiments and the one that best discriminates between susceptible and resistant genotypes. Our data suggest that the pre-formed defenses are crucial for the resistance of C. crenata to P. cinnamomi. A lower and delayed expression of the eight studied genes was found in the susceptible Castanea sativa, which may be related with the establishment and spread of the disease in this species. A working model integrating the obtained results is presented.


[Effect of prostaglandin E2 on enzyme activity during parenteral feeding].
It has been shown that prostaglandin E2 increases the activity of aspartate aminotransferase, alanine aminotransferase in the liver and striated muscle in parenteral feeding and increases the activity of aldolase in the liver but reduces it in the striated muscle. This demonstrates the enzymatic component in the mechanism of action of prostaglandin E2 on organ-tissue metabolism in parenteral feeding.


How well do family practitioner committee and general practice records agree? Experience in a semi-rural practice.
General practice notes may be inaccurate for various reasons. A study was carried out in one semi-rural practice to investigate the agreement between records held by the family practitioner committee and those kept in the practice. Details on the practice notes and the family practitioner committee list were compared for 800 patients. The details examined included name, sex, date of birth, address and National Health Service number. While 58% of records agreed, discrepancies occurred in 339 records (42%). The most common discrepancies concerned the patient's address (30.6%), date of birth (9.4%) and NHS number (8.0%). Nearly 5% of the practice notes appeared to be for patients who were no longer on the practice list or dependent on its care. These findings have implications under the new general practitioner contract where screening programmes, target related payments, and increased capitation fees require accurate practice records.


In silico approach in reveal traditional medicine plants pharmacological material basis.
In recent years, studies of traditional medicinal plants have gradually increased worldwide because the natural sources and variety of such plants allow them to complement modern pharmacological approaches. As computer technology has developed, in silico approaches such as virtual screening and network analysis have been widely utilized in efforts to elucidate the pharmacological basis of the functions of traditional medicinal plants. In the process of new drug discovery, the application of virtual screening and network pharmacology can enrich active compounds among the candidates and adequately indicate the mechanism of action of medicinal plants, reducing the cost and increasing the efficiency of the whole procedure. In this review, we first provide a detailed research routine for examining traditional medicinal plants by in silico techniques and elaborate on their theoretical principles. We also survey common databases, software programs and website tools that can be used for virtual screening and pharmacological network construction. Furthermore, we conclude with a simple example that illustrates the whole methodology, and we present perspectives on the development and application of this in silico methodology to reveal the pharmacological basis of the effects of traditional medicinal plants.


Mucormycosis of the bovine udder.
Nine cross-bred cows suffering from mucormycosis of the udder were observed. Histopathological and cultural examination of the lesions revealed the presence of Mucor spec.


Prevalence of malocclusion in a sample of Lebanese schoolchildren: an epidemiological study.
The study aimed to provide oral health planners in Lebanon with information on the prevalence of malocclusion in schoolchildren in an attempt to define the target population for orthodontic services in the future. A total of 851 schoolchildren (446 males and 405 females) aged 9-15 years were examined for malocclusion using Angle's classification. In all, 59.5% of the sample had malocclusions, 35.5% of which were of dental origin and 24% had skeletal discrepancy (19% Class II and 5% Class III malocclusions). A statistically significant difference was found between males and females. The findings are compared with those of studies of other ethnic groups and suggestions for future epidemiological research are presented.


Preoperative surgical briefings do not delay operating room start times and are popular with surgical team members.
: This study was carried out to evaluate the introduction of preoperative safety briefings on operating theater start times. In addition, we assessed staff attitudes toward the safety briefings. Lack of time, motivation, and a negative perception in staff are often cited as barriers to the implementation of safety briefings. : The preoperative safety briefing consisted of a 5- to 10-minute meeting between anesthetic staff, surgeons, and nursing staff to discuss the operating list before the commencement of surgery. Using the hospital database, the operating theater start times were obtained for 2 months before and after the introduction of the safety briefings. A questionnaire using a 5-point Likert scale was distributed to the operating room theater staff to evaluate attitudes toward the safety briefing. : There was no statistical difference in operating theater start time after the introduction of the safety briefing. The questionnaire responses from 37 theater staff demonstrated positive attitudes toward the safety briefings including agreeing strongly with factors affecting patient safety and communication. This included 97% replying that the safety briefing highlighted potential patient problems, whereas 89% believed it improved communication. : The safety briefings were popular among staff and did not delay the operating theater start time.


The temperature size rule in arthropods: independent of macro-environmental variables but size dependent.
Temperature is a key factor that affects the rates of growth and development in animals, which ultimately determine body size. Although not universal, a widely documented and poorly understood pattern is the inverse relationship between the temperature at which an ectothermic animal is reared and its body size (temperature size rule [TSR]). The proximate and ultimate mechanisms for the TSR remain unclear. To explore possible explanations for the TSR, we tested for correlations between the magnitude/direction of the TSR and latitude, temperature, elevation, habitat, availability of oxygen, capacity for flight, and taxonomic grouping in 98 species/populations of arthropods. The magnitude and direction of the TSR was not correlated with any of the macro-environmental variables we examined, supporting the generality of the TSR. However, body size affected the magnitude and direction of the TSR, with smaller arthropods more likely to demonstrate a classic TSR. Considerable variation among species exists in the TSR, suggesting either strong interactions with nutrition, or selection based on microclimatic or seasonal variation not captured in classic macro-environmental variables.


Leading organisational learning in health care.
As healthcare organisations seek to enhance safety and quality in a changing environment, organisational learning practices can help to improve existing skills and knowledge and provide opportunities to discover better ways of working together. Leadership at executive, middle management, and local levels is needed to create a sense of shared purpose. This shared vision should help to build effective relationships, facilitate connections between action and reflection, and strengthen the desirable elements of the healthcare culture while modifying outdated assumptions, procedures, and structures.


Magnetic-field induced multiple topological phases in pyrochlore iridates with Mott criticality.
The interplay between electron correlation and spin-orbit coupling in solids has been proven to be an abundant gold mine for emergent topological phases. Here we report the results of systematic magnetotransport study on bandwidth-controlled pyrochlore iridates R2Ir2O7 near quantum metal-insulator transition (MIT). The application of a magnetic field along [001] crystallographic direction (H//[001]) significantly decreases resistivity while producing a unique Hall response, which indicates the emergence of the novel semi-metallic state in the course of the magnetic transformation from all-in all-out (AIAO, 4/0) to 2-in 2-out (2/2) spin configuration. For H//[111] that favours 3-in 1-out (3/1) configuration, by contrast, the resistivity exhibits saturation at a relatively high value typical of a semimetal. The observed properties can be identified to reflect the emergence of multiple Weyl semimetal states with varying numbers of Weyl points and line nodes in respective spin configurations. With tuning effective bandwidth, all these states appear to concentrate around the quantum MIT region, which may open a promising venue for topological phenomena and functions.


Novel mix-family homeobox genes in zebrafish and their differential regulation.
We report the isolation of two novel zebrafish mix-type homeobox genes, mtx1 and mtx2. The homeodomains of both Mtx1 and Mtx2 exhibited a 50% amino acid identity to other Mix-family protein homeodomains. mtx1 was expressed throughout the yolk syncytial layer (YSL), an extraembryonic structure in teleosts, from the late-blastula to the mid-gastrula period. mtx2 was first expressed in the dorsal blastomeres soon after the mid-blastula transition, and slightly later in the entire blastoderm margin. After the late blastula period, mtx2 transcripts were detected in the YSL, and they were restricted to the dorsal YSL by the early gastrula period. The expression of mtx2 was dependent on Wnt signals but not on Nodal signals. mtx1 expression was not regulated by either Wnt or Nodal signals. This is in complete contrast to the Nodal signal-dependent expression of mixer. These results indicate the complexity of the regulation of mix-type homeobox genes.


Rates of revision surgery using Chevron-Austin osteotomy, Lapidus arthrodesis, and closing base wedge osteotomy for correction of hallux valgus deformity.
To identify complications that necessitated revision surgery after the primary operation, a multicenter retrospective chart review was conducted for 646 patients who received either a modified chevron-Austin osteotomy (270 patients), modified Lapidus arthrodesis (342 patients), or closing base wedge osteotomy (34 patients) to correct hallux valgus deformity. Revision surgery for complications was calculated and compared. All surgery was performed by 1 of 5 staff foot and ankle surgeons at Kaiser Permanente medical centers. Complications included recurrent hallux valgus, iatrogenic hallux varus, painful retained hardware, nonunion, postoperative infection, and capital fragment dislocation. The rates of revision surgery after Lapidus arthrodesis, closing base wedge osteotomy and chevron-Austin osteotomy were similar with no statistical difference between them. The total rate for re-operation was 5.56% among patients who received chevron-Austin osteotomy, 8.82% among those who had a closing base wedge osteotomy, and 8.19% for patients who received modified Lapidus arthrodesis. Among patients who had the chevron-Austin osteotomy procedure, rates of re-operation were 1.85% for recurrent hallux valgus and 1.48% for hallux varus. Among patients who had the modified Lapidus arthrodesis, rates of re-operation were 2.92% for recurrent hallux valgus and 0.29% for hallux varus. Among patients who had the closing base wedge osteotomy, rates of reoperation were 2.94% for recurrent hallux valgus and 2.94% for hallux varus. The collected comparative complication rates should serve to provide adjunctive information for foot and ankle surgeons and patients regarding hallux valgus surgery.


[Effect of a tortoise spleen extract on the functional state of liver mitochondria in irradiated mice].
A study was made of the effect of a drug prepared from a spleen extract of Testudo horsfieldi on energy metabolism and lipid composition of liver mitochondria of irradiated mice (2.06 X 10(-1) C/kg). It was shown that the decompensated low-energy state of liver mitochondria of the exposed mice was changed into the state of the compensated low-energy shift: the physicochemical properties of lipid microenvironment of mitochondria proteins were partially restored.