Observation of Anisotropic Strain-Wave Dynamics and Few-Layer Dephasing in MoS2 with Ultrafast Electron Microscopy.
The large elastic strains that can be sustained by transition metal dichalcogenides (TMDs), and the sensitivity of electronic properties to that strain, make these materials attractive targets for tunable optoelectronic devices. Defects have also been shown to influence the optical and electronic properties, characteristics that are especially important to understand for applications requiring high precision and sensitivity. Importantly, photoexcitation of TMDs is known to generate transient strain effects but the associated intralayer and interlayer low-frequency (tens of GHz) acoustic-phonon modes are largely unexplored, especially in relation to defects common to such materials. Here, with femtosecond electron imaging in an ultrafast electron microscope (UEM), we directly observe distinct photoexcited strain-wave dynamics specific to both the ab basal planes and the principal c-axis crystallographic stacking direction in multilayer 2H-MoS2, and we elucidate the microscopic interconnectedness of these modes to one another and to discrete defects, such as few-layer crystal step edges. By probing 3D structural information within a nanometer-picosecond 2D projected UEM image series, we were able to observe the excitation and evolution of both modes simultaneously. In this way, we found evidence of a delay between mode excitations; initiation of the interlayer (c-axis) strain-wave mode precedes the intralayer (ab plane) mode by 2.4 ps. Further, the intralayer mode is preferentially excited at free basal-plane edges, thus suggesting the initial impulsive structural changes along the c-axis direction and the increased freedom of motion of the MoS2 layer edges at terraces and step edges combine to launch in-plane strain waves at the longitudinal speed of sound (here observed to be 7.8 nm/ps). Sensitivity of the c-axis mode to layer number is observed through direct imaging of a picosecond spatiotemporal dephasing of the lattice oscillation in discrete crystal regions separated by a step edge consisting of four MoS2 layers. These results uncover new insights into the fundamental nanoscale structural responses of layered materials to ultrafast photoexcitation and illustrate the influence defects common to these materials have on behaviors that may impact the emergent optoelectronic properties.


Controlling for seasonal patterns and time varying confounders in time-series epidemiological models: a simulation study.
An important topic when estimating the effect of air pollutants on human health is choosing the best method to control for seasonal patterns and time varying confounders, such as temperature and humidity. Semi-parametric Poisson time-series models include smooth functions of calendar time and weather effects to control for potential confounders. Case-crossover (CC) approaches are considered efficient alternatives that control seasonal confounding by design and allow inclusion of smooth functions of weather confounders through their equivalent Poisson representations. We evaluate both methodological designs with respect to seasonal control and compare spline-based approaches, using natural splines and penalized splines, and two time-stratified CC approaches. For the spline-based methods, we consider fixed degrees of freedom, minimization of the partial autocorrelation function, and general cross-validation as smoothing criteria. Issues of model misspecification with respect to weather confounding are investigated under simulation scenarios, which allow quantifying omitted, misspecified, and irrelevant-variable bias. The simulations are based on fully parametric mechanisms designed to replicate two datasets with different mortality and atmospheric patterns. Overall, minimum partial autocorrelation function approaches provide more stable results for high mortality counts and strong seasonal trends, whereas natural splines with fixed degrees of freedom perform better for low mortality counts and weak seasonal trends followed by the time-season-stratified CC model, which performs equally well in terms of bias but yields higher standard errors.


Sequential liver imaging in the hypereosinophilic syndrome: discordant images with scintigraphy, ultrasound, and computed tomography.
Sequential liver scintigrams in a patient with hypereosinophilic syndrome were used to demonstrate liver involvement initially and then to show progression of hepatic disease followed by gradual normalization on treatment. Computed tomography and ultrasound images of the liver were normal; thus, tissue density differences and sonar interfaces were apparently not sufficiently large for detection of tissue infiltrates, whereas abnormalities in Kupffer cell function resulted in abnormal scintigram images. A pattern of changing and vanishing filling defects on the scintigram while computed tomography and ultrasound images were normal was observed in the hypereosinophilic syndrome.


The EQ-5D-5L Valuation Study in Egypt.
No value sets exist for either the EQ-5D-3L or the EQ-5D-5L in Egypt, despite local pharmacoeconomic guidelines recommending the use of the EQ-5D to derive utility. Most published Egyptian economic evaluation studies have used utility values from other published studies and systematic reviews. Our objective was to develop an Egyptian EQ-5D-5L value set using the international EuroQol standardized protocol (EQ-VT-2.1). Adult Egyptian participants were recruited from public places using multi-stratified quota sampling based on age, sex, and geographical distribution. Two elicitation techniques were applied: the composite time trade-off (cTTO) and discrete-choice experiments (DCEs). Before actual data collection, interviewers' performance was assessed in a pilot phase. Data were modelled using generalized least square, Tobit, heteroskedastic, logit, and hybrid models, and the best fitting model was selected based on the value range between observed and predicted values, logical consistency of the parameters, significance level, and prediction accuracy. A total of 1378 interviews were conducted, of which 188 were excluded because they were incomplete or did not comply with protocol, 216 were pilot interviews, and 974 were included in the final analysis. The heteroskedastic model (model 4) based on the cTTO data was selected as the preferred model to generate the value set. Values ranged from - 0.93 for the worst health state (55555) to 1 for full health (11111), with 1136 (36.3%) of all predicted health states being worse than dead. Mobility had the largest impact on health state preference values. This is the first value set for the EQ-5D-5L based on social preferences obtained from a nationally representative sample in Egypt or any Arabic-speaking country. The value set can be used as a scoring system for economic evaluations and to improve the quality of health technology assessment in the Egyptian healthcare system.


(3-Amino-pyrazin-4-ium-2-carboxyl-ate-κN,O)diaqua-zinc(II) dinitrate.
The water-coordinated Zn(II) atom in the title salt, [Zn(C(5)H(5)N(3)O(2))(2)(H(2)O)(2)](NO(3))(2), is N,O-chelated by a zwitterionic amino-pyraziniocarboxyl-ate unit; the metal atom, which lies on a center of inversion, shows an octa-hedral coordination. The nitrate ion inter-acts indirectly, through N-H⋯O hydrogen bonds. In the crystal, adjacent cations and anions are connected by O-H⋯O hydrogen bonds into a three-dimensional network motif. The crystal studied was a non-merohedral twin with two minor components of 15.1 (1) and 8.0 (1)%.


Chemical Composition and Bio-efficacy of Essential Oils from Italian Aromatic Plants: Mentha suaveolens, Coridothymus capitatus, Origanum hirtum and Rosmarinus officinalis.
The chemical composition, antifungal, antioxidant and cytotoxic activities of the essential oils (EOs) of mint (Mentha suaveolens), thyme (Coridothymus capitatus), oregano (Origanum hirtum) and rosemary (Rosmarinus officinalis) were investigated. The antifingal properties of the EOs were investigated againstfour species of Candida by a microdilution method. Cytotoxicity was tested on human keratinocyte (HaCaT) and lung cancer (A549) cell lines using the MTT test. DPPH· and ABTS·+ spectrophotometric assays and DPPH-- ABTS-+(HP)TLC-bioautographic assays were used to evaluate the antioxidant activity. The main compounds of thyme and oregano EOs were carvacrol and thymol, respectively; piperitenone oxide and y-terpinene were the most abundant compounds ofmint and rosemary EOs, respectively. All EOs showed activity against all Candida species in a range between 760 ± 290 to 3120 ± 0.0 μg/mL. Among the EOs, that of M suaveolens showed a stronger cytotoxic activity on HaCaT cells. Thyme, oregano and rosemary EQs exhibited important antioxidant activities by ABTS` assay compared with trolox.


Effect of acrylamide on testis of albino rats. Ultrastructure and DNA cytometry study.
To explore the harmful effects of acrylamide on the structure of testis in albino rats, in an attempt to clarify its potential risks on human health. The present study was carried out in the Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia from December 2010 to December 2011. Forty-eight adult male albino rats (250-300 g) were divided randomly into 6 groups. Electron microscopy and histochemical techniques using Feulgen stain were used to conduct the morphological study. In addition, DNA cytometry method was used. Rats treated with acrylamide 25 mg/kg body weight for 10 days showed mild affection, whether acrylamide was administered orally or intraperitoneally. On the other hand, the testis of the group treated with a dose of 50 mg/kg/10 days showed damage, especially with intraperitoneal administration in comparison to oral treatment. This was in the form of degeneration of germ cells, numerous multinucleated giant cells with sloughed seminiferous epithelium, and vacuolation in-between the germ cells. Exposure to acrylamide produced degenerative changes in the testis, which were more prominent with a longer period of exposure. Recommendations are necessary to decrease acrylamide level in different foods, and ways to decrease acrylamide formation during preparation of different foods should be advertised.


Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection.
We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice. The original syntheses of these two carbapenems were optimized to provide multigram quantities of each compound. One of the two experimental carbapenems, JSF-2204, exhibited efficacy equivalent to that of meropenem, while both were inferior to rifampin. The lessons learned in this study point toward the need to further enhance the pharmacokinetic profiles of experimental carbapenems to positively impact in vivo efficacy performance.


An examination of executive dysfunction associated with frontostriatal circuitry in Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson's disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.


Double-balloon enteroscopy and outcomes in patients older than 80.
double-balloon enteroscopy (DBE) is becoming more commonly used for investigation of small bowel pathology. Currently, there are limited data to describe its safety and efficacy in the population over age 65. to investigate the indications, findings and outcomes of DBE performed in patients older than 80, as well as the correlation between DBE and prior capsule endoscopy (CE) findings. we retrospectively reviewed our large DBE database, including procedures from January 2006 to September 2012. Patients aged 80 or older at the time of DBE were included in the study. The indications, findings, outcomes and diagnostic yield of DBE were calculated by frequency analysis. two hundred and fifteen DBEs were performed in 130 patients aged 80 or older. The mean age was 83.6 ± 3.03 years (range: 80-94). Twelve patients (9.2%) were assigned an American Society of Anaesthesiologists score of II prior to procedure, 102 patients (78.4%) were assigned a score of III and 16 patients (12.3%) were given a score of IV. The most common indication for DBE was obscure gastrointestinal bleeding (N = 204, 94.9%). One hundred and fourteen patients (87.7%) underwent CE prior to DBE, and correlation between findings of CE and DBE occurred in 74.6% of these patients. The overall diagnostic yield of DBE was 77.2% (N = 166). There were no immediate post-procedural complications or failed procedures. DBE is a safe and effective technique for investigation of the small bowel in patients aged 80 and older. Age alone should not be a contraindication to performing DBE when clinically indicated.


Definition of osteoporosis by bone density criteria in men: effect of using female instead of male young reference data depends on skeletal site and densitometer manufacturer.
Whether to use young male or young female reference data to calculate bone mineral density (BMD) T-scores in men remains controversial. The third National Health and Nutrition Examination and Survey (NHANES III) data show that the mean and standard deviation of femoral neck and total hip BMD is greater in young men than young women, and therefore differences in T-scores at these sites using NHANES III female vs male norms becomes less as BMD decreases. In contrast, manufacturer-specific reference databases generally assume similar standard deviations of BMD in men and women. Using NHANES III reference data for the femoral neck and total hip, respectively we found that men with T-scores of -2.5 when young male norms are used have T-scores of -2.4 and -2.3 when young female norms are used. Using manufacturer-specific reference data, we found that men with T-scores of -2.5 when young male norms are used at the femoral neck, total hip, lumbar spine, or one-third of the forearm would have T-scores ranging from -2.4 to -0.4 when young female norms are used, depending on skeletal site and densitometer manufacturer. The change of proportions of men diagnosed with osteoporosis when young female norms are used instead of young male reference data differs substantially according to skeletal site and densitometer manufacturer.


Extraction, identification and characterization of the water-insoluble proteins from tobacco biomass.
Tobacco leaves are a potential candidate for plant proteins, yielding fourfold more protein per acre than soybeans. However, more than 60% of these proteins are water-insoluble and remain in the residue (referred to as 'tobacco biomass') after aqueous extraction. Efficient extraction of tobacco biomass proteins (TBPs) could boost the development of value-added products from tobaccos. TBPs were resistant to salt extraction at pH 2.0-12.0, but they were readily extracted by organic solvents. A simplified extracting method, including mechanical homogenization, a first extraction with a methanol-water mixture (40/60, v/v) and a second one with water at pH 6.0, recovered at most 68% of the TBPs. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated the presence of both the water-soluble tobacco F(1) protein and the less soluble cell wall proteins in TBPs, while Fourier transform infrared spectra suggested the coexistence of TBPs with polysaccharides (especially pectin). Meanwhile, a higher content of hydrophobic amino acids was found in TBPs compared with water-extractable tobacco proteins. The amino acid score of TBPs was 0.71, with cysteine and methionine being the primary limiting amino acids. Satisfying recovery of TBPs was achieved using a two-step organic solvent extraction. The hydrophobicity and protein-pectin interaction of TBPs explained for this result.


High-throughput small molecule screening reveals structurally diverse compounds that inhibit the growth of Escherichia coli O157:H7 in vitro.
Escherichia coli O157:H7 colonizes the gastrointestinal tract of ruminants asymptomatically and may enter the human food supply through fecal contamination. A fraction of individuals infected by E. coli O157:H7 develop hemolytic uremic syndrome, a life-threatening condition. When individuals infected by E. coli O157:H7 are treated with certain antibiotics, an increased incidence of hemolytic uremic syndrome may result. This finding supports the need to identify novel compounds that can either reduce the load of E. coli O157:H7 entering the human food supply or serve as alternative therapeutic treatments for infected individuals. We developed a high-throughput turbidometric assay to identify novel compounds that inhibit E. coli O157:H7 growth. Pin transfers were performed to introduce small molecule libraries into 384-well plates, where each well contained approximately 5.0 log CFU of E. coli O157:H7. Plates were incubated at 37°C for 18 h, and the optical density was measured to determine the effect of each small molecule. A total of 64,562 compounds were screened in duplicate, and 43 unique compounds inhibited E. coli O157:H7 growth. Thirty-eight of the 43 inhibitory compounds belonged to known bioactive libraries, and the other 5 compounds were from commercial libraries derived from splitting and pooling. Inhibitory compounds from known bioactive libraries were most frequently therapeutic antibiotics (n = 34) but also included an antiviral compound, a compound that disrupts the citric acid cycle, and two biguanide compounds, which have been used for various nonclinical applications. We identified two novel compounds (i.e., biguanides) that should be studied further for their ability to reduce pathogen populations in foods.


Characterization of the rolipram-sensitive, cyclic AMP-specific phosphodiesterases: identification and differential expression of immunologically distinct forms in the rat brain.
To determine the properties of the cAMP-specific, rolipram-sensitive phosphodiesterases (cAMP-PDEs) that are expressed in different organs, monoclonal and polyclonal antibodies were raised against different epitopes present in the cAMP-PDE sequences. Of the several antibodies generated against peptides and fusion proteins, one monoclonal and four polyclonal antibodies recognized both the native cAMP-PDEs as well as the denatured proteins on Western immunoblot analysis. An immunoprecipitation assay demonstrated that these antibodies recognized the recombinant rat PDE4A, PDE4B, and PDE4D proteins with different avidity. The polyclonal antibody K118 and the monoclonal M3S1 were most specific for rat PDE4B and PDE4D forms, respectively, whereas the AC55 antiserum displayed the highest affinity for PDE4A forms. This selectivity was confirmed by Western blot analysis using recombinant rat PDE4A, PDE4B, and PDE4D proteins expressed in a heterologous system. These antibodies were used to characterize the cAMP-PDEs expressed in the rat brain. An immunoblot of extract of cortex and cerebellum demonstrated that at least seven different polypeptides specifically cross-reacted with the different antibodies, indicating that multiple cAMP-PDEs are expressed in this tissue. On the basis of cross-reactivity with PDE4D but not PDE4A or PDE4B antibodies, 93- and 105-kDa PDE4D species were detected in the cortex and cerebellum extract. These forms are different from the 68-kDa PDE4D form expressed in endocrine cells after hormonal stimulation. Although the 93-kDa form was recovered in both the soluble and particulate fractions, the 105-kDa polypeptide was mostly particulate in the cortex and cerebellum extracts. PDE4B forms of 90-87 kDa were recovered in both soluble and particulate compartments of the brain extract. These forms were different from the previously identified PDE4A variants of 110 and 75 kDa. These data demonstrate that the presence of multiple cAMP-PDE genes is translated into cAMP-PDE proteins of different sizes and distinct immunological properties and that multiple variants derived from these cAMP-PDE genes are expressed in different regions of the brain and different subcellular compartments. These immunological tools will be useful to identify different cAMP-PDE forms expressed in organs targeted for pharmacological intervention with PDE4 inhibitors.


A comparative analysis of complementary therapies use among patients attending diabetic clinics in Taiwan: 2007 vs. 2023.
We conducted a comparative study to examine the differences in the use of complementary therapies (CT) among patients who attended diabetic clinics for follow-up treatment between 2007 and 2023 in Taiwan. This study employed a cross-sectional survey design to recruit individuals with diabetes from two regions (northern and southern) of Taiwan. A total of 183 and 307 participants were included in the surveys of 2007 and 2023, respectively. The data were analyzed using IBM SPSS Statistics version 28.0 to compare the survey results between the two time periods. Among the various CTs, nutritional supplements remained the most prevalent, with a significant increase in usage from 68.3% in 2007 to 89.9% in 2023. Conversely, other therapies, such as Chinese herbal medicines, manipulative-based therapies, supernatural healings, and bioelectromagnetic-based therapies, demonstrated a significant decrease in usage between the two time periods. Furthermore, the disclosure rate of CT use to healthcare professionals remained persistently low, with only 24.6% in 2007 and a slight increase to 30.3% in 2023. The significant rise in the use of nutritional supplements in conjunction with conventional medicine, without adequate monitoring and guidance from healthcare professionals, poses a substantial risk of unregulated blood sugar control, compromised diabetes management, and potential harm to health outcomes.


Histomorphometry of bone.
This review of the histomorphometry of bone outlines methods of biopsy and processing of specimens in the laboratory, the basic principles of morphometry, and the measurements made in order to obtain estimates of the proportional volumes and surfaces occupied by different components of bone. Variability such as that between methods, observers and laboratories is discussed and a brief outline of automatic and semiautomatic methods of image analysis also given.


Revision after total knee arthroplasty.
Revision of a total knee arthroplasty is most frequently required because of prosthetic loosening, instability, and failure to restore proper axial alignment. The instability and improper axial alignment may result in abnormal stresses that predispose to component loosening, component failure, and stress fracture of the tibia. Therefore, it is essential to obtain correct axial alignment and soft tissue balance at the time of the initial arthroplasty. Approximately two thirds of those knees having one or more revisions of their arthroplasty will have a satisfactory result. One third will have an unsatisfactory result related to continued pain or restricted motion, or both. We have reported the results in 142 knees, 95 of which had one revision, 37 of which had two revisions, and 10 of which had three revisions. It is essential in such revisions, in our opinion, to thoroughly debride the knee, restore quadriceps balance, establish the correct alignment, minimize bone loss, and use the least possible constraint in the prosthesis combined with an external brace for three to six months.


Enriched PUFA environment of Leishmania infantum promastigotes promotes the accumulation of lipid mediators and favors parasite infectivity towards J774 murine macrophages.
Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We previously showed changes in the fatty acid composition (FA) of lipids in two strains of Leishmania donovani upon differentiation of promastigote to amastigote, including increased proportions of arachidonic acid (AA) and to a less extent of docosahexaenoic acid (DHA). Here, we carried out supplementation with AA or DHA on two Leishmania infantum strains, a visceral (MON-1) and a cutaneous (MON-24), to evaluate the role of these FA in parasite/macrophage interactions. The proportions of AA or DHA in total lipids were significantly increased in promastigotes cultured in AA- or DHA-supplemented media compared to controls. The content of FA-derived oxygenated metabolites was enhanced in supplemented strains, generating especially epoxyeicosatrienoic acids (11,12- and 14,15-EET) and hydroxyeicosatetraenoic acids (5- and 8- HETE) from AA, and hydroxydocosahexaenoic acids (14- and 17-HDoHE) from DHA. For both MON-1 and MON-24, AA-supplemented promastigotes showed higher infectivity towards J774 macrophages as evidenced by higher intracellular amastigote numbers. Higher infectivity was observed after DHA supplementation for MON-24 but not MON-1 strain. ROS production by macrophages increased upon parasite infection, but only minor change was observed between control and supplemented parasites. We propose that under high AA or DHA environment that is associated with AA or DHA enrichment of promastigote lipids, FA derivatives can accumulate in the parasite, thereby modulating parasite infectivity towards host macrophages.


Comparison of the Effect of Clomiphene- Estradiol Valerate vs Letrozole on Endometrial Thickness, Abortion and Pregnancy Rate in Infertile Women with Polycystic Ovarian Syndrome.
Clomiphene citrate is the first-line therapy for ovulation induction in Polycystic Ovarian Syndrome (PCOS). This drug binds and blocks estrogen receptors and thought to have an anti estrogenic effect on endometrium volume, thus may have adverse effect on fertility. This study aimed to compare the effect of Clomiphene citrate plus Estradiol Valerate with Letrozole on endometrial thickness, abortion and pregnancy rate in infertile women with PCOS undergoing ovulation induction. This was a randomized double blind clinical trial study on 100 women with PCOS, with an endometrial thickness less than 7mm in spite of follicles greater than 18mm after administration of Clomiphene citrate 100mg/d from 3(th) to 7(th) day of menstruation. They were randomly divided in two groups. Group A received 100mg Clomiphene citrate from day 3 to day 7 of menstruation and 4 mg Estradiol Valerate after the 8(th) day of menstruation until 14(th) day. Group B treated by 5mg Letrozole from day 3 to 7 of menstruation with placebo from 8(th) to 14(th) day of menstruation. In both groups endometrial thickness was measured by transvaginal sonography in the 14(th) day of menstruation. Data were analysed using SPSS Ver.18.0. The mean age was 30.34 years in group A and 29.62 years in group B (p=0.381). The number of infertility years in group A was 3.73 years and in group B was 3.85 years. There was no significant relationship statistically between the two groups in terms of mean age and infertility years (p=0.99). Endometrial thickness in group A was 7.26mm and in group B was 8.17 mm. Pregnancy rates in group A and group B was 32% and 16% respectively. There was significant relationship statistically between the two groups in terms of endometrial thickness and pregnancy rates (p=0.021 and p=0.05). There was no abortion in group A and 5 cases had abortion in group B, there was a significant relationship between the two groups statistically (p=0.028). Letrozole increased endometrial thickness and pregnancy rate in infertile women, therefore its administration is recommended.


Self-reported health-related experiences, psychological capital, and psychological wellbeing in Lithuanian adults sample.
The purpose of this research was to examine psychological wellbeing and psychological capital in groups of subjectively healthy and unhealthy individuals and identify significant associations. We have analyzed the results of a Lithuanian representative sample of adults (n = 1001). Results showed that adult respondents who reported the absence of cardiovascular diseases, nervous system diseases, autoimmune diseases, diabetes, vision disorders, physical or mental disability, and substance abuse demonstrated significantly higher scores for flourishing, life satisfaction, psychological capital, self-efficacy, hope, and resilience. The model on associations between the number of reported diseases, psychological capital, and wellbeing in the representative sample of adults (χ2 = 110.786, df = 16; CFI = .981; RMSEA = .077; NFI = 0.978; TLI = 0.968) indicated that a higher number of diseases (per person) predicts a weakening effect on psychological capital, while psychological capital predicts psychological wellbeing.


Naringenin prevents ischaemic stroke damage via anti-apoptotic and anti-oxidant effects.
Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischaemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague-Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups. MTT and RT-PCR were used for cell proliferation and apoptosis-related proteins analyses. The effects of NAR on the Nrf2 signalling pathway were investigated using transfection approaches. Differences in mitochondrial dysfunction were analyzed by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed and recorded; apoptosis was measured based on the TUNEL assay. Additionally, biochemical indices were detected both in vitro and in vivo. NAR promoted cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological defects, and reduce apoptosis and oxidative stress (P<.05). These findings demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2 signalling pathway is involved in this regulatory process. NAR has health-promoting properties because of its anti-apoptotic and anti-oxidant effects in cases of ischaemic stroke.


Parity and 11-Year Serum Thyrotropin and Thyroid Autoantibody Change: A Longitudinal Population-Based Study.
A role for female reproductive factors in the pathogenesis of thyroid autoimmunity has been suggested. This study investigated the prospective association between parity, abortion, use of oral contraceptive pill (OCP), and use of hormone replacement therapy (HRT), and 11-year change in serum thyrotropin (TSH), as well as change in thyroid peroxidase autoantibody (TPOAb) status. A random sample of 4649 people aged 18-65 years participated in a population-based study in the period 1997-1998. In the study presented here, 1749 non-pregnant women with no history of thyroid disease were included who participated in the 11-year follow-up examination in the period 2008-2010. Gynecological exposures were reported in a self-administered questionnaire at baseline and follow-up. TSH and TPOAb were measured at baseline and follow-up. Increased TPOAb status during follow-up was defined as a TPOAb below the assay cutoff (<30 kIU/L) at baseline and a TPOAb ≥30 kIU/L at follow-up. Multiple linear regression models were used, adjusted for age, smoking status, and urinary iodine excretion. An inverse association was found between the number of years on HRT and the risk (odds ratio) of increased TPOAb status during follow-up (0.735 [confidence interval 0.558-0.968], p = 0.03). However, this association was not statistically significant when applying the Bonferroni adjusted significance level. The remaining reproductive factors showed no statistically significant association with risk of increased TPOAb during follow-up. Furthermore, parity, abortions, use of OCP, HRT use, age at menarche, and being pre- or postmenopausal were not significantly associated with 11-year TSH change. No statistically significant association was found between the studied female reproductive measures and 11-year risk of TSH or TPO change. A possible protective role for HRT in the etiology of thyroid autoimmunity, however, deserves further research.


The cerebellum contributes to proprioception during motion.
Proprioception, the sense of limb position and motion, is essential for generating accurate movements. Limb position sense has typically been studied under static conditions (i.e., the fixed position of a limb in space), with less known about dynamic position sense (i.e., limb position during movement). Here we investigated how a person's estimate of hand position varies when using spatial or temporal information to judge the unseen hand's location during reaching. We assessed the acuity of dynamic position sense in two directions, orthogonal to hand movement, which only requires spatial information, and in line with hand movement, which has both spatial and temporal components. Our results showed that people have better proprioceptive acuity in the orthogonal condition where only spatial information is used. We then assessed whether cerebellar damage impairs proprioceptive acuity in both tasks during passive and active movement. Cerebellar patients showed reduced acuity in both tasks and in both movement conditions relative to age-matched controls. However, patients' deficits were most apparent when judgments of active movement relied on temporal information. Furthermore, both cerebellar patient and control performance correlated with the trial-to-trial variability of their active movements: subjects are worse at the proprioceptive tasks when movements are variable. Our results suggest that, during active movements, proprioceptive acuity may be reliant on the motor system's ability to predict motor output. Therefore, the resultant proprioceptive deficits occurring after cerebellar damage may be related to a more general impairment in movement prediction.NEW & NOTEWORTHY We assessed limb position sense during movement in patients with cerebellar damage and found deficits in proprioceptive acuity during both passive and active movement. The effect of cerebellar damage was most apparent when individuals relied on both timing and spatial information during active movement. Thus proprioceptive acuity during active movements may be reliant on the motor system's ability to predict motor output.


Eps8 decreases chemosensitivity and affects survival of cervical cancer patients.
The oncoprotein Eps8 facilitates proliferation in fibroblasts and colon cancer cells. However, its role in human cervical cancer is unclear. By immunohistochemical staining and Western blotting, aberrant Eps8 expression was observed in cervical carcinoma compared with normal cervical epithelial cells. Clinicopathologic analysis of 45 patients indicated that Eps8 expression was associated with parametrium invasion and lymph node metastasis, two major poor prognostic factors for early-stage cervical cancer. Kaplan-Meier analysis of cervical cancer specimens also indicated an inverse relationship between the level of Eps8 and the patients' survival rate. Using small interfering RNA of eps8, we observed reduced proliferation and tumorigenesis in Eps8-attenuated HeLa and SiHa cells cultured in dishes or inoculated in mice. Furthermore, diminished Eps8 impeded G(1)-phase progression in HeLa and SiHa cells that might be attributable to reduced expression of cyclins D1, D3, and E, elevated accumulation of p53 and its downstream target p21(Waf1/Cip1), and suppressed hyperphosphorylation of retinoblastoma. Alteration of these cell cycle-related proteins could be reversed by ectopic Eps8, implicating that the effect of Eps8 on the mentioned cell cycle modulators was specific. Notably, the augmented expression of p53 by diminished Eps8 was at least due to its decreased turnover rate. Concurrent with p53 up-regulation and the decrement of Src and AKT activity, Eps8-attenuated HeLa and SiHa cells exhibited increased chemosensitivity to cisplatin and paclitaxel. Together, our findings implicate the involvement of Eps8 in chemoresistance and show its importance in prognosis of cervical cancer patients.


Prevalence of virulence genes in Escherichia coli strains isolated from piglets in the suckling and weaning period in Mexico.
Faecal Escherichia coli isolates from suckling (n = 503) and weaning (n = 450) piglets with and without diarrhoea from 10 farms in Mexico were examined for identification and prevalence of virulence genes. E. coli isolates were tested further for enterotoxin (LT, STa, STb, Stx1, Stx2 and EAST1), fimbrial (F4, F5, F6, F17, F18 and F41) and eae adhesin genes by multiplex PCR. Of the 953 isolates of E. coli examined by multiplex PCR, 650 (68.2 %) isolates were positive for at least one adhesin gene. Among the isolates from diarrhoeic piglets, F41 (72 %) was the most prevalent adhesin followed by eae adhesin (27 %), F6 (12 %), F17 (9 %), F18 (9 %), F5 (8 %) and F4 (3 %). Enterotoxin genes were detected in 424 (44.5 %) of the isolates, of which EAST1 (38 %) and STa (30 %) were the most common, followed by STb (17 %), Stx2 (6 %) and LT (5 %). Twenty-three per cent of isolates from suckling piglets and 43 % of isolates from weaned piglets carried both enterotoxin and adhesin genes, the most common virotypes being F41 : STa, F41 : EAST1, EAST1 : eae, F41 : F6, F41 : STa : STb, F41 : eae and F17 : eae. The present study examined for the first time, to our knowledge, the prevalence of 13 virulence genes among E. coli strains isolated from piglets with and without diarrhoea in Mexico. The results suggested that there are a wide variety of virulence genes associated with diarrhoea in piglets. This study provides baseline information on the significance of specific virotypes associated with suckling and weaning periods in piglets in Mexico.


Attitudes and beliefs of Australian chiropractors' about managing back pain: a cross-sectional study.
Chiropractors are frequent providers of care for patients with lower back pain. Biopsychosocial approaches to managing patients are regarded as best practice and are gaining wider acceptance. Recent evidence suggests that practitioners' attitudes and beliefs may also have an important effect on patients' recovery from back pain. Past studies have pooled manual therapists from differing professions. Dissonant findings have been hypothesised as being a result of the chiropractic subpopulation within multi-practitioner participant pools who are hypothesised to focus on biomedical aspects of treatment and minimize biopsychosocial dimensions. The aim of this study is to determine whether a study population of only chiropractors would demonstrate similar attitudes and beliefs to other manual therapists' biopsychosocial or biomedical approach to the management of their patients. A survey of chiropractors in Victoria Australia in September 2010 was undertaken utilising the Pain Attitude and Belief Scale (PABS.PT), a tool which has been developed to determine the orientation (biopsychosocial or biomedical approach) of practitioners to the management of people with low back pain. The survey also obtained demographic data from respondents to determine whether variables such as education, gender or practice related factors influenced their orientation. The overall response rate was 29% (n = 218). The majority of the sample was male (68%), with a mean age of 44 years. The 6 point Likert scale scores were 34.5 (6.3) for the biomedical factor scale and 31.4 (4.1) for the biopsychosocial scale. Internal consistency of the psychosocial subscale was poor. None of the demographic variables were found to influence the biomedical or psychosocial scales. Chiropractors in the state of Victoria were found to have similar biomedical and psychosocial orientations in their attitudes and beliefs when compared to other manual therapists' levels of previous studies from differing cultural and educational backgrounds. This study was unable to replicate any of the relationships from past studies with any of the demographic variables. The psychosocial scale internal consistency may be a significant factor in this non-finding. Future research should address the identification of more robust items of the biopsychosocial attitudes of Victorian chiropractors toward treating lower back pain.


Phytocystatin 6 is a context-dependent, tight-binding inhibitor of Arabidopsis thaliana legumain isoform β.
Plant legumains are crucial for processing seed storage proteins and are critical regulators of plant programmed cell death. Although research on legumains boosted recently, little is known about their activity regulation. In our study, we used pull-down experiments to identify AtCYT6 as a natural inhibitor of legumain isoform β (AtLEGβ) in Arabidopsis thaliana. Biochemical analysis revealed that AtCYT6 inhibits both AtLEGβ and papain-like cysteine proteases through two separate cystatin domains. The N-terminal domain inhibits papain-like proteases, while the C-terminal domain inhibits AtLEGβ. Furthermore, we showed that AtCYT6 interacts with legumain in a substrate-like manner, facilitated by a conserved asparagine residue in its reactive center loop. Complex formation was additionally stabilized by charged exosite interactions, contributing to pH-dependent inhibition. Processing of AtCYT6 by AtLEGβ suggests a context-specific regulatory mechanism with implications for plant physiology, development, and programmed cell death. These findings enhance our understanding of AtLEGβ regulation and its broader physiological significance.


Behavioral and Psychological Symptoms of Dementia in Different Dementia Disorders: A Large-Scale Study of 10,000 Individuals.
The majority of individuals with dementia will suffer from behavioral and psychological symptoms of dementia (BPSD). These symptoms contribute to functional impairment and caregiver burden. To characterize BPSD in Alzheimer's disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and unspecified dementia in individuals residing in long-term care facilities. We included 10,405 individuals with dementia living in long-term care facilities from the Swedish registry for cognitive/dementia disorders (SveDem) and the Swedish BPSD registry. BPSD was assessed with the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). Multivariate logistic regression models were used to evaluate the associations between dementia diagnoses and different BPSDs. The most common symptoms were aberrant motor behavior, agitation, and irritability. Compared to AD, we found a lower risk of delusions (in FTD, unspecified dementia), hallucinations (FTD), agitation (VaD, PDD, unspecified dementia), elation/euphoria (DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD), irritability (in DLB, FTD, unspecified dementia), aberrant motor behavior (Mixed, VaD, unspecified dementia), and sleep and night-time behavior changes (unspecified dementia). Higher risk of delusions (DLB), hallucinations (DLB, PDD), apathy (VaD, FTD), disinhibition (FTD), and appetite and eating abnormalities (FTD) were also found in comparison to AD. Although individuals in our sample were diagnosed with different dementia disorders, they all exhibited aberrant motor behavior, agitation, and irritability. This suggests common underlying psychosocial or biological mechanisms. We recommend prioritizing these symptoms while planning interventions in long-term care facilities.


Sociodemographic Predictors of Anal Cancer Screening and Follow-up in Human Immunodeficiency Virus-Infected Individuals.
Anal cancer in the United States is generally rare; however, human immunodeficiency virus (HIV)-infected individuals are 28 times more likely to be given a diagnosis of anal cancer than the general population. The aim of this study was to examine the rates and sociodemographic predictors of anal cancer screening and follow-up anoscopy in a sample of HIV-infected individuals. Data for this study (n = 200) were derived from a retrospective chart review of randomly selected HIV-infected individuals. Data analyses included Pearson's correlation coefficient statistic to examine bivariate associations and logistic regression modeling for prediction of anal Papanicolaou test screening and follow-up anoscopy. Screening rates and follow-up after an abnormal anal Pap test were low. Women were less likely to be screened for anal cancer (odds ratio [OR], 0.244; P = .007). Men who have sex with men were almost 4 times more likely to be screened for anal cancer (OR, 3.7; P = .02). Men who have sex with men were 6 times more likely to have follow-up after an abnormal anal Pap test compared with heterosexual men or women of any sexual orientation (OR, 6.88; P = .002). High-risk groups for anal cancer should be targeted for preventative measures as part of a cancer prevention plan to decrease the personal and clinical burden associated with anal cancer. Cancer prevention is a multistep process that requires screening and follow-up efforts, where healthcare providers play a vital role in these efforts. Findings from this study can inform strategies to improve screening and follow-up rates in HIV-infected individuals.


Identification of S-hydroxylysyl-methionine as the covalent cross-link of the noncollagenous (NC1) hexamer of the alpha1alpha1alpha2 collagen IV network: a role for the post-translational modification of lysine 211 to hydroxylysine 211 in hexamer assembly.
Collagen IV networks are present in all metazoans as components of basement membranes that underlie epithelia. They are assembled by the oligomerization of triple-helical protomers, composed of three alpha-chains. The trimeric noncollagenous domains (NC1) of each protomer interact forming a hexamer structure. Upon exposure to acidic pH or denaturants, the hexamer dissociates into monomer and dimer subunits, the latter reflect distinct interactions that reinforce/cross-link the quaternary structure of hexamer. Recently, the cross-link site of the alpha1alpha1alpha2 network was identified, on the basis of x-ray crystal structures at 1.9-A resolution, in which the side chains of Met93 and Lys211 were proposed to be connected by a novel thioether bond (Than, M. E., Henrich, S., Huber, R., Ries, A., Mann, K., Kuhn, K., Timpl, R., Bourenkov, G. P., Bartunik, H. D., and Bode, W. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 6607-6612); however, at the higher resolution of 1.5 A, we found no evidence for this cross-link (Vanacore, R. M., Shanmugasundararaj, S., Friedman, D. B., Bondar, O., Hudson, B. G., and Sundaramoorthy, M. (2004) J. Biol. Chem. 279, 44723-44730). Given this discrepancy in crystallographic findings, we sought chemical evidence for the location and nature of the reinforcement/cross-link site. Trypsin digestion of monomer and dimer subunits excised a approximately 5,000-Da complex that distinguished dimers from monomers; the complex was characterized by mass spectrometry, Edman degradation, and amino acid composition analyses. The tryptic complex, composed of two peptides of 44 residues derived from two alpha1 NC1 monomers, contained Met93 and Lys211 post-translationally modified to hydroxylysine (Hyl211). Truncation of the tryptic complex with post-proline endopeptidase reduced its size to 14 residues to facilitate characterization by tandem mass spectrometry, which revealed a covalent linkage between Met93 and Hyl211. The novel cross-link, termed S-hydroxylysyl-methionine, reflects at least two post-translational events in its formation: the hydroxylation of Lys211 to Hyl211 within the NC1 domain during the biosynthesis of alpha-chains and the connection of Hyl211 to Met93 between the trimeric NC1 domains of two adjoining triple-helical protomers, reinforcing the stability of collagen IV networks.


Unintended transplantation of three organs from an HIV-positive donor: report of the analysis of an adverse event in a regional health care service in Italy.
In February 2007, three organs from an human immunodeficiency virus (HIV)-positive donor were transplanted at two hospitals in the Tuscany Regional Health Care Service, owing to a chain of errors during the donation process. The heart-beating donor was a 41-year-old woman who died as a result of head trauma. The patient's history did not highlight any risky behavior. The available data on previous hospital admissions reported a negative result on HIV testing. During the donation process, the result of the lab test performed for evaluation of organ suitability was mistakenly transcribed from positive to negative. This wrong negative result was then included in the donation record without any cross-check. Therefore, the Regional Transplant Center allocated the liver and both kidneys. The patient also donated tissues, and a second laboratory conducted an evaluation of suitability for the tissue banks. During this process, only 5 days after the successful transplantation procedures, the positive HIV result was fed back to the Regional Transplant Center and the previous error discovered. Transplanted patients were immediately assessed and then treated with antiretroviral medications. A national commission soon performed a systems analysis of the adverse event. Besides the active error committed during the manual transcription for the HIV lab test result, the commission also identified technological factors, such as the lack of integration between the lab machine, the laboratory information system (LIS), and the donor record, as well as organizational factors, such as the distribution to two different labs of the suitability evaluation for organs and tissues. Recommendations included: automatic transmission of lab test results from the lab machine to the LIS and to the donor record, centralization of lab tests for suitability evaluation of organs and tissues, a training program to develop a proactive quality and safety culture in the regional network of donation and transplantations.


Versatile role of Rab27 in membrane trafficking: focus on the Rab27 effector families.
Rab27A was the only Rab protein whose dysfunction was found to cause human immunodeficiency. Since Griscelli syndrome patients (i.e., Rab27A-deficient) exhibit silvery hair color (i.e., pigmentary dilution) in addition to loss of cytotoxic killing activity by cytotoxic T lymphocytes, and Rab27A protein is expressed in a wide variety of secretory cells, Rab27A (or its closely related isoform Rab27B) has been implicated in the regulation of different types of membrane trafficking, including melanosome transport and various regulated secretion events. How does Rab27 protein regulate these different types of membrane trafficking? Recent discoveries of three different families of Rab27-binding proteins (a total of eleven distinct proteins) have supplied an important clue to the answer of this question: different types of Rab27 effectors function in different cell types. In this review I describe the literature on the identification of Rab27-binding proteins (i.e., the synaptotagmin-like protein (Slp) family with tandem C2 Ca(2+)-binding motifs, the Slac2 family without any C2 motifs, and Munc13-4, a putative priming factor for exocytosis) and the current state of our understanding of the molecular mechanism of the Rab27-dependent membrane trafficking.


CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity.
Centrosomal P4.1-associated protein (CPAP) is overexpressed in hepatocellular carcinoma (HCC) and positively correlated with recurrence and vascular invasion. Here, we found that CPAP plays an important role in HCC malignancies. Functional characterization indicated that CPAP overexpression increases tumor growth, angiogenesis, and metastasis ex vivo and in vivo. In addition, overexpressed CPAP contributes to sorafenib resistance. Mechanical investigation showed that the expression level of CPAP is positively correlated with activated STAT3 in HCC. CPAP acts as a transcriptional coactivator of STAT3 by directly binding with STAT3. Interrupting the interaction between CPAP and STAT3 attenuates STAT3-mediated tumor growth and angiogenesis. Overexpression of CPAP upregulates several STAT3 target genes such as IL-8 and CD44 that are involved in angiogenesis, and CPAP mRNA expression is positively correlated with the levels of both mRNAs in HCC. Knocked-down expression of CPAP impairs IL-6-mediated STAT3 activation, target gene expression, cell migration, and invasion abilities. IL-6/STAT3-mediated angiogenesis is significantly increased by CPAP overexpression and can be blocked by decreased expression of IL-8. Our findings not only shed light on the importance of CPAP in HCC malignancies, but also provide potential therapeutic strategies for inhibiting the angiogenesis pathway and treating metastatic HCC.


Stability of CART peptide expression in the nucleus accumbens in aging.
Aging is accompanied by changes of several anorexigenic and orexigenic neuropeptides expressed in various brain areas that control food intake and these changes correlate with senescent anorexia. During aging expression of cocaine- and amphetamine-regulated transcript (CART) peptide was reported to be reduced in the hypothalamic nuclei related to food intake. Although CART peptide is abundant in the nucleus accumbens that also plays a crucial role in the food intake regulation, no data is available about the CART peptide expression in this region through aging. In the present study, CART peptide immunoreactivity was compared in the nucleus accumbens of young adult (4- and 7-month-old) middle-aged (15-month-old) and aging (25-32-month-old) Long-Evans rats. The density of CART-immunoreactive cells and axon terminals in the nucleus accumbens was measured with computer-aided densitometry. CART-immunodensity was similar in the old rats and in the younger animals without significant difference between age groups. In addition, no gender-difference was observed when CART-immunoreactivities in the nucleus accumbens of male and female animals were compared. Our results indicate that CART peptide expression in the nucleus accumbens is stable in adults and does not change with age.


Omega-3 fatty acids effect on wound healing.
Physiological events in the initial inflammatory stage of cutaneous wound healing influence subsequent stages. Proinflammatory cytokines coordinate molecular and cellular processes during the inflammatory stage. Polyunsaturated fatty acids (PUFA) alter proinflammatory cytokine production, but how this phenomenon specifically influences wound healing is not clearly understood. In the present study, effects of marine-derived omega-3 eicosapentaenoic and docosahexaenoic PUFA on proinflammatory cytokines in wound serum and time to complete healing in healthy, human skin were evaluated. We compared plasma fatty acid levels in two groups (N=30) at baseline and after 4 weeks of eicosapentaenoic/docosahexaenoic PUFA supplements (active) or placebo (control). Eight small blisters on participants' forearms were created. Proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha were quantified in blister fluid at 5 and 24 hours after creation. Wound area was calculated daily. Eicosapentaenoic and docosahexaenoic plasma fatty acid levels were significantly higher in the active group. Additionally, we found significantly higher IL-1beta levels in blister fluid in the active group and time to complete wound closure was somewhat longer. These results suggest that eicosapentaenoic and docosahexaenoic PUFA may increase proinflammatory cytokine production at wound sites and thus, depending on the clinical context, have noninvasive, therapeutic potential to affect cutaneous wound healing.


Zero-dimensional lumped approach to incorporate the dynamic part of the pressure at vessel junctions in a 1D wave propagation model.
A benchmark study by Boileau et al tested 6 commonly used numerical schemes for 1D wave propagation, for their ability to capture the main features of pressure, flow, and area waveforms in large arteries. While all numerical schemes showed good agreement in pressure and flow waveforms for smaller arterial networks, the simplified trapezium rule method proposed by Kroon et al showed an overestimation for the systolic pressure of 1% in proximal regions and an underestimation of 3% in distal regions in comparison with the 5 other schemes when using a larger arterial network, published as the ADAN56 model. The authors attributed this difference to the neglection of the dynamic part of the pressure at vessel junctions. Carson et al resolved these differences by proposing 2 methods to implement the dynamic part of the pressure in the simplified trapezium rule method scheme. In the present study, an alternative method is introduced extending the work by Kroon et al. This alternative method consists of a new 0D element, which is placed at vessel junctions. The strength of this new element is the ease of implementation and its flexible coupling with other elements, without introducing additional degrees of freedom or the need of a penalty function. This new approach is compared with 5 other numerical schemes, which already have the dynamic part of the pressure incorporated. The new method shows excellent agreement with these schemes for the ADAN56 model.


A novel mini-DNA barcoding assay to identify processed fins from internationally protected shark species.
There is a growing need to identify shark products in trade, in part due to the recent listing of five commercially important species on the Appendices of the Convention on International Trade in Endangered Species (CITES; porbeagle, Lamna nasus, oceanic whitetip, Carcharhinus longimanus scalloped hammerhead, Sphyrna lewini, smooth hammerhead, S. zygaena and great hammerhead S. mokarran) in addition to three species listed in the early part of this century (whale, Rhincodon typus, basking, Cetorhinus maximus, and white, Carcharodon carcharias). Shark fins are traded internationally to supply the Asian dried seafood market, in which they are used to make the luxury dish shark fin soup. Shark fins usually enter international trade with their skin still intact and can be identified using morphological characters or standard DNA-barcoding approaches. Once they reach Asia and are traded in this region the skin is removed and they are treated with chemicals that eliminate many key diagnostic characters and degrade their DNA ("processed fins"). Here, we present a validated mini-barcode assay based on partial sequences of the cytochrome oxidase I gene that can reliably identify the processed fins of seven of the eight CITES listed shark species. We also demonstrate that the assay can even frequently identify the species or genus of origin of shark fin soup (31 out of 50 samples).


Equine herpesvirus 2-associated granulomatous dermatitis in a horse.
Granulomatous dermatitis in horses has been linked to many etiologies, including various parasites, fungi, and bacteria. Idiopathic forms of granulomatous inflammation-producing diseases, some of which are localized to the skin, also have been reported in horses. Herein we describe a case of recurrent equine granulomatous skin disease characterized by intranuclear viral inclusions within macrophages and giant cells. The histologic changes were primarily noted in the deep dermis and included multifocal to coalescing areas of necrosis marked by histiocytic cell infiltration and presence of giant cells. Electron microscopic examination revealed intranuclear and intracytoplasmic viral particles consistent with herpesvirus. Sequence results of the polymerase chain reaction product were consistent with equine herpesvirus 2, adding another possible etiology to the list of differentials in cases of equine granulomatous skin disease.


Chemical characterization of the proteins and glycoproteins of mouse liver plasma membranes solubilized by sequential extraction with aqueous and organic solvents.
1. A procedure for the stepwise fractionation of the proteins of mouse liver plasma membranes is described. 2. Of the membrane protein 20-25% was soluble in 50mm-sodium carbonate-bicarbonate buffer (pH9.7). This fraction contained a large number of proteins but only 1 major glycoprotein. It was low in sialic acid, amino sugars and phospholipid. 3. Extraction of the alkali-insoluble residue with aq. 33% pyridine solubilized an additional 30-35% of the membrane protein. The pyridine-soluble membrane components were enriched in sialic acid and glucosamine and it was shown that this procedure resulted in the selective extraction of glycoproteins. 4. Gel filtration in sodium dodecyl sulphate resolved the pyridine-soluble proteins into five fractions of decreasing molecular weight and an inverse relationship between molecular weight and sialic acid content was indicated.


LINPS: a database for cancer-cell-specific perturbations of biological networks.
Screening for potential cancer therapies using existing large datasets of drug perturbations requires expertise and resources not available to all. This is often a barrier for lab scientists to tap into these valuable resources. To address these issues, one can take advantage of prior knowledge especially those coded in standard formats such as causal biological networks (CBN). Large datasets can be converted into appropriate structures, analyzed once and the results made freely available in easy-to-use formats. We used the Library of Integrated Cellular Signatures to model the cell-specific effect of hundreds of drug treatments on gene expression. These signatures were then used to predict the effect of the treatments on several CBN using the network perturbation amplitudes analysis. We packaged the pre-computed scores in a database with an interactive web interface. The intuitive user-friendly interface can be used to query the database for drug perturbations and quantify their effect on multiple key biological functions in cancer cell lines. In addition to describing the process of building the database and the interface, we provide a realistic use case to explain how to use and interpret the results. To sum, we pre-computed cancer-cell-specific perturbation amplitudes of several biological networks and made the output available in a database with an interactive web interface. Database URL https://mahshaaban.shinyapps.io/LINPSAPP/.


Factors associated with depressive state in patients with myasthenia gravis: a multicentre cross-sectional study.
Objectives The objective of this study was to examine clinical factors associated with depressive state in patients with myasthenia gravis (MG). Design Cross-sectional study. Setting and participants We evaluated 287 consecutive cases of MG seen at six neurological centres located in Eastern Japan. Outcome measures All MG patients completed the Japanese version of the Beck Depression Inventory-Second Edition (BDI-II). Disease severity was determined according to the MG Foundation of America (MGFA) quantitative MG score, MG activities of daily living scale and MG composite scale (MG composite). Clinical state following treatment was categorised according to MGFA postintervention status. Associations between detailed clinical parameters of MG and BDI-II score were then examined statistically. Results Mean BDI-II score for patients with MG (11.0±8.1) did not differ substantially from and overlapped with that reported as the Japanese standard (8.7±6.4). The mean +2 SDs for the Japanese standard is 21.5, approximately equal to the cut-off level indicative of moderate or worse depression (>20 points) in the original English version. We thus defined BDI-II >21.5 as depressive state, with a frequency of 13.6% in patients with MG. Multivariate logistic regression analysis revealed current dose of oral prednisolone (OR 1.09, 95% CI 1.02 to 1.17; p=0.01), unchanged MGFA postintervention status (OR 3.55, 95% CI 1.18 to 10.71; p=0.02), time since onset (OR 0.93, 95% CI 0.87 to 0.99; p=0.03) and MG composite (OR 1.16, 95% CI 1.00 to 1.34; p=0.046) as factors independently associated with depressive state in MG. Conclusions Dose of oral corticosteroids appears to represent the major factor associated with depressive state in MG. Unchanged status despite treatment and early disease stage are also significant background factors for depressive state, along with disease severity.


Symptoms frequency and medical implications of severe asthma in children.
The frequency of asthma symptoms, drug therapy and medical intervention have been studied in a group of 200 children with severe asthma attending an asthma clinic. There was wide use of all the common asthma preparations, usually in combination. An average of 6.4 general practitioner consultations per year per child occurred for asthma episodes. Antibiotics were prescribed regularly in 57% for asthma symptoms. Forty-six percent had attended breathing exercises and physiotherapy for an extended period.


Characterization of biofilm formed on intrauterine devices.
Intrauterine device (IUD) is one of the most convenient contraceptive procedures used by women of Asian and African countries. Previous surveys have revealed that 75% of the IUDs recovered from patients suffering from reproductive tract infections (RTIs) were covered with a consortium of microbes. This study was designed to characterize these microbes and recommend remedial measures. Quantitative measurement of biofilm formation was assessed by a microtitre plate assay on 86 samples of microorganisms dislodged from IUDs of patients with RTIs. Susceptibility of biofilm to various antimicrobial agents was also quantified. Scanning electron microscopy (SEM) was used to scrutinize the microorganisms adherent to IUDs. The organisms associated with IUDs were predominantly composed of Staphylococcus aureus (16%), Staphylococcus epidermidis (18%), Pseudomonas aeruginosa (5%), Escherichia coli (27%), Neisseria gonorrhoeae (2%), Candida albicans (20%) and Candida dubliniesis (12%). SEM studies indicated that these organisms were organized into biofilms. Studies on the in vitro adherence pattern by crystal violet staining on 96 well microtitre plates revealed that the biofilms were stably established after 60 hours. These biofilms are resistant to an array of antibiotics tested. Biofilm formation may be one of the major causes for persistent infection and antibiotic resistance in IUD users.


[Therapeutic effects of Quercus extract in urolithiasis].
97 patients suffering from urolithiasis were treated with Litiax. 82 of them presented ureteral stones and the other 15 kidney stones. The product was administered in doses of 1350 mg. a day. The treatment lasted between 8 and 225 days, the average duration being 58 days. It was revealed from the results obtained that the product tested has an inhibiting effect on the growth of the stone, antiinflammatory and diuretic. It also seems to inhibit the bacteria proliferation to a certain extent. The excellent tolerance of the product is stressed.


A hemispherical contact model for simplifying 3D occlusal surfaces.
Currently, dental articulators can recreate mandibular movements and occlusal contacts. However, whether virtual articulators can also provide information about occluding dental surfaces, functional movements, and the mandibular condyles is unclear. The purpose of this in vitro study was to evaluate the occluding surfaces on dental casts obtained from a patient and approximate them to a hemispherical contact model. Both models were tested by digitizing the Dentatus ARL dental articulator. A combination of photogrammetry and structure from motion methods were used to scan a Dentatus ARL articulator and representative dental casts. Using computer-aided engineering and finite element analysis, contact points and action vectors to the forces on occluding surfaces and condyles were obtained for cast and hemispherical models. This experiment was performed using centric occlusion and 3 different condylar inclinations. The Kruskal-Wallis 1-way analysis of variance on ranks test was used to allow all pairwise comparisons between condylar inclination and mechanical action vector values in each location (α=.05). Action vectors from the cast model and each location of the hemispherical model were calculated to show the mechanical consequences and the similarity among models. Overall, no significant differences were observed for action vectors (A20 versus A40 versus A60) at each location (dental cast/hemisphere, right condylar, and left condylar) in the analysis of dental casts and the hemisphere model (.382≤P≤.999). This study provided graphical information that may assist the dental professional in determining which occlusal contacts should be modified to attain condylar and balanced centric occlusion.


CFTR chloride channel regulation by an interdomain interaction.
The cystic fibrosis gene encodes a chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates CFTR by an unknown mechanism. The amino-terminal cytoplasmic tail of CFTR was found to control protein kinase A-dependent channel gating through a physical interaction with the R domain. This regulatory activity mapped to a cluster of acidic residues in the NH(2)-terminal tail; mutating these residues proportionately inhibited R domain binding and CFTR channel function. CFTR activity appears to be governed by an interdomain interaction involving the amino-terminal tail, which is a potential target for physiologic and pharmacologic modulators of this ion channel.


Two-stage study designs for analyzing disease-associated covariates: linkage thresholds and case-selection strategies.
The incorporation of disease-associated covariates into studies aiming to identify susceptibility genes for complex human traits is a challenging problem. Accounting for such covariates in genetic linkage and association analyses may help reduce the genetic heterogeneity inherent in these complex phenotypes. For Genetic Analysis Workshop 15 (GAW15) Problem 3 simulated data, our goal was to compare the power of several two-stage study designs to identify rheumatoid arthritis-related genes on chromosome 9 (disease severity), 11 (IgM), and 18 (anti-cyclic citrinullated protein), with knowledge of the answers. Five study designs incorporating an initial linkage step, followed by a case-selection scheme and case-control association analysis by logistic regression, were considered. The linkage step was either qualitative-trait linkage analysis as implemented in MERLIN-nonparametric linkage (NPL), or quantitative-trait locus analysis as implemented in MERLIN-REGRESS. A set of cases representing either one case from each available family, one case per linked family (NPL >/= 0), or one case from each family identified by ordered-subset analysis was chosen for comparison with the full set of 2000 simulated controls. As expected, the performance of these study designs depended on the disease model used to generate the data, especially the simulated allele frequency difference between cases and controls. The quantitative trait loci analysis performed well in identifying these loci, and the power to identify disease-associated alleles was increased by using ordered-subset analysis as a case selection tool.


A candidate gene study of canine joint diseases.
Canine osteoarthritis (OA) commonly occurs in association with articular diseases, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament rupture (CCLR). We hypothesized that a common genomic risk for the development of canine joint disease and canine OA would be identified by evaluating the allele frequencies of candidate gene single nucleotide polymorphisms (SNPs) in dogs with OA associated with different articular diseases when compared with a general population of breed-matched dogs. DNA was extracted from blood samples obtained from Labrador Retrievers and Golden Retrievers surgically treated for ED, HD, and CCLR and confirmed to have radiographic evidence of OA. One hundred and thirteen SNPs in 20 candidate genes were genotyped. No significant associations were identified for SNPs or haplotypes in the candidate genes for the diseases evaluated. The candidate gene approach for the study of genetic association is unlikely to be successful for complex canine diseases such as OA without prior trait mapping evaluation.


Short interfering RNA accumulation correlates with host recovery in DNA virus-infected hosts, and gene silencing targets specific viral sequences.
Viruses are both inducers and targets of posttranscriptional gene silencing (PTGS), a natural defense mechanism in plants. Here we report molecular evidence of the ability of single-stranded DNA (ssDNA) viruses to induce PTGS in infected plants irrespective of the severity of or recovery from the symptoms. Our results reveal that five distinct species of cassava-infecting geminiviruses were capable of triggering PTGS by producing two classes of virus-specific short interfering RNAs (siRNAs) of 21 to 26 nucleotides in two plant hosts, tobacco (Nicotiana benthamiana) and cassava (Manihot esculenta, Crantz). However, the efficacy of virus-induced PTGS varied depending on the intrinsic features of the virus and its interaction with the plant host. We found that symptom recovery over time in plants infected with the isolates of African cassava mosaic virus (ACMV-[CM]) or Sri Lankan cassava mosaic virus was associated with a much higher level of virus-derived siRNA accumulation compared to plants infected with viruses that do not show symptom recovery. Furthermore, we determined that the C terminus of AC1 that overlaps with the N terminus of AC2 early viral genes involved in virus replication were the primary targets for ACMV-[CM]-induced PTGS, whereas the C terminus of BC1 was targeted for the East African cassava mosaic Cameroon virus. In addition, our results reveal the possibility for double-stranded RNA formation during transcription in ssDNA viruses, which explains in part how these viruses can trigger PTGS in plants.


Health Technology Agency insights: informing modification of a qualitative benefit risk framework for Health Technology Reassessment of prescription medications.
This study's intent was to determine if a qualitative benefit risk framework could be used or modified to further enable Health Technology Reassessment (HTR) of prescription medicine recommendations. The purpose of this research was to understand Canadian Health Technology Agency assessors past experiences and insights to inform any modifications to the Universal Methodology for Benefit-Risk Assessment (UMBRA) qualitative framework. The UMBRA framework consists of an eight-step process, used during the assessment phase, to aid in decision making and dissemination. A qualitative descriptive study was conducted and included a purposeful, criterion-based sample of eight assessors who had participated in Health Technology Assessment (HTA) or HTR for prescription medicines or in qualitative decision-making frameworks. Participant interviews lead to four common themes: "adoption of a qualitative benefit risk framework," "data (either too much or not enough)," "importance of incorporating stakeholder values," and "feasibility of the UMBRA framework." Methodological challenges with HTR were highlighted including the lack of clinical outcome data and the ability to compare clinically relevant meaningful differences. The implementation of a ranking or weighing process found within the UMBRA framework was not favored by half of the participants. Research participants did not consider all steps of the UMBRA framework to be transferable to the assessment phase of HTR given the need for simplicity, resource efficiency, and stakeholder input throughout the process. The assessor experiences and insights and the resultant key themes can be used in future research to aid in the development of a qualitative recommendation framework for HTR.


Proteomic profiling of vetiver grass (Chrysopogon zizanioides) under 2,4,6-trinitrotoluene (TNT) stress.
Vetiver grass is an ideal plant for 2,4,6-trinitrotoluene (TNT) phytoremediation, due to its ability to tolerate and metabolize TNT as previously reported. The current study is the first attempt to investigate the changes in the proteomic profile of a plant under TNT stress. Vetiver plants were grown in nutrient media with varying concentrations of TNT (0, 25, 50, and 100 mg L-1) for 10 days. Although the plants appeared healthy, significant biomass reductions (p = 0.0008) were observed in treated plants. Total proteins in the root decreased significantly (p = 0.0003). Proteomic analysis of root proteins revealed the downregulation of functional proteins involved in key cellular mechanisms such as transcription, ribosome biogenesis, nucleo-cytoplasmic transport of proteins, protein glycosylation, and translation. Growth-related proteins were downregulated; plant defense proteins were upregulated at lower TNT concentrations but downregulated at higher concentrations. Comprehensive understanding of changes in the proteomic profile provides important clues to the mechanism of TNT stress response and tolerance in vetiver.


Reconstructive surgery of the lower extremity.
Non-operative treatments for degenerative arthritis, such as physiotherapy, anti-inflammatory medication, and occupational therapy, can help reduce the impact of the disease on the joint and hence on the mobility of the patient. Once the joint has become so diseased that non-operative modalities are inadequate, it is the task of the orthopedic surgeon to evaluate these individuals and determine which ones would benefit from a reconstructive procedure. The author explores the indications for arthrotomies, resection arthroplasties, arthrodeses, osteotomies, and total joint replacements. Total joint arthroplasty has revolutionized the treatment of degenerative arthritis of the lower extremity, although it is not a panacea for arthritis in the lower extremity.


Ethnomedical properties of taxus wallichiana zucc. (Himalayan yew).
Taxus wallichiana Zucc., known as Himalayan yew, belongs to the family Taxaceae. It is a medium-sized, temperate, Himalayan forest tree of medicinal importance. In India, this evergreen tree is found at altitudes between 1800 and 3300 m above mean sea level (MSL). It has been used by the native populations for treating common cold, cough, fever, and pain. Its uses are described in Ayurveda and Unani medicine. It received attention recently as its leaves and bark were found to be the prime source of taxol, a potent anticancer drug. It possesses many other biological activities also. We focus on its importance in traditional medicine for its multiple medicinal properties.


A novel ultrasensitive phosphate amperometric nanobiosensor based on the integration of pyruvate oxidase with highly ordered gold nanowires array.
A novel phosphate amperometric nanobiosensor, based on an intimate integration of pyruvate oxidase (PyOx) and its cofactors, thiamine pyrophosphate (TPP) and flavin adenine dinucleotide (FAD), with a highly ordered gold nanowires array (AuNWA) has been developed. The successful integration of PyOx and the co-factors, via crosslinking with bovine serum albumin (BSA) and glutaraldehyde (GLA), onto the AuNWA was confirmed by cyclic voltammetry and amperometry. The resulting nanobiosensor achieved a detection limit of 0.1 µM, a linear concentration range of 12.5-1000 µM, and a sensitivity of 140.3 µA mM(-1)cm(-2). Notably, the incorporation of the AuNWA reduced the required PyOx concentration by 70-120 fold and the presence of common interferants, such as chloride, sulfate, fluoride, nitrite and nitrate ions did not interfere with phosphate detection. Furthermore, the nanobiosensor demonstrated a very high stability with repeated use over two weeks and was successfully used for the determination of phosphate in water samples with an average recovery of 96.6 ± 4.9%.


Ultrastructure of the testis of Pekin ducks fed methyl mercury chloride: seminiferous epithelium.
Testicular cells of Pekin ducks (Anas platyrhynchos) fed with 0 (control), 0.5 (group 1), 5 (group 2), or 15 (group 3) mg of methyl mercury chloride (CH3HgCl)/kg of basal feed for 12 weeks were examined by electron microscope. Sertoli's cells from ducks in group 2 had dilated smooth endoplasm reticulum, increased lysosomes, and large vacuoles, some with lipid droplets. Degenerative changes were more advanced in group 3 ducks. There were increases in lysosomes, myelinoid figures, vacuolations, cytoplasmic and nuclear debris, cristolyses of mitochondria, and distended Golgi's complexes, and a reduction in smooth endoplasm reticulum and microtubules when compared with those of the controls. Spermatogonia were resistant to CH3HgCl exposure, except in 2 ducks from group 3 which had cells that showed electron-lucent cytoplasm, abnormal mitochondria, and membrane-bound vacuoles. In primary spermatocytes, degenerative changes were evident in ducks fed the larger dose levels. In nuclei, synaptonemal complexes showed unpaired elements. In cytoplasm, cellular debris and vacuoles predominated. There was an increase in synchronized meiosis and apparent incomplete cell division. In ducks from group 3, the cellular damage was more severe and was present throughout the germinal epithelium. Spermatids differentiation was affected variably in groups 2 and 3. Severity of damage increased with the increased dosage of mercury. Where there was spermiogenic activity, the electron-dense acrosome granules, manchette, and midpiece were rarely found. Since the seminiferous tubules from 2 ducks in group 3 had severe destruction of spermatocytes and spermatids, the spermiogenic activity was negligible. Ingestion of CH3HgCl caused toxic injury to seminiferous tubules in groups 2 and 3 ducks. The degree of damage was related to the dietary amount of mercury.


Europium as a fluorescent probe of transfer RNA structure.
The binding of europium(III) to Escherichia coli tRNA-fMet,Glu and to unfractionated E. coli tRNA has been investigated by using the 4-thiouridine sensitization of europium 5-Do yields 7-F1 emission and changes in the lifetime of the 5-Do state of europium reported earlier (J. M. Wolfson and D. R. Kearns (1974), J. Am. Chem. Soc. 96, 3653). Binding of the first 3-4 europium ions is independent and sequential, approximately 600 times stronger than the magnesium binding, and the binding sites are located near the 4-thiouridine residue found at position 8 in a number of E. coli tRNA. Competition experiments suggest the strong binding sites are the same for magnesium and europium. The europium binding properties of both unfractionated E. coli tRNA and purified tRNA-fMet are quite similar, indicating that the location of the strong binding sites and their binding constants are nearly the same for a large group of tRNA. The europium binding properties of native and denatured tRNA are quite different, however.


Further insights in the ability of classical nonadditive potentials to model actinide ion-water interactions.
Pursuing our efforts on the development of accurate classical models to simulate radionuclides in complex environments (Réal et al., J. Phys. Chem. A 2010, 114, 15913; Trumm et al. J. Chem. Phys. 2012, 136, 044509), this article places a large emphasis on the discussion of the influence of models/parameters uncertainties on the computed structural, dynamical, and temporal properties. Two actinide test cases, trivalent curium and tetravalent thorium, have been studied with three different potential energy functions, which allow us to account for the polarization and charge-transfer effects occurring in hydrated actinide ion systems. The first type of models considers only an additive energy term for modeling ion/water charge-transfer effects, whereas the other two treat cooperative charge-transfer interactions with two different analytical expressions. Model parameters are assigned to reproduce high-level ab initio data concerning only hydrated ion species in gas phase. For the two types of cooperative charge-transfer models, we define two sets of parameters allowing or not to cancel out possible errors inherent to the force field used to model water/water interactions at the ion vicinity. We define thus five different models to characterize the solvation of each ion. For both ions, our cooperative charge-transfer models lead to close results in terms of structure in solution: the coordination number is included within 8 and 9, and the mean ion/water oxygen distances are 2.45 and 2.49 Å, respectively, for Th(IV) and Cm(III).


A detailed description and 16-year validation of a new suturing method for stabilizing connective tissue grafts at recipient sites for root coverage and gingival augmentation.
Which are the different ways of stabilizing connective tissue grafts (CTGs) for root coverage and gingival augmentation by means of placement of sutures? There are various defined and undefined ways of stabilizing CTGs depending on experience and personal preferences. Most of the techniques profess use of absorbable sutures in separate interrupted fashion (sutures at the corners of the graft wherever possible). This paper describes a new suturing method, "the lingually-tied horizontal mattress contouring suture," for stabilization of CTGs with or without epithelialized collar at the recipient site, for use with papilla retention and sparing techniques to treat marginal tissue recessions. The suturing technique is described in detail. It can be indicated for good number of root coverage cases, with additional objectives of gingival augmentation, specifically developed for papilla sparing and papillary buccal de-epithelialization recipient site preparations. Over a period of last 16 years this suturing technique showed promising results in terms of graft stabilization and survival. The main advantage of this technique lies in the use of cost-effective nonabsorbable sutures that usually retain some amount of tension on the soft tissues longer. The primary objective of the suturing technique, per se, is to stabilize the CTG firmly along the contours of the root surface and to expedite a very close adaptation to the interdental soft tissues as well. The secondary objective of the article or publication is to disseminate the knowledge acquired through long periods of performance and observation for the benefit of the periodontal community as whole. Further validation is advocated.


Ephrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour.
Innate emotion response to environmental stimuli is a fundamental brain function that is controlled by specific neural circuits. Dysfunction of early emotional circuits may lead to neurodevelopmental disorders such as autism and schizophrenia. However, how the functional circuits are formed to prime initial emotional behaviours remain elusive. We reveal here using gene-targeted mutations an essential role for ephrin-B3 ligand-like activity in the development of innate fear in the neonatal brain. We further demonstrate that ephrin-B3 controls axon targeting and coordinates spinogenesis and neuronal activity within the amygdala. The morphological and behavioural abnormalities in ephrin-B3 mutant mice are rescued by conditional knock-in of wild-type ephrin-B3 during the critical period when axon targeting and fear responses are initiated. Our results thus define a key axonal molecule that participates in the wiring of amygdala circuits and helps bring about fear emotion during the important adolescence period.


Correlations of dimensional and discrete dental traits in the post-canine and anterior dental segments.
The present study explores the associations of metric and discrete variation in human canines and first molars. Emphasis is placed on the relation between tooth size and the various grades of expression of the canine distal accessory ridge (CDAR) and Carabelli's trait, in order to test the hypothesis that metric and non-metric variation in the posterior teeth are less well integrated than in the anterior teeth. Metric and discrete dental data were gathered from 120 Lengua Indians (52 male, 68 female), 100 Negroes (52 male, 48 female) and 100 caucasoids (50 male, 50 female). Our results indicate that first maxillary molar size and the Carabelli trait vary independently of one another. Similarly, variation in canine size and in the CDAR appears to be independently determined. Hence it is concluded that tooth size and morphology in the maxillary canines and molars are poorly integrated, irrespective of intra-arcadal position. Furthermore, sex dimorphism and interpopulation differences in the expressivity of Carabelli's trait and the CDAR appear to be unrelated to odontometric differences.


What attracts people to a career in oral and maxillofacial surgery? A questionnaire survey.
A key aspect of recruiting and retaining the best trainees is identification of the factors that attracted them to OMFS. Although such factors have been examined for medicine in general, we know of no previous study that has looked at those that are specific to OMFS. We distributed a survey online to roughly 1500 people who had registered an interest in OMFS over the past seven years. Personal data, and those about education and employment, were recorded, together with particular factors that drew them to OMFS. Of the 251 trainees who responded, 177 (71%) were interested in a career in OMFS. Differences among sub-groups related to dual qualification, sex, and relationships. Open comments identified the following attractive factors: variety of work, intellectually interesting work, collegiate atmosphere within OMFS, and making a difference to patients. The personalities of those who continued with OMFS training placed high value on achievement, and were more conscientious. The factors identified suggest that the positioning of OMFS as a complex, challenging, and varied hospital-based surgical specialty is key to attracting trainees, and these will be used in future research so that we can move forward from identifying preferences to assessing the relative value placed on those preferences. The data will be useful in the development of strategies to attract new trainees and retain them in the specialty.


Collinearity in ecological niche modeling: Confusions and challenges.
Ecological niche models are widely used in ecology and biogeography. Maxent is one of the most frequently used niche modeling tools, and many studies have aimed to optimize its performance. However, scholars have conflicting views on the treatment of predictor collinearity in Maxent modeling. Despite this lack of consensus, quantitative examinations of the effects of collinearity on Maxent modeling, especially in model transfer scenarios, are lacking. To address this knowledge gap, here we quantify the effects of collinearity under different scenarios of Maxent model training and projection. We separately examine the effects of predictor collinearity, collinearity shifts between training and testing data, and environmental novelty on model performance. We demonstrate that excluding highly correlated predictor variables does not significantly influence model performance. However, we find that collinearity shift and environmental novelty have significant negative effects on the performance of model transfer. We thus conclude that (a) Maxent is robust to predictor collinearity in model training; (b) the strategy of excluding highly correlated variables has little impact because Maxent accounts for redundant variables; and (c) collinearity shift and environmental novelty can negatively affect Maxent model transferability. We therefore recommend to quantify and report collinearity shift and environmental novelty to better infer model accuracy when models are spatially and/or temporally transferred.


Social supports and serotonin transporter gene moderate depression in maltreated children.
In this study, measures of the quality and availability of social supports were found to moderate risk for depression associated with a history of maltreatment and the presence of the short (s) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR). The present investigation (i) replicates research in adults showing that 5-HTTLPR variation moderates the development of depression after stress, (ii) extends the finding to children, and (iii) demonstrates the ability of social supports to further moderate risk for depression. Maltreated children with the s/s genotype and no positive supports had the highest depression ratings, scores that were twice as high as the non-maltreated comparison children with the same genotype. However, the presence of positive supports reduced risk associated with maltreatment and the s/s genotype, such that maltreated children with this profile had only minimal increases in their depression scores. These findings are consistent with emerging preclinical and clinical data suggesting that the negative sequelae associated with early stress are not inevitable. Risk for negative outcomes may be modified by both genetic and environmental factors, with the quality and availability of social supports among the most important environmental factors in promoting resiliency in maltreated children, even in the presence of a genotype expected to confer vulnerability for psychiatric disorder.


Brain Lipids and Lipid Droplet Dysregulation in Alzheimer's Disease and Neuropsychiatric Disorders.
Lipids are essential components of the structure and for the function of brain cells. The intricate balance of lipids, including phospholipids, glycolipids, cholesterol, cholesterol ester, and triglycerides, is crucial for maintaining normal brain function. The roles of lipids and lipid droplets and their relevance to neurodegenerative and neuropsychiatric disorders (NPDs) remain largely unknown. Here, we reviewed the basic role of lipid components as well as a specific lipid organelle, lipid droplets, in brain function, highlighting the potential impact of altered lipid metabolism in the pathogenesis of Alzheimer's disease (AD) and NDPs. Brain lipid dysregulation plays a pivotal role in the pathogenesis and progression of neurodegenerative and NPDs including AD and schizophrenia. Understanding the cell type-specific mechanisms of lipid dysregulation in these diseases is crucial for identifying better diagnostic biomarkers and for developing therapeutic strategies aiming at restoring lipid homeostasis.


Novel method to study neutron capture of 235U and 238U simultaneously at keV energies.
The neutron capture cross sections of the main uranium isotopes, (235)U and (238)U, were measured simultaneously for keV energies, for the first time by combining activation technique and atom counting of the reaction products using accelerator mass spectrometry. New data, with a precision of 3%-5%, were obtained from mg-sized natural uranium samples for neutron energies with an equivalent Maxwell-Boltzmann distribution of kT ∼ 25 keV and for a broad energy distribution peaking at 426 keV. The cross-section ratio of (235)U(n,γ)/(238)U(n,γ) can be deduced in accelerator mass spectrometry directly from the atom ratio of the reaction products (236)U/(239)U, independent of any fluence normalization. Our results confirm the values at the lower band of existing data. They serve as important anchor points to resolve present discrepancies in nuclear data libraries as well as for the normalization of cross-section data used in the nuclear astrophysics community for s-process studies.


Vesicoureteral reflux in the primate. III. Effect of urinary tract infection on maturation of the ureterovesical junction.
Our study of the monkey supports the authors who believe that reflux normally occurs in children. It further suggests that recurrent bladder infections may delay maturation of the ureterovesical junction but it does not prevent it. Therefore, we suggest that moderate reflux should be treated conservatively.