To establish the storage conditions of oxytocin in a health facility in a low-income country with a tropical climate, as suboptimal storage may lead to ineffectiveness of drugs essential to prevent and treat postpartum hemorrhage.

At Mulago National Referral Hospital (28000-33000 deliveries/year) in Kampala, Uganda, temperature logging Safe-Rx cards were placed in boxes of oxytocin and in every known storage location. The route of the boxes through the hospital was tracked for 54days, and storage conditions were observed.

Oxytocin was stored within the recommended temperature range (2°C-8°C) 24% of the time. The average temperature measured within the oxytocin boxes was 18.2°C, with a minimum of -2.3°C and maximum of 30.4°C. Six out of twelve known storage places had a refrigerator, but not one location stored medication at the recommended temperature constantly. The average temperature in the storage places ranged from 9.5°C to 27.6°C, with a minimum temperature of 2.3°C and maximum of 30.9°C.

Oxytocin is not stored in the recommended temperature range for the majority of time. The presence of refrigerators does not ensure adherence to advised temperature storage conditions.

Oxytocin is not stored in the recommended temperature range for the majority of time. The presence of refrigerators does not ensure adherence to advised temperature storage conditions.The cytological features of granular cell tumour (GCT) are generally quite typical but, in some cases, the fine needle aspiration cytology (FNAC) diagnosis of GCT may be difficult or impossible because of unusual sites of onset or equivocal cytological features. In this report, two GCTs with atypical FNAC features are described in order to investigate the causes and provide possible diagnostic tips. From a series of nine histologically proven GCTs, two inconclusive FNAC cases were retrieved. Smears were poorly cellular showing isolated naked nuclei, anisonucleosis, granular chromatin and occasional small nucleoli. The background was finely granular in one case. Histological controls of these cases revealed marked fibrosis. Tumour-associated fibrosis in GCT is variable and does not seem to influence clinical behaviour but it influences the harvest and the integrity of granular cells collected by FNAC. When GCT smears are poorly cellular, attention should be paid to the granular background and to the few granular cells, if any, as they might be the only features to suggest a GCT.

To evaluate the risk of fetal involvement when trisomy 8 mosaicism (T8M) is detected in chorionic villus samples (CVS).

A retrospective descriptive study of registered pregnancies in Denmark with T8M in CVS identified through a database search and a review of published cases of T8M found through a systematic literature search and inclusion of cross references. Pregnancies with T8M in CVS and no additional numerical chromosomal aberrations were included.

A total of 37 Danish cases and 60 published cases were included. T8M detected in a CVS was associated with fetal involvement in 18 out of 97 pregnancies (18.6% [95%CI 11.4-27.7]). Eight out of 70 (11.4% [95%CI 5.1-21.3]) interpreted prenatally to be confined placental mosaicism (CPM) were subsequently found to be true fetal mosaicisms (TFM).

T8M detected in CVS poses a significant risk of fetal involvement, and examination of amniotic fluid (AF) and/or fetal tissue should be offered. However, a normal result of AF still has a considerable residual risk of fetal involvement. Genetic counselling at an early gestational age is essential, and follow-up ultrasonography should be performed to predict fetal involvement if possible.

T8M detected in CVS poses a significant risk of fetal involvement, and examination of amniotic fluid (AF) and/or fetal tissue should be offered. However, a normal result of AF still has a considerable residual risk of fetal involvement. Genetic counselling at an early gestational age is essential, and follow-up ultrasonography should be performed to predict fetal involvement if possible.Disclosure rates of child sexual abuse (CSA) to both social supports and law enforcement are concerningly low, although more research is needed to understand factors that impact disclosure. Thus, the present study examined rates of informal (i.e., to a social support) and formal (i.e., to law enforcement) disclosure of CSA, as well as victims’ self-reported experiences with telling others about their own abuse and their perceptions of the overall advantages and disadvantages of disclosure. In all, 76 undergraduate women (who collectively experienced 105 instances of abuse) participated in a semi-structured interview regarding their history of CSA. Results revealed that approximately 50% of cases involved the victim informally disclosing, and only 10% of cases being formally disclosed to authorities. The quantitative and qualitative data shed light on a number of factors that lead victims to not disclose, as well as the identification of factors that may promote a victim to share their abuse with others. The implications for improved prevention and responses to CSA disclosure are discussed.Bone morphogenetic protein (BMP) signaling is well known in bone homeostasis. However, the physiological effects of BMP signaling on mandibles are largely unknown, as the mandible has distinct functions and characteristics from other bones. In this study, we investigated the roles of BMP signaling in bone homeostasis of the mandibles by deleting BMP type I receptor Acvr1 in osteoblast lineage cells with Osterix-Cre. We found mandibular bone loss in conditional knockout mice at the ages of postnatal day 21 and 42 in an age-dependent manner. The decreased bone mass was related to compromised osteoblast differentiation together with enhanced osteoclastogenesis, which was secondary to the changes in osteoblasts in vivo. In vitro study revealed that deletion of Acvr1 in the mandibular bone marrow stromal cells (BMSCs) significantly compromised osteoblast differentiation. When wild type bone marrow macrophages were cocultured with BMSCs lacking Acvr1 both directly and indirectly, both proliferation and differentiation of osteoclasts were induced as evidenced by an increase of multinucleated cells, compared with cocultured with control BMSCs. Furthermore, we demonstrated that the increased osteoclastogenesis in vitro was at least partially due to the secretion of soluble receptor activator of nuclear factor-κB ligand (sRANKL), which is probably the reason for the mandibular bone loss in vivo. Overall, our results proposed that ACVR1 played essential roles in maintaining mandibular bone homeostasis through osteoblast differentiation and osteoblast-osteoclast communication via sRANKL.

Limitations of functional capacity and balance are common features of the natural history of spinocerebellar ataxias (SCA). However, their onset and progression patterns differ according to subtype. The aim of our study was to compare physical functionality and balance parameters in SCA10 and SCA3 patients, correlating with clinical variables.

Cross-sectional study evaluating ninety-five SCA patients (60 with SCA3 and 35 with SCA10) with validated scales for functional independence, balance and the severity of signs and symptoms.

The groups were similar in terms of age and gender, and results were adjusted for age at symptom onset. The SCA10 patients had better results for balance and functional independence (p<0.007). They also had lower scores for disease severity (p<0.0002) and the subitems gait (p<0.0005), posture (p<0.0021) and sitting balance (p<0.0008). Symptom progression in both groups was similar for patients with a disease duration of up to ten years, but there was a more marked decline in SCA3 patients after this period.

We have shown that disease progression as assessed by balance and physical functioning is slower in SCA10 patients than SCA3 patients, particularly after 10years of disease. These findings are important as they can help to characterize the disease, assisting in the development of new therapies and rehabilitation programs.

We have shown that disease progression as assessed by balance and physical functioning is slower in SCA10 patients than SCA3 patients, particularly after 10 years of disease. These findings are important as they can help to characterize the disease, assisting in the development of new therapies and rehabilitation programs.Early embryogenesis is marked by a frail Spindle Assembly Checkpoint (SAC). The time of SAC acquisition varies depending on the species, cell size or a yet to be uncovered developmental timer. This means that for a specific number of divisions, biorientation of sister chromatids occurs unsupervised. When error-prone segregation is an issue, an aneuploidy-selective apoptosis system can come into play to eliminate chromosomally unbalanced cells resulting in healthy newborns. However, aneuploidy content can be too great to overcome, endangering viability. SAC generates a diffusible signal to lengthen time spent in mitosis if needed, ensuring correct chromosome segregation, a fundamental factor in the generation of euploid cells. Thus, it remains puzzling what benefit could come from delaying SAC acquisition till later in the development. In this review, we describe what is known on SAC acquisition in distinct species and highlight pending research as well as potential applications for such knowledge.The plant apoplast is a harsh environment in which hydrolytic enzymes, especially proteases, accumulate during pathogen infection. However, the defense functions of most apoplastic proteases remain largely elusive. We show here that a newly identified small cysteine-rich secreted protein PC2 from the potato late blight pathogen Phytophthora infestans induces immunity in Solanum plants only after cleavage by plant apoplastic subtilisin-like proteases, such as tomato P69B. A minimal 61 amino acid core peptide carrying two key cysteines, conserved widely in most oomycete species, is sufficient for PC2-induced cell death. Furthermore, we showed that Kazal-like protease inhibitors, such as EPI1, produced by P. infestans prevent PC2 cleavage and dampen PC2 elicited host immunity. This study reveals that cleavage of pathogen proteins to release immunogenic peptides is an important function of plant apoplastic proteases.Endothelial dysfunction is the early marker and precursor for the development of a series of vascular disease. Epidemiologic and experimental evidences have suggested that regular consumptions of polyphenol rich extracts or individual phenolic compounds both improve endothelial function. The present review concludes the recent advances in the protective effects of polyphenol-rich extracts and individual phenolic compounds on the endothelial function. The vascular protective benefits of polyphenol have been well established with so many in vitro and in vivo studies. The mechanisms underlying the protection actions have also been elucidated much. Further studies may lay efforts on understanding the controversies among results from different assays, exploring deeper and more comprehensive mechanisms, elaborating the structure-activity relationship, and improving the safety evaluation research.Birth prevalence of cerebral palsy (CP) is declining in high-income countries, to as low as 1.4 per 1000 live births in the most recent international reports. This represents a 35% reduction in birth prevalence over a 15-year period. This reduction is underpinned by a heightened focus of attention towards all aspects of CP, including increased awareness, better data collection, development of national networks and registries, an explosion of research in basic science, perinatal care, neonatal neurology, public health, early detection, and targeted early intervention. Quick uptake of evidence into practice has ensued and overall improvements in clinical care occurred concurrently. It is anticipated that with continued partnerships with families, ongoing research driving further clinical improvement and vice versa, birth prevalence and severity of CP will further decline and the focus will shift to prevention in low- and middle-income countries. WHAT THIS PAPER ADDS Research in the field of perinatal care and cerebral palsy (CP) prevention has increased significantly. In high-income countries, increased awareness of CP and scientific advances have improved clinical care. Population-based registers have limitations but remain the best mechanism to quantify birth prevalence of CP and accurately track trends. There have been recent reductions in the birth prevalence of CP.

The ion collection efficiency of vented ionization chambers has been investigated in an ultra-high dose-per-pulse (DPP) electron beam. The role of the chamber design and the electric field strength in the sensitive air volume have been evaluated.

An advanced Markus chamber and three specially designed parallel plate air-filled ionization chambers (EWC End Window Chamber) with varying electrode distance of 0.5, 1, and 2mm have been investigated. Their ion collection efficiencies were determined experimentally using two methods extrapolation of Jaffé plots and comparison against a DPP-independent reference detector. The latter was achieved by calibrating a current transformer against alanine dosimeters. All measurements were performed in a 24 MeV electron beam with DPP values between 0.01 and 3Gy. Additionally, the numerical approach introduced by Gotz et al. was implemented taking into account space charge effects at these ultra-high DPPs. The method has been extended to obtain time-resolved and position-dvoltage or a reduction of the electrode distance, improves the ion collection efficiency and also reduces the polarity effect. For the Advanced Markus chamber, the experimental results obtained by comparison against a reference agree well with the numerical solution. Based on these results, it seems possible to keep the recombination loss less than or equal to 5% up to a dose-per-pulse of 3 Gy with an appropriately designed ionization chamber, which corresponds to the level accepted in conventional radiotherapy dosimetry protocols.SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56- CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.The availability of intensive care beds during the COVID-19 epidemic is crucial to guarantee the best possible treatment to severely affected patients. In this work we show a simple strategy for short-term prediction of COVID-19 intensive care unit (ICU) beds, that has proved very effective during the Italian outbreak in February to May 2020. Our approach is based on an optimal ensemble of two simple methods a generalized linear mixed regression model, which pools information over different areas, and an area-specific nonstationary integer autoregressive methodology. Optimal weights are estimated using a leave-last-out rationale. The approach has been set up and validated during the first epidemic wave in Italy. A report of its performance for predicting ICU occupancy at regional level is included.Various lines of evidence implicate oxidative stress in the pathogenic mechanism(s) underpinning tauopathies. Consequently, antioxidant therapies have been considered in clinical practice for the treatment of tauopathies such as Alzheimer’s disease (AD), but with mixed results. We and others have previously reported increased protein oxidation upon expression of both human 0N3R (hTau0N3R ) and 0N4R (hTau0N4R ) tau in vivo. Building on these studies, we demonstrate here the suppression of hTau0N3R associated phenotypes in Drosophila melanogaster after treatment with vitamin C or vitamin E. Curiously the rescue of phenotype was seen without alteration in total tau level or alteration in phosphorylation at a number of disease-associated sites. Moreover, treatment with paraquat, a pro-oxidant drug, did not exacerbate the hTau0N3R phenotypes. This result following paraquat treatment is reminiscent of our previous findings with hTau0N4R which also causes greater oxidative stress when compared to hTau0N3R but has a milder phenotype. Collectively our data imply that the role of oxidative stress in tau-mediated toxicity is not straight forward and there may be isoform-specific effects as well as contribution of other factors. This may explain the ambiguous effects of anti-oxidant treatments on clinical outcome in dementia patients.Lithium-rich layered oxides (LLOs) are prospective cathode materials for next-generation lithium-ion batteries (LIBs), but severe voltage decay and energy attenuation with cycling still hinder their practical applications. Herein, a series of full concentration gradient-tailored agglomerated-sphere LLOs are designed with linearly decreasing Mn and linearly increasing Ni and Co from the particle center to the surface. The gradient-tailored LLOs exhibit noticeably reduced voltage decay, enhanced rate performance, improved cycle stability, and thermal stability. Without any material modifications or electrolyte optimizations, the gradient-tailored LLO with medium-slope shows the best electrochemical performance, with a very low average voltage decay of 0.8 mV per cycle as well as a capacity retention of 88.4% within 200 cycles at 200 mA g-1 . These excellent findings are due to spinel structure suppression, electrochemical stress optimization, and Jahn-Teller effect inhibition. Further investigation shows that the gradient-tailored LLO reduces the thermal release percentage by as much as about 41% when the battery is charged to 4.4 V. This study provides an effective method to suppress the voltage decay of LLOs for further practical utilization in LIBs and also puts forward a bulk-structure design strategy to prepare better electrode materials for different rechargeable batteries.Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.

Data visualization techniques were used to ascertain (1) site-specific effects of cigarette smoking on the periodontium compared to never-smokers; (2) patterns of site-specific effects by age among current and never-smokers using contour maps.

Data from 10,713 dentate participants aged ≥30 years in NHANES 2009-2014 were used. Pocket depth (PD) and clinical attachment level (CAL) for six sites/tooth were ascertained by smoking status and plotted using contour maps to identify new patterns.

In the overall sample, 19% (n=2015) were current smokers and 56% (n=6013) were never-smokers. Contour maps of the overall sample showed teeth/sites most affected with mean PD>2.1mm were molars (2,3,15,18,19,30,31) in mesio-lingual (ML) and disto-lingual (DL) sites. Most affected sites for current smokers were interproximal sites of most posterior teeth. Among never-smokers, fewer teeth/sites were affected with PD>2.1mm, whereas among smokers, number of affected teeth/sites increased with age. Overall, teeth/siteserent contour pattern than never-smokers.Fibrosis is one of the largest sources of human morbidity. The skin is a complex organ where interplay between diverse cell types and signalling pathways is essential both in homeostasis and wound repair, which can result in fibrosis or regeneration. This makes skin a useful model to study fibrosis and regeneration. While fibrosis often occurs postinjury, both clinical and laboratory observations suggest skin regeneration, complete with reconstituted cell diversity and de novo hair follicles, is possible. Extensive research performed in pursuit of skin regeneration has elucidated the key players, both cellular and molecular. Interestingly, some cells known for their homeostatic function are not implicated in regeneration or wound-induced hair neogenesis (WIHN), suggesting regeneration harnesses separate functional pathways from embryogenesis or other non-homeostatic mechanisms. For example, classic bulge cells, noted for their role in normally cycling hair follicles, do not finally contribute to long-lived cells in the regenerated tissue. During healing, multiple populations of cells, among them specific epithelial lineages, mesenchymal cells, and immune cells promote regenerative outcomes in the wounded skin. Ultimately, targeting specific populations of cells will be essential in manipulating a postwound environment to favour regeneration in lieu of fibrosis.

Cutaneous tuberculosis (CTB) rarely involves the ear as the primary site, but while diagnosing and treating ear infections, it should be considered a differential diagnosis in a tropical country such as India. The present study reports the incidence and clinical presentation of auricular tuberculosis (TB) in a tertiary care hospital in New Delhi.

A retrospective, observational study was conducted from 2005 to 2019 whereby all cases of CTB confirmed by biopsy were retrieved from the database. The demographic details, clinical details, Mantoux results, and photographs were extracted and studied. The data were entered into MS Excel and analyzed.

In a retrospective analysis of 886 cases of CTB over a period of 15years, we found 20 cases (2.26%) of ear involvement (1 case with bilateral involvement). The median age of the patients with ear involvement was 29years with 42.11% men and 57.89% women. Morphological variants seen over pinna were predominantly classic plaque type (31.58%) and nodular (31.58%), with few ulcerative (21.05%) and tumoral forms (15.79%). CTB of the pinna showed predominant involvement of either helix or ear lobule (7 cases each). All cases were strongly positive to tuberculin and showed response to the empirical antitubercular treatment.

CTB can exclusively affect the pinna in varied presentations. The ear lobules and the helix are the usual sites of affection. It is rare for both ears to be affected with CTB, unlike bacilliferous leprosy. Regression following institution of antitubercular treatment is a reasonable way to confirm CTB.

CTB can exclusively affect the pinna in varied presentations. The ear lobules and the helix are the usual sites of affection. It is rare for both ears to be affected with CTB, unlike bacilliferous leprosy. Regression following institution of antitubercular treatment is a reasonable way to confirm CTB.

Long-term potentiation of glutamatergic transmission to hippocampal interneurons in stratum oriens does not require NMDA receptors and the induction mechanisms are incompletely understood. Extracellular stimulation, conventionally used to monitor synaptic strength and induce long-term potentiation (LTP), does not exclusively recruit glutamatergic axons. We used optogenetic stimulation of either glutamatergic or cholinergic afferents to probe the relative roles of different signalling mechanisms in LTP induction. Selective stimulation of cholinergic axons was sufficient to induce LTP, which was prevented by chelating postsynaptic Ca

or blocking nicotinic receptors. The present study adds nicotinic receptors to the list of sources of Ca

that induce NMDA receptor independent LTP in hippocampal oriens interneurons.

Many interneurons located in stratum oriens of the rodent hippocampus exhibit a form of long-term potentiation (LTP) of glutamatergic transmission that does not depend on NMDA receptors for itsnsmission that does not depend on NMDA receptors for its induction but, instead, requires Ca2+ -permeable AMPA receptors and group I metabotropic glutamate receptors. A role for cholinergic signalling has also been reported. However, electrical stimulation of presynaptic axons, conventionally used to evoke synaptic responses, does not allow the relative roles of glutamatergic and cholinergic synapses in the induction of LTP to be distinguished. Here, we show that repetitive optogenetic stimulation confined to cholinergic axons is sufficient to trigger a lasting potentiation of glutamatergic signalling. This phenomenon shows partial occlusion with LTP induced by electrical stimulation, and is sensitive to postsynaptic Ca2+ chelation and blockers of nicotinic receptors. ACh release from cholinergic axons is thus sufficient to trigger heterosynaptic potentiation of glutamatergic signalling to oriens interneurons in the hippocampus.Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first reported in December 2019 in Wuhan, China, but now more than 200 countries have been affected and the coronavirus pandemic is still ongoing. The severity of COVID-19 symptoms can range from mild to severe. FDA approved remdesivir as a treatment of COVID-19 so far. Various clinical trials are underway to find an effective method to treat patients with COVID-19. This review aimed at summarizing 219 registered clinical trials in the ClinicalTrials.gov database with possible mechanisms, and novel findings of them, and other recent publications related to COVID-19. According to our analyses, various treatment approaches and drugs are being investigated to find an effective drug to cure COVID-19 and among all strategies, three important mechanisms are suggested to be important against COVID-19 including antiviral, anti-inflammatory, and immunomodulatory properties. Our review can help future studies get on the way to finding an effective drug for COVID-19 treatment by providing ideas for similar researches.Stable-isotope analysis (SIA) provides a valuable tool to address complex questions pertaining to elasmobranch ecology. Liver, a metabolically active, high turnover tissue (~166 days for 95% turnover), has the potential to reveal novel insights into recent feeding/movement behaviours of this diverse group. To date, limited work has used this tissue, but ecological application of SIA in liver requires consideration of tissue preparation techniques given the potential for high concentrations of urea and lipid that could bias δ13 C and δ15 N values (i.e., result in artificially lower δ13 C and δ15 N values). Here we investigated the effectiveness of (a) deionized water washing (WW) for urea removal from liver tissue and (b) chloroform-methanol for extraction of lipids from this lipid rich tissue. We then (a) established CN thresholds for deriving ecologically relevant liver isotopic values given complications of removing all lipid and (b) undertook a preliminary comparison of δ13 C values between tissue pairs (mδ13 C values were observed for known regional movements of DUS and RAG (δ13 CDiffs = 0.24 ± 0.99‰ and 0.57 ± 0.38‰, respectively), while SCA and GRE showed greater differences (1.24 ± 0.63‰ and 1.08 ± 0.71‰, respectively) correlated to large-scale movements between temperate/tropical and pelagic/coastal environments. These data provide an approach for the successful application of liver δ13 C and δ15 N values to examine elasmobranch ecology.

A key principle of individual differences research is that biological and environmental factors jointly influence personality and psychopathology. Genes and environments interact to influence the emergence and stability of both normal and abnormal behavior (i.e., genetic predisposition, X, is exacerbated or buffered under environmental conditions, Y, or vice versa), including by shaping the neural circuits underpinning behavior. The interplay of genes and environments is also reflected in various ways in which they are correlated (i.e., rGE). That is, the same genetic factors that give rise to personality or psychopathology also shape that person’s environment.

In this review, we outline passive, evocative, and active rGE processes and review the findings of studies that have addressed rGE in relation to understanding individual differences in personality and psychopathology across development.

Throughout, we evaluate the question of whether it is possible, not only to differentiate the person from their problems, but also to differentiate the person from their problems and their environment.

We provide recommendations for future research to model rGE and better inform our ability to study personality and psychopathology, while separating the influence of the environment.

We provide recommendations for future research to model rGE and better inform our ability to study personality and psychopathology, while separating the influence of the environment.Healthy individuals perform a task such as hitting the head of a nail with an infinite coordination spectrum. This motor redundancy is healthy and allows for learning through exploration and uniform load distribution across muscles. Assessing movement complexity within repetitive movement trajectories may provide insight into the available motor redundancy during aging. We quantified complexity of repetitive arm elevation trajectories in the aging shoulder and assessed test-retest reliability of this quantification. In a cross-sectional study using 3D-electromagnetic tracking, 120 asymptomatic subjects, aged between 18 and 70 years performed repetitive abduction and forward/anteflexion movements. Movement complexity was calculated using the Approximate Entropy (ApEn-value) [0,2], where lower values indicate reduced complexity. Thirty-three participants performed the protocol twice, to determine reliability (intraclass correlation coefficient [ICC]). The association between age and ApEn was corrected for task characteristics (e.g., sample length) with multiple linear regression analysis. Reproducibility was determined using scatter plots and ICC’s. Higher age was associated with lower ApEn-values during abduction (unstandardized estimate -0.003/year; 95% confidence interval [-0.005; -0.002]; p  less then  .001). ICC’s revealed poor to good reliability depending on differences in sample length between repeated measurements. The results may imply more stereotype movement during abduction in the ageing shoulder, making this movement prone to the development of shoulder complaints. Future studies may investigate the pathophysiology and clinical course of shoulder complaints by assessment of movement complexity. To this end, the ApEn-value calculated over repetitive movement trajectories may be used, although biasing factors such as sample length should be taken into account.The Rasptail skate Rostroraja velezi is commercially exploited in artisanal elasmobranch fisheries along the west coast of Baja California Sur, Mexico, but information on its life history is limited. This study aimed to investigate the reproductive biology of R. velezi. A total of 105 specimens were caught from April 2008 to May 2012, including the largest reported specimen with 121 cm total length, 96 cm disc width (DW ). Females attained larger sizes than males. Males and females presented functional gonads. There was an asymmetry in the testes of males, with the left testis being larger. Histological analysis of the reproductive biology of R. velezi was performed here for the first time. The presence of sperm storage in females and spermatogenic development beginning at the first stages of maturity in males was recorded. It was possible to identify the development of secretions in the club, baffle and terminal zone of the oviducal gland. DW at maturity, defined as the DW at which 50% of the population is mature, was estimated at 68-72 cm for females and 65.1 cm for males. Egg-bearing females caught in April and May presented one egg capsule per uterus. Furthermore, a description of the egg capsule of R. velezi is provided. Elucidating the reproductive cycle, the type of reproductive strategies, and the fecundity of R. velezi will allow us to understand the impact of fisheries on this species.

Gender dysphoria is described as a mismatch between an individual’s experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person’s sexual characteristics to their desired sex is called 'transition.’ Current guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body’s male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these tras of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.

To evaluate the sensitivity, specificity, and predictive value of the Hand Assessment for Infants (HAI) in identifying infants at risk of being diagnosed with unilateral cerebral palsy (CP), and to determine cut-off values for this purpose.

A convenience sample of 203 infants (106 females, 97 males) was assessed by the HAI at 3, 6, 9, and 12months. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using receiver operating characteristic curve analysis. Cut-off values were derived for different ages. The clinical outcome (unilateral CP yes/no) at 24months or more served as an external criterion to investigate the predictive validity of HAI.

Half of the infants developed unilateral CP. The area under the curve ranged from 0.77 (95% CI [confidence interval] 0.63-0.91) to 0.95 (95% CI 0.90-1.00) across HAI scales and age intervals. Likewise, sensitivity ranged from 63% to 93%, specificity from 62% to 91%, and accuracy from 73% to 94%.

HAI scores demonstrated overall accurace for early identification and diagnosis of unilateral CP.We explore here our mechanistic understanding of the environmental and physiological processes that determine the oxygen isotope composition of leaf cellulose (δ18 Ocellulose ) in a drought-prone, temperate grassland ecosystem. A new allocation-and-growth model was designed and added to an 18 O-enabled soil-vegetation-atmosphere transfer model (MuSICA) to predict seasonal (April-October) and multi-annual (2007-2012) variation of δ18 Ocellulose and 18 O-enrichment of leaf cellulose (Δ18 Ocellulose ) based on the Barbour-Farquhar model. Modelled δ18 Ocellulose agreed best with observations when integrated over c. 400 growing-degree-days, similar to the average leaf lifespan observed at the site. Over the integration time, air temperature ranged from 7 to 22°C and midday relative humidity from 47 to 73%. Model agreement with observations of δ18 Ocellulose (R2 = 0.57) and Δ18 Ocellulose (R2 = 0.74), and their negative relationship with canopy conductance, was improved significantly when both the biochemical 18 O-fractionation between water and substrate for cellulose synthesis (εbio , range 26-30‰) was temperature-sensitive, as previously reported for aquatic plants and heterotrophically grown wheat seedlings, and the proportion of oxygen in cellulose reflecting leaf water 18 O-enrichment (1 – pex px , range 0.23-0.63) was dependent on air relative humidity, as observed in independent controlled experiments with grasses. Understanding physiological information in δ18 Ocellulose requires quantitative knowledge of climatic effects on pex px and εbio .The mechanism of heat stress response in plants has been studied, focusing on the function of transcription factors (TFs). Generally, TFs recruit coactivators, such as Mediator, are needed to assemble the transcriptional machinery. However, despite the close relationship with TFs, how coactivators are involved in transcriptional regulation under heat stress conditions is largely unclear. We found a severe thermosensitive phenotype of Arabidopsis mutants of MED14 and MED17. Transcriptomic analysis revealed that a quarter of the heat stress (HS)-inducible genes were commonly downregulated in these mutants. Furthermore, chromatin immunoprecipitation assay showed that the recruitment of Mediator by HsfA1s, the master regulators of heat stress response, is an important step for the expression of HS-inducible genes. There was a differential requirement of Mediator among genes; TF genes have a high requirement whereas heat shock proteins (HSPs) have a low requirement. Furthermore, artificial activation of HsfA1d mimicking perturbation of protein homeostasis induced HSP gene expression without MED14 recruitment but not TF gene expression. Considering the essential role of MED14 in Mediator function, other coactivators may play major roles in HSP activation depending on the cellular conditions. Our findings highlight the importance of differential recruitment of Mediator for the precise control of HS responses in plants.Hydrogen sulphide (H2 S) is an endogenously produced gasotransmitter that has rapidly emerged as an active signalling component of several plant processes, stomatal movement regulation among them. The guard cells (GCs), pairs of cells that neighbour the stomatal pores, transduce endogenous and environmental signals, through signalling network, to control stomatal pore size. In this complex network, which has become a model system for plant signalling, few highly connected components form a core that links most of the pathways. The evidence summarized in this insight, on the interplay between H2 S and different key components of the GC networks, points towards H2 S as a regulator of the GC core signalling pathway.

Obesity, diabetes and cardiovascular disease are associated with COVID-19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat.

Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open-heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real-time PCR of ACE1, ACE2 and ADAM17. From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA.

Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49-1.61] vs 1.51 [1.47-1.56] a.u., P<.05) and lower ADAM17 than subcutaneous fat (1.67 [1.65-1.70] vs 1.70 [1.66-1.74] a.u., P<.001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50-2.28] vs 1.52 [1.49-1.55] a.u-CoV-2 infection.

Sparse evidence of the prognostic benefit of the anti-inflammatory drug colchicine in chronic and acute coronary syndromes (CCS/ACS) exists.

We performed a systematic search of studies on CCS or ACS comparing colchicine vs. placebo and reporting data on cardiovascular outcomes (primary end points of each study) and/or changes in hs-CRP.

Ten studies were selected three on CCS (LoDoCo, LoDoCo2 and the CCS subgroup of COLCHICINE-PCI; total patient number=6256), three on ACS (COLCOT, COPS, ACS subgroup of COLCHICINE-PCI; n=5,654) and five (n=532) on hs-CRP changes from 1week to 12months, in CCS and/or ACS. In patients with CCS, colchicine reduced by 49% risk of a composite end point (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32 to 0.81, P=.005). The favourable effect of colchicine on the risk of cardiovascular events did not change when excluding COLCHICINE-PCI from analysis (HR 0.51, 95% CI 0.25 to 1.03, P=.061). In patients with ACS, the use of colchicine tended to decrease the occurrence of the combined end point compared with placebo (HR=0.77, 95% CI 0.56 to 1.05, P=.100), and colchicine became significantly protective when removing COLCHICINE-PCI from analysis (HR=0.72, 95% CI 0.56 to 0.92, P=.009). Furthermore, colchicine tended to reduce the hs-CRP increase (standardized mean difference=-0.31, 95% CI -0.72 to 0.1, P=.133) compared with placebo.

Colchicine therapy near halves the risk of cardiovascular events in CCS compared with placebo and is associated with a nonsignificant 23% risk reduction in ACS, together with a trend towards a greater reduction of hs-CRP.

Colchicine therapy near halves the risk of cardiovascular events in CCS compared with placebo and is associated with a nonsignificant 23% risk reduction in ACS, together with a trend towards a greater reduction of hs-CRP.The information available on program websites concerning geriatric fellowships in internal medicine and family medicine is a crucial factor in generating applicants’ interest in individual programs. Our study aimed to quantify the accessibility and quality of information available on accredited geriatric (family medicine and internal medicine) fellowship program websites and further analyze the implications of the results obtained. A list of geriatric (family medicine and internal medicine) fellowship programs was analyzed through quantified measures after being verified for accreditation. Certain criteria were evaluated for each of these programs, such as website accessibility and whether critical information was available on online program websites. These criteria were centered on academic, administrative, and application-based factors. Hundred and fifty eight Family Medicine and Internal Medicine geriatric fellowship programs were identified in total, of which only 150 were accredited by the Accreditation Council for Graduate Medical Education and considered for analysis. Of these, 20 (13.33%) programs had website links that were nonfunctional and only 145 programs had websites at all. On programs’ websites, information regarding aspects such as contact information-including phone number or email for the program-were lacking. Other information regarding past and current fellows, research, and curriculum were also generally lacking. Geriatric Fellowship websites in Family Medicine and Internal Medicine can gain better traction from those interested in applying for their programs by updating information more often and providing more and better information concerning critical aspects of the programs themselves online.

To identify urodynamic predictors for de novo overactive bladder (OAB) after single-incision sling implantation.

This retrospective study analyzed women with pure, urodynamically proven stress urinary incontinence, without OAB, between 2008 and 2015, in a university hospital. De novo OAB was investigated during clinical interviews.

A total of 192 patients were analyzed; 21 patients with de novo OAB were considered as group A while 171 control patients formed group B. Univariate analysis demonstrated that patients with de novo OAB have the first desire to void at a lower bladder volume (124mL versus 160mL, P=0.0052), smaller maximum cystometric capacity (357mL versus 406mL, P=0.0061), lower maximum flow (17mL/s versus 23mL/s, P=0.0006), and higher bladder outlet obstruction index (BOOI; -11 versus -23, P=0.0022) compared with controls. According to multivariate analysis, maximum cystometric capacity (parameter estimate [PE]=0.008, P=0.04) and BOOI (PE=-0.029, P=0.01) were independent urodynamic predictors of de novo OAB. The final model showed good predictive accuracy (area under the curve=0.81).

The present study identified maximum cystometric capacity and BOOI as independent predictors of de novo overactive bladder after single-incision sling implantation. Therefore, preoperative urodynamics may be useful to improve preoperative counseling and to tailor surgical treatment.

The present study identified maximum cystometric capacity and BOOI as independent predictors of de novo overactive bladder after single-incision sling implantation. Therefore, preoperative urodynamics may be useful to improve preoperative counseling and to tailor surgical treatment.

Patients hesitate to consent to electroconvulsive therapy (ECT) because of the fear of memory impairment. The mechanisms underlying this impairment are unclear, but several observations suggest hippocampal alterations may be involved. We investigated whether ECT-induced change in hippocampal volume correlates with memory impairment.

Using a 3T MRI scanner, we acquired brain images and assessed cognitive performance in 22 severely depressed patients at three time points (1) before ECT series, (2) within one week after the series, and (3) at six-month follow-up. The hippocampus was segmented into subregions using FreeSurfer. The dentate gyri (DG) were the primary regions of interest (ROIs) and major hippocampal subregions secondary ROIs. Cognitive performance was assessed using the Screen for Cognitive Impairment in Psychiatry and verbal memory using the Verbal Learning subtest. The linear mixed model and the repeated-measures correlation were used for statistical analyses.

ECT induced an increase in the right and left DG volume with co-occurring worsening in verbal memory, and these changes were within-patients negatively correlated (right DG, r

=-0.85, df=18, p=0.0000002; left DG, r

=-0.58, df=18, p=0.008). At a six-month follow-up, the volume of both DG decreased with a co-occurring improvement in verbal memory, and these changes were negatively correlated in the right DG (r

=-0.64, df=15, p=0.005). Volume increases in 14 secondary ROIs were also negatively correlated with memory impairment.

ECT-related transient increases in the volume of major hippocampal subregions within-patients are associated with memory impairment. Hippocampal alterations following ECT should be the focus in searching for causes of the cognitive side effects.

ECT-related transient increases in the volume of major hippocampal subregions within-patients are associated with memory impairment. Hippocampal alterations following ECT should be the focus in searching for causes of the cognitive side effects.

Sickle cell diseaseencompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormalallelethat could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.

The objectives of this review are – to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; – to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.