Rethinking the concepts of “local or global processors”: evidence from Williams syndrome, Down syndrome, and Autism Spectrum Disorders

Both Williams syndrome (WS) and Autism Spectrum Disorder (ASD) have been characterised as preferentially processing local information, whereas in Down syndrome (DS) the reported tendency is to process stimuli globally. We designed a cross-syndrome, cross-task comparison to reveal similarities and differences in local/global processing in these disorders. Our in-depth study compared local/global processing across modalities (auditory-verbal/visuo-spatial) and levels of processing (high/low) in the three syndromes. Despite claims in the literature, participants with ASD or WS failed to show a consistent local processing bias, while those with DS failed to show a reliable global processing bias. Depending on the nature of the stimuli and the task, both local and global processing biases were evident in all three neurodevelopmental disorders. These findings indicate that individuals with neurodevelopmental disorders cannot simply be characterised as local or global processors

Economic evaluation of Medically Assisted Reproduction : an educational overview of methods and applications for healthcare professionals

Acknowledgements Medical writing support was provided by Steven Goodrick of in Science Communications, Springer Healthcare Ltd, UK, and was funded by Merck Healthcare KGaA, Darmstadt, GermanyPeer reviewedPostprin

Zebra mussels (Dreissena polymorpha) are effective sentinels of water quality irrespective of their size

Zebra mussels (Dreissena polymorpha) are recognised biomonitors in determining the presence and viability of the human\ud waterborne pathogens Cryptosporidium parvum, C. hominis, Giardia intestinalis and microsporidia in surface waters. This study\ud investigated whether the size of zebra mussels is a significant factor in the concentration of protozoan Cryptosporidium oocysts,\ud Giardia cysts and microsporidian spores. Zebra mussels were collected in Lough Arrow, a small Irish lake, which is utilized for\ud drinking water abstraction and is subject to agricultural and human wastewater pollution drivers, both recognised risk factors for\ud human waterborne pathogens. Zebra mussels were cleaned, divided into size (5 mm) interval classes based on their shell length\ud and made up to 150 g samples (wet weight with shell). Combined fluorescence in situ hybridization (FISH) and\ud immunofluorescent antibody (IFA) techniques were utilized as biomolecular techniques to assess the presence and concentration\ud of the pathogens. PCR analysis provided source-tracking information on human and animal pollution sources. There was no\ud significant relationship between the size of D. polymorpha and pathogen loads in similar sized samples, indicating that different\ud sites in the same or different waterbody can be compared in terms of relative concentrations of human waterborne parasites\ud irrespective of the zebra mussels’ size. Cryptosporidium was the most abundant species, with lower counts of Giardia and the\ud microsporidian Encephalitozoon hellem, respectively. Cryptosporidium oocysts and Giardia cysts were detected in zebra mussel\ud samples at all three lake water abstraction points. A lake transect showed a decline in Cryptosporidium with increasing distance\ud from a stream discharging sewage. Samples from agricultural sites indicated faecal inputs contaminated with these pathogens.\ud Species identification implicated both human and animal faecal inputs to the lake from treated effluent, septic tanks, and\ud agriculture. The research demonstrates the efficacy of zebra mussels as sentinels of water quality irrespective of their size

Adiponectin reduces glomerular endothelial glycocalyx disruption and restores glomerular barrier function in a mouse model of type 2 diabetes

Adiponectin has vascular anti-inflammatory and protective effects. Although adiponectin protects against the development of albuminuria, historically, the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnCs). In diabetes, eGlx dysfunction occurs before podocyte damage; hence, we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD). Globular adiponectin (gAd) activated AMPK signaling in human GEnCs through AdipoR1. It significantly reduced eGlx shedding and the TNF-α–mediated increase in syndecan-4 (SDC4) and MMP2 mRNA expression in GEnCs in vitro. It protected against increased TNF-α mRNA expression in glomeruli isolated from db/db mice and against expression of genes associated with glycocalyx shedding (namely, SDC4, MMP2, and MMP9). In addition, gAd protected against increased glomerular albumin permeability (Ps’alb) in glomeruli isolated from db/db mice when administered intraperitoneally and when applied directly to glomeruli (ex vivo). Ps’alb was inversely correlated with eGlx depth in vivo. In summary, adiponectin restored eGlx depth, which was correlated with improved glomerular barrier function, in diabetes

Pandemic-related changes in alcohol use among LGB+ people with and without mental health and neurodevelopmental conditions: a multinational cross-sectional study

Purpose: Using data from 36,981 respondents to the Global Drug Survey (GDS) COVID-19 Special Edition, this study aims to compare changes, following the first “lockdown,” in alcohol consumption between lesbian, gay, bisexual and other sexual minority (LGB+) and heterosexual respondents with and without lifetime mental health and neurodevelopmental (MHND) conditions. Design/methodology/approach: Characteristics and drinking behavior of respondents to GDS who disclosed their sexual orientation and past 30-day alcohol use were described and compared. LGB+ participants with and without MHND conditions were compared, and logistic regression models identified correlates of increased drinking among LGB+ people. The impact of changed drinking on the lives of LGB+ participants with and without MHND conditions was assessed. Findings: LGB+ participants who reported that they were “not coping well at all” with the pandemic had twofold greater odds of reporting increased binge drinking. LGB+ participants with MHND conditions were significantly more likely than those without to report increased drinking frequency (18.7% vs 12.4%), quantity (13.8% vs 8.8%) and that changed drinking had impacted their lives. Originality/value: This study, which has a uniquely large and international sample, explores aspects of alcohol use not considered in other COVID-19 alcohol use research with LGB+ people; and to the best of the authors’ knowledge, this is the first study to explore alcohol use among LGB+ people with MHND conditions

Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

Modern living challenges female reproductive health. We are witnessing a rise in reproductive disorders and drop in birth rates across the world. The reasons for these manifestations are multifaceted and most likely include continuous exposure to an ever-increasing number of chemicals. The cause-effect relationships between chemical exposure and female reproductive disorders, however, have proven problematic to determine. This has made it difficult to assess the risks chemical exposures pose to a woman's reproductive development and function. To address this challenge, this review uses the adverse outcome pathway (AOP) concept to summarize current knowledge about how chemical exposure can affect female reproductive health. We have a special focus on effects on the ovaries, since they are essential for lifelong reproductive health in women, being the source of both oocytes and several reproductive hormones, including sex steroids. The AOP framework is widely accepted as a new tool for toxicological safety assessment that enables better use of mechanistic knowledge for regulatory purposes. AOPs equip assessors and regulators with a pragmatic network of linear cause-effect relationships, enabling the use of a wider range of test method data in chemical risk assessment and regulation. Based on current knowledge, we propose ten putative AOPs relevant for female reproductive disorders that can be further elaborated and potentially be included in the AOPwiki. This effort is an important step towards better safeguarding the reproductive health of all girls and women.Peer reviewe

Male × Female Interaction for a Pre-Copulatory Trait, but Not a Post-Copulatory Trait, among Cosmopolitan Populations of Drosophila melanogaster

Sexual coevolution occurs when changes in the phenotype of one sex select for changes in the other sex. We can identify the “footprint” of this coevolution by mating males and females from different populations and testing for a male-female genotype interaction for a trait associated with male (or female) performance. Here we mated male Drosophila melanogaster from five different continents with females from their own and different continents to test for a male-female interaction for mating speed, a pre-copulatory trait, and female reproductive investment, a post-copulatory trait. We found a strong male-female interaction for mating speed, consistent with previous studies using different populations, suggesting that the potential for sexual coevolution for this trait is present in this species. In contrast, we did not detect a male-female interaction for female reproductive investment. Although a male-female interaction for mating speed is compatible with the hypothesis of ongoing sexual coevolution, the nature of our experimental design is unable to exclude alternate explanations. Thus, the evolutionary mechanisms promoting male-female genotype interactions for pre-copulatory mating traits in D. melanogaster warrant further investigation

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1. yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS