Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior.

Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially recruits mPFC D2R+ cells, but that this recruitment is attenuated in VPA-exposed mice. Stimulating mPFC D2R+ neurons disrupts normal social interaction. Conversely, inhibiting these cells enhances social behavior in VPA-exposed mice. Importantly, this effect was not reproduced by nonspecifically inhibiting mPFC neurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice. These findings suggest that multiple forms of autism may alter the physiology of specific deep-layer prefrontal neurons that project to subcortical targets. Furthermore, a highly overlapping population-prefrontal D2R+ neurons-plays an important role in both normal and abnormal social behavior, such that targeting these cells can elicit potentially therapeutic effects

Associations between gastro-oesophageal reflux, its management and exacerbations of chronic obstructive pulmonary disease

To determine factors, overall and by sex, associated with self-reported gastro-oesophageal reflux disease (GORD) in chronic obstructive pulmonary disease (COPD) patients, and to evaluate relationships between GORD, its modification by acid suppression medications (Proton Pump Inhibitors [PPI]/histamine-2 receptor antagonists [H2RA]) and exacerbations of COPD and mortality

Prevalence, causes, and risk factors for functional low vision in Nigeria: results from the national survey of blindness and visual impairment.

PURPOSE: To estimate prevalence and describe causes of functional low vision (FLV) among a nationally representative sample of Nigerian adults, assess socioeconomic risk factors, and estimate the number of adults in Nigeria who might benefit from low vision assessment or rehabilitation services. METHODS: Multistage, stratified, cluster random sampling with probability proportional to size procedures were used to identify a nationally representative sample of 15,027 persons aged 40 years or older. Distance vision was measured using a reduced logMAR tumbling E-chart. All participants with presenting acuity of <6/12 in one or both eyes had their corrected acuity measured and underwent detailed clinical examination to determine the cause. FLV was defined as best corrected vision <6/18 in the better eye, after excluding those with no light perception in both eyes and those with treatable causes. Analysis took account of the clustered design. RESULTS: In all, 13,591 individuals were examined in 305 clusters (response rate, 89.9%). The crude prevalence of FLV was 3.5% (95% confidence interval, 3.1-3.9%). This was lower than the prevalence of blindness, which was 4.2%. Glaucoma was the most common cause and age the most important risk factor. There are estimated to be approximately 5000 adults with FLV per million population and 340 who are totally blind. Only 9.3% of those with FLV were of working age and literate. CONCLUSIONS: These are the first data on the prevalence, causes, and risk factors for FLV from Africa. Results support studies from Asia that the prevalence of FLV is lower than previously thought. Because the majority of adults with FLV in Nigeria live in rural areas and are elderly and not literate, further research is required to assess the nature of the interventions required and who might best deliver them

Mask-free OVIS: Open-Vocabulary Instance Segmentation without Manual Mask Annotations

Existing instance segmentation models learn task-specific information using manual mask annotations from base (training) categories. These mask annotations require tremendous human effort, limiting the scalability to annotate novel (new) categories. To alleviate this problem, Open-Vocabulary (OV) methods leverage large-scale image-caption pairs and vision-language models to learn novel categories. In summary, an OV method learns task-specific information using strong supervision from base annotations and novel category information using weak supervision from image-captions pairs. This difference between strong and weak supervision leads to overfitting on base categories, resulting in poor generalization towards novel categories. In this work, we overcome this issue by learning both base and novel categories from pseudo-mask annotations generated by the vision-language model in a weakly supervised manner using our proposed Mask-free OVIS pipeline. Our method automatically generates pseudo-mask annotations by leveraging the localization ability of a pre-trained vision-language model for objects present in image-caption pairs. The generated pseudo-mask annotations are then used to supervise an instance segmentation model, freeing the entire pipeline from any labour-expensive instance-level annotations and overfitting. Our extensive experiments show that our method trained with just pseudo-masks significantly improves the mAP scores on the MS-COCO dataset and OpenImages dataset compared to the recent state-of-the-art methods trained with manual masks. Codes and models are provided in https://vibashan.github.io/ovis-web/.Comment: Accepted to CVPR 2023. Project site: https://vibashan.github.io/ovis-web

Community-based rehabilitation for people with disabilities in low- and middle-income countries: a systematic review

Review question: We reviewed the evidence about the impact of community-based rehabilitation on the lives of people with disabilities and their carers in low- and middle-income countries. Background: People with disabilities include those who have long-term physical, mental, intellectual or sensory impairments, which in interaction with various barriers may hinder their full and effective participation in society on an equal basis with others. There are estimated to be over one billion people with disabilities globally and 80% of them live in low- and middle-income countries. They are often excluded from education, health, and employment and other aspects of society leading to an increased risk of poverty. Community-based rehabilitation interventions are the strategy endorsed by the World Health Organization and other international organisations (e.g. ILO, IDDC) for addressing the needs of this group of people in low- and middle-income countries. These interventions aim to enhance the quality of life of people with disabilities and their carers, by trying to meet their basic needs and ensuring inclusion and participation using predominantly local resources. These interventions are composed of up to five components: health, education, livelihood, social and empowerment. Currently only few people who need them benefit from these interventions, and so it is important to assess the available evidence to identify how to best implement these programmes. Study characteristics: The evidence in this review is current to July 2012. This review identified 15 studies that assessed the impact of community-based rehabilitation on the lives of people with disabilities and their carers in low- and middle-income countries. The studies included in the review used different types of community-based rehabilitation interventions and targeted different types of physical (stroke, arthritis, chronic 7 The Campbell Collaboration | www.campbellcollaboration.org obstructive pulmonary disease) and mental disabilities (schizophrenia, dementia, intellectual impairment). Key results: Overall, randomised controlled trials suggested a beneficial effect of community-based rehabilitation interventions in the lives of people with physical disabilities (stroke and chronic obstructive pulmonary disease). Similar results were found for non-randomised studies for physical disabilities (stroke and arthritis) with the exception of one non-randomised study on stroke showing community-based rehabilitation was less favourable than hospital-based rehabilitation. Overall, randomised controlled trials suggested a modest beneficial effect of community-based rehabilitation interventions for people with mental disabilities (schizophrenia, dementia, intellectual impairment), and for their carers (dementia). Similar results were found for non-randomised studies for mental disabilities (schizophrenia). However, the methodological constraints of many of these studies limit the strength of our results. In order to build stronger evidence, future studies will need to adopt better study designs, will need to focus on broader clients group, and to include economic evaluations

Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.</p> <p>Methods/Design</p> <p>The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.</p> <p>Discussion</p> <p>It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=ISRCTN02839188">ISRCTN02839188</a></p

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

&lt;p&gt;Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.&lt;/p&gt; &lt;p&gt;Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.&lt;/p&gt; &lt;p&gt;Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.&lt;/p&gt