Heterogeneity of Glia in the Retina and Optic Nerve of Birds and Mammals

We have recently described a novel type of glial cell that is scattered across the inner layers of the avian retina [1]. These cells are stimulated by insulin-like growth factor 1 (IGF1) to proliferate, migrate distally into the retina, and up-regulate the nestin-related intermediate filament transitin. These changes in glial activity correspond with increased susceptibility of neurons to excitotoxic damage. This novel cell-type has been termed the Non-astrocytic Inner Retinal Glia-like (NIRG) cells. The purpose of the study was to investigate whether the retinas of non-avian species contain cells that resemble NIRG cells. We assayed for NIRG cells by probing for the expression of Sox2, Sox9, Nkx2.2, vimentin and nestin. NIRG cells were distinguished from astrocytes by a lack of expression for Glial Fibrilliary Acidic Protein (GFAP). We examined the retinas of adult mice, guinea pigs, dogs and monkeys (Macaca fasicularis). In the mouse retina and optic nerve head, we identified numerous astrocytes that expressed GFAP, S100β, Sox2 and Sox9; however, we found no evidence for NIRG-like cells that were positive for Nkx2.2, nestin, and negative for GFAP. In the guinea pig retina, we did not find astrocytes or NIRG cells in the retina, whereas we identified astrocytes in the optic nerve. In the eyes of dogs and monkeys, we found astrocytes and NIRG-like cells scattered across inner layers of the retina and within the optic nerve. We conclude that NIRG-like cells are present in the retinas of canines and non-human primates, whereas the retinas of mice and guinea pigs do not contain NIRG cells

Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

Stochastic expression of genes produces heterogeneity in clonal populations of bacteria under identical conditions. We analyze and compare the behavior of the inducible lac genetic switch using well-stirred and spatially resolved simulations for Escherichia coli cells modeled under fast and slow-growth conditions. Our new kinetic model describing the switching of the lac operon from one phenotype to the other incorporates parameters obtained from recently published in vivo single-molecule fluorescence experiments along with in vitro rate constants. For the well-stirred system, investigation of the intrinsic noise in the circuit as a function of the inducer concentration and in the presence/absence of the feedback mechanism reveals that the noise peaks near the switching threshold. Applying maximum likelihood estimation, we show that the analytic two-state model of gene expression can be used to extract stochastic rates from the simulation data. The simulations also provide mRNA–protein probability landscapes, which demonstrate that switching is the result of crossing both mRNA and protein thresholds. Using cryoelectron tomography of an E. coli cell and data from proteomics studies, we construct spatial in vivo models of cells and quantify the noise contributions and effects on repressor rebinding due to cell structure and crowding in the cytoplasm. Compared to systems without spatial heterogeneity, the model for the fast-growth cells predicts a slight decrease in the overall noise and an increase in the repressors rebinding rate due to anomalous subdiffusion. The tomograms for E. coli grown under slow-growth conditions identify the positions of the ribosomes and the condensed nucleoid. The smaller slow-growth cells have increased mRNA localization and a larger internal inducer concentration, leading to a significant decrease in the lifetime of the repressor–operator complex and an increase in the frequency of transcriptional bursts

Consensus statement on abusive head trauma in infants and young children

Abusive head trauma (AHT) is the leading cause of fatal head injuries in children younger than 2 years. A multidisciplinary team bases this diagnosis on history, physical examination, imaging and laboratory findings. Because the etiology of the injury is multifactorial (shaking, shaking and impact, impact, etc.) the current best and inclusive term is AHT. There is no controversy concerning the medical validity of the existence of AHT, with multiple components including subdural hematoma, intracranial and spinal changes, complex retinal hemorrhages, and rib and other fractures that are inconsistent with the provided mechanism of trauma. The workup must exclude medical diseases that can mimic AHT. However, the courtroom has become a forum for speculative theories that cannot be reconciled with generally accepted medical literature. There is no reliable medical evidence that the following processes are causative in the constellation of injuries of AHT: cerebral sinovenous thrombosis, hypoxic-ischemic injury, lumbar puncture or dysphagic choking/vomiting. There is no substantiation, at a time remote from birth, that an asymptomatic birth-related subdural hemorrhage can result in rebleeding and sudden collapse. Further, a diagnosis of AHT is a medical conclusion, not a legal determination of the intent of the perpetrator or a diagnosis of murder. We hope that this consensus document reduces confusion by recommending to judges and jurors the tools necessary to distinguish genuine evidence-based opinions of the relevant medical community from legal arguments or etiological speculations that are unwarranted by the clinical findings, medical evidence and evidence-based literature

Family-led rehabilitation after stroke in India (ATTEND): a randomised controlled trial

Background Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting. Methods The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training—including information provision, joint goal setting, carer training, and task-specific training—that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3–6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707). Findings Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78–1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80). Interpretation Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care

Development of metal sulfide-poly (3-octylthiophene) composite LB multilayers

Langmuir–Blodgett (LB) technique has been used to deposit composite multilayers of poly(3-octylthiophene) with cadmium arachidate (POT-CdA), zinc arachidate (POT-ZnA) and copper arachidate (POT-CuA). These composite multilayers were used as precursors to develop the respective semiconducting CdS, ZnS and Cu2S nanoclusters in the POT-arachidic acid (POT-AA) matrix. The formation of sulphide nanoclusters in the multilayer was determined by FTIR and UV-Vis spectroscopy. X-ray reflectivity measurements showed a drastic reduction in the layered structural order on sulphide formation. Single layer LED structures were fabricated using POT-CdA, CdS-POT-AA and ZnS-POT-AA composites as active layers. The Electoluminescence peaks from these structures are attributed to POT and nanoclusters of CdS and ZnS, respectively. The electroluminescent devices with nanoclusters containing emitter layers exhibited low turn-on voltage ~5 V. Blue electroluminescence was observed at room temperature from FTO/ZnS-POT-AA/Al devices.© Elsevie

Structure of CdS–arachidic acid composite LB multilayers

Langmuir–Blodgett (LB) multilayers of cadmium arachidate were used as precursors to grow semiconducting CdS nanoclusters. The formation of CdS in the multilayers was determined by Fourier transform-infrared (FT-IR), ultraviolet–visible (UV–vis) and Raman spectroscopy. The structural changes occurring as a consequence of CdS formation have been characterized using X-ray reflection (XR) and grazing incidence X-ray diffraction (GIXD) techniques. The CdS containing composite multilayers exhibit the presence of two types of molecular domains, one with close packed herringbone arrangement and the other with tilted molecular chains with no in-plane order. The structural and spectroscopic evidences together suggest that the CdS nanoclusters formed within the arachidic acid LB matrix are quasi two-dimensional in nature with lateral dimension ~5–10 nm and thickness ~1.1 nm.© Elsevie

Molecular packing in CdS containing conducting polymer composite LB multilayers

Langmuir–Blodgett (LB) technique has been used to deposit composite multilayers of poly (3-octylthiophene)-cadmium arachidate (POT-CdA) and polyaniline-cadmium arachidate (PANI-CdA). These were used as precursors to develop semiconducting CdS nanoclusters within the conducting polymer based multilayers. The presence of CdS in the multilayers was determined by Fourier transform infrared spectroscopy (FTIR), UV–Vis and Raman spectroscopy. The structural changes occurring as a consequence of CdS formation have been characterized using X-ray reflection and grazing incidence X-ray diffraction (GIXD) techniques. As-deposited POT-CdA multilayers exhibit good vertical as well as in-plane structure similar to that of CdA. In contrast, PANI-CdA multilayers have poor structural order. The in-plane molecular packing in CdA and PANI-CdA multilayers after H2S exposure has mixed domains of rectangular (herringbone) and hexagonal arrangements. In the case of POT-CdA multilayers, however, the original rectangular packing is retained.© Elsevie