The classification of glomerulonephritis in systemic lupus erythematosus revisited

The classification of glomerulonephritis in systemic lupus erythematosus revisited.The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involvin

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

De novo mutations in CHD8 are strongly associated with autism spectrum disorder, but the basic biology of CHD8 remains poorly understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural-specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8.National Institutes of Health (U.S.) (Grant UH1-MH106018-03

Tigers of Sundarbans in India: Is the Population a Separate Conservation Unit?

The Sundarbans tiger inhabits a unique mangrove habitat and are morphologically distinct from the recognized tiger subspecies in terms of skull morphometrics and body size. Thus, there is an urgent need to assess their ecological and genetic distinctiveness and determine if Sundarbans tigers should be defined and managed as separate conservation unit. We utilized nine microsatellites and 3 kb from four mitochondrial DNA (mtDNA) genes to estimate genetic variability, population structure, demographic parameters and visualize historic and contemporary connectivity among tiger populations from Sundarbans and mainland India. We also evaluated the traits that determine exchangeability or adaptive differences among tiger populations. Data from both markers suggest that Sundarbans tiger is not a separate tiger subspecies and should be regarded as Bengal tiger (P. t. tigris) subspecies. Maximum likelihood phylogenetic analyses of the mtDNA data revealed reciprocal monophyly. Genetic differentiation was found stronger for mtDNA than nuclear DNA. Microsatellite markers indicated low genetic variation in Sundarbans tigers (He= 0.58) as compared to other mainland populations, such as northern and Peninsular (Hebetween 0.67- 0.70). Molecular data supports migration between mainland and Sundarbans populations until very recent times. We attribute this reduction in gene flow to accelerated fragmentation and habitat alteration in the landscape over the past few centuries. Demographic analyses suggest that Sundarbans tigers have diverged recently from peninsular tiger population within last 2000 years. Sundarbans tigers are the most divergent group of Bengal tigers, and ecologically non-exchangeable with other tiger populations, and thus should be managed as a separate "evolutionarily significant unit" (ESU) following the adaptive evolutionary conservation (AEC) concept.Wildlife Institute of India, Dehra Dun (India)

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study

Background: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. Methods: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. Results: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58–81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6–24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1–3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97–4.11); CFS 5, 3.77 (1.94–7.32); CFS 6, 4.04 (2.09–7.82); CFS 7, 2.16 (1.12–4.20); and CFS 8, 3.19 (1.06–9.56). Conclusions: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning

Low-cost and earth-abundant nanocrystal synthesis for solar energy conversion and thermoelectric device applications

In as little as 35 years, the human population is expected to increase to 8.7 billion, resulting in an increasing demand for energy. This ever-growing energy crisis will be met in the short term using a rapidly diminishing supply of non-renewable and unsustainable fossil fuels such as coal, natural gas and oil. In the long term, additional energy from sustainable and renewable sources must be implemented and improved to supplement the current global energy infrastructure to sustain future energy needs. Many options are available but two main strategies paramount in accomplishing this goal are low-cost and clean electricity generation through solar cells and reclamation of waste heat energy. The most direct, clean and potentially efficient energy production method is through the use of photovoltaic devices, which directly converts solar radiation into electricity. Current industrially viable technologies consist of silicon-based solar cells capable of producing electricity at approximately 15% efficiency; however, efficiencies as high as about 87% can theoretically be obtained using a multiple junction approach. Nevertheless, end user limitations of solar energy production exist not in device efficiency and cost of materials, but rather in the final cost of electricity produced, which includes many factors such as manufacturing and installation costs, lifetime of the modules, maintenance and upkeep costs and “balance of systems” costs (energy storage, inverters, etc.). Significant cost reduction can be realized through use of novel thin film material systems capable of high-throughput manufacturing methods currently unavailable for commercialized silicon solar cells. Reclamation of waste heat has significant implications in the energy sector as well. As much as 50% of energy consumed by the U.S. industrial sector is predicted to be lost as waste heat. Thermoelectric (TE) materials offer a reliable, clean and simple solution. Unfortunately, traditionally low conversion efficiencies has greatly hindered the widespread use of TEs, but the recent discovery of nanostructured TE materials has spurred considerable improvements in performance leading to device efficiencies capable of 10–20% efficiency. Integration of nanoparticle (NP) based materials presents a potential solution for both of the limiting factors of photovoltaic and TE devices. This dissertation will discuss the advantages of NPs, the design and construction of a furnace and gas bubbling apparatus for the processing and synthesis of novel NP materials, and property tuning and performance enhancement through synthesis of chalcogenide alloys for photovoltaic and TE materials