Impact of COVID-19 on journalism in Nepal.

This bilingual rapid response report presents findings from a national survey undertaken to ascertain the impact of Covid-19 on Nepali journalists and their working conditions. Covid-19 spread as Nepal was approaching the fifth anniversary of the devastating 2015 earthquakes, the effects of which can still be felt in the nation. As such, Nepal faces additional economic, cultural, and social pressures because of the global pandemic. This report outlines how national and regional journalists, and news organisations responded to the pandemic, and identifies the training and capacity building requirements of Nepali journalists to strengthen future disaster resilience

AYURVEDIC MANAGEMENT OF PRIMARY INFERTILITY DUE TO POLYCYSTIC OVARIAN SYNDROME ASSOCIATED WITH MULTIPLE UTERINE FIBROIDS: A CASE REPORT

Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. As one of the leading causes of anovulatory infertility, it is believed that 5-10% of the reproductive-aged female population is living with polycystic ovary syndrome. Ayurveda considers the excellence of 4 factors- Ritu (ovulatory phase), Kshetra (garbhasaya), Ambu (proper nourishment to embryo), and Bija (healthy sperm and ovum) for a successful pregnancy. Impairment to any of these factors leads to Vandhytva or pregnancy failure. This case study helps to plan a treatment protocol for the patient with PCOS having infertility. A 25 yr old female having regular cycles came to OPD of Streeroga of IPGT & RA, having the complaints of weight gain and failure to conceive since 2 year of active married life. On presentation she was a medium sized woman with android body habits and had mild hirsute and acanthosis nigricans over nape of neck. Gynaecological examination revealed a normal sized uterus with no other abnormalities. Sonography revealed bulky ovaries with multiple small follicles with no evidence of ovulation along with small fibroids on anterior wall (1.8cm×1.5cm) and posterior wall (2.7cm×2.8cm). Her husbands semen analysis was normal. Based on clinical findings and investigation, anovulatory factor infertility due to PCOS was diagnosed along with fibroid. Virechana and Samana were decided due to both of these factors and Sthanyasodhana gana kashaya was selected as Samana drug. Treatment was done for 3 months, during treatment itself ovulation occured and the patient conceived after 3 months. This case being a Krichrasadhya vyadhi, proper care was taken including correction of the lifestyle and food habits. This case will help to understand the importance of Sodhana in gynecological disorders and explore the probable mode of action of Sthanyasodhana gana kashaya which helped in menstrual regulation

Retinoids regulate TGFβ signaling at the level of Smad2 phosphorylation and nuclear accumulation

AbstractIndirect regulation of transforming growth factor (TGF)-β signaling by retinoids occurs on a long-term timescale, secondary to transcriptional events. Studies by our group show loss of retinoid X receptor (RXR) alpha results in increased TGFβ2 in the midgestational heart, which may play a role in the cardiac defects seen in this model [S.W. Kubalak, D.R. Hutson, K.K. Scott and R.A. Shannon, Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos, Development 129 (2002) 733–746.]. Acute and direct interactions between retinoid and TGFβ signaling, however, are not clearly understood. Treatment of dispersed hearts and NIH3T3 cells for 1 h with TGFβ and retinoids (dual treatment) resulted in increased phosphorylated Smad2 and Smad3 when compared to treatment with TGFβ alone. Of all dual treatments, those with the RXR agonist Bexarotene, resulted in the highest level of phosphorylated Smad2, a 7-fold increase over TGFβ2 alone. Additionally, during dual treatment phosphorylation of Smad2 occurs via the TGFβ type I receptor but not by increased activation of the receptor. As loss of RXRα results in increased levels of Smad2 phosphorylation in response to TGFβ treatment and since nuclear accumulation of phosphorylated Smad2 is decreased during dual treatment, we propose that RXRα directly regulates the activities of Smad2. These data show retinoid signaling influences the TGFβ pathway in an acute and direct manner that has been unappreciated until now

Performance Evaluation of RISC-V Microcontroller System on FPGA: A Study of the NEORV32 Core

This paper evaluates a RISC-V microcontroller system on an FPGA platform using the NEORV32 core. This research aims to identify performance gaps in the NEORV32 system on an FPGA. The evaluation was carried out using the CoreMark benchmark programs. The hardware utilisation of the NEORV32 core is examined using Quartus Prime software with a particular focus on slice look-up tables (LUTs), total registers, memory bits, RAM blocks, and DSP blocks. In this work, two NEORV32 implementations are evaluated, which are RV32I and RV32I with M and Zfinx extension (RV32I_MC_zfinx). The effect of dedicated hardware and special operations on the performance of the processors is also evaluated on an FPGA board. The experiment results show that RV32I_MC_zfinx consumes 55% and 65% more LUT and registers resources, respectively, compared to the RV32I. Implementing hardware accelerators to RV32I_MC_zfinx results in a 48% increase in CoreMark score. Compared with other existing RISC-V cores, NEORV32 is a good option for embedded system development since it balances performance and resource efficiency for low-power applications

Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are relentlessly progressive neurodegenerative disorders with overlapping clinical, genetic and pathological features. Cytoplasmic inclusions of fused in sarcoma (FUS) are the hallmark of several forms of FTLD and ALS patients with mutations in the FUS gene. FUS is a multifunctional, predominantly nuclear, DNA and RNA binding protein. Here, we report that transgenic mice overexpressing wild-type human FUS develop an aggressive phenotype with an early onset tremor followed by progressive hind limb paralysis and death by 12 weeks in homozygous animals. Large motor neurons were lost from the spinal cord accompanied by neurophysiological evidence of denervation and focal muscle atrophy. Surviving motor neurons in the spinal cord had greatly increased cytoplasmic expression of FUS, with globular and skein-like FUS-positive and ubiquitin-negative inclusions associated with astroglial and microglial reactivity. Cytoplasmic FUS inclusions were also detected in the brain of transgenic mice without apparent neuronal loss and little astroglial or microglial activation. Hemizygous FUS overexpressing mice showed no evidence of a motor phenotype or pathology. These findings recapitulate several pathological features seen in human ALS and FTLD patients, and suggest that overexpression of wild-type FUS in vulnerable neurons may be one of the root causes of disease. Furthermore, these mice will provide a new model to study disease mechanism, and test therapies

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Terminal PEGylated DNA-Gold Nanoparticle Conjugates Offering High Resistance to Nuclease Degradation and Efficient Intracellular Delivery of DNA Binding Agents

Over the past 10 years, polyvalent DNA–gold nanoparticle (DNA–GNP) conjugate has been demonstrated as an efficient, universal nanocarrier for drug and gene delivery with high uptake by over 50 different types of primary and cancer cell lines. A barrier limiting its in vivo effectiveness is limited resistance to nuclease degradation and nonspecific interaction with blood serum contents. Herein we show that terminal PEGylation of the complementary DNA strand hybridized to a polyvalent DNA–GNP conjugate can eliminate nonspecific adsorption of serum proteins and greatly increases its resistance against DNase I-based degradation. The PEGylated DNA–GNP conjugate still retains a high cell uptake property, making it an attractive intracellular delivery nanocarrier for DNA binding reagents. We show that it can be used for successful intracellular delivery of doxorubicin, a widely used clinical cancer chemotherapeutic drug. Moreover, it can be used for efficient delivery of some cell-membrane-impermeable reagents such as propidium iodide (a DNA intercalating fluorescent dye currently limited to the use of staining dead cells only) and a diruthenium complex (a DNA groove binder), for successful staining of live cells

Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GC/TOFMS

The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF.Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls.The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar.Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease