Assessing the Socio-Economic and Environmental Impacts of 2014 Drought in District Tharparkar, Sindh-Pakistan

Thar Desert constitutes the largest desert of Pakistan. It is the only densely populated desert in the world, whose inhabitants is attached to their location and is unwilling to migrate. In recent past, Thar has been struck three times by droughts, the most recent was of 2014 while, and the most severe was in 1992-2002, following which it was declared one of the food insecure regions of the world e.g. Yemen, Syrian Arab Republic, Sudan, Somalia, Iraq, Democratic Republic of the Congo, Central African Republic, Burundi, Afghanistan. Understanding people perception of drought can assist to identify barriers to and drivers of adaptation that later help to develop adaptation related policies. This study seeks to assess the present condition of Thar natives and to understand from the views of people that how much negative impact of drought has on their lives. Primary data were obtained through personal interviews from local people (N=251) during field survey which was conducted in July 2015. Natives indicated that drought is a natural phenomenon; it does affect their lives, but not to a significant level. Among the affected people, the poor who live in rural areas and depend directly on agriculture have been hit especially hard. The installation of a solar reverse osmosis (SRO) plant that serves District Tharparkar has resolved most of the water shortage issues. However, water quality remains an issue for villagers, dependent on well water that is saline or polluted. Human activities such as deforestation and use of non-renewable resources for fuel are increasing environmental degradation. There is a dire need to establish best medical centers other than urban sites of the district to improve health condition of the native

Impact of Climate Change on Land use/Land cover of Chakwal District

Alterations in land use and land cover, either natural or anthropogenic can disturb the balance of fragile ecosystems. Climate change plays a unique role in governing the structure and state of land features and alters the structure of ecosystem as well as its services required by earth. Human health and environment are matter of concern due to changes induced by human in its natural environment (Jat et al., 2008). Human has an urge to remain near nature, for that they shift from dense urban areas to less dense areas (Western, 2001). So is the case of new housing societies where the land mafias intimate the people about new settlements (Zaman and Baloch, 2011), which are made by cutting the forests, removing trees and disturbing the ecosystem. For proper planning and management of natural resources, it is necessary to study the land cover and its associated changes (Asselman and Middelkoop, 1995). Modelling of changes within land cover to identify environmental trends on the local, national or regional level, have been realized in the scientific community (Nath et al., 2020). GIS/RS provides continuous change dynamics (Berlanga-Robles and Ruiz-Luna, 2011) of land cover/land use, i.e. by satellite monitoring (Ruiz-Ruano et al., 2016). The understanding of land cover changes is necessary for decision making (Lu et al., 2004) in the natural resource management (Seif et al., 2012). This study was carried out to identify the impact of changes in climate upon land use and land cover of Chakwal district from 1995 to 2020. Geospatial techniques were applied to estimate the differences in land features, using different time interval satellite datasets (Table 1). Six major classes of land features including, agriculture, bare land, built-up, forest, shrubs/grass and water were selected for this study, with respect to time

Systemic Comorbidities in Patients with Primary Fascial Space Infections of Odontogenic Orogin: Experience of a Tertiary Care Center

OBJECTIVES To assess systemic immune-compromised comorbidities in patients presenting with odontogenic infections that extend to fascial spaces. This study was designed to investigate the incidence of immune-compromising systemic comorbidities among patient presenting with odontogenic infections.METHODOLOGY This cross-sectional study was performed at the Department of Maxillofacial Surgery, Hayatabad Medical Complex (HMC) Peshawar from October 2018 through April 2019. However, patients older than 10 years of age, presenting with fascial space infections other than odontogenic cause, secondary fascial space infections and patients with multiple organ failure were excluded. The odontogenic infections were categorized according to their anatomical location. The prevalence of comorbidities was also assessed.RESULTSA total of 145 patients were included, where the male to female ratio was 3.8:1, mean age ~ 56 ± 14.74 years (range: 12-80 years) and mean duration of the odontogenic infections was 5± 1.2 days. The submandibular space was the most frequent site involved in odontogenic infections with a frequency of 60 (41.4%), followed by buccal space with 44 (30.3%) patients &    canine space with 31 (21.4%) patients. Of the 79 patients with comorbidities out of total 145 patients, diabetes mellitus was recorded in 60 patients. Other comorbidities included hypertension, renal and hepatic impairment. CONCLUSION Diabetes mellitus was the most common immune compromising comorbidity presented in patients with odontogenic infections extending in fascial spaces. Assessment of diabetes in routine dental practice is emphasized to avoid exacerbation of the odontogenic infections

Putative second hit rare genetic variants in families with seemingly GBA-associated Parkinson's disease

Rare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson's disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments

Segregation and potential functional impact of a rare stop-gain PABPC4L variant in familial atypical parkinsonism

Atypical parkinsonian disorders (APDs) comprise a group of neurodegenerative diseases with heterogeneous clinical and pathological features. Most APDs are sporadic, but rare familial forms have also been reported. Epidemiological and post-mortem studies associated APDs with oxidative stress and cellular protein aggregates. Identifying molecular mechanisms that translate stress into toxic protein aggregation and neurodegeneration in APDs is an active area of research. Recently, ribonucleic acid (RNA) stress granule (SG) pathways were discussed to be pathogenically relevant in several neurodegenerative disorders including APDs. Using whole genome sequencing, mRNA expression analysis, transfection assays and cell imaging, we investigated the genetic and molecular basis of a familial neurodegenerative atypical parkinsonian disorder. We investigated a family with six living members in two generations exhibiting clinical symptoms consistent with atypical parkinsonism. Two affected family members suffered from parkinsonism that was associated with ataxia. Magnetic resonance imaging (MRI) of these patients showed brainstem and cerebellar atrophy. Whole genome sequencing identified a heterozygous stop-gain variant (c.C811T; p.R271X) in the Poly(A) binding protein, cytoplasmic 4-like (PABPC4L) gene, which co-segregated with the disease in the family. In situ hybridization showed that the murine pabpc4l is expressed in several brain regions and in particular in the cerebellum and brainstem. To determine the functional impact of the stop-gain variant in the PABPC4L gene, we investigated the subcellular localization of PABPC4L in heterologous cells. Wild-type PABPC4L protein localized predominantly to the cell nucleus, in contrast to the truncated protein encoded by the stop-gain variant p.R271X, which was found homogeneously throughout the cell. Interestingly, the wild-type, but not the truncated protein localized to RasGAP SH3 domain Binding Protein (G3BP)-labeled cytoplasmic granules in response to oxidative stress induction. This suggests that the PABPC4L variant alters intracellular distribution and possibly the stress granule associated function of the protein, which may underlie APD in this family. In conclusion, we present genetic and molecular evidence supporting the role of a stop-gain PABPC4L variant in a rare familial APD. Our data shows that the variant results in cellular mislocalization and inability of the protein to associate with stress granules

Traditional healers working with primary care and mental health for early intervention in psychosis in young persons: protocol for the feasibility cluster randomised controlled trial

Objectives In low/middle-income countries (LMICs), more than half of patients with first-episode psychosis initially seek treatment from traditional and religious healers as their first care. This contributes to an excessively long duration of untreated psychosis (DUP). There is a need for culturally appropriate interventions to involve traditional and spiritual healers to work collaboratively with primary care practitioners and psychiatrists through task-shifting for early detection, referral and treatment of first episode of psychosis. Methods To prevent the consequences of long DUP in adolescents in LMICs, we aim to develop and pilot test a culturally appropriate and context-bespoke intervention. Traditional HEalers working with primary care and mental Health for early interventiOn in Psychosis in young pErsons (THE HOPE) will be developed using ethnographic and qualitative methods with traditional healers and caregivers. We will conduct a randomised controlled cluster feasibility trial with a nested qualitative study to assess study recruitment and acceptability of the intervention. Ninety-three union councils in district Peshawar, Pakistan will be randomised and allocated using a 1:1 ratio to either intervention arm (THE HOPE) or enhanced treatment as usual and stratified by urban/rural setting. Data on feasibility outcomes will be collected at baseline and follow-up. Patients, carers, clinicians and policymakers will be interviewed to ascertain their views about the intervention. The decision to proceed to the phase III trial will be based on prespecified stop–go criteria. Ethics and dissemination Ethical approval has been obtained from Keele University Ethical Review Panel (ref: MH210177), Khyber Medical University Ethical Review Board (ref: DIR/KMU-EB/IG/001005) and National Bioethics Committee Pakistan (ref no. 4-87/NBC-840/22/621). The results of THE HOPE feasibility trial will be reported in peer-reviewed journals and academic conferences and disseminated to local stakeholders and policymakers. Trial registration number ISRCTN75347421

Evaluation of acute oral toxicity of Ipomoea turpethum extract loaded polymeric nanoparticles in Wistar rats

Introduction: The amalgamation of novel drug delivery techniques and potential drugs is considered the most promising tool for the treatment of diseases. In our study, we have employed N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid (NIPAAM-VP-AA) copolymeric nanoparticles for delivering Ipomoea turpethum root extract. I. turpethum is a perennial herb (Convolvulaceae family) and has been used as medicine for ages. The present study was conducted to evaluate the safety of I. turpethum root extract-loaded NIPAAM-VP-AA polymeric nanoparticles (NVA-IT) in Wistar rats.Methods: An acute oral toxicity study was conducted in accordance with OECD guidelines 423 for the testing of chemicals. Different doses of NVA-IT i.e., 5 mg/kg, 50 mg/kg, 300 mg/kg, and 2000 mg/kg were administered to female Wistar rats in a stepwise manner using oral gavage. The toxicity signs were thoroughly observed for the next 14 days. At the end of the study, the blood and vital organs were harvested for hematological, biochemical, and histopathological studies.Result: No mortality or pathological anomalies were observed even at the highest dose which exemplifies that the lethal dose would be more than 2000 mg/kg body weight (GSH category 5). Behavioral changes, biochemical parameters, and histopathology of vital organs were normal after NVA-IT administration.Conclusion: This study demonstrated that NVA-IT nanoparticles are non-toxic and can be considered for therapeutic use in different diseases, such as inflammation, CNS diseases, Cancer, etc

A constitutive expression system for cellulase secretion in Escherichia coli and its use in bioethanol production.

The production of biofuels from lignocellulosic biomass appears to be attractive and viable due to the abundance and availability of this biomass. The hydrolysis of this biomass, however, is challenging because of the complex lignocellulosic structure. The ability to produce hydrolytic cellulase enzymes in a cost-effective manner will certainly accelerate the process of making lignocellulosic ethanol production a commercial reality. These cellulases may need to be produced aerobically to generate large amounts of protein in a short time or anaerobically to produce biofuels from cellulose via consolidated bioprocessing. Therefore, it is important to identify a promoter that can constitutively drive the expression of cellulases under both aerobic and anaerobic conditions without the need for an inducer. Using lacZ as reporter gene, we analyzed the strength of the promoters of four genes, namely lacZ, gapA, ldhA and pflB, and found that the gapA promoter yielded the maximum expression of the β-galactosidase enzyme under both aerobic and anaerobic conditions. We further cloned the genes for two cellulolytic enzymes, β-1,4-endoglucanase and β-1,4-glucosidase, under the control of the gapA promoter, and we expressed these genes in Escherichia coli, which secreted the products into the extracellular medium. An ethanologenic E. colistrain transformed with the secretory β-glucosidase gene construct fermented cellobiose in both defined and complex medium. This recombinant strain also fermented wheat straw hydrolysate containing glucose, xylose and cellobiose into ethanol with an 85% efficiency of biotransformation. An ethanologenic strain that constitutively secretes a cellulolytic enzyme is a promising platform for producing lignocellulosic ethanol

Expression of β-galactosidase via its native and heterologous promoter in genome integration based system.

<p>Cells were grown (A) aerobically and (B) anaerobically, harvested and used to monitor β-galactosidase activity. The data are presented as the average and standard deviation of two independent experiments.</p