Genetic Investigation of Consanguineous Pakistani Families Segregating Rare Spinocerebellar Disorders

Spinocerebellar disorders are a vast group of rare neurogenetic conditions, generally characterized by overlapping clinical symptoms including progressive cerebellar ataxia, spastic paraparesis, cognitive deficiencies, skeletal/muscular and ocular abnormalities. The objective of the present study is to identify the underlying genetic causes of the rare spinocerebellar disorders in the Pakistani population. Herein, nine consanguineous families presenting different spinocerebellar phenotypes have been investigated using whole exome sequencing. Sanger sequencing was performed for segregation analysis in all the available individuals of each family. The molecular analysis of these families identified six novel pathogenic/likely pathogenic variants; ZFYVE26: c.1093del, SACS: c.1201C>T, BICD2: c.2156A>T, ALS2: c.2171-3T>G, ALS2: c.3145T>A, and B4GALNT1: c.334_335dup, and three already reported pathogenic variants; FA2H: c.159_176del, APTX: c.689T>G, and SETX: c.5308_5311del. The clinical features of all patients in each family are concurrent with the already reported cases. Hence, the current study expands the mutation spectrum of rare spinocerebellar disorders and implies the usefulness of next-generation sequencing in combination with clinical investigation for better diagnosis of these overlapping phenotypes

Effect of Phytosynthesized Selenium and Cerium Oxide Nanoparticles on Wheat (Triticum aestivum L.) against Stripe Rust Disease

In this study, selenium nanoparticles (SeNPs) and cerium oxide nanoparticles (CeONPs) were synthesized by using the extract of Melia azedarach leaves, and Acorus calamusas rhizomes, respectively, and investigated for the biological and sustainable control of yellow, or stripe rust, disease in wheat. The green synthesized NPs were characterized by UV-Visible spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and X-ray diffraction (XRD). The SeNPs and CeONPs, with different concentrations (i.e., 10, 20, 30, and 40 mg/L), were exogenously applied to wheat infected with Puccinia striformis. SeNPs and CeONPs, at a concentration of 30 mg/L, were found to be the most suitable concentrations, which reduced the disease severity and enhanced the morphological (plant height, root length, shoot length, leaf length, and ear length), physiological (chlorophyll and membrane stability index), biochemical (proline, phenolics and flavonoids) and antioxidant (SOD and POD) parameters. The antioxidant activity of SeNPs and CeONPs was also measured. For this purpose, different concentrations (50, 100, 150, 200 and 400 ppm) of both SeNPs and CeONPs were used. The concentration of 400 ppm most promoted the DPPH, ABTS and reducing power activity of both SeNPs and CeONPs. This study is considered the first biocompatible approach to evaluate the potential of green synthesized SeNPs and CeONPs to improve the health of yellow, or stripe rust, infected wheat plants and to provide an effective management strategy to inhibit the growth of Puccinia striformis.This research was funded by projects APOGEO (Cooperation Program INTERREG-MAC 2014–2020, with European Funds for Regional Development-FEDER). “Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) del Gobierno de Canarias” (Project ProID2020010134), and Fundación CajaCanarias (Project 2019SP43).Peer reviewe

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

A Novel Nonsense Variant in GRM1 Causes Autosomal Recessive Spinocerebellar Ataxia 13 in a Consanguineous Pakistani Family

Background and objectives: Autosomal recessive spinocerebellar ataxia-13 (SCAR13) is an ultra-rare disorder characterized by slowly progressive cerebellar ataxia, cognitive deficiencies, and skeletal and oculomotor abnormalities. The objective of this case report is to expand the clinical and molecular spectrum of SCAR13. Methods: We investigated a consanguineous Pakistani family with four patients partially presenting with clinical features of SCAR13 using whole exome sequencing. Segregation analysis was performed by Sanger sequencing in all the available individuals of the family. Results: Patients presented with quadrupedal gait, delayed developmental milestones, non-progressive peripheral neuropathy, and cognitive impairment. Whole exome sequencing identified a novel pathogenic nonsense homozygous variant, Gly240*, in the gene GRM1 as a cause of SCAR13 that segregates with the recessive disease. Discussion: We report a novel homozygous nonsense variant in the GRM1 gene in four Pakistani patients presenting with clinical features that partially overlap with the already reported phenotype of SCAR13. In addition, the family presented quadrupedal gait and non-progressive symptoms, manifestations which have not been recognized previously. So far, only four variants in GRM1 have been reported, in families of Roma, Iranian, and Tunisian origins. The current study adds to the mutation spectrum of GRM1 and provides a rare presentation of SCAR13, the first from the Pakistani population

Incidence of food and aero allergies among patients visiting Allergy center National Institute of Health (NIH), Islamabad

Objective: To identify the most common allergy type among patients visiting an urban allergy centre. Methods: The descriptive cross-sectional study was conducted at the Allergy Centre of the National Institute of Health, Islamabad, Pakistan, from December 2019 to June 2020, and comprised subjects of either gender aged 20-50 years. Skin prick test was used to determine the skin reactivity for 11 common allergen extracts.  Patients with a wheal diameter >3mm were considered positive. Data was analysed using SPSS 22. Results: Of the 100 patients, 55(55%) were males and 45(45%) were females. The overall mean age was 34.03±8.16 years. Majority of the respondents 93(93%) were sensitive to aeroallergen, 7(7%) to food allergens, and 2(2%) exhibited sensitivity against both types of allergens. Poly-sensitisation was found among 86(86%) respondents. Conclusion: Aeroallergens were found to be the main triggering factor for allergies compared to the food allergens. Continue..

A Review of Swarm Robotics in a NutShell

A swarm of robots is the coordination of multiple robots that can perform a collective task and solve a problem more efficiently than a single robot. Over the last decade, this area of research has received significant interest from scientists due to its large field of applications in military or civil, including area exploration, target search and rescue, security and surveillance, agriculture, air defense, area coverage and real-time monitoring, providing wireless services, and delivery of goods. This research domain of collective behaviour draws inspiration from self-organizing systems in nature, such as honey bees, fish schools, social insects, bird flocks, and other social animals. By replicating the same set of interaction rules observed in these natural swarm systems, robot swarms can be created. The deployment of robot swarm or group of intelligent robots in a real-world scenario that can collectively perform a task or solve a problem is still a substantial research challenge. Swarm robots are differentiated from multi-agent robots by specific qualifying criteria, including the presence of at least three agents and the sharing of relative information such as altitude, position, and velocity among all agents. Each agent should be intelligent and follow the same set of interaction rules over the whole network. Also, the system’s stability should not be affected by leaving or disconnecting an agent from a swarm. This survey illustrates swarm systems’ basics and draws some projections from its history to its future. It discusses the important features of swarm robots, simulators, real-world applications, and future ideas

Pattern of medication selling and self-medication practices: A study from Punjab, Pakistan

<div><p>Background</p><p>Access to medicines without prescription is a major contributing factor for self-medication practices. This study was designed to examine the ratio of non-prescribed medicines sales and self-medication practices in Punjab, Pakistan. This study also evaluates the reasons for self-medication within its communities.</p><p>Methods</p><p>An observational study was conducted in 272 systemically selected pharmacies to analyze medicines-related sales, with or without prescription. A cross-sectional survey was performed between June 2015 and November 2016. Consumers were interviewed about their self-medication practices.</p><p>Results</p><p>Of the pharmacies surveyed, 65.3% participated in the study. A total of 4348 medicines were purchased for self-medication by 3037 consumers (15.2% of all study participants), of which 873 (28.7%) participated in an interview. Majority (81.2%) medicine purchaser, (90.9%) interview participants, and (59.4%) drug users were male. On average, each community pharmacy sold 7.9 medicines without prescription each day, to an average of 5.5 customers. Many participants (28.9%) had matriculation in their formal education. The medicines most often sold for self-medication were analgesics and antipyretics(39.4%). More than 25% of participants reported fever symptoms and 47.8% assumed their illness was too trivial to consult a doctor. Media advertisements were the most common source of information for participants (46.7%).</p><p>Conclusion</p><p>Many types of medicines were often sold without prescription from community pharmacies. Self-medication was common practice for a wide range of illnesses. Pakistan also needs effective implementation of policies to monitor medication sales. Public education about rational medication and limits to advertising medicine are very necessary.</p></div