Epidermal growth factor receptor rs17337023 polymorphism in hypertensive gestational diabetic women: A pilot study

Background: Women with gestational diabetes mellitus have an increased risk of developing gestational hypertension, which can increase fetal and neonatal morbidity and mortality. In the past decade, single nucleotide polymorphisms in several genes have been identified as risk factors for development of gestational hypertension. The epidermal growth factor receptor activates tyrosine kinase mediated blood vessels contractility; and inflammatory cascades. Abnormalities in these mechanism are known to contribute towards hypertension. It is thus plausible that polymorphisms in the epidermal growth factor receptor gene would be associated with the development of hypertension in women with gestational diabetes.Aim: To determine whether the epidermal growth factor receptor rs17337023 SNP is associated with the occurrence of hypertension in gestational diabetic women.Methods: This pilot case-control study was conducted at two tertiary care hospitals in Karachi, from January 2017-August 2018. Two hundred and two women at 28 week of gestation with gestational diabetes were recruited and classified into normotensive (n = 80) and hypertensive (n = 122) groups. Their blood samples were genotyped for epidermal growth factor receptor polymorphism rs17337023 using tetra-ARMS polymerase chain reaction. Descriptive analysis was applied on baseline data. Polymorphism data was analyzed for genotype and allele frequency determination using chi-squared statistics. In all cases, a P value of \u3c 0.05 was considered significant.Results: Subjects were age-matched and thus no difference was observed in relation to age of the study subjects (P \u3e0.05). Body fat percentage was significantly higher in hypertensive females as compared to normotensive subjects (35.138 ± 4.29 Case vs 25.01 ± 8.28 Control; P \u3c 0.05). Similarly, systolic and diastolic blood pressures among groups were significantly higher in hypertensive group than the normotensive group (P \u3c 0.05). Overall epidermal growth factor receptor rs17337023 polymorphism genotype frequency was similar in both groups, with the heterozygous AT genotype (56 in Case vs 48 in Control; P = 0. 079) showing predominance in both groups. Furthermore, the odds ratio for A allele was 1.282 (P = 0.219) and for T allele was 0.780 (P = 0.221) in this study.Conclusion: This pilot study indicates that polymorphisms in rs17337023 may not be involved in the pathophysiology of gestational hypertension in gestational diabetes via inflammatory cascade mechanism. Further large-scale studies should explore polymorphism in epidermal growth factor receptor and other genes in this regard

Neurotoxicity: A rare side effect of programmed cell death 1 (PD-1) inhibitors

Immunotherapy is a biological therapy that helps the body\u27s immune system to fight against cancer cells. The Food and Drug Administration (FDA) approved the first immune checkpoint inhibitor in 2011. Since 2011, many immune checkpoint inhibitors have been approved. Programmed cell death 1 (PD-1) inhibitors are now commonly used in multiple malignancies due to their remarkable response. Thus, immune-related adverse events are now coming into the limelight due to the increasing use of PD-1 inhibitors. Here, we present a case of a 54-year-old female with non-small cell lung cancers (NSCLC) treated with pembrolizumab and later presented with severe neurotoxicity

Low-cost peer-taught virtual research workshops for medical students in Pakistan: A creative, scalable, and sustainable solution for student research

Background: Pakistan has not been a major contributor to medical research, mainly because of the lack of learning opportunities to medical students. With the increase in online learning systems during COVID-19, research related skills can be taught to medical students via low-cost peer taught virtual research workshops.Aim of the study: To assess the effectiveness of a comprehensive low-cost peer-taught virtual research workshops amongst medical students in Pakistan.Methods: This quasi-experimental study assessed the effectiveness of five virtual research workshops (RWs) in improving core research skills. RWs for medical students from across Pakistan were conducted over Zoom by medical students (peer-teachers) at the Aga Khan University, Pakistan, with minimal associated costs. The content of the workshops included types of research, ethical approval and research protocols, data collection and analysis, manuscript writing, and improving networking skills for research. Improvement was assessed via pre-and post-quizzes for each RW, self-efficacy scores across 16 domains, and feedback forms. Minimum criteria for completion of the RW series was attending at least 4/5 RWs and filling the post-RW series feedback form. A 6-month post-RW series follow-up survey was also emailed to the participants.Results: Four hundred medical students from 36 (/117; 30.8%) different medical colleges in Pakistan were enrolled in the RWs. However, only 307/400 (76.75%) medical students met the minimum requirement for completion of the RW series. 56.4% of the participants belonged to the pre-clinical years while the rest were currently to clinical years. The cohort demonstrated significant improvement in pre-and post-quiz scores for all 5 RWs (p \u3c 0.001) with the greatest improvement in Data Collection and Analysis (+ 34.65%), and in self-efficacy scores across all domains (p \u3c 0.001). 166/307 (54.1%) participants responded to the 6 months post-RWs follow-up survey. Compared to pre-RWs, Research involvement increased from 40.4 to 62.8% (p \u3c 0.001) while proportion of participants with peer-reviewed publications increased from 8.4 to 15.8% (p = 0.043).Conclusion: Virtual RWs allow for a wide outreach while effectively improving research-related knowledge and skills, with minimal associated costs. In lower-middle-income countries, virtual RWs are a creative and cost-effective use of web-based technologies to facilitate medical students to contribute to the local and global healthcare research community

Integral effects of brassinosteroids and timber waste biochar enhances the drought tolerance capacity of wheat plant

Drought stress is among the major threats that affect negatively crop productivity in arid and semi-arid regions. Probably, application of some additives such as biochar and/or brassinosteroids could mitigate this stress; however, the mechanism beyond the interaction of these two applications is not well inspected. Accordingly, a greenhouse experiment was conducted on wheat (a strategic crop) grown under deficit irrigation levels (factor A) i.e., 35% of the water holding capacity (WHC) versus 75% of WHC for 35 days while considering the following additives, i.e., (1) biochar [BC, factor B, 0, 2%] and (2) the foliar application of 24-epibrassinolide [BR, factor C, 0 (control treatment, C), 1 (BR1) or 3 (BR2) mu mol)]. All treatments were replicated trice and the obtained results were statistically analyzed via the analyses of variance. Also, heat-map conceits between measured variables were calculated using the Python software. Key results indicate that drought stress led to significant reductions in all studied vegetative growth parameters (root and shoot biomasses) and photosynthetic pigments (chlorophyll a, b and total contents) while raised the levels of oxidative stress indicators. However, with the application of BC and/or BR, significance increases occurred in the growth attributes of wheat plants, its photosynthetic pigments, especially the combined additions. They also upraised the levels of enzymatic and non-enzymatic antioxidants while decreased stress indicators. Furthermore, they increased calcium (Ca), phosphorus (P) and potassium (K) content within plants. It can therefore be deduced that the integral application of BR and BC is essential to mitigate drought stress in plants.Peer reviewe

Associative effects of activated carbon biochar and arbuscular mycorrhizal fungi on wheat for reducing nickel food chain bioavailability

Heavy metal stress and less nutrient availability are some of the major concerns in agriculture. Both abiotic stresses have potential to decrease the crops productivity. On the other hand, organic fertilizers i.e., activated carbon biochar (ACB) and arbuscular mycorrhizal fungi (AMF) increase nutritional and heavy metal like Nickel (Ni) stress tolerance and provide immunity to plants for their survival in unfavorable environments. Previous studies have only looked at single applications of either ACB or AMF thus far. There is limited evidence of their synergistic effects, especially in plants growing in soil contaminated with nickel (Ni). To cover the knowledge gap of combined use of AMF inoculation (Glomus intraradices) and/or wheat straw biochar amendments on wheat growth, antioxidant activities and osmolytes concentration, present study is conducted. The use of either the AMF inoculant or the ACB alone resulted in improved wheat growth and decreased Ni uptake. Furthermore, sole AMF or ACB also reduced Ni stress effectively, allowing wheat to grow faster and reducing soil Ni transfer into plant tissue. In comparison to a control, adding ACB with AMF inoculant considerably increased fungal populations. The most significant increase in wheat growth and decrease in tissue Ni contents came from amending soil with AMF inoculant and biochar. Inducing soil alkalinization and causing Ni immobilization, as well as decreasing Ni phyto-availability, the combination treatment had a synergistic impact. These findings imply that AMF inoculation in ACB treatment could be used not only for wheat production but also for Ni-contaminated soil phyto-stabilization. (C) 2022 The Author(s). Published by Elsevier B.V.Peer reviewe

Examining queue-jumping phenomenon in heterogeneous traffic stream at signalized intersection using UAV-based data

© 2020, Springer-Verlag London Ltd., part of Springer Nature. This research presents an in-depth microscopic analysis of heterogeneous and undisciplined traffic at the signalized intersection. Traffic data extracted from the video recorded using an unmanned aerial vehicle (UAV) at an approach of a signalized intersection is analyzed to study the within green time dynamics of traffic flow. Various parameters of Wiedemann 74, Wiedemann 99, and lateral behavior models used in microscopic traffic simulation package, Vissim, are calibrated for the local heterogeneous traffic. This research is aimed at exploring the queue-jumping phenomenon of motorbikes at signalized intersections and its impact on the saturation flow rate, travel time, and delay. The study of within green time flow dynamics shows that the flow of traffic within green time is not uniform. Surprisingly, the results indicate that the traffic flow for the first few seconds of the green time is significantly higher than the remaining period of green time, which shows a contradiction to the fact that traffic flow for the first few seconds is lower due to accelerating vehicles. Mode-wise traffic counted per second shows that this anomaly is attributed to the presence of motorbikes in front of the queue. Consequently, the outputs of simulation results obtained from calibrated Vissim show that the simulated travel time for motorbikes is significantly lower than the field-observed travel times even though the average simulated traffic flow matches accurately with the field-observed traffic flow. The findings of this research highlight the need to incorporate the queue-jumping behavior of motorbikes in the microsimulation packages to enhance their capability to model heterogeneous and undisciplined traffic

Exogenously applied ZnO nanoparticles induced salt tolerance in potentially high yielding modern wheat (Triticum aestivum L.) cultivars

Salinity stress is one of the potential threats that adversely affect the productivity of many cereal crops worldwide. Spraying plants with nano-Zn particles may lessen effectively such negative impacts on plants; yet its mode of action is still not well explored. This study was performed to evaluate the effects of spraying nano-Zn particles with varying concentrations (0, 20, 50 and 80 mg L-1) on two wheat cultivars irrigated with saline water (EC = 6.3 dS m-1) versus a non-saline one. The key results revealed that root and shoot weights decreased significantly under salinity stress conditions, while improved considerably with nano-Zn-particles foliar application up to 50 mg nanoZn L-1; thereafter significant reductions occurred. Also, shoot and root lengths as well as plant leaf area index improved considerably owing to this foliar application. Clearly, roots and shoots weights of wheat plants sprayed with nano-Zn particles under salinity stress conditions exhibited higher values than the corresponding ones that was grown under non-saline conditions without nano-Zn-particles applications. Unexpectedly, this foliar spray led to significant reductions in plant pigments and also in enzymatic and non-enzymatic antioxidants in plants. Yet, this foliar spray enhanced formation of total soluble sugars and proline, and raised significantly Ca contents in wheat roots and shoots, and to some extent K contents. In conclusion, the foliar application of nano-Zn particles increased plant growth under salty stress conditions via two parallel processes, i.e., stimulating formation of osmolytes and stimulating nutrient uptake which may, in turn, increase plant metabolism. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CCPeer reviewe

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.Clefts of the lip and palate are common birth defects, and require long-term multidisciplinary management. Their etiology involves genetic factors and environmental influences and/or a combination of both, however, these interactions are poorly defined. Moreover, although clefts of the lip may or may not involve the palate, the determinants predisposing to specific subphenotypes are largely unknown. Here we demonstrate that variations in the non-coding region near the GREM1 gene show a highly significant association with a particular phenotype in which cleft lip and cleft palate co-occ

Influenza in Outpatient ILI Case-Patients in National Hospital-Based Surveillance, Bangladesh, 2007–2008

Recent population-based estimates in a Dhaka low-income community suggest that influenza was prevalent among children. To explore the epidemiology and seasonality of influenza throughout the country and among all age groups, we established nationally representative hospital-based surveillance necessary to guide influenza prevention and control efforts.We conducted influenza-like illness and severe acute respiratory illness sentinel surveillance in 12 hospitals across Bangladesh during May 2007–December 2008. We collected specimens from 3,699 patients, 385 (10%) which were influenza positive by real time RT-PCR. Among the sample-positive patients, 192 (51%) were type A and 188 (49%) were type B. Hemagglutinin subtyping of type A viruses detected 137 (71%) A/H1 and 55 (29%) A/H3, but no A/H5 or other novel influenza strains. The frequency of influenza cases was highest among children aged under 5 years (44%), while the proportions of laboratory confirmed cases was highest among participants aged 11–15 (18%). We applied kriging, a geo-statistical technique, to explore the spatial and temporal spread of influenza and found that, during 2008, influenza was first identified in large port cities and then gradually spread to other parts of the country. We identified a distinct influenza peak during the rainy season (May–September).Our surveillance data confirms that influenza is prevalent throughout Bangladesh, affecting a wide range of ages and causing considerable morbidity and hospital care. A unimodal influenza seasonality may allow Bangladesh to time annual influenza prevention messages and vaccination campaigns to reduce the national influenza burden. To scale-up such national interventions, we need to quantify the national rates of influenza and the economic burden associated with this disease through further studies

Pathogenic mtDNA mutations causing mitochondrial myopathy: The need for muscle biopsy.

Pathogenic mitochondrial tRNA (mt-tRNA) gene mutations represent a prominent cause of primary mitochondrial DNA (mtDNA)-related disease despite accounting for only 5%-10% of the mitochondrial genome.(1,2) Although some common mt-tRNA mutations, such as the m.3243A>G mutation, exist, the majority are rare and have been reported in only a small number of cases.(3) The MT-TP gene, encoding mt-tRNA(Pro), is one of the less polymorphic mt-tRNA genes, and only 5 MT-TP mutations have been reported as a cause of mitochondrial muscle disease to date (table e-1 at Neurology.org/ng, P6-10). We report 5 patients with myopathic phenotypes, each harboring different pathogenic mutations in the MT-TP gene, highlighting the importance of MT-TP mutations as a cause of mitochondrial muscle disease and the requirement to study clinically relevant tissue