Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice.

Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Here we report on DNA variants in MINAR2, encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation of affected individuals at ages ranging from 4 to 80 y old does not show additional abnormalities. MINAR2 is a recently annotated gene with limited functional understanding. We detected three MINAR2 variants, c.144G > A (p.Trp48*), c.412_419delCGGTTTTG (p.Arg138Valfs*10), and c.393G > T, in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL). The c.393G > T variant is shown to disrupt a splice donor site. We show that Minar2 is expressed in the mouse inner ear, with the protein localizing mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis. Mice with loss of function of the Minar2 protein (Minar2tm1b/tm1b) present with rapidly progressive sensorineural HL associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age. We conclude that MINAR2 is essential for hearing in humans and mice and its disruption leads to sensorineural HL. Progressive HL observed in mice and in some affected individuals and as well as relative preservation of hair cells provides an opportunity to interfere with HL using genetic therapies.

Influence of Solvent on Selective Catalytic Reduction of Nitrogen Oxides with Ammonia over Cu-CHA Zeolite.

The copper-exchanged zeolite Cu-CHA has received considerable attention in recent years, owing to its application in the selective catalytic reduction (SCR) of NOx species. Here, we study the NH3-SCR reaction mechanism on Cu-CHA using the hybrid quantum mechanical/molecular mechanical (QM/MM) technique and investigate the effects of solvent on the reactivity of active Cu species. To this end, a comparison is made between water- and ammonia-solvated and bare Cu species. The results show the promoting effect of solvent on the oxidation component of the NH3-SCR cycle since the formation of important nitrate species is found to be energetically more favorable on the solvated Cu sites than in the absence of solvent molecules. Conversely, both solvent molecules are predicted to inhibit the reduction component of the NH3-SCR cycle. Diffuse reflectance infrared fourier-transform spectroscopy (DRIFTS) experiments exploiting (concentration) modulation excitation spectroscopy (MES) and phase-sensitive detection (PSD) identified spectroscopic signatures of Cu-nitrate and Cu-nitrosamine (H2NNO), important species which had not been previously observed experimentally. This is further supported by the QM/MM-calculated harmonic vibrational analysis. Additional insights are provided into the reactivity of solvated active sites and the formation of key intermediates including their formation energies and vibrational spectroscopic signatures, allowing the development of a detailed understanding of the reaction mechanism. We demonstrate the role of solvated active sites and their influence on the energetics of important species that must be explicitly considered for an accurate understanding of NH3-SCR kinetics.

De novo and inherited variants in coding and regulatory regions in genetic cardiomyopathies.

BACKGROUND: Cardiomyopathies are a leading cause of progressive heart failure and sudden cardiac death; however, their genetic aetiology remains poorly understood. We hypothesised that variants in noncoding regulatory regions and oligogenic inheritance mechanisms may help close the diagnostic gap. METHODS: We first analysed whole-genome sequencing data of 143 parent-offspring trios from Genomics England 100,000 Genomes Project. We used gene panel testing and a phenotype-based, variant prioritisation framework called Exomiser to identify candidate genes in trios. To assess the contribution of noncoding DNVs to cardiomyopathies, we intersected DNVs with open chromatin sequences from single-cell ATAC-seq data of cardiomyocytes. We also performed a case-control analysis in an exome-negative cohort, including 843 probands and 19,467 controls, to assess the association between noncoding variants in known cardiomyopathy genes and disease. RESULTS: In the trio analysis, a definite or probable genetic diagnosis was identified in 21 probands according to the American College of Medical Genetics guidelines. We identified novel DNVs in diagnostic-grade genes (RYR2, TNNT2, PTPN11, MYH7, LZR1, NKX2-5), and five cases harbouring a combination of prioritised variants, suggesting that oligogenic inheritance and genetic modifiers contribute to cardiomyopathies. Phenotype-based ranking of candidate genes identified in noncoding DNV analysis revealed JPH2 as the top candidate. Moreover, a case-control analysis revealed an enrichment of rare noncoding variants in regulatory elements of cardiomyopathy genes (p = .035, OR = 1.43, 95% Cl = 1.095-1.767) versus controls. Of the 25 variants associated with disease  (p< 0.5), 23 are novel and nine are predicted to disrupt transcription factor binding motifs. CONCLUSION: Our results highlight complex genetic mechanisms in cardiomyopathies and reveal novel genes for future investigations.

Computational infrared and Raman spectra by hybrid QM/MM techniques: a study on molecular and catalytic material systems.

Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms.  This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'.

Multiscale QM/MM modelling of catalytic systems with ChemShell.

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are a powerful computational tool for the investigation of all forms of catalysis, as they allow for an accurate description of reactions occurring at catalytic sites in the context of a complicated electrostatic environment. The scriptable computational chemistry environment ChemShell is a leading software package for QM/MM calculations, providing a flexible, high performance framework for modelling both biomolecular and materials catalysis. We present an overview of recent applications of ChemShell to problems in catalysis and review new functionality introduced into the redeveloped Python-based version of ChemShell to support catalytic modelling. These include a fully guided workflow for biomolecular QM/MM modelling, starting from an experimental structure, a periodic QM/MM embedding scheme to support modelling of metallic materials, and a comprehensive set of tutorials for biomolecular and materials modelling.

Factor Associated with HIV/AIDS knowledge among males: Findings from 2017-18 Pakistan Demographic and Health Survey.

Acquired immune deficiency syndrome (UNAIDS) has risen as the serious public health problem across the world. Knowledge about HIV/AIDS is the cornerstone for prevention and treatment. Research is needed to explore the attitude and the effect of different demographic, geographic, and socioeconomic and media exposure factors on males knowledge about HIV in Pakistan. In this study, latest secondary data are used from Pakistan Demographic and Health Survey 2017-18. Sample results show that the majority of the respondents (70%) have knowledge about AIDS. Regression Modeling reveals that man's knowledge about HIV/AIDS is associated with age, place of residence, educational level, wealth index, ethnicity and media exposure factors. Males of age group 35-39, with higher education, belonging to Pukthon ethnicity, having exposure to mass media on a daily basis and belonging to richest wealth quintile has high Knowledge of HIV/AIDS. For example, the regression model predicts that men between the ages of 35 and 39 from Islamabad who live in urban areas, have higher education, are of Pukhtoon ethnicity, are the head of the household, belong to the richest quintile, work in professional occupations, and use media exposure factors on a daily basis would have probability of 97% of having knowledge of HIV/AIDS. But there is still need to focus to increase the men's knowledge of HIV/AIDS.

Effects of Mutual Coupling on Gain and Beam Width of a Linear Array of a Dielectric Resonator Antenna for Main Beam Scanning Applications.

The effects of mutual coupling on the scanning characteristics of a four-element linear rectangular dielectric resonator antenna array (RDRA) are investigated for different inter-element spacing in this work. In particular, the gain and half-power beam width (HPBW) of an RDRA are studied for various scan angles in the E- and H-plane configurations. It is shown that for both the E and H planes, mutual coupling has an adverse effect on the performance of both phased array configurations. The H-plane array, however, is more stable than the E-plane array in terms of a gain and beam width performance comparison. The HPBW increases and gain decreases more in the E plane than the H plane when the scan angle is increased.

The prevalence of diabetes in Afghanistan: a systematic review and meta-analysis.

BACKGROUND: The aim of this paper is to investigate the prevalence of diabetes and its associated risk factors in Afghanistan through a systematic review and meta-analysis. METHODS: A comprehensive literature search was conducted using EMBASE, PubMed, Web of Sciences, Google Scholar and the Cochrane library, carried out from inception to April 312,020, without language restriction. Meta-analysis was performed using DerSimonian and Laird random-effects models with inverse variance weighting. The existence of publication bias was initially assessed by visual inspection of a funnel plot and then tested by the Egger regression test. Subgroup analyses and meta-regression were used to explore potential sources of heterogeneity. This systematic review was reported by following the PRISMA guidelines and the methodological quality of each included study was evaluated using the STROBE guidelines. RESULTS: Out of 64 potentially relevant studies, only 06 studies fulfilled the inclusion criteria and were considered for meta-analysis. The pooled prevalence of diabetes in the general population based on population-based studies were 12.13% (95% CI: 8.86-16.24%), based on a pooled sample of 7071 individuals. Results of univariate meta-regression analysis revealed that the prevalence of diabetes increased with mean age, hypertension and obesity. There was no significant association between sex (male vs female), smoking, the methodological quality of included articles or education (illiterate vs literate) and the prevalence of diabetes. CONCLUSIONS: This meta-analysis reports the 12.13% prevalence of diabetes in Afghanistan,with the highest prevalence in Kandahar and the lowest in Balkh province. The main risk factors include increasing age, obesity and hypertension. Community-based care and preventive training programmes are recommended. TRIAL REGISTRATION: This review was registered on PROSPERO (registration number CRD42020172624 ).

Surgical outcome of repair of aortic valve prolapse and regurgitation associated with ventricular septal defect.

OBJECTIVE: To analyze the outcome of repair of aortic valve disease associated with various types of ventricular septal defect. METHODS: In a retrospective observational study design, data of seventy-two patients of ventricular septal defect (VSD) associated with aortic valve prolapse (AVP) and aortic regurgitation (AR) who was operated in Punjab Institute of cardiology from May 2016 to April 2020 was collected. Depending on presence of AR, all patients were divided in four groups. Group-I (VSD and AVP but no AR) had fifteen patients. Only VSD was closed in this group. Group-II (VSD and Mild AR) had forty patients, only VSD was closed in this group as well. Group-III (VSD and Moderate AR) had ten patients, VSD closure and aortic valve repair was done. Group-IV (VSD and severe AR) had seven patients. Aortic valve was repaired in five patients and replaced (AVR) in two patients along with VSD closure. Associated anomalies were addressed as well. RESULTS: Group-I: Twelve out of fifteen patients (80%) showed no post-operative AR. While two patients (13.3%) showed Trace AR. Single patient (6.6%) showed mild AR. There results were unchanged after mean follow up of 36 months. Group-II: Eight out of forty patients (20%) had no AR, while eight (20%) had trace AR. Twenty-three (57.5%) patients had mild AR. Single (2.5%) patient had moderate AR. After follow up of 24 months the patient with moderate AR progressed to severe AR. We are planning to do Aortic Valve Replacement (AVR) in this case. Rest of cases showed no progression of disease. Group-III: Two out of ten patients (20%) had no AR, four (40%) had trace AR, while four (40%) had mild AR. Mean follow up was 42 months (2.5 years). Neither trace nor mild AR progressed to severe or moderate AR. Group-IV: Among seven patients, five underwent repair while two had AVR. Out of five patients who underwent aortic valve repair, four patients (57.1%) were declared mild AR, while severe AR was converted to moderate AR in single patient (14.28%). Mean follow up was 18 months. The moderate AR patient has progressed to severe AR for last six months and we are planning to do AVR in this patient. Postoperative echo of patients with AVR showed adequately functioning aortic valve with AVPG mean 10 mmHg and 15 mm Hg respectively, with no residual AR. CONCLUSIONS: Aortic regurgitation associated with VSD is a congenital lesion with continuously active aortic valve disease resulting in significant morbidity and mortality. Early diagnosis, effective treatment and meticulous follow up decelerate and in most cases arrest the disease process.

A mutation in the major autophagy gene, WIPI2, associated with global developmental abnormalities.

We describe a large consanguineous pedigree from a remote area of Northern Pakistan, with a complex developmental disorder associated with wide-ranging symptoms, including mental retardation, speech and language impairment and other neurological, psychiatric, skeletal and cardiac abnormalities. We initially carried out a genetic study using the HumanCytoSNP-12 v2.1 Illumina gene chip on nine family members and identified a single region of homozygosity shared amongst four affected individuals on chromosome 7p22 (positions 3059377-5478971). We performed whole-exome sequencing on two affected individuals from two separate branches of the extended pedigree and identified a novel nonsynonymous homozygous mutation in exon 9 of the WIPI2 (WD-repeat protein interacting with phosphoinositide 2) gene at position 5265458 (c.G745A;pV249M). WIPI2 plays a critical role in autophagy, an evolutionary conserved cellular pathway implicated in a growing number of medical conditions. The mutation is situated in a highly conserved and critically important region of WIPI2, responsible for binding PI(3)P and PI(3,5)P2, an essential requirement for autophagy to proceed. The mutation is absent in all public databases, is predicted to be damaging and segregates with the disease phenotype. We performed functional studies in vitro to determine the potential effects of the mutation on downstream pathways leading to autophagosome assembly. Binding of the V231M mutant of WIPI2b to ATG16L1 (as well as ATG5-12) is significantly reduced in GFP pull-down experiments, and fibroblasts derived from the patients show reduced WIPI2 puncta, reduced LC3 lipidation and reduced autophagic flux.

Quantitative thresholds based decision support approach for the home health care scheduling and routing problem.

In the domain of Home Health Care (HHC), precise decisions regarding patient's selection, staffing level, and scheduling of health care staff have a significant impact on the efficiency and effectiveness of the HHC system. However, decentralized planning, the absence of well defined decision rules, delayed decisions and lack of interactive tools typically lead towards low satisfaction level among all the stakeholders of the HHC system. In order to address these issues, we propose an integrated three phase decision support methodology for the HHC system. More specifically, the proposed methodology exploits the structure of the HHC problem and logistic regression based approaches to identify the decision rules for patient acceptance, staff hiring, and staff utilization. In the first phase, a mathematical model is constructed for the HHC scheduling and routing problem using Mixed-Integer Linear Programming (MILP). The mathematical model is solved with the MILP solver CPLEX and a Variable Neighbourhood Search (VNS) based method is used to find the heuristic solution for the HHC problem. The model considers the planning concerns related to compatibility, time restrictions, distance, and cost. In the second phase, Bender's method and Receiver Operating Characteristic (ROC) curves are implemented to identify the thresholds based on the CPLEX and VNS solution. While the third phase creates a fresh solution for the HHC problem with a new data set and validates the thresholds predicted in the second phase. The effectiveness of these thresholds is evaluated by utilizing performance measures of the widely-used confusion matrix. The evaluation of the thresholds shows that the ROC curves based thresholds of the first two parameters achieved 67% to 71% accuracy against the two considered solution methods. While the Bender's method based thresholds for the same parameters attained more than 70% accuracy in cases where probability value is small (p ≤ 0.5). The promising results indicate that the proposed methodology is applicable to define the decision rules for the HHC problem and beneficial to all the concerned stakeholders in making relevant decisions.

The prevalence of hepatitis C virus infection in ß-thalassemia patients in Pakistan: a systematic review and meta-analysis.

BACKGROUND: Hepatitis C virus infection is the most commonly reported bloodborne infection in Pakistan. Frequent blood transfusions in ß-thalassemia patients expose them to a high risk of HCV infection. The purpose of this paper is to summarise the current data on the prevalence of HCV infection in ß-thalassemia patients in Pakistan by using a systematic review and meta-analysis. METHODS: PubMed, EMBASE, Web of Sciences, the Cochrane Library, Directory of Open Access Journal and local databases were systematically searched for studies published between January 1st, 1995 and May 31st, 2019. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger test, and the methodological quality of each included article was evaluated by the STROBE. RESULTS: We identified a total of 229 potential studies, of which 27 studies were finally considered in the meta-analysis. The pooled prevalence of HCV in ß-thalassemia patients in Pakistan was 36.21% (95% CI: 28.98-43.75%) based on 5789 ß-thalassemia patients, but there was considerable heterogeneity. Meta-analysis estimated the HCV prevalence among the ß-thalassemia patients at 45.98% (95% CI: 38.15-53.90%) in Punjab, 31.81% (95% CI: 20.27-44.59%) in Sindh, and 28.04% (95% CI: 13.58-45.26%) in Khyber Pakhtunkhwa. Meta-regression analysis showed that geographical location was a key source of heterogeneity. CONCLUSIONS: The pooled prevalence of HCV in ß-thalassemia patients in Pakistan was more than one in three, and higher than in neighbouring countries. It varies regionally within the country. With the use of standard prevention procedures during blood transfusion, the risk of HCV transmission in ß-thalassemia patients could be controlled and the prevalence of HCV in ß-thalassemia patients reduced.

A genome-wide approach to the comprehensive analysis of GASA gene family in Glycine max.

A vital role of short amino acid gene family, gibberellic acid stimulated arabidopsis (GASA), has been reported in plant growth and development. Although, little information is available about these cysteine rich short proteins in different plant species and this is the first comprehensive approach to exploit available genomic data and to analyze the GASA family in G. max. The phylogenetic and sequence composition analysis distributed the 37 identified GmGASA genes into three groups. Further investigation of the tissue expression pattern, phylogenetic analysis, motif, gene structure, chromosome distributions, duplication patterns, positive-selection pressure and cis-element analysis of 37 GmGASA genes. A conserved GASA domain was found in all identified GmGASA genes and exhibited similar characteristics. The online gene expression profile based analysis of GmGASA genes reveled that these genes were highly expressed in almost all soybean parts and some have high expression in flower which indicates that GmGASA genes displayed special or distinct expression pattern among different tissues. The segmental duplication was found in five pairs from 37 GmGASA genes and was distributed on 15 different chromosomes. The Ka/Ks ratio of 5 pairs of segmentally duplicated gene indicated that after the occurrence of duplication events, the duplicated gene pairs were purified and selected after restrictive functional differentiation. This investigated study of GmGASA gene will useful to support the statement about GASA genes role during flower induction in flowering plants.

Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke.

Stroke is a common disorder with significant morbidity and mortality, and complex aetiology involving both environmental and genetic risk factors. Although some of the major risk factors for stoke, such as smoking and hypertension, are well-documented, the underlying genetic and detailed molecular mechanisms remain elusive. Exploring the relevant biochemical pathways may contribute to the clinical diagnosis of stroke and shed light on its aetiology. A comparative proteomic analysis of blood serum of a pair of monozygotic (MZ) twins discordant for ischaemic stroke (IS) was performed using a label-free quantitative proteomics approach. To overcome the limit of reproducibility in the serum preparation, two separate runs were performed, each consisting of three technical replicates per sample. Biological processes associated with proteins differentially expressed between the twins were explored with gene ontology (GO) classification using the functional analysis tool g:Profiler. ANOVA test performed in Progenesis LC-MS identified 179 (run 1) and 209 (run 2) proteins as differentially expressed between the affected and unaffected twin (p < 0.05). Furthermore, the level of serum fibulin 1, an extracellular matrix protein associated with arterial stiffness, was on average 13.37-fold higher in the affected twin. Each dataset was then analysed independently, and the proteins were classified according to GO terms. The categories overrepresented in the affected twin predominantly corresponded to stroke-relevant processes, including wound healing, blood coagulation and haemostasis, with a high proportion of the proteins overexpressed in the affected twin associated with these terms. By contrast, in the unaffected twin diagnosed with atopic dermatitis, there were increased levels of keratin proteins and GO terms associated with skin development. The identification of cellular pathways enriched in IS as well as the upregulation of fibulin 1 sheds new light on the underlying disease-causing mechanisms at the molecular level. Our findings of distinct proteomic signatures associated with IS and atopic dermatitis suggest proteomic profiling could be used as a general approach for improved diagnostic, prognostic and therapeutic strategies.

Diabetes in Pakistan: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was assess the time trend of the prevalence of prediabetes and diabetes and risk factors associated with diabetes in Pakistan by using a systematic review and meta-analysis. METHODS: A systematic literature search of Embase, PubMed, and the Cochrane library was carried out between January 1, 1995 and August 30, 2018. Diabetes and prediabetes prevalence estimates were combined by the random-effects model. The existence of publication bias was tested by Egger regression. This systematic review was reported following the PRISMA guidelines. RESULTS: The search conceded a total of 635 studies, only 14 studies were considered for meta-analysis. The prevalence of diabetes in Pakistan was revealed 14.62% (10.651%-19.094%; 14 studies) based on 49,418 people using the inverse-variance random-effects model. The prevalence of prediabetes was 11.43% (8.26%-15.03%; 10 studies) based on a total sample of 26,999 people. The risk factors associated with diabetes were mean age (ß = 0.48%, 95% CI: 0.21-0.78, p<0.001), the proportion of participants with a family history of diabetes (ß = 0. 45%, 95% CI: 0.08-0.82, p =0.018, p<0.001), hypertension (ß = 0.40%, 95% CI: 0.06-0.75, p = 0.022), weight (BMI) (ß = 0.21%, 95% CI: 0.02-0.4, p=0.030). CONCLUSIONS: There has been a continuous increase in the prevalence of prediabetes and diabetes in Pakistan. All parts of the country have been affected, with the highest in Sindh and lowest in Khyber Pakhtunkhwa. The main factors include growing age, family history, hypertension and obesity. A nationwide diabetes care survey on risk factors and prevention policy is highly recommended.

Metal- and Carbon-Based Materials as Heterogeneous Electrocatalysts for CO2 Reduction.

Climate change caused by continuous rising level of CO2 and the depletion of fossil fuels reserves has made it highly desirable to electrochemically convert CO2 into fuels and commodity chemicals. Implementing this approach will close the carbon cycle by recycling CO2 providing a sustainable way to store energy in the chemical bonds of portable molecular fuels. In order to make the process commercially viable, the challenge of slow kinetics of CO2 electroreduction and low energy efficiency of the process need to be addressed. To this end, this review summarizes the progress made in the past few years in the development of heterogeneous electrocatalysts with a focus on nanostructured material for CO2 reduction to CO, HCOOH/HCOO-, CH2O, CH4, H2C2O4/HC2O-4, C2H4, CH3OH, CH3CH2OH, etc. The electrocatalysts presented here are classified into metals, metal alloys, metal oxides, metal chalcogenides and carbon based materials on the basis of their elemental composition, whose performance is discussed in light of catalyst activity, product selectivity, Faradaic efficiency (FE), catalytic durability and in selected cases mechanism of CO2 electroreduction. The effect of particle size, morphology and solution-electrolyte type and composition on the catalyst property/activity is also discussed and finally some strategies are proposed for the development of CO2 electroreduction catalysts. The aim of this article is to review the recent advances in the field of CO2 electroreduction in order to further facilitate research and development in this area.

Throughput Measurement of a Dual-Band MIMO Rectangular Dielectric Resonator Antenna for LTE Applications.

An L-shaped dual-band multiple-input multiple-output (MIMO) rectangular dielectric resonator antenna (RDRA) for long term evolution (LTE) applications is proposed. The presented antenna can transmit and receive information independently using fundamental TE111 and higher order TE121 modes of the DRA. TE111 degenerate mode covers LTE band 2 (1.85-1.99 GHz), 3 (1.71-1.88 GHz), and 9 (1.7499-1.7849 GHz) at fr = 1.8 GHz whereas TE121 covers LTE band 7 (2.5-2.69 GHz) at fr = 2.6 GHz, respectively. An efficient design method has been used to reduce mutual coupling between ports by changing the effective permittivity values of DRA by introducing a cylindrical air-gap at an optimal position in the dielectric resonator. This air-gap along with matching strips at the corners of the dielectric resonator keeps the isolation at a value more than 17 dB at both the bands. The diversity performance has also been evaluated by calculating the envelope correlation coefficient, diversity gain, and mean effective gain of the proposed design. MIMO performance has been evaluated by measuring the throughput of the proposed MIMO antenna. Experimental results successfully validate the presented design methodology in this work.

Case-based interprofessional learning for undergraduate healthcare professionals in the clinical setting.

Interprofessional learning (IPL) within the healthcare setting has well documented positive outcomes for patients, yet it is not widely offered at the undergraduate level, particularly in a clinical setting. We set up case-based teaching scenarios involving a real patient, aimed at small groups of four students representing two or more healthcare professions. The aim of the sessions was to give students a greater awareness of the roles of all the different healthcare professions involved in patient care in a hospital setting. Weekly sessions were offered on six wards covering different clinical specialties. Three hundred and twenty-nine undergraduate students from different healthcare professions (nursing, medicine, pharmacy, midwifery, physician associate, physiotherapy, occupational therapy, speech, and language therapy) each attended one IPL session during the current academic year. Students were given an evaluation sheet at the end of each session to be filled out anonymously. Forty per cent of the students reported experiencing interprofessional case-based learning for the first time. Over 90% of students agreed or strongly agreed with a list of statements promoting the advantages and benefits of case-based IPL for undergraduate students and many of them requested more sessions. Seventy per cent of all respondents stated they would alter their future professional behaviour as a result of this session. We propose to introduce the sessions into the undergraduate curriculum across all healthcare related professions.

THE QUANTITATIVE EVIDENCE OF MALARIAL TRANSMISSION AND ITS ASSOCIATES IN BAHAWALPUR, PAKISTAN.

BACKGROUND: Malaria transmission is an extremely complex condition that is manifested differently in different parts of the world. In Pakistan, malaria is still endemic in many areas. Plasmodium vivax and Plasmodium falciparum are identified to be the most prevalent species of malaria in-Pakistan. A great deal of work regarding malarial transmission is available at regional level in Pakistan but the evidence of malaria with its associates in Bahawalpur is scarce. The present study was planned to see the pattern of malarial transmission in the city of Bahawalpur, Pakistan. METHODS: In this cross-sectional study data on 1623 subjects was collected. Giemsa stain thick and thin blood films were used as diagnostic tools for malarial transmission. Bivariate statistical analysis in addition was employed to identify the associates of malarial prevalence. RESULTS: Out of 1623 subjects screened, 70 (4.3%) were found infected. Plasmodium vivax was seen in the majority 61 (77.2%). Plasmodium falciparum was the second common-species identified in 16 (22.8%) cases. As expected place of residence, window screening, malarial knowledge and behaviours of sleeping were seen to be significant associates of malarial transmission in Bahawalpur. CONCLUSION: The findings revealed that Bahawalpur falls in the category of low to moderate level malarial transmission as compared to other regions of Pakistan. Plasmodium vivax was the commonest type of malaria diagnosed in Bahawalpur. Geographic location, house safety, malarial knowledge, and behaviour of sleeping are the highly significant associates of malarial transmission in Bahawalpur.

Clinically significant missense variants in human GALNT3, GALNT8, GALNT12, and GALNT13 genes: intriguing in silico findings.

Aberrant glycosylation by N-acetylgalactosaminyl transferases (GALNTs) is a well-described pathological alteration that is widespread in hereditary diseases, prominently including human cancers, familial tumoral calcinosis and hyperostosis-hyperphosphatemia. In this study, we integrated different computational tools to perform the in silico analysis of clinically significant mutations (nsSNPs/single amino acid change) at both functional and structural levels, found in human GALNT3, GALNT8, GALNT12, and GALNT13 genes. From function and structure based insights, mutations encoding R162Q, T359K, C574G, G359D, R297W, D303N, Y396C, and D313N substitutions were concordantly predicted highly deleterious for relevant GALNTs proteins. From intriguing findings, T359K-GALNT3 was simulated with high contribution for disease susceptibility (tumor calcinosis) as compared to its partner variant T272K (Ichikawa et al. [2006] J. Clin. Endocrinol. Metab. 91:4472-4475). Similarly, the prediction of high damaging behavior, evolutionary conservation and structural destabilization for C574G were proposed as major contributing factors to regulate metabolic disorder underlying tumor calcinosis and hyperostosis-hyperphosphatemia syndrome. In case of R297W-GALNT12, prediction of highly deleterious effect and disruption in ionic interactions were anticipated with reduction in enzymatic activity, associated with bilateral breast cancer and primary colorectal cancers. The second GALNT12 mutation (D303N)-known splice variant-was predicted with disease severity as a result of decrease in charge density and buried behavior neighboring the catalytic B domain. In the lack of adequate in silico data about systematic characterization of clinically significant mutations in GALNTs genes, current study can be used as a significant tool to interpret the role of GALNTs reaction chemistry in disease-association risks in body.