Search

Applications of clinical decision support systems (CDSS) have become essential for physicians seeking to make appropriate decisions. The implementation of CDSS, however, is complicated if the factors affecting physician’s acceptance are not recognised. This study aims to explore the various factors that may influence the acceptance of CDSS in Saudi Arabia. A qualitative method was used to collect data from interviews with 54 GPs, with interviews conducted in three stages. The study then integrated the Unified Theory of Acceptance and Use of Technology (UTAUT) and Task-Technology Fit (TTF) models to communicate the findings. It is suggested that all factors of both UTAUT and TTF influence acceptance of CDSS by GPs, with the sole exception of the social influence factor. Some additional factors were also discovered by means of in-depth interviews, including accessibility, patient satisfaction, informativeness (increased knowledge), connectedness (informing patients), communication and shared knowledge, privacy and security, and perceived risk (functional performance risk and time risk). The study thus offers a new insight of the factors influencing GPs’ acceptance of CDSS.

In transfer learning, two major activities, i.e., pretraining and fine-tuning, are carried out to perform downstream tasks. The advent of transformer architecture and bidirectional language models, e.g., bidirectional encoder representation from transformer (BERT), enables the functionality of transfer learning. Besides, BERT bridges the limitations of unidirectional language models by removing the dependency on the recurrent neural network (RNN). BERT also supports the attention mechanism to read input from any side and understand sentence context better. It is analyzed that the performance of downstream tasks in transfer learning depends upon the various factors such as dataset size, step size, and the number of selected parameters. In state-of-the-art, various research studies produced efficient results by contributing to the pretraining phase. However, a comprehensive investigation and analysis of these research studies is not available yet. Therefore, in this article, a systematic literature review (SLR) is presented investigating thirty-one (31) influential research studies published during 2018–2020. Following contributions are made in this paper: (1) thirty-one (31) models inspired by BERT are extracted. (2) Every model in this paper is compared with RoBERTa (replicated BERT model) having large dataset and batch size but with a small step size. It is concluded that seven (7) out of thirty-one (31) models in this SLR outperforms RoBERTa in which three were trained on a larger dataset while the other four models are trained on a smaller dataset. Besides, among these seven models, six models shared both feedforward network (FFN) and attention across the layers. Rest of the twenty-four (24) models are also studied in this SLR with different parameter settings. Furthermore, it has been concluded that a pretrained model with a large dataset, hidden layers, attention heads, and small step size with parameter sharing produces better results. This SLR will help researchers to pick a suitable model based on their requirements.

Objectives Self-medication with antibiotics is a common public health problem worldwide. It is the main driving factor for the development of microbial resistance. The world is facing the challenge of losing effective antibiotics. The study aim is to determine the prevalence and related factors of self-medication with antibiotics among visitors of a clinic in Kabul, Afghanistan. Methods A cross-sectional questionnaire-based survey on a sample of 384 consecutively selected visitors of the Central Polyclinic of Kabul, Afghanistan, was conducted. Key findings Approximately 34.9% of the sample self-medicated with antibiotics in the past 12 months. Amoxicillin was the most common antibiotic used for self-medication. The sore throat was a common health problem, and previous experience was the source of recommendation for self-medication. The most common reasons for self-medication with antibiotics were cost-saving, previous experience and lack of time. Conclusions Self-medication with antibiotics was prevalent among visitors to the clinic. Patterns of self-medication with antibiotics indicate the inappropriate practice of medicines. Pharmacists, friends and family approve the self-medication with antibiotics.

There is a growing interest in the impact of light intensity and temperature on vegetable growth and dietary quality characteristics. Lettuce (Lactuca sativa L.), as one of the model vegetables in ...

Purpose The emergence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) is associated with the acquisition of multiple carbapenemases. Their clonal spread is a worldwide concern due to their critical role in nosocomial infections. Therefore, the identification of high-risk clones with antibiotic resistance genes is very crucial for controlling its global spread. Materials and methods A total of 227 K. pneumoniae strains collected during April 2018 to November 2019 were confirmed by PCR. Carbapenemases and extended-spectrum β-lactamases (ESBL) were detected phenotypically. Confirmation of carbapenemases was carried out by PCR and Sanger sequencing. The clonal lineages were assigned to selected isolates by multilocus sequence typing (MLST), and the plasmid analysis was done by PCR-based detection of the plasmid replicon typing. Results Of the total K. pneumoniae, 117 (51.5%) were carbapenem resistant (CRKP) and 140 (61.7%) were identified as ESBL producers. Intermediate to high resistance was detected in the tested β-lactam drugs while polymyxin-B and tigecycline were found to be susceptible. Among CRKP, 91 (77.8%) isolates were detected as carbapenemase producing, while 55 (47%) were positive for bla NDM-1 23.9% (n=28), bla OXA-48 22.2% (n=26) and bla VIM 0.85% (n=1) while 12.7% (n=7) carried both bla NDM-1 and bla OXA-48 genes. The CRKP coharboring bla NDM-1 and bla OXA-48 genes (n=7) were positive for bla CTX-M bla SHV (n=3), bla SHV (n=1) and bla CTX-M (n=3). The novel CRKP with the coexistence of bla NDM-1, bla OXA-48, bla CTX-M and bla SHV genes were associated with the high-risk clone ST147 (n=5) and ST11 (n=2). The assigned replicon types were IncL/M, IncFII, IncA/C and IncH1. Conclusion This is the first report of the coexistence of bla NDM-1, bla OXA-48, bla CTX-M and bla SHV genes on a high-risk lineage ST147 from Pakistan. This study highlights the successful dissemination of carbapenemase resistance genes in the high-risk clones that emphasizes the importance of monitoring and controlling the spread of these diverse clones globally.

Previous studies identified alarming use of potentially inappropriate medications (PIMs) in Pakistani population but its effect on health-related quality of life (HRQoL) is still largely unknown. This study aimed to determine the association between PIMs use and HRQoL among elderly cardiac outpatients. A descriptive, non-experimental, cross-sectional study was carried out from June 2018 to September 2018 in two outpatient departments of tertiary-care hospitals in the Punjab Province of Pakistan. The population under study were patients aged ≥ 65 years with at least one cardiovascular condition taking at ≥ 1 prescribed medication. Patients with PIMs were identified by using Beers criteria. HRQoL was assessed using EuroQoL-5 dimension (EQ-5D) and EuroQoL-visual analogue scale (EQ-VAS). The association of PIMs with HRQoL was analyzed using χ2 tests, independent sample t-test, and one-way ANOVA tests. Multiple linear regression analysis was used to determine how HRQoL varied by PIMs use after adjusting for patient-level covariates. Of 386 elderly cardiac patients, 260 (67.4%) patients were receiving at least one PIM. Mean EQ-5D scores were significantly lower among patients with PIMs (0.51) compared to patients without PIMs (0.65) (P

Polystichum braunii (Spenn.) Fee is a traditional remedy for rheumatoid arthritis, a chronic inflammatory disorder of polygenetic origin. The current project was intended to demonstrate the role of inflammatory and oxidative stress biomarkers in the anti-arthritic activity of the P. braunii extracts. Methanolic and aqueous extracts of the plant roots were prepared by triple maceration. The phytochemical evaluation of the plant extracts was carried out by high-performance liquid chromatography (HPLC). The plant extracts at 150, 300, and 600 mg/kg/day and piroxicam (10 mg/kg/day) were orally administered to Wistar rats for 21 days that were previously immunized with Complete Freund’s adjuvant (150 µl on right hind paw) except normal and arthritic control rats. Both plant extracts mitigated the paw oedema, restored the immune organ and body weights, and ameliorated the level of blood parameters such as haemoglobin, red blood cells, platelets, white blood cells, alkaline phosphatase (ALP), C-reactive proteins, and rheumatoid factor. The evaluation of gene expression using quantitative-real-time polymerase chain reaction (qRT-PCR) revealed the substantial downregulation of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-1β, cyclo-oxygenase (COX)-2, nuclear factor (NF)-κB, and upregulation of IL-4, IL-10 and I-κB in polyarthritic rats treated with the plant extracts. Methanolic plant extract exhibited the maximum effect on upregulation of IL-4 (79 ± 3%), IL-10 (62.66 ± 4.93%), and I-κB (73.66 ± 3.05%) at 600 mg/kg/day. Treatment with the plant extracts also reduced the level of prostaglandin E2 and TNF-α in the serum of arthritic rats’ dose dependently. It was also found that the plant extracts and piroxicam increased (p

BackgroundAlthough widely used in treating severe abdominal trauma, damage control laparotomy (DCL) has not been assessed in any randomized controlled trial. We conducted a pilot trial among patients for whom our surgeons had equipoise and hypothesized that definitive laparotomy (DEF) would reduce major abdominal complications (MAC) or death within 30 days compared with DCL.MethodsEligible patients undergoing emergency laparotomy were randomized during surgery to DCL or DEF from July 2016 to May 2019. The primary outcome was MAC or death within 30 days. Prespecified frequentist and Bayesian analyses were performed.ResultsOf 489 eligible patients, 39 patients were randomized (DCL 18, DEF 21) and included. Groups were similar in demographics and mechanism of injury. The DEF group had a higher Injury Severity Score (DEF median 34 (IQR 20, 43) vs DCL 29 (IQR 22, 41)) and received more prerandomization blood products (DEF median red blood cells 8 units (IQR 6, 11) vs DCL 6 units (IQR 2, 11)). In unadjusted analyses, the DEF group had more MAC or death within 30 days (1.71, 95% CI 0.81 to 3.63, p=0.159) due to more deaths within 30 days (DEF 33% vs DCL 0%, p=0.010). Adjustment for Injury Severity Score and prerandomization blood products reduced the risk ratio for MAC or death within 30 days to 1.54 (95% CI 0.71 to 3.32, p=0.274). The Bayesian probability that DEF increased MAC or death within 30 days was 85% in unadjusted analyses and 66% in adjusted analyses.ConclusionThe findings of our single center pilot trial were inconclusive. Outcomes were not worse with DCL and, in fact, may have been better. A randomized clinical trial of DCL is feasible and a larger, multicenter trial is needed to compare DCL and DEF for patients with severe abdominal trauma.Level of evidenceLevel II.

Hepatocellular carcinoma (HCC) has been increasing among Pakistani males. Aim: The main objective of this study was to evaluate the role of TGF-β-1 gene polymorphism as a risk factor in chronic hepatitis C virus (HCV) infected HCC patients in Pakistan. Patients & methods: A total of 286 subjects were recruited into three different groups (Group I: 96 healthy controls, Group II: 96 HCV, Group III: 94 HCC). Results: A significant increase in genotype and allele frequencies of TGF-β-1 gene was observed in HCC, HCV with OR = 1.9; 95% CI: 1.275–2.871; p > 0.05, OR = 1.6; 95% CI: 1.12–2.51; p > 0.05 and OR = 1.7; 95% CI: 1.036–1.923; p > 0.05. Conclusion: A higher frequency of the TT genotype and T allele of the TGF-β-1 gene is observed in Pakistani HCV and HCC patients.

To understand the mechanism by which exogenous putrescine (Put) alleviated starch overaccumulation in the leaves of cucumber subjected to salt stress, a greenhouse experiment was conducted. Our research findings focused on NaCl stress leading to an increase in the number of starch granules in the chloroplast and starch content in the leaves, resulting in the destruction of photosynthetic organs and reduced photosynthesis. However, exogenous Put reduced the number of starch granules and protected the photosynthetic organs, thereby enhancing photosynthesis. On the other hand, Put-treated seedlings reduced AGPase activity by downregulating AGPase and increased β-amylase activity by upregulating BAM1, resulting in relief from excess accumulation of leaf starch. The application of d -Arg under salt stress decreased the expression of ADC, inhibited Put synthesis, reduced the endogenous polyamine (PAs) content, and inhibited the growth of seedlings; exogenous Put partly alleviated the inhibitory effect of d -Arg and significantly increased the endogenous PAs content, indicating that the ADC pathway is important for Put synthesis in plants suffering from salt stress. Taken together, exogenous application of PAs could increase levels of endogenous PAs via important ADC pathways, mainly inducing AGPase and BAM1 expression, leading to changes in AGPase and β-amylase activities involved in starch metabolism to reduce excessive starch accumulation in leaves, relieve photosynthetic feedback repression and protect photosynthetic organs, thus enhancing cucumber seedling salt stress tolerance.

HPP (Hydropower Projects) are very complex and risky in nature. For HPP, it is extremely important not only to identify risks but also to adopt proper mitigation measure to complete the project with in defined schedule and budget. Attempt has been made in this paper to identify critical risks associated with Dasu HPP and their mitigation measure to complete the project within predefined time and budget. The research methodology involved the questionnaire survey for identification of potential risks with their probabilities and impact. Pert-Master (Oracle Risk) software was used for simulation purposes. After feeding all data in the software, Monte Carlo simulation was run at 1,000 iterations to generate most probable duration of project, most probable cost of the project, critical risks sensitive to duration, critical risk sensitive to cost and statistically analyzed critical tasks/activities, which need due consideration for successful completion of project. Simulated schedule and budget was compared with planned one to find possible deviations, which may be eliminated by using mitigation measures proposed in the last section of the paper.

Aim: To determine the prevalence of New Delhi metallo-β-lactamase (NDM)-producing Gram-negative pathogens isolated from children’s samples. Materials & methods: Carbapenem-resistant clinical isolates (n = 117) were confirmed by VITEK® 2 compact system, matrix-assisted laser desorption ionization–time of flight and multilocus sequence typing. MIC (μg/ml) of various antibiotics was determined by VITEK 2 compact system. Molecular characterization of the isolates was performed by PCR, DNA sequencing, PFGE and DNA hybridization. Results: Out of 117 carbapenemase producers, 37 (31.6%) and 29 (24.7%) were Klebsiella pneumoniae and Acinetobacter baumannii, respectively. 72 (61.5%) isolates were NDM positive and among these 60, 9 and 3 were NDM-1, -5 and -7, respectively. Majority of the NDM-producing K. pneumoniae belonged to ST11 and ST273 while most of the Escherichia coli belonged to ST405 and ST101. blaNDM were mainly located on 150kb plasmids. MIC displayed high resistance against β-lactams drugs including carbapenems, and the most sensitive drugs were tigecycline and colistin. Conclusion: Dissemination of blaNDM-producing pathogens, particularly in children clinical settings, is a matter of great public health concern.

Heat stress seriously inhibits plant growth and development through damage the photosynthetic components and antioxidant enzymes functions. Salicylic acid (SA) is an important growth hormone regulator for combating heat stress, but its roles in response to high temperature in tomato are largely unknown. The present study was undertaken with a view to investigate the functional along with the potentiality of SA and how to nullify the adverse effects of heat stress (42 °C) in tomato seedlings. Our findings revealed that supplementation of 1 mM SA enhanced the gas exchange parameters (Pn, Gs, Ci, Tr, Ls), maximum quantum yield of photosystem II (Fv/Fm), water use efficiency, reduced electrolyte leakage and increased the antioxidant enzymes (SOD, POD, CAT, and APX) activity that helps to reduce oxidative damage through scavenging more reactive oxygen species (ROS) which directly impacts on plants by protecting cell membrane from damage, higher chlorophyll content, lower accumulation of lipid peroxidation, and H2O2. Additionally, exogenous application of SA increased the proline content thus added on osmotic potential which influencing plants for better uptake of water that caused to beneficial effects on stomatal aperture together with photosynthetic apparatus, whereas, high temperature reduced leaf chlorophyll pigment, carotenoid content, leaf water potential, and osmotic potential. Taken together, we concluded that the adverse effects of heat stress could be suppressed by pretreated SA through both in increased photosynthesis activity and antioxidant enzymes functions.

Background Evidence-based practice (EBP) is both a goal and an approach that requires a combination of clinical experience with the most credible recent research evidence when making decisions in healthcare practice. The approach has been widely embraced; however, an evidence-to-practice gap still exists. Aim To assess barriers to EBP among nurses in low- and middle-income countries. Methods This review conforms to the PRISMA statement. Databases PubMed, Scopus, EMBASE, and Web of Science/Knowledge were searched using a combination of keywords that included "barriers," "evidence-based practice," and "nurses." The references of the selected articles were also hand-searched to obtain additional relevant articles. Studies published in peer-reviewed journals in English between 2000 and 2018 were included in the review. Results Sixteen articles were included in the analysis, with a total number of 8,409 participants. Both qualitative and quantitative studies were included in the review. Three main themes emerged from eight categories found. The three main themes were institutional-related barriers, interdisciplinary barriers, and nurse-related barriers. The theme of institutional-related barriers emerged from four categories, which included scant resources, limited access to information, inadequate staffing, and lack of institutional support. The theme of interdisciplinary barriers emerged from subcategories that included lack of communication between academic and clinical practice environments, inconsistency between education and practice in the nursing discipline, lack of teamwork, and the public's negative image about the nursing profession. Finally, the theme of nurse-related barriers emerged from categories including perceived limitations in the scope of nurses' practice, time, knowledge of EBP, and individual-related barriers. Linking evidence to action These findings may guide the design of future interventions aimed at fostering EBP. Implementing EBP in practice should be systematic and requires institutional will and interdisciplinary and individual commitment. It should be a collective goal and a win-win situation for nurses, clinicians, and healthcare organizations.

BackgroundHIV and Hepatitis C Virus (HCV) infections are responsible for a significant burden of mortality and morbidity, particularly in developing countries. This study sought to determine the prevalence of HIV and Hepatitis C among injecting drug users in Afghanistan, Iran, and Pakistan.MethodsThis review conforms to the Preferred Reporting Guidelines for Systematic Reviews and Meta-Analysis (PRISMA) statement. Databases including PubMed, Scopus, Web of Science/Knowledge, SID.ir, and MAGIRAN were searched. Studies that were published from 2003 up to 2018 were considered for analysis. Studies were screened for inclusion in duplicate, and also, that data were narratively synthesized.ResultsWe report on data from 79 articles. The total number of participants in studies that assessed the prevalence of HIV among injecting drug users included 68,926 participants, while those from studies that assessed HCV prevalence were 23,016 participants. Overall HIV and HCV prevalence among injecting drug users in the three selected countries were 9.1% (95% CI 6.9–12.0%) and 48.3% (95% CI 43.9–52.7%), respectively. Iran had the highest HIV prevalence of 11.0% among injectable drug users (95% CI 8.4–14.2%), while Afghanistan had the lowest HIV prevalence of 3.1% (95% CI 1.5–6.3%) among three selected countries. In Pakistan, the prevalence of HIV was 8.6% (95% CI 4.8–15.0%). Regarding HCV prevalence, Pakistan had the highest while Afghanistan had the lowest, 54.4% (95% CI 33.5–73.9%) and 37.3% (95% CI 35.2–39.4%), respectively. HCV prevalence in Iran was 47.7% (95% CI 43.4–52.0%).ConclusionInjecting drug users form a special cohort of persons at risk of HIV and Hepatitis C infections. The prevalence of HIV and Hepatitis noted from our findings is significantly high. Awareness of the grave risk of spreading HIV and Hepatitis C associated with sharing needles is recommended among this sub-group of drug users.

The Bcl-2-associated athanogene (BAG) family is a group of evolutionarily conserved cochaperones involved in diverse cellular functions. Here, ten putative SlBAG genes were identified in tomato. SlBAG2 and SlBAG5b have the same gene structure and conserved domains, along with highly similar identity to their homologs in Arabidopsis thaliana, Oryza sativa, and Triticum aestivum. The qPCR data showed that BAG2 and BAG5b were highly expressed in stems and flowers. Moreover, both genes were differentially expressed under diverse abiotic stimuli, including cold stress, heat stress, salt treatment, and UV irradiation, and treatments with phytohormones, namely, ABA, SA, MeJA, and ETH. Subcellular localization showed that SlBAG2 and SlBAG5b were located in the cell membrane and nucleus. To elucidate the functions in leaf senescence of BAG2 and BAG5b, the full-length CDSs of BAG2 and BAG5b were cloned, and transgenic tomatoes were developed. Compared with WT plants, those overexpressing BAG2 and BAG5b had significantly increased chlorophyll contents, chlorophyll fluorescence parameters and photosynthetic rates but obviously decreased ROS levels, chlorophyll degradation and leaf senescence related gene expression under dark stress. Conclusively, overexpression SlBAG2 and SlBAG5b could improve the tolerance of tomato leaves to dark stress and delay leaf senescence.

This article reports the intent to receive a SARS-COV-2 vaccine, its predictors and willingness to pay in Bangladesh. We carried out an online cross-sectional survey of 697 adults from the general population of Bangladesh in January 2021. A structured questionnaire was used to assess vaccination intent. The questionnaire included sociodemographic variables and health belief model constructs which may predict vaccination intent. Among the participants, 26% demonstrated a definite intent, 43% probable intent, 24% probable negative, and 7% a definite negative intention. Multivariable logistic regression analyses suggest an association between definite intent and previous COVID-19 infection (OR: 2.86, 95% CI: 1.71–4.78), perceiving COVID-19 as serious (OR: 1.93, 1.04–3.59), the belief that vaccination would make them feel less worried about catching COVID-19 (OR: 4.42, 2.25–8.68), and concerns about vaccine affordability (OR: 1.51, 1.01–2.25). Individuals afraid of the side effects (OR: 0.34, 0.21–0.53) and those who would take the vaccine if the vaccine were taken by many others (OR: 0.44, 0.29–0.67) are less likely to have a definite intent. A definite negative intent is associated with the concern that the vaccine may not be halal (OR: 2.03, 1.04–3.96). Furthermore, 68.4% are willing to pay for the vaccine. The median amount that they are willing to pay is USD 7.08. The study findings reveal that the definite intent to receive the SARS-CoV-2 vaccination among the general population varies depending on their COVID-19-related health beliefs and no significant association was found with sociodemographic variables.

Background: Bangladesh has been attracting international students with interests in various subjects recently. Every year students from different parts of the world come to study undergraduate and postgraduate courses, mostly at private universities in Bangladesh. This study evaluates the depression status among international students who are studying dentistry in Bangladesh. Methods: This cross-sectional survey was conducted among International undergraduate dental students who enrolled in the Bachelor of Dental Surgery program in nine public and private dental colleges in Bangladesh. Participants were selected using a convenience sampling method. A total of 206 students completed the survey where 78.5% of them were female students and 21.5% students were male, and a CES-D 10-item Likert scale questionnaire was used for data collection. The Cronbach alpha for the 10-item CES-D scale for this population is 0.812. Results: The majority of the students (79.5%) are below 24 years of age with a mean age of 23.22 years and standard deviation of 2.3, and are students who cannot communicate well in Bengali (Bangla), about 60% of them have experienced depression. About 77.3% (p &lt, 0.00) of the international students having financial difficulties exhibited depression. The international students who went through financial problems were two times more likely to suffer from depression (OR = 2.38, p-value &lt, 0.01). Conclusion: This study tried to highlight the struggles faced by international students in Bangladesh studying dentistry. It is evident from the findings that several factors influence students’ mental well-being during demanding dental education years.

Background — Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by production of autoantibodies and deposition within various organs. The incidence of SLE averages 5 cases per 100,000 population. Various genome wide studies have shown association of STAT4 (signal transducer and activator of transcription 4) gene with SLE and lupus nephritis (LN). Therefore, this study was designed to determine single nucleotide polymorphism (SNP) in STAT4 (rs7582694) in local SLE, LN patients and healthy controls. Objective — To determine the frequency of STAT4 (rs7582694) gene polymorphism in systemic lupus erythematosus, lupus nephritis patients and healthy controls. Methods — It was a case-control study. Eighty samples were recruited for each of two study groups. Deoxyribonucleic acid (DNA) extraction was carried out using standard phenol chloroform method. Further, samples were processed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) conventional technique and genotypes were determined. Polymorphism analysis and allele frequencies were compared between groups using the chi-square test. Project was approved by the Ethical Review Board at the University of Health Sciences, Lahore, Pakistan. Results — Females were more inclined towards developing SLE. The study unveiled that SNP in STAT 4 gene (rs7582694) was associated with SLE patients in Pakistani population which indicates that this may play a role in susceptibility to SLE. Moreover, we infer that genetic variations within STAT4 (rs7582694) predispose patients to lupus nephritis. It was also evident that GG and GC genotypes were more susceptible of further transforming into SLE and LN. Conclusion: The findings of this study may contribute to a better understanding of underlying etiological and prognostic factors regarding SLE and LN.

Transglutaminase (TGase), the ubiquitous protein in plants, catalyzes the post-translational transformation of proteins and plays a vital role in photosynthesis. However, its role and mechanism in tomato subjected to heat stress still remain unknown. Here, we carried out a transcriptomic assay to compare the differentially expressed genes (DEGs) between wild type (WT) and TGase overexpression (TGaseOE) plants employed to high-temperature at 42 °C and samples were collected after 0, 6, and 12 h, respectively. A total of 11,516 DEGs were identified from heat-stressed seedlings, while 1,148 and 1,353 DEGs were up-and down-regulated, respectively. The DEGs upon high-temperature stress were closely associated with the pathways encompassing protein processing in the endoplasmic reticulum, carbon fixation, and photosynthetic metabolism. In addition, 425 putative transcription factors (TFs) were identified, and the majority of them associated with the bHLH, HSF, AP2/ERF, MYB, and WRKY families. RNA-seq data validation further confirmed that 8 genes were linked to protein processing and photosynthesis, and the mRNA level of these genes in TGaseOE was higher than that in WT plants, which is consistent in transcriptome results. In conclusion, these results reveal the transcriptional regulation between WT and TGaseOE in tomato under heat stress and shed light on a new dimension of knowledge of TGase-mediated thermotolerance mechanism at the molecular level.

In recent years, research on spermine (Spm) has turned up a lot of new information about this essential polyamine, especially as it is able to counteract damage from abiotic stresses. Spm has been shown to protect plants from a variety of environmental insults, but whether it can prevent the adverse effects of drought has not yet been reported. Drought stress increases endogenous Spm in plants and exogenous application of Spm improves the plants’ ability to tolerate drought stress. Spm’s role in enhancing antioxidant defense mechanisms, glyoxalase systems, methylglyoxal (MG) detoxification, and creating tolerance for drought-induced oxidative stress is well documented in plants. However, the influences of enzyme activity and osmoregulation on Spm biosynthesis and metabolism are variable. Spm interacts with other molecules like nitric oxide (NO) and phytohormones such as abscisic acid, salicylic acid, brassinosteroids, and ethylene, to coordinate the reactions necessary for developing drought tolerance. This review focuses on the role of Spm in plants under severe drought stress. We have proposed models to explain how Spm interacts with existing defense mechanisms in plants to improve drought tolerance.

Compound light is required for plant growth and development, but the response mechanisms of plants are undercharacterized and not fully understood. The present study was undertaken to evaluate the effect of supplemental light (green light, G; white light, W; yellow light, Y) added to red–blue light (RB) and sole W on the growth and photosynthesis of rapeseed seedlings. The results revealed that supplemental G/W improved the growth and photosynthesis of seedlings, but supplemental Y significantly reduced the photosynthetic rate and palisade tissue layer. Sole W caused similar responses in terms of growth, leaf development, oxidative damage, and antioxidant capability as supplemental Y. In total, 449, 367, 813, and 751 differentially expressed genes (DEGs) were identified under supplemental G, Y, and W and sole W, respectively, compared to RB. The DEGs under different lights were closely associated with pathways such as light stimulus and high-light response, root growth, leaf development, photosynthesis, photosynthesis-antenna proteins, carbohydrate synthesis and degradation, secondary metabolism, plant hormones, and antioxidant capacity, which contributed to the distinct growth and photosynthesis under different treatments. Our results suggest that Y is more likely substituted by other wavelengths to achieve certain effects similar to those of supplemental Y, while G has a more distinctive effect on rapeseed. Taken together, supplementation RB with G/W promotes the growth of rapeseed seedlings in a controlled environment.

Background The global emergence of plasmid-mediated colistin resistance (Col-R) conferred by mcr genes in gram-negative rods (GNRs) has jeopardized the last treatment option for multidrug-resistant bacterial infections in humans. This study aimed to assess the emergence of mcr gene-mediated Col-R in GNRs isolated from humans and animals in Pakistan. Methods Animal and clinical specimens collected from various sources were prospectively analysed using standard microbiological procedures. Pathogens were identified using the API 20E and API 20NE systems (bioMerieux). Minimum inhibitory concentration (MIC) against colistin was determined using the MIC detection methods, and multiplex polymerase chain reaction (PCR) was used to amplify the mcr-1 to mcr-5 genes. Results We isolated 126 (88.1%) animal and 17 (11.9%) human Col-R phenotypes, among which there was a significant association (P Escherichia coli and Proteus mirabilis with animals and of Acinetobacter baumannii with humans. Animal strains exhibited statistically significant (P 50 values were > 6 µg/mL and > 12 µg/mL for human and animal isolates, respectively. mcr genes were detected in 110 (76.9%) bacterial strains, of which 108 (98.2%) were mcr-1 and 2 (1.8%) were mcr-2. Conclusions The detection of a considerable number of mcr-1 and mcr-2 genes in animals is worrisome, as they are now being detected in clinical pathogens. The acquisition of mcr genes by colistin-susceptible bacteria could leave us in a post-antibiotic era.

Objective: To assess vancomycin MIC creep phenomenon in methicillin-resistant Staphylococcus aureus isolated from clinical specimens. Methods: This descriptive study was conducted in Microbiology department of University of Health Sciences, Lahore from January 2016- December 2019. In this study, vancomycin MICs were revealed by E test method for clinical MRSA strains. For the final evaluation, a single isolate from each patient was taken. The reported vancomycin MICs results were used and the values were not rounded up to the next upward value. For every study year, MIC50, MIC90, median and geometrical mean MIC, percentages of susceptible and resistant strains were calculated. Results: A total of 352 MRSA strains were isolated out of 2704 staphylococcal isolates. Our study showed elevated vancomycin MIC among MRSA isolates. The majority of isolates showed MIC values ≥1.5µg/ml. MIC50, MIC 90 was constant throughout four years period. However, geometric mean MIC increased gradually during the study period. The MIC greater than base year median was overall 17.3%. A complete shift can be observed between MIC “1.0” and “2.0” the percent of cases with MIC “1.0” decreased and with MIC “2.0” increased over time crossing each other in 2017. Conclusion: Vancomycin MIC creep was identified in clinical isolates of MRSA, during four years of study period. Even though there is an absence of VISA and VRSA strains; this significant increase in vancomycin MIC trend is indeed worrying for the clinicians about the threat of potential failure of treatment in MRSA infections. doi: https://doi.org/10.12669/pjms.36.7.3273 How to cite this:Arshad F, Saleem S, Jahan S, Tahir R. Assessment of Vancomycin MIC Creep Phenomenon in Methicillin-Resistant Staphylococcus aureus isolates in a Tertiary Care Hospital of Lahore. Pak J Med Sci. 2020;36(7):1505-1510. doi: https://doi.org/10.12669/pjms.36.7.3273 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Research in Smart City development has been proliferated over the past few years, which focused heavily on various supporting service sectors, such as healthcare. However, little effort has been made to design health surveillance support systems, which is also important for the advancement of public healthcare monitoring as an essential smart city initiatives. From an information system (IS) design perspective, this paper introduces a social media-based health surveillance supporting method, which can automatically extricates relevant online posts for health symptom management and prediction. We describe and demonstrate an IS design approach in this paper for hay-fever prediction solution concept based on Twitter posts. This concept can be applicable to fully functional solution design by relevant practitioners in this field.

BACKGROUND: Tuberculosis (TB) is an infectious disease that affects millions of people around the world. The innate immune response against TB starts by interaction of several receptors on monocytes with mycobacterium tuberculosis (MTB). CD14 is one of these receptors present on the monocytes which facilitate the entry of MTB into the cell. Certain polymorphisms in CD14 gene, for example, CD14 (−159 C>T) in the promotor region have suggested susceptibility of TB. AIM: This study was designed to determine and compare CD14 (−159 C>T) gene polymorphism and its surface expression in pulmonary TB patients (before and during anti-TB treatment) and healthy controls. MATERIALS AND METHODS: The study population comprised three groups (pulmonary TB patients before treatment, pulmonary TB patients during treatment, and healthy controls) whereas 53 blood samples were collected from each group. The percentage of monocytes and CD14 mean fluorescence intensity (MFI) was measured by flow cytometry whereas polymerase chain reaction-restriction fragment length polymorphism was used to determine gene polymorphism. RESULTS: CD14 MFI was significantly high in healthy controls than in TB patients (432 as compared to 193 and 365, p < 0.0001). There was no significant difference in CD14 single nucleotide polymorphism allele frequencies or genotypes between TB patients and healthy controls. CONCLUSION: CD14 gene (−159 C>T) polymorphism was not associated with pulmonary TB disease in a sample of Pakistani population and surface expression of CD14 receptor on peripheral blood monocytes decreases with active TB disease and during treatment.

High temperature is considered a critical abiotic stressor that is increasing continuously, which is severely affecting plant growth and development. The use of heat-resistant rootstock grafting is a viable technique that is practiced globally to improve plant resistance towards abiotic stresses. In this experiment, we explored the efficacy of bitter melon rootstock and how it regulates photosynthesis and the antioxidant defense system to alleviate heat stress (42 &deg, C/32 &deg, C) in cucumber. Our results revealed that bitter-melon-grafted seedlings significantly relieved heat-induced growth inhibition and photoinhibition, maintained better photosynthesis activity, and accumulated a greater biomass than self-grafted seedlings. We measured the endogenous polyamine and hydrogen peroxide (H2O2) contents to determine the inherent mechanism responsible for these effects, and the results showed that heat stress induced a transient increase in polyamines and H2O2 in the inner courtyard of grafted seedlings. This increment was greater and more robust in bitter-melon-grafted seedlings. In addition, the use of polyamine synthesis inhibitors MGBG (methylglyoxal bis-guanylhydrazone) and D-Arg (D-arginine), further confirmed that the production of H2O2 under heat stress is mediated by the accumulation of endogenous polyamines. Moreover, compared with other treatments, the bitter-melon-grafted seedlings maintained high levels of antioxidant enzyme activity under high temperature conditions. However, these activities were significantly inhibited by polyamine synthesis inhibitors and H2O2 scavengers (dimethylthiourea, DMTU), indicating that bitter melon rootstock not only maintained better photosynthetic activity under conditions of high temperature stress but also mediated the production of H2O2 through the regulation of the high level of endogenous polyamines, thereby boosting the antioxidant defense system and comprehensively improving the heat tolerance of cucumber seedlings. Taken together, these results indicate that grafting with a resistant cultivar is a promising alternative tool for reducing stress-induced damage.

Knowledge gained from a Decision Support Systems (DSS) design should ideally be reusable by DSS designers and researchers. The majority of existing DSS research has mainly focused on empirical problem solving rather than on developing principles that could inform solution approaches for other user contexts. Design Science Research (DSR) has contributed to effective development of various innovative DSS artefacts and associated knowledge development, but there has been limited progress on new knowledge development from a practical problem context, going beyond product and process descriptions. For DSS applications such as Clinical Decision Support Systems (CDSS) design and development, relevant reusable prescriptive knowledge is of significance not only to understand mutability but also to extend application of theory across domains. In this paper, we develop new design knowledge abstracted from the approach taken in a representative case of innovative CDSS development, specified as an architecture and six design principles. The CDSS design artefact was initially designed for a specific clinical need is shown to be flexible for meeting demands of knowledge production both for diagnosis and treatment. It is argued that the proposed general strategy is applicable to designing CDSS artefacts in similar problem domains representing an important contribution of design knowledge both in DSS and DSR fields.

BackgroundPatient participation in the health care domain has surged dramatically through the availability of digital health platforms and online health communities (OHCs). Such patient-driven service innovation has both potential and challenges for health care organizations. Over the last 5 years, articles have surfaced that focus on value cocreation in health care services and the importance of engaging patients and other actors in service delivery. However, a theoretical understanding of how to use OHCs for this purpose is still underdeveloped within the health care service ecosystem.ObjectiveThis paper aimed to introduce a theoretical discussion for better understanding of the potential of OHCs for health care organizations, in particular, for patient empowerment.MethodsThis literature review study involved a comprehensive search using 12 electronic databases (EMBASE, PsycINFO, Web of Science, Scopus, ScienceDirect, Medical Literature Analysis and Retrieval System Online, PubMed, Elton B Stephens Co [academic], Cumulative Index of Nursing and Allied Health Literature, Accelerated Information Sharing for Law Enforcement, Association for Computing Machinery, and Google Scholar) from 2013 to 2019. A total of 1388 studies were identified from the database search. After removing duplicates and applying inclusion criteria, we thematically analyzed 56 articles using the Braun and Clarke thematic analysis approach.ResultsWe identified a list of 5 salient themes: communication extension, improved health literacy for patients and health care organizations, communication transparency with patients, informational and social support for patients, and patient empowerment in self-management. The most frequent theme was communication extension, which covers 39% (22/56) of the literature. This theme reported that an extension of communication between patients, caregivers, and physicians and organizations led to new opportunities to create value with minimal time and cost restrictions. Improved health literacy and communication transparency with patients were the second and third most frequent themes, respectively, covering 26% (15/56) and 25% (14/56) of the literature, respectively. The frequency of these themes indicated that the use of OHCs to generate new knowledge from patients’ interactions helped health care organizations to customize treatment plans and establish transparent and effective communication between health care organizations and patients. Furthermore, of the 56 studies, 13 (23%) and 10 (17%) studies contended the opportunity of using OHCs in terms of informational and emotional support and empowering patients in their self-management of diseases.ConclusionsThis review enables better understanding of the current state of the art of the online value cocreation and its potential for health care organizations. This study found that the opportunities for health care organizations through enhancement of patient participation and their cocreation of value in digital health platforms have been rapidly increasing. The identified gaps and opportunities in this study would identify avenues for future directions in modernized and more effective value-oriented health care informatics research.

Peptide: N-glycanase (PNGase; EC 3.5.1.52) is a deglycosylation enzyme that is responsible for deglycosylating misfolded glycoproteins in the endoplasmic reticulum. However, the role of PNGase in plants is largely unknown. Here, we cloned and characterized the function of peptide: N-glycanase (CsPNG1) from cucumber. The amino acid encoded by CsPNG1 gene contained a typical transglutaminase (TGase) catalytic triad domain and belonged to the "TGase superfamily". Subcellular localization showed that CsPNG1 was located in the cell membrane and nucleus. Promoter sequence analysis and qPCR tests showed that CsPNG1 could respond to a variety of abiotic stresses and hormone treatments. Yeast one-hybrid assays revealed the interaction between the transcription factor CsGT-3b and CsPNG1 promoter. Importantly, overexpression of CsPNG1 in tobacco increased the tolerance to salt stress of transgenic plants. In addition, CsPNG1 interacted with CsRAD23 family proteins and the C-terminal UBA domain of CsRAD23 protein was responsible for binding to CsPNG1, indicating that CsPNG1 was involved in the ER-associated degradation pathway (ERAD). Taken together, our study demonstrated that CsPNG1 plays a positive role in improving plant salt tolerance, and these findings might provide a basis for further functional analysis of CsPNG1 genes in abiotic stress and ERAD.

Autophagy, an evolutionally conserved cellular degradation process, plays critical roles in plant development and stress response. Despite the wealth of information on the vital role of autophagy in responses to environmental stresses, little is known about the regulation of autophagy. In this study, we demonstrated that spermidine (Spd), a kind of polyamine, was involved in the regulation of salt tolerance through activating the expression of ATG (autophagy-related) genes and the formation of autophagosomes in cucumber under salt stress. Furthermore, NADPH oxidase-derived apoplastic H2O2-mediated Spd-induced salt tolerance and autophagy. Exogenous Spd significantly increased the tolerance to salt stress and inhibited the accumulation and ubiquitination of insoluble proteins. Foliar application of Spd promoted the transcript levels of ATG genes and autophagosomes formation. Besides, Spd induced the expression of RBOH (respiratory burst oxidase homolog), and the accumulation of H2O2 both in leaves and roots. However, either pretreatment with dimethylthiourea (DMTU, an H2O2 scavenger) or diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidase) reduced Spd-induced accumulation of apoplastic H2O2. Importantly, Spd-induced salt tolerance and autophagy were compromised when plants were pretreated with DMTU or DPI. Furthermore, the silencing of ATG4 and ATG7 reduced Spd-induced salt tolerance and autophagosomes formation. Taken together, these results revealed that RBOH-dependent H2O2 mediated the Spd-induced autophagy and salt tolerance in cucumber. Abbreviations: Asat: light-saturated rate of CO2 assimilation; ATG: autophagy-related; DCF-DA: 2, 7-dichlorofluorescein diacetate; DMTU: dimethylthiourea; DPI: diphenyleneiodonium chloride; DW: dry weight; EL: electrolyte leakage; FW: fresh weight; Fv/Fm: the maximum quantum yield of photosystem II; GFP: green fluorescent protein; MDC: monodansylcadaverine; PDS: phytoene desaturase; PE: phosphatidylethanolamine; PLD: phospholipase D; RBOH: respiratory burst oxidase homolog; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SIN1: salt induced NAC1; Spd: spermidine; TOR: target of rapamycin; VIGS: virus-induced gene silencing.

Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200 mg/kg for 28 days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p

Healthcare analytics has been a rapidly emerging research domain in recent years. In general, healthcare solution design studies focus on developing analytic solutions that enhance product, process and practice values for clinical and non-clinical decision support. The objective of this study is to explore the scope of healthcare analytics research and in particular its utilisation of design and development methodologies. Using six prominent electronic databases, qualifying articles between 2010 and mid-2018 were sourced and categorised. A total of 52 articles on healthcare analytics solutions were selected for relevant content on public healthcare. The research team scrutinised the articles, using established content analysis protocols. Analysis identified that various methodologies have been used for developing analytics solutions, such as prototyping, traditional software engineering, agile approaches and others, but despite its clear advantages, few show the use of design science. Key topic areas are also identified throughout the content analysis suggesting topical research priorities in the field.

In our article entitled “Moringa rivae leaf extracts attenuate Complete Freund’s adjuvant-induced arthritis in Wistar rats via modulation of inflammatory and oxidative stress biomarkers”, we described the anti-arthritic effects of the plant leaves from Pakistan that we referred to as Moringa rivae (Saleem et al. 2019). Unfortunately, the identity of the plant material was incorrect. In fact, the plant leaves under study were later identified as belonging to wild type Moringa oleifera Lam. rather than Moringa rivae Chiov.

Polymorphisms in Toll-like receptor 4 (TLR4) gene may exaggerate the chances and pathogenesis of HCV. Aim: This study intends to examine the relationship of genetic polymorphisms of TLR4 with HCV disease in Pakistani patients. Methodology: For this purpose, 500 blood samples were collected to confirm the genetic profile of all the subjects. Results: Single nucleotide polymorphism (SNP) in the TLR4 gene, rs4986790 (A>G), was genotyped in 400 HCV infected and 100 healthy individuals. The TLR4 gene was associated with a significantly increased risk of HCV-related diseases in comparing genotype assessments in patients and controls (pooled OR [95%CI]: 1.671 [0.946–2.949] for dominant; 0.503 [0.221–1.145] for recessive; 2.33 [1.518–3.576] for allele frequency). Subgroup analyses showed an increased risk of HCV infection and effect on interferon therapy associated with AA+AG/GG genotypes of rs4986790 (2.033 [1.094–3.778]). Conclusion: TLR4 SNP rs4986790 was found to be related to HCV-infected patients in the Pakistani population.

Tomato is considered an important vegetable crop for studying the response to abiotic stresses, which deteriorate the growth and development of plants, particularly salt stress. Melatonin is a crucial pleiotropic nontoxic signaling molecule that has a various role in modulating of plant responses to environmental stresses. The purpose of the study was to reckon the alleviating effects of melatonin on tomato plant growth and development in salinity condition. The results exhibited that the pretreatment of tomato seedlings with 100 μM melatonin for 3 days effectively improved the root architecture, photosynthetic pigments, photosynthetic assimilation and growth status of plants under subsequent salt stress (150 mM). The pretreatment slashed sodium ions concentration in leaf and stem by checking sodium ions transport from roots to shoot. Furthermore, melatonin notably surged potassium contents. Melatonin pretreatment (3 days) followed by salinity exposure (7 days) efficiently lowered the oxidative stress by checking the over accumulation of superoxide (O2•−) and hydrogen peroxide (H2O2), reducing the malondialdehyde (MDA) content and electrolyte leakage (EL). This was associated with increased activities of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and ascorbate peroxidase (APX)] and non-enzymatic antioxidants [ascorbic acid (AsA) and glutathione (GSH)]. In conclusion, melatonin pretreatment significantly escalates the salinity tolerance of tomato seedlings by scavenging the excessive ROS and improving cellular membrane stability of, thus mitigating salinity-induced oxidative damage.

Ozone (O3) is a gaseous environmental pollutant that can enter leaves through stomatal pores and cause damage to foliage. It can induce oxidative stress through the generation of reactive oxygen species (ROS) like hydrogen peroxide (H2O2) that can actively participate in stomatal closing or opening in plants. A number of phytohormones, including abscisic acid (ABA), ethylene (ET), salicylic acid (SA), and jasmonic acid (JA) are involved in stomatal regulation in plants. The effects of ozone on these phytohormones’ ability to regulate the guard cells of stomata have been little studied, however, and the goal of this paper is to explore and understand the effects of ozone on stomatal regulation through guard cell signaling by phytohormones. In this review, we updated the existing knowledge by considering several physiological mechanisms related to stomatal regulation after response to ozone. The collected information should deepen our understanding of the molecular pathways associated with response to ozone stress, in particular, how it influences stomatal regulation, mitogen-activated protein kinase (MAPK) activity, and phytohormone signaling. After summarizing the findings and noting the gaps in the literature, we present some ideas for future research on ozone stress in plants

Whilst researchers and professionals recognise that mobile health (M-health) systems offer unprecedented opportunities, most existing work has comprised individual project-based developments in specialised areas. Existing review articles generally utilise medical literature and categories: none investigates M-health from an information systems (IS) design point of view. Identifying application areas, design issues and IS research techniques will demonstrate models, issues, approaches and gaps to inform future research. A comprehensive analysis of the literature from this viewpoint is thus valuable, both for theoretical progression and for guiding real-world innovative system developments. Drawing from key IS and healthcare multidisciplinary journals we analyse recent (2010–2016) articles concerning M-health application developments and their associated design or development issues, with particular focus on the use of contemporary research methods. Our analysis suggests that M-health is an emerging field to which, although underused, contemporary approaches such as design science research are particularly appropriate. We identify eight application categories, eleven design issues (security, privacy, literacy, accessibility, acceptability, reliability, usability, confidentiality, integrity, knowledge sharing and flexibility) as well as the stakeholders and development techniques involved. This goes beyond previous frameworks, and theoretically integrates the central role of IS design within the sub-field.

Emerging digital technologies for healthcare information support have already contributed to reducing the digital divide among rural communities. Although mobile health (m-health) applications facilitate provision of support for treatment consultation in real-time, their substantial potential has not yet been operationalised for decision support to meet citizen demand in developing nations. Modern healthcare information access, especially in rural areas of developing countries, is critical to effective healthcare, since both information and expert opinions are limited. Mobile phone and social media penetration, however, is often extensive. In this paper, we design and evaluate an innovative mobile decision support system (MDSS) solution for rural citizens healthcare decision support and information dissemination.Developed using a design science approach, the instantiated artifact connects underserved rural patients in Bangladesh to general practitioners (GPs) allowing GPs, based on queries and information support provided, to evaluate patient conditions virtually and provide answers for further diagnosis or treatment. A cloud platform using social media embodies health record information and is used with a rating technique that matches queries to profiled remote experts, participating asynchronously. A comprehensive evaluation of the MDSS artifact ensures its utility, efficacy, and reliability. This paper introduces a new decision support solution for rural citizen's healthcare decision aid.The design artifact is specified as an instantiation that connects underserved rural patients in Bangladesh to general practitioners (GPs) to evaluate patient conditions virtually.The capability of the DSS artefact is evaluated through focus group sessions for its efficacy, usability and utility.

Direct conversion through transdifferentiation is a promising cell reprogramming approach that induces a cell lineage conversion among adult cells without passing through an intermediate pluripotent phase. However, there is a need to critically evaluate the efficacy and safety of direct conversion to establish its feasibility as a clinically viable cell reprogramming technique. This review article aims to delineate some critical constraints of direct conversion as a cellular reprogramming approach. We report the most important challenges of lineage reprogramming through direct conversion and divide them into two major sections. The first section explores the obstacles that limit the efficiency of the direct conversion process. In this study, we discuss challenges such as lack of understanding of molecular mechanism and transcriptional control of direct conversion, low proliferative capacity of converted cells, and senescence and apoptosis as critical barriers of direct conversion. The second section focuses on addressing concerns of safety of directly converted cells. We describe issues of transgene load and epigenetic memory retention along with the constraints of currently available validation tools to characterize reprogrammed cells. Each issue mentioned above is evaluated in view of their origin, implications, progress made toward their resolution and scope for development of new strategies to address the constraints of the present technique.

Background Melatonin is a pleiotropic signaling molecule that plays multifarious roles in plants stress tolerance. The polyamine (PAs) metabolic pathway has been suggested to eliminate the effects of environmental stresses. However, the underlying mechanism of how melatonin and PAs function together under heat stress largely remains unknown. In this study, we investigated the potential role of melatonin in regulating PAs and nitric oxide (NO) biosynthesis, and counterbalancing oxidative damage induced by heat stress in tomato seedlings. Results Heat stress enhanced the overproduction of reactive oxygen species (ROS) and damaged inherent defense system, thus reduced plant growth. However, pretreatment with 100 μM melatonin (7 days) followed by exposure to heat stress (24 h) effectively reduced the oxidative stress by controlling the overaccumulation of superoxide (O2•−) and hydrogen peroxide (H2O2), lowering the lipid peroxidation content (as inferred based on malondialdehyde content) and less membrane injury index (MII). This was associated with increased the enzymatic and non-enzymatic antioxidants activities by regulating their related gene expression and modulating the ascorbate–glutathione cycle. The presence of melatonin induced respiratory burst oxidase (RBOH), heat shock transcription factors A2 (HsfA2), heat shock protein 90 (HSP90), and delta 1-pyrroline-5-carboxylate synthetase (P5CS) gene expression, which helped detoxify excess ROS via the hydrogen peroxide-mediated signaling pathway. In addition, heat stress boosted the endogenous levels of putrescine, spermidine and spermine, and increased the PAs contents, indicating higher metabolic gene expression. Moreover, melatonin-pretreated seedlings had further increased PAs levels and upregulated transcript abundance, which coincided with suppression of catabolic-related genes expression. Under heat stress, exogenous melatonin increased endogenous NO content along with nitrate reductase- and NO synthase-related activities, and expression of their related genes were also elevated. Conclusions Melatonin pretreatment positively increased the heat tolerance of tomato seedlings by improving their antioxidant defense mechanism, inducing ascorbate–glutathione cycle, and reprogramming the PAs metabolic and NO biosynthesis pathways. These attributes facilitated the scavenging of excess ROS and increased stability of the cellular membrane, which mitigated heat-induced oxidative stress.

Gastric cancer is the second commonest cause of death among all cancers and the fifth most common cancer in the world. The number of deaths due to gastric cancer is about 723,000 annually. It is more common in men compared to women. The incidence of gastric cancer has 20-fold variation worldwide. In Asia, it is the third most prevalent cancer after breast and colorectal cancers. The prevalence of gastric cancer in Middle East varies from very high in Iran to low in Israel and very low in Egypt. The purpose of this study was to assess the demographic profile of gastric cancer in Afghanistan. A retrospective analysis of patient’s records at the Oncology Department of Jamhoriat Hospital in Kabul, Afghanistan was conducted in a 1 year period. Data of patients diagnosed with gastric cancer was obtained from the registers of the oncology department from March 2018 to February 2019. Variables of interest included age, gender, ethnicity, and place of residence of the patients. Totally, 1324 cancer patients attended to the oncology department in 1 year; of these, 174 patients were diagnosed with gastric cancer. There were significantly more gastric cancer patients among males (69.5%) relative to females. With regard to ethnicity, the Tajeks contributed majority of the cases presenting with gastric cancer. The majority of the patients presenting with gastric cancer were from Kabul province. There were more cases of gastric cancer were in northern provinces. Majority of the cases were contributed by patients above 50 years of age and male gender. This retrospective study aims to provide information about prevalence and demographic characteristics of patient with gastric cancer in Afghanistan. However, there is lack of literature regarding gastric cancer in this war-torn country.

Type 2 diabetes mellitus (T2DM) is the most common metabolic and multifactorial disease in which both genetic and environmental factors are involved. In diabetes, the defects in the cellular metabolism result in higher levels of free radicals. These radicals react with other vital cellular molecules, which are responsible in diabetes side effects and known as diabetic retinopathy (DR), a disease of the retina that results in impairment or loss of vision. In the present study, we investigated the expression of glutathione S-transferases class theta 1 (GSTT1) in type 2 DR subjects. Highly significant differences (P ≤ 0.05) were observed in GSST1 expression in DR patients compared with diabetic and control groups.

This paper presents a contemporary literature review to provide insights into the current health informatics literature. The objective of this study is to identify emerging directions of current health informatics research from the latest and existing studies in the health informatics domain. We analyse existing health informatics studies using a thematic analysis, so that justified sets of research agenda can be outlined on the basis of these findings. We selected articles that are published in the science direct online database. The selected 73 sample articles (published from 2014 to 2018 in premier health informatics journals) are considered as representative samples of health informatics studies. The analysis revealed ten topic areas and themes that would be of paramount importance for researchers and practitioners to follow. The findings provide an important foundational understanding for new health informatics studies.

Mental health is an important determinant of communities’ well-being, influenced not only by individual attributes, but also by social and organisational environments in which people work and live. Despite studies examining mental health status among specific populations, few attempts are evident that focus on solution designs for detecting and measuring impact of mental health conditions. In this study, we develop a construct utilising design science research principles for outlining common vocabulary around the problem, and solution design relevant to a mental health management system. For the case of IT professionals, the developed construct is informed through a social-media based dataset containing more than 65,000 cells and 100 attributes potentially identifying influencing factors. Machine learning techniques are applied to the dataset to discover new findings for this specific group. It is anticipated that the analysis reported in this study would contribute in developing other electronic health management systems both for communities and healthcare professionals.

Moringa rivae is widely used as a traditional remedy against arthritis. The present research was designed to evaluate the anti-arthritic potential of Moringa rivae extracts. Treatment of rats with adjuvant-induced arthritis with methanolic and aqueous extracts of M. rivae (150, 300 or 600 mg/kg), and piroxicam (10 mg/kg) was started orally at day 8 post-administration of complete Freund’s adjuvant and continued till 28th day. The therapeutic effect of the plant extracts was assessed in arthritic rats by arthritic index, body weight, and haematological and biochemical parameters. Furthermore, the modulatory effect on gene expression (I-κB, IL-4 and IL-10, COX-2, IL-1β and IL-6, NF-κB, and TNF-α) in the blood was determined using qRT-PCR, while ELISA assay was used to find PGE2 and TNF-α concentrations in the serum. Oxidative stress parameters in the liver and ankle joint histopathology were also evaluated. Moreover, the most effective methanolic extract was further characterized by GC–MS for the presence of phytochemicals. Treatment with the plant extracts significantly restored arthritic index, change in the body weight and immune organ weight, and the histopathological indices. Both extracts significantly (p

Ethnopharmacological relevance Caralluma tuberculata (C. tuberculata) has traditionally been used in Pakistan and other parts of the world as a folk treatment for diabetes mellitus. A few studies indicated its antihyperglycemic effect, however, the mystery remained unfolded as how did it modify the pathophysiological condition. Aim of study Hence, this study aimed to explore underlying mechanism(s) for its hypoglycemic activity at biochemical and molecular levels. Materials and methods Methanol extract (ME) of C. tuberculata as well as its hexane (HF) and aqueous (AF) fractions were explored for their effect on total glycogen in liver and skeletal muscle of alloxan-induced rats by spectroscopy. Moreover, the expression of genes related to hepatic carbohydrate metabolizing enzymes was quantified. At molecular level, mRNA expression of glucose transporter 2 (GLUT-2), glycogen synthase (GS), glucokinase (GK), hexokinase 1 (HK-1), pyruvate kinase (PK), glucose 6 phosphate dehydrogenase (G-6-PDH), pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G-6-Pase) was determined by using quantitative real time polymerase chain reaction (qRT-PCR) after administration of ME (350 mg), HF(3 mg), AF (10 mg) and metformin (500 mg). The doses were administered twice daily according to per kg of body weight. Results A significant reduction in hepatic and skeletal muscle glycogen content was exhibited. The data of qRT-PCR revealed that gene's expression of GLUT-2 was significantly decreased after treatment with ME and HF, whilst it was unaltered by AF, however, a significant decrease was observed in genes corresponding to GS, GK and HK-1 after treatment with ME. Similarly, there was a significant decrease in expression of genes corresponding to GS, GK and HK-1 following treatment with HF. Surprisingly, post-treatment with AF didn't modify the gene's expression of GS and GK, whilst it caused a profound decrease in expression of HK-1 gene. Contrarily, the expression of gene related to PK was significantly up-regulated post-administration with ME, HF and AF. The expression levels of G-6-PDH, however, remained unaltered after treatment with the experimental extract and fractions of the plant. In addition, HF and AF did not cause any modification in PEPCK, whereas ME caused a significant down-regulation of the gene. Treatment with all the extract and fractions of the plant caused a substantial decrease in the gene's expression of PC, while there was a significant increase in the expression of gene related to G-6-Pase. Conclusion The three experimental extract and fractions caused a substantial decrease in glycogen content in liver and skeletal muscle tissues. The analysis by qRT-PCR showed that glucose transport via GLUT-2 was profoundly declined by ME and HF. The expression of genes related to various metabolic pathways involved in metabolism of carbohydrate in hepatocytes revealed explicitly that the ME, HF and AF decreased the phenomena of glycogenesis and gluconeogenesis. Contrarily, all the extract and fractions of the plant activated glycogenolysis and glycolysis but did not modify the pentose phosphate shunt pathway.

Cervical radiculopathy presents with upper extremity pain, decreased sensation, and decreased strength caused by irritation of specific nerve root(s). After failure of conservative management, surgical options include anterior cervical decompression and fusion, disk arthroplasty, and posterior cervical foraminotomy. In this review, we discuss indications, techniques, and outcomes of posterior cervical laminoforaminotomy.

Background: Allergic asthma is a chronic inflammatory disorder of the airways caused by hypersensitivity and characterized by Th2 cytokine i.e. IL-4, that contribute to enhanced proliferation and differentiation of Th2 cells and switch of B cells from IgM to IgE production. Vitamin D also has a role in proliferation, differentiation, apoptosis of cells of the immune system, production of cytokines, and immunoglobulins. Elevated levels of IL-17 have been documented in bronchial submucosa and relationship of IL-17 and severe hyper responsiveness of airways have been established. Therefore, a study was conducted to determine serum level of vitamin D, IgE and IL-17 in patients of bronchial asthma. Methodology: It was a comparative study, which included 82 subjects i.e. Group-I (41 subjects without asthma), and group-II (41 asthmatic patients). Serum levels of IL-17, IgE and vitamin D