Search

Abstract Identifying sources of variance that contribute to residual feed intake (RFI) can aid in improving feed efficiency. The objectives of this study were to investigate immune cells phenotype and bioenergetic measures in CD4+ T cells in low feed efficient (LE) and high feed efficient (HE) dairy cows. Sixty-four Holstein cows were enrolled at 93 ± 22 days in milk (DIM) and monitored for 7 weeks to measure RFI. Cows with the highest RFI (LE; n = 14) or lowest RFI (HE; n = 14) were selected to determine immune cells phenotype using flow cytometry. Blood was sampled in the same LE and HE cows at 234 ± 22 DIM to isolate peripheral blood mononuclear cells, followed by magnetic separation of CD4+ T lymphocytes using bovine specific monoclonal antibodies. The metabolic function of isolated CD4+ T lymphocytes was evaluated under resting and activated states. An increased expression of CD62L+ cells within CD8+ T lymphocytes and CD21+ B lymphocytes was observed in HE cows compared to LE cows. CD4+ T lymphocytes of HE cows exhibited an increased mitochondrial and glycolytic activity in resting and activated states compared to LE cows. These data suggest that immune cells in HE cows exhibit an increased metabolic function, which might influence nutrient partitioning and utilization and serve as a source of variation in feed efficiency that warrants future investigation.

Abstract Background Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum. Methods PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment. Results Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P

ABSTRACT With some exceptions, global policymakers have recommended against the use of existing monoclonal antibodies in COVID-19 due to loss of neutralization of newer variants. The purpose of this study was to investigate the impact of Ronapreve on compartmental viral replication using paradigms for susceptible and insusceptible variants. Virological efficacy and impact on pathogenicity was assessed in K18-hACE2 mice inoculated with either the Delta or BA.1 Omicron variants. Ronapreve reduced sub-genomic viral RNA levels in lung and nasal turbinate, 4 and 6 days post-infection, for the Delta variant but not the Omicron variant. It also blocked brain infection, which is seen with high frequency in K18-hACE2 mice after Delta variant infection. At day 6, the inflammatory response to lung infection with the Delta variant was altered to a multifocal granulomatous inflammation in which the virus appeared to be confined. The current study provides evidence of an altered tissue response to SARS-CoV-2 after treatment with a monoclonal antibody combination that retains neutralization activity. These data demonstrate that experimental designs that reflect treatment use cases are achievable in animal models for monoclonal antibodies. Extreme caution should be taken when interpreting prophylactic experimental designs that may not be representative of treatment.IMPORTANCEFollowing the emergence of the SARS-CoV-2 Omicron variant, the WHO recommended against the use of Ronapreve in its COVID-19 treatment guidelines due to a lack of efficacy based on current pharmacokinetic-pharmacodynamic understanding. However, the continued use of Ronapreve, specifically in vulnerable patients, was advocated by some based on in vitro neutralization data. Here, the virological efficacy of Ronapreve was demonstrated in both the lung and brain compartments using Delta as a paradigm for a susceptible variant. Conversely, a lack of virological efficacy was demonstrated for the Omicron variant. Comparable concentrations of both monoclonal antibodies were observed in the plasma of Delta- and Omicron-infected mice. This study made use of a reliable murine model for SARS-CoV-2 infection, an experimental design reflective of treatment, and demonstrated the utility of this approach when assessing the effectiveness of monoclonal antibodies.

Background: Microorganisms are turning out to be greatly resistant to existing antibiotics, specifically gram-negative rods which shows resistance to currently accessible antibiotics. Beta-lactam antibiotics are the main therapeutic option to treat infections of gram-negative microorganisms i.e., ESBL and Carbapenemase producers. Saussurea lappa herb is a medicinal herb use since many times. Basically, the roots of S. lappa herb were used as medicines. Current study was conducted to find out activity of various fractions of S. lappa herb against multidrug resistant gram-negative rods. Methods: Crude extracts of ethanol, methanol and water and fractions of n-hexane, chloroform, and methanol from S. lappa herb were used. Total of sixty multidrug resistant organisms were included in which thirty were ESBL and thirty were carbapenemase producing organisms. Mean MIC and comparative analysis of various extracts and fractions have been evaluated. Results: The mean MIC value of crude extracts of ethanol, methanol, n-hexane, chloroform and methanol fractions and water extract from S. lappa against ESBL producing organisms were 109.33± 6.915 mg/ml, 154.67± 5.164 mg/ml, 150.00± 5.345 mg/ml, 55.33±5.164 mg/ml, 178.00±6.103 mg/ml, 64.00± 7.701 mg/ml respectively. Similarly, the mean MIC value against carbapenemase producing organisms were 100.67± 8.683 mg/ml, 158.67± 3.519 mg/ml, 150.67± 5.936 mg/ml, 54.67±5.164 mg/ml, 176.67±14.223 mg/ml, 64.33± 9.353 mg/ml respectively. Conclusion: This study suggests that extracts and fractions of S. lappa herb can form the basis to develop novel broad-spectrum formulation for antimicrobial drugs as it contains compounds that has novelty to perform its action against multi-resistant mechanisms.

Aims The COVID-19 pandemic has significantly impacted healthcare systems, economies, and global health, raising concerns about its potential effects on mental health. A recent systematic review found a 40% prevalence of poor sleep quality, with 34%, 26%, and 27% prevalence for psychological distress, depression, and anxiety. The systematic review investigated COVID-19-related stress, suicidal ideation, and self-harm thoughts among low- and lower-middle-income countries (LLMICs). Methods We search four electronic databases (PsycINFO, Medline, Embase, and PubMed). Quantitative studies, including both published and grey literature, from LLMICs focused on the prevalence of suicidal ideation or psychological distress during COVID-19 were included. Qualitative studies, non-English studies without full-text English translation, meta-analysis, commentary, books, and discussion articles were excluded. Results 1157 titles and abstracts were screened for inclusion and exclusion, resulting in 79 full-text articles. After full text screening, 11 articles were included. In Bangladesh, 12.8% of university students reported suicidal ideation (SI), while 19% of young adults had SI, and 18.5% reported suicidal planning. In addition to this, in Iran, 12.8% of pregnant women and in the Philippines, 24.9% of the general population reported SI. Mental health conditions like depression and anxiety, female gender, younger age groups, economic loss or financial stress, fear of COVID-19 infection, lack of social support, family problems, lower education levels, smoking, and substance use are identified as risk factors. Moreover, anosmia and dysgeusia symptoms were associated with a 30–80% increased risk of transitioning to suicidal ideation or depression in India. A study from Nepal reported a 44% increase in suicide attempts during lockdown compared with pre-pandemic periods in Nepal. Conclusion The findings of this review suggest that the impact of the COVID-19 pandemic on mental health in LLMICs is substantial. In addition to the increased risk of SI and suicide attempts, there was a significant rise in depression and SI associated with anosmia and dysgeusia symptoms. These results underscore the urgent need for increased psychosocial support in LLMICs to address the growing mental health burden caused by the pandemic. Moreover, understanding the long-term effects of the pandemic is crucial for developing effective interventions and support systems. Further research is needed to examine the lasting impact of the pandemic on mental well-being and identify future strategies.

Aims Background: Mental health policy is crucial for enhancing mental health and well-being. Despite the significant contribution of mental disorders to the global burden of disease, 68% of the countries possess a comprehensive mental health policy. This review aimed to identify similarities and differences between low-income countries' (LICs) and lower middle-income countries' (LMICs) mental health policies, along with key gaps, limitations, and strengths, to inform Pakistan's mental health policy. Methods We conducted searches on Google, the WHO Mental Health Atlas, and the country's Ministry of Health website for mental health and general health policies. Recent mental health policies were included from LMICs that were available in English, whether published or unpublished. Scholarly articles, commentaries, books, and health policies that did not address mental health were excluded. Data extraction covered document title, policy status, country, policy formulation process, human resources, suicide prevention, finances, health service delivery, governance, leadership, involvement of ministries, and implementation plans. We synthesized the data through a comparative narrative review in both text and tables. Results Fifty percent (8/16) of LICs and sixty-five percent (17/26) of LMICs have health and mental health policies in English. These policies cover topics like psychiatric disorders, psychotropic drugs, forensic mental health, substance abuse disorders, and communicable and non-communicable diseases. Approximately 65% of LMICs' policies outline the structure of their federal or national government, and 59% provide information on provincial and local government structures. Most LICs include their vision, mission, and objectives in their policies. Conclusion Mental health is often neglected in the healthcare policies of LICs and LMICs. To reduce the burden of mental illness and prevent self-harm, suicide, and substance misuse disorders, the implementation of evidence-based mental health policies in line with the Sustainable Development Goals (SDGs) is crucial.

Purpose: Despite growing access to e-government services, people must learn how to use them. Previous studies have engrossed mainly on the motivations for using e-government but the reasons why such services may not be used, have not been researched much. Therefore, this study aims at identifying the impediments to e-government services’ adoption in Pakistan. Design/Methodology/Approach: Semi-structured interviews with the Pakistani citizens were conducted to develop an understanding of how individuals appraise e-government and what inhibits its acceptance. Findings: The research identifies eleven main hurdles to e-government’s adoption, the most significant of which are a lack of need for occasional use of government services, a lack of a personal adviser, and a lack of trust. The findings imply that the quality of service is vital in the decision to utilize e-government. In contrast, technical problems such as data security or a lack of usability have little influence. Implications/Originality/Value: The uniqueness of this study lies in the exploration of how people in Pakistan perceive the barriers they face while utilizing e-government services.

ATMs generate vast amounts of data daily, which needs to be analyzed and stored. Dealing with this data, also termed big data, is a complex task, and here comes the role of ETL pipelines. ETL pipelines need extensive resources for operations, and their performance optimization is necessary as data must be dealt with in near or even real-time. If the pipeline deals with financial data such as ATM transactions, steps should be taken to ensure the data's security, privacy, confidentiality, and integrity. This can be achieved using Blockchain technology. It is a distributed ledger technology having an immutable nature. It has significant advantages in terms of providing security, but it has disadvantages as well, such as low throughput and transactional latency. If blockchain is used in an ETL pipeline, it will affect the overall performance. So, to prevent the decline in performance, steps should be taken to optimize it. In this paper, we are using parallelization and partitioning as techniques to optimize performance. The primary goal here is to achieve maximum security while maintaining performance.

Abstract Background Self-harm is an important predictor of a suicide death. Culturally appropriate strategies for the prevention of self-harm and suicide are needed but the evidence is very limited from low- and middle-income countries (LMICs). This study aims to investigate the effectiveness of a culturally adapted manual-assisted problem-solving intervention (CMAP) for patients presenting after self-harm. Methods This was a rater-blind, multicenter randomised controlled trial. The study sites were all participating emergency departments, medical wards of general hospitals and primary care centres in Karachi, Lahore, Rawalpindi, Peshawar, and Quetta, Pakistan. Patients presenting after a self-harm episode (n = 901) to participating recruitment sites were assessed and randomised (1:1) to one of the two arms; CMAP with enhanced treatment as usual (E-TAU) or E-TAU. The intervention (CMAP) is a manual-assisted, cognitive behaviour therapy (CBT)-informed problem-focused therapy, comprising six one-to-one sessions delivered over three months. Repetition of self-harm at 12-month post-randomisation was the primary outcome and secondary outcomes included suicidal ideation, hopelessness, depression, health-related quality of life (QoL), coping resources, and level of satisfaction with service received, assessed at baseline, 3-, 6-, 9-, and 12-month post-randomisation. The trial is registered on ClinicalTrials.gov. NCT02742922 (April 2016). Results We screened 3786 patients for eligibility and 901 eligible, consented patients were randomly assigned to the CMAP plus E-TAU arm (n = 440) and E-TAU arm (N = 461). The number of self-harm repetitions for CMAP plus E-TAU was lower (n = 17) compared to the E-TAU arm (n = 23) at 12-month post-randomisation, but the difference was not statistically significant (p = 0.407). There was a statistically and clinically significant reduction in other outcomes including suicidal ideation (− 3.6 (− 4.9, − 2.4)), depression (− 7.1 (− 8.7, − 5.4)), hopelessness (− 2.6 (− 3.4, − 1.8), and improvement in health-related QoL and coping resources after completion of the intervention in the CMAP plus E-TAU arm compared to the E-TAU arm. The effect was sustained at 12-month follow-up for all the outcomes except for suicidal ideation and hopelessness. On suicidal ideation and hopelessness, participants in the intervention arm scored lower compared to the E-TAU arm but the difference was not statistically significant, though the participants in both arms were in low-risk category at 12-month follow-up. The improvement in both arms is explained by the established role of enhanced care in suicide prevention. Conclusions Suicidal ideation is considered an important target for the prevention of suicide, therefore, CMAP intervention should be considered for inclusion in the self-harm and suicide prevention guidelines. Given the improvement in the E-TAU arm, the potential use of brief interventions such as regular contact requires further exploration.

Background Suicidal ideation and attempts are growing public health concerns globally. Evidence from high-income countries suggests that individuals with psychosis and bipolar disorder are at increased risk of suicidal ideation and attempts, but there is a scarcity of evidence from South Asia. Aims To estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia. Method In this systematic review and meta-analysis, four databases (PsycINFO, Web of Science, EMBASE and Medline) were searched until December 2022. Pooled prevalence was estimated with random-effects models. Heterogeneity was quantified with the I2-statistic. Results The pooled sample size across the 21 studies was 3745 participants, 1941 (51.8%) of which were male. The pooled prevalence of suicide attempts in South Asian people with either psychosis or bipolar disorder was 22% (95% CI 17–27; n = 15). The pooled prevalence of suicidal ideation with psychosis or bipolar disorder combined was 38% (95% CI 27–51; n = 10). Meta-regression, subgroup and sensitivity analysis showed that the pooled prevalence estimates for both suicide attempt and ideation remained unaffected by variations in critical appraisal ratings and study designs. Only one study reported data on suicide-related deaths. Conclusions One in four individuals diagnosed with psychosis or bipolar disorder have reported suicide attempts, whereas up to one in three have experienced suicidal ideation. These findings underscore the urgent need for clinicians to regularly assess and monitor suicidal ideation and attempts among individuals with these disorders in South Asia.

Abstract Background In drug development, few molecules from a large pool of early candidates become successful medicines after demonstrating a favourable benefit-risk ratio. Many decisions are made along the way to continue or stop the development of a molecule. The probability of pharmacological success, or PoPS, is a tool for informing early-stage decisions based on benefit and risk data available at the time. Results The PoPS is the probability that most patients can achieve adequate pharmacology for the intended indication while minimising the number of subjects exposed to safety risk. This probability is usually a function of dose; hence its computation typically requires exposure–response models for pharmacology and safety. The levels of adequate pharmacology and acceptable risk must be specified. The uncertainties in these levels, in the exposure–response relationships, and in relevant translation all need to be identified. Several examples of different indications are used to illustrate how this approach can facilitate molecule progression decisions for preclinical and early clinical development. The examples show that PoPS assessment is an effective mechanism for integrating multi-source data, identifying knowledge gaps, and forcing transparency of assumptions. With its application, translational modelling becomes more meaningful and dose prediction more rigorous. Its successful implementation calls for early planning, sound understanding of the disease-drug system, and cross-discipline collaboration. Furthermore, the PoPS evolves as relevant knowledge grows. Conclusion The PoPS is a powerful evidence-based framework to formally capture multiple uncertainties into a single probability term for assessing benefit-risk ratio. In GSK, it is now expected for governance review at all early-phase decision gates.

Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed.

Personality disorders (PDs) have a global prevalence of 7.8% and are associated with increased rates of morbidity and mortality. Most research on PDs has been conducted in High Income Countries (HICs). We conducted a systematic review to investigate the effectiveness of psychosocial and pharmacological interventions for personality disorders (PDs) in individuals from Low- and Middle-Income Countries (LMICs.) We systematically searched MEDLINE, Embase, APA PsycInfo, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and The Cochrane Library from inception to January 5, 2023. Inclusion criteria were quantitative studies and grey literature where participants received a psychosocial or pharmacological intervention for PD. Exclusion criteria were qualitative studies, review articles, studies in which PD was not the primary condition, and articles not available in English. The Cochrane Risk of Bias tool version 2.0 and Joanna Briggs Institute instruments were used to measure risk of bias. Studies were pooled by type of study, PD investigated, type of intervention, assessment methods, and outcomes. Sixteen studies met inclusion criteria and were included. Fifteen were intervention studies related to borderline PD. Only one studied mixed PDs. Twelve studies were of psychotherapy, one pharmacotherapy, one combination of both, and two neurostimulation. Most of the studies showed improvement in symptoms though data was largely collected using self-report measures. There were only six RCTs. There is a dearth of literature on interventions for PDs in LMICs and funding bodies should prioritize research in LMICs. Systematic Review Registration Number: PROSPERO CRD42021233415.

Objectives were to determine the effects of supplementing increasing amounts of choline ion on hepatic composition and mRNA abundance in pregnant dry cows subjected to a fatty liver induction protocol. Holstein cows (35 primiparous and 41 multiparous) at mean (± standard deviation) of 211 ± 9.9 days of gestation were blocked by body condition (3.59 ± 0.33) and assigned to receive 0, 6.45, 12.90, 19.35, and 25.80 g/day of choline ion as rumen-protected choline (RPC) as a top-dress for 14 days. Cows were fed for ad libitum intake on days 1 to 5 and restricted to 30% of the required net energy for lactation from days 6 to 14 of the experiment. Hepatic tissue was sampled on days 5 and 14 and analyzed for concentrations of triacylglycerol and glycogen, and mRNA abundance was investigated. Orthogonal contrasts evaluated the effects of supplementing RPC (0 g/day vs. rest), and the linear, quadratic, and cubic effects of increasing intake of choline ion from 6.45 to 25.80 g/day. Results are depicted in sequence of treatments from 0 to 25.8. During feed restriction, RPC reduced the concentration of hepatic triacylglycerol by 28.5% and increased that of glycogen by 26.1%, and the effect of increasing RPC intake on triacylglycerol was linear (6.67 vs. 5.45 vs. 4.68 vs. 5.13 vs. 3.81 ± 0.92% wet-basis). Feeding RPC during feed restriction increased abundance of transcripts involved in choline metabolism (CHKA, PLD1), synthesis of apolipoprotein-B100 (APOB100), and antioxidant activity (GPX3), and decreased the abundance of transcripts involved in hepatic lipogenesis (DGAT2, SREBF1) and acute phase response (SAA3). Most effects were linear with amount of choline fed. Changes in hepatic mRNA abundance followed a pattern of reduced lipogenesis and enhanced lipids export, which help explain the reduced hepatic triacylglycerol content in cows fed RPC. Choline exerts lipotropic effects in dairy cows by altering transcript pathways linked to hepatic lipids metabolism.

The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection.

Abstract Introduction There has been a global increase in the prevalence of common mental disorders (CMD), particularly in conflict hotspots. The limited amount of resources is one of the key barriers to effective treatment within Low- and Middle-income countries (LAMICs). The lack of service provision for mental health disorders in LAMICs has resulted in limited opportunities to conduct mental health research. Libya is a North African country that has suffered from ongoing conflict with the current political unrest in Libya further impacting the mental health of the population. Main text The aim of this review is to conduct a synthesis of evidence regarding the estimated prevalence and associated risk factors of CMD in Libya. A search was completed in the academic databases; PubMed, Medline, EMBASE, PsychINFO, CINHAL, and the Institute for Development, Research, Advocacy and Applied Care (IDRAAC) from inception to March 2020. Only studies that investigated prevalence and associated risk factors of CMD in Libya were included. A total of 219 studies were identified of which 15 met the inclusion criteria for the review. There were (n = 3) papers investigated the prevalence of depression, (n = 4) studies were focused on stress-related disorders and the remaining papers looked at both anxiety and depression. Statistically, sample sizes of the included studies ranged from (n = 41–13,031) for the prevalence studies (mean = 1188.6, median = 233). Conclusion The status of Libya as a conflict hotspot has led to a reduced level of epidemiological data on mental health, with a vital need to conduct research in CMD. Libya requires better clinical governance which can allow for more scientific research into CMD and enabling the Libyan government to develop evidence-based policy initiatives for CMD.

Abstract Background The aim of this study was to identify sources of variability including patient gender and body surface area (BSA) in pharmacokinetic (PK) exposure for high-dose methotrexate (MTX) continuous infusion in a large cohort of patients with hematological and solid malignancies. Methods We conducted a retrospective PK analysis of MTX plasma concentration data from hematological/oncological patients treated at the University Hospital of Cologne between 2005 and 2018. Nonlinear mixed effects modeling was performed. Covariate data on patient demographics and clinical chemistry parameters was incorporated to assess relationships with PK parameters. Simulations were conducted to compare exposure and probability of target attainment (PTA) under BSA adjusted, flat and stratified dosing regimens. Results Plasma concentration over time data (2182 measurements) from therapeutic drug monitoring from 229 patients was available. PK of MTX were best described by a three-compartment model. Values for clearance (CL) of 4.33 [2.95–5.92] L h− 1 and central volume of distribution of 4.29 [1.81–7.33] L were estimated. An inter-occasion variability of 23.1% (coefficient of variation) and an inter-individual variability of 29.7% were associated to CL, which was 16 [7–25] % lower in women. Serum creatinine, patient age, sex and BSA were significantly related to CL of MTX. Simulations suggested that differences in PTA between flat and BSA-based dosing were marginal, with stratified dosing performing best overall. Conclusion A dosing scheme with doses stratified across BSA quartiles is suggested to optimize target exposure attainment. Influence of patient sex on CL of MTX is present but small in magnitude.

Abstract Graphene oxide–silver (Ag–GO) nanocomposite has emerged as a vital antibacterial agent very recently. In this work, we report a facile one step route of Ag–GO nanocomposite formation excluding the aid of surfactants and reductants and was successfully applied to negative Escherichia Coli (E coli) to investigate antibacterial activity by varying doze concentration. The successful formation of Ag–GO nanocomposite via facile one step route was confirmed using Fourier transform infrared spectroscopy (FTIR) and Raman Spectroscopy. The absorption spectra (peak ~ 300 nm) for GO and the (peak ~ 420 nm) for silver nanoparticles were observed. XRD study confirmed the formation of Ag–GO nanocomposite while atomic force microscopy (AFM) showed crumbled GO sheets decorated with Ag nanoparticles. It was observed that the functional groups of GO facilitated the binding of Ag nanoparticles to GO network and enhanced the antibacterial activity of the nanocomposite.

The outbreak of pneumonia that broke out in Wuhan, in December 2019, later rapidly spread to the rest of the world. This was identified as Coronavirus disease 2019 (COVID-19) [officially renamed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2)] caused by a zoonotic beta Coronavirus entitled 2019 novel Coronavirus (2019-nCoV). The aim of this study was to summarize the biological features of SARSCoV-2, its clinical features and the possible antiviral effect of honey against SARS-CoV-2. For this purpose, recently published literature, official documents and selected up-to-date preprint studies were reviewed. The initial source of SARS-CoV-2 is still unknown but a possible animal-to-human transmission is indicated. Human spread of SARS-CoV-2 is due to droplet spread. The infected individual may present as symptomatic or asymptomatic, this varies from patient to patient mainly depending upon his/her immunity. To combat the current pandemic various modalities are under study, an important and harmless way of treatment might be the use of honey. Various studies have demonstrated antiviral effects of honey. Propolis and honey have shown promising anti-viral effect against SARS-CoV-2. Thus, the combined effect of honey and its products might open a door for developing a safe and highly efficient natural drug against COVID-19infection.

The objective of this study was to determine if there are differences in luteal size (LS), progesterone (P4), and luteal blood flow (LBF) between pregnant and non-pregnant Bos indicus dairy cows during the first three weeks after insemination, and whether these parameters are related to each other. Lactating cows (n = 13) of mixed parity with a body weight of 430 ± 18 kg (mean ± SD), showing regular estrous cycle were used in the study. All cows were artificially inseminated and were classified as pregnant (embryonic heartbeat on day 30; n = 8) or non-pregnant (inter-estrus interval 17 to 21 days, n = 5). In order to compare the LS and LBF after artificial insemination, B-mode and color Doppler ultrasonography of ovaries were performed on days 4, 5, 6, 7 (first week), 8, 10, 12, 14, (second week), and 16, 17, 18, 19, 20, 21 (third week) in pregnant and non-pregnant cows. Results revealed that the mean LBF was consistently higher (P < 0.05) during days 7 through 21 in pregnant cows than in non-pregnant cows. The mean LS was higher (P < 0.05) on days 6 and 7, and from day 17 onwards, and the mean concentration of P4 was higher (P < 0.05) on days 19, 20, and 21 in pregnant cows. In conclusion, LBF is a more sensitive parameter than LS and P4 for detection of differences in luteal function between pregnant and non-pregnant Bos indicus dairy cows during the first three weeks after AI.

Pharmaceuticals wastes have been recognized as emerging pollutants to the environment. Among those, antibiotics in the aquatic environment are one of the major sources of concern, as chronic, low-dose exposure can lead to antibiotic resistance. Herein, we report on molecularly imprinted polymers (MIP) to recognize penicillin V potassium salt (PenV-K), penicillin G potassium salt (PenG-K), and amoxicillin sodium salt (Amo-Na), which belong to the most widespread group of antibiotics worldwide. Characterization and optimization led to two MIPs comprising methacrylic acid as the monomer and roughly 55% ethylene glycol dimethacrylate as the crosslinker. The obtained layers led to sensitive, selective, repeatable, and reusable sensor responses on quartz crystal microbalances (QCM). The LoD for PenV-K, PenG-K, and Amo-Na sensors are 0.25 mM, 0.30 mM, and 0.28 mM, respectively; imprinting factors reach at least around three. Furthermore, the sensors displayed relative selectivity factors of up to 50% among the three penicillins, which is appreciable given their structural similarity.

Proper sowing orientation and spacing are important factors for best crop growth. A field experiment was conducted to study the effect of different planting patterns with and without lentil intercropping on sugarcane growth and yield and farm economics. Each of these treatments were planted as sole crop and intercropped with lentil. Data were collected on plant cane and first ratoon crop. The maximum stripped cane yields (154.36 t/ha and 130.28 t/ha in plant and ratoon crop, respectively) were obtained from sugarcane planted at 120 cm trench planting both as sole as well as lentil intercropped. This treatment also attained 61% and 43% higher total sugar yields compared to traditional 60 cm single rows planting in plant and ratoon crops, respectively. Lentil intercropping did not have any significant effect on sugarcane yield, but trench planting at 120 cm with lentil intercropping had the highest lentil seed yield (598.0 in 2013–2014 and 629.8 kg ha−1 in 2014–2015) along with maximum land equivalent ratio (1.40 and 1.37), net return (Rs.321254/ha), net field benefit (Rs.491703/ha) and benefit cost ratio (2.01). Sugarcane at 120 cm trench planting with lentil intercropping also outperformed other planting patterns in improving economic returns.

The present research aimed to investigate the long-run and short-run effects of different sources of financial development on FDI inflow for middle-income economies during the period of study, 1980 to 2020. An annual frequency of data was obtained for the required set of variables from WDI and the IMF. The estimations revealed no cross-sectional dependence, a significant cointegration, and the stationarity of FDI inflow at first difference, while the explanatory and controlled variables were as mixed level. It validated the panel ARDL estimations methods such as mean group, pooled mean group, and a dynamic fixed effect for testing the required set of hypotheses. The Hausman test confirmed the consistency and efficiency of the dynamic fixed effect as the method of estimations. The panel estimations revealed the significance of financial market development, inflation rate, trade openness, and real economic growth as the most critical factors for FDI inflow in middle-income economies. The policymakers should consider these factors for making their policies regarding FDI inflow in their economies. Future research may consider time series ARDL for each independent middle-income country. The findings of the study are generalized only to middle-income economies rather than higher-income and lower-income countries.

Objective: To determine lipid profile in patients of age-related cataract and compared them with agematched controls. Study Design: Case Control study. Setting: Naseer Memorial Hospital, Dadyal. Period: January 2022 to December 2022. Material & Methods: A total of 300 patients were recruited using a consecutive non-probability sampling method and divided in two groups, one control and the other having cataract. The patients underwent a thorough ocular assessment and lipid profile evaluation. Inclusion criteria was age 40 years or older of any gender having senile cataracts of any morphological form. Exclusion criteria was history of ocular trauma, systemic disease, ocular surgery, oral steroids or cataract other than senile cause. The data was analyzed using SPSS version 23. The results showed that patients with senile cataracts had significantly higher levels of total cholesterol, triglycerides, and LDL cholesterol, and significantly lower levels of HDL cholesterol than the controls. The collected data was entered in the statistical package for social sciences (SPSS) version 21 for analysis. Independent t test was applied and p value = 0.05 was considered as significant. Results: It was found that patients with senile cataracts had significantly higher levels of total cholesterol, triglycerides and LDL and significantly lower levels of HDL than the age-matched controls. Conclusion: The findings suggested that dyslipidemia is a modifiable risk factor for age-related cataract. [ABSTRACT FROM AUTHOR]

Background: Stroke with mortality rate up to 25% is a fatal clinical syndrome. Most common risk factors are Hypertension, smoking, family history of stroke and diabetes mellitus. The objective was to study the pattern of brain strokes, areas and vascular territories of brain affected as per computerized tomography scan (CT scan) findings and risk factors in stroke patients admitted in Allied hospitals of Rawalpindi Medical University, Rawalpindi Methods: This descriptive cross-sectional study was conducted in Allied hospitals of Rawalpindi Medical College (RMC), Rawalpindi from September 2016 to February 2017 after taking ethical approval from Institutional Research Forum (IRF). All diagnosed cases of Stroke (Ischemic stroke or Hemorrhagic stroke) on the basis of Computerized Tomography Scan (CT-Scan) or Magnetic Resonance Imaging (MRI) admitted to Medical Units of Allied Hospitals of RMC were included in the study irrespective of their age and gender. A Structured Questionnaire designed according to the objectives of this study was used for data collection. SPSS (Version-22) for windows was used for analysis through frequencies, percentages and cross tabulations. Result: Out of 200 diagnosed cases of stroke 115 (57.5%) were males and 85 (42.5%) were females. Mean age of patients was 53.73 years. Regarding the types of stroke, predominance of ischemic stroke 121 (60.5%) was seen as compared to hemorrhagic stroke which constitutes of 73 (36.5%) of the cases and the remaining 6 (3%) were the cases where both types of stroke were diagnosed based on CT scan reports. Male predominance 66 (54.54%) was seen in Ischemic stroke as well as in Hemorrhagic stroke 48(65.75%) as compared to females (Ischemic stroke 55 (45.50%) and Hemorrhagic stroke 25 (34.24%).Most common vascular territory involved in all types of stroke was of middle cerebral artery 115 (57.5%). Among Hemorrhagic stroke subarachnoid hemorrhage 49 (67.1%) was the most common site. In our study most common potential risk factors were Hypertension 115 (57.5%), Smoking 91 (45.5%), Family history of stroke 60 (33 %) and Diabetes 55 (27.5%). Conclusion: Most commonly ischemic stroke, with overall male predominance was seen in our study. Hypertension, smoking and diabetes were the most common modifiable risk factors. Vascular territory of Middle cerebral artery and subarachnoid area were most commonly involved regions of brain in stroke. More than 63 % of patients were above the age of 45 years.

The present era has witnessed intensive changes in last few decades. The transformation of conventional financial system to Islamic financial system is one of these drastic changes the world has faced. Islamic banking is the major constituent of the Islamic finance. In line with these transformations, Islamic banks and financial institutions are facing several problems due to non-existence of comprehensive framework. However, some prominent issues are convergence issues, stability and regulatory issues, existence of different schools of thought and sensitivity towards role of religion in commercial and financial sector. A careful analysis of these issues can lead to sort out the solutions. The approach to overcome these challenges will determine the future success or failure of the industry. Therefore, this study shed a light on some major challenges that can hinder the progress and benefits of Islamic finance promises.

Background: To determine the pattern of different types of congenital heart diseases, in paediatric age group. Methods: In this observational cross sectional study cases of congenital heart defects (CHD) were included, through simple random sampling irrespective of age and gender. Every patient’s data on echocardiographic report clearly indicating his CHD type along with age and gender was recorded. Variables of study i.e. type of CHDs, age, and gender with relative frequencies were presented separately graphically. Results: Out of 298 diagnosed patients of CHD 156 were males and 142 were females. Isolated ventricular septal defect found to be the most common anomaly (32.6%). In combination atrial septal defect and ventricular defect were found to be most common with 5.4% burden rate. Out of 298 patients Acyanotic CHDs were 67.1% while Cyanotic CHDs were found to be 32.9%. Conclusion: Acyanotic CHDs were found to be dominant over Cyanotic CHDs with relative percentages of 67.1% and 32.9% respectively