ABSTRACT Introduction The emergence of antimicrobial resistance (AMR) is a threat to public health. In 2015, the World Health Organization (WHO) introduced a global action plan to tackle AMR in the World Health Assembly. Pakistan’s national action plan (NAP) for AMR was released in May 2017 by the Ministry of National Health Services. Based on the NAP, strategies have been initiated on a national and provincial scale in Pakistan. Areas covered This narrative review of the five components of the Pakistan NAP has been undertaken to discuss some of the challenges in implementation of the NAP for AMR in Pakistan including different opinions and views of key stakeholders, combined with suggestions on potential ways to reduce the burden of the AMR. Expert opinion Going forward, healthcare authorities should focus on screening and monitoring of all the objectives of the NAP by establishing proper policies as well as promoting antimicrobial stewardship interventions and Infection prevention and control (IPC) practices. Overall, the comprehensive strengthening of the healthcare system is required to adequately implement the NAP, tackle continued inappropriate antimicrobial use and high AMR rates in Pakistan.

O objetivo do presente estudo foi analisar a associação entre o nível de atividade física e o comportamento sedentário de estudantes de Educação Física de uma faculdade da Zona Oeste do Estado do Rio de Janeiro. Para isso um grupo amostral com 90 estudantes, sendo 56 do sexo masculino e 34 do sexo feminino foi formado por conveniência. Todos os sujeitos responderam ao Questionário Internacional de Atividade Física e foram categorizados como satisfatoriamente ativos ou insatisfatoriamente ativos, bem como, tiveram o relato de seu tempo sentado quantificados representando o comportamento sedentário. Para avaliar a associação entre as distribuições se aplicou o teste do Qui-Quadrado e foi aceito um nível de significância de 5% (p < 0,05). Não foi encontrada associação entre nível de atividade física e comportamento sedentário no grupo amostral (p = 0,408). Conclui-se então, que indivíduos considerados satisfatoriamente ativos não estão necessariamente dentro dos critérios que hipoteticamente exercem proteção no que diz respeito à saúde se for levado em consideração o contraponto que o comportamento sedentário representa sobre tal tela. Ainda, a falta de associação aponta um caminho incongruente no que diz respeito as categorizações do questionário, retratando uma possível fragilidade desse instrumento.

Resumo: Neste artigo se discute as desigualdades de genero nos cursos de engenharia de um campus de uma universidade publica, na perspectiva de discentes de ambos os sexos e pesquisadoras/docentes do sexo feminino. Foram analisados o numero de discentes mulheres ingressos e egressos por curso, o tempo de integralizacao na graduacao, os influenciadores para a escolha da carreira, a discriminacao de genero na academia, o numero de mulheres nos departamentos, a conciliacao entre familia, maternidade e carreira, bem como os obstaculos enfrentados no mercado de trabalho pelo publico feminino.

Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population. A rare case of cytokine release syndrome in a patient on anti-PD-1 blockade that was likely related to BNT162b2 vaccination supports prospective monitoring of patients with cancer after COVID-19 vaccine administration.

Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is a protein with roles in early development, activation of the transcription factor NF-κB, and production of mitochondrial reactive oxygen species (mROS) that facilitates clearance of intracellular bacteria like Salmonella. ECSIT is also an important assembly factor for mitochondrial complex I. Unlike the murine form of Ecsit (mEcsit), we demonstrate here that human ECSIT (hECSIT) is highly labile. To explore whether the instability of hECSIT affects functions previously ascribed to its murine counterpart, we created a potentially novel transgenic mouse in which the murine Ecsit gene is replaced by the human ECSIT gene. The humanized mouse has low levels of hECSIT protein, in keeping with its intrinsic instability. Whereas low-level expression of hECSIT was capable of fully compensating for mEcsit in its roles in early development and activation of the NF-κB pathway, macrophages from humanized mice showed impaired clearance of Salmonella that was associated with reduced production of mROS. Notably, severe cardiac hypertrophy was manifested in aging humanized mice, leading to premature death. The cellular and molecular basis of this phenotype was delineated by showing that low levels of human ECSIT protein led to a marked reduction in assembly and activity of mitochondrial complex I with impaired oxidative phosphorylation and reduced production of ATP. Cardiac tissue from humanized hECSIT mice also showed reduced mitochondrial fusion and more fission but impaired clearance of fragmented mitochondria. A cardiomyocyte-intrinsic role for Ecsit in mitochondrial function and cardioprotection is also demonstrated. We also show that cardiac fibrosis and damage in humans correlated with low expression of human ECSIT. In summary, our findings identify a role for ECSIT in cardioprotection, while generating a valuable experimental model to study mitochondrial dysfunction and cardiac pathophysiology.

Electricity is one of the fundamental necessities of human beings, which has many uses in our day to day life. It is used for different purposes like domestic, industrial and agricultural. The biggest challenge facing electricity distribution is data collection and meter reading. Right now, meter reading is collected manually which give scope for corruption and human error in reading, moreover the wastage of manpower and resources of utility. Prepaid Energy Meter has been implemented in several countries. In fact, the disadvantage of the system is the behavioral control of the users. Moreover, recharging should be carried out on the meter. The problem occurs when consumers leave their premises and electrical pulses are discharged. That's why we need a system to control the electrical pulse wherever they are. In this work, a prepaid energy meter was proposed, implemented and simulated using PROTEUS software. The system was designed using ATmega128 as a microcontroller and GSM technology is advancement over conventional energy meter, which enables consumer to effectively manage their electricity usage. Additionally, it evaluates the accuracy of voltage and current measured by means of this model. Our Suggested model of the prepaid power meter produces the lowest error compared to actual voltage and current. The proposed system replaces traditional meter reading methods and enables remote monitor and control the meter readings regularly not manually. Also, it alerts the consumer when the energy consumption exceeds above the set limit and alerts the utility company if there is any theft that might be happened.

The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing , a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands of samples in parallel. SARSeq relies on next generation sequencing of multiple amplicons generated in a multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous and scalable assignment of reads to individual samples. We calibrate SARSeq on SARS-CoV-2 synthetic RNA, virions, and hundreds of human samples of various types. Robustness and sensitivity were virtually identical to quantitative RT-PCR. Double-blinded benchmarking to gold standard quantitative-RT-PCR performed by human diagnostics laboratories confirms this high sensitivity. SARSeq can be used to detect Influenza A and B viruses and human rhinovirus in parallel, and can be expanded for detection of other pathogens. Thus, SARSeq is ideally suited for differential diagnostic of infections during a pandemic. Massively parallel but cost-effective testing is essential to monitor the spread of pathogenic agents. Here the authors present SARSseq, which uses a dual indexing strategy in a multiplexed RT-PCR reaction to diagnose SARS-CoV-2 at scale.

The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing, a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands of samples in parallel. SARSeq relies on next generation sequencing of multiple amplicons generated in a multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous and scalable assignment of reads to individual samples. We calibrate SARSeq on SARS-CoV-2 synthetic RNA, virions, and hundreds of human samples of various types. Robustness and sensitivity were virtually identical to quantitative RT-PCR. Double-blinded benchmarking to gold standard quantitative-RT-PCR performed by human diagnostics laboratories confirms this high sensitivity. SARSeq can be used to detect Influenza A and B viruses and human rhinovirus in parallel, and can be expanded for detection of other pathogens. Thus, SARSeq is ideally suited for differential diagnostic of infections during a pandemic. Massively parallel but cost-effective testing is essential to monitor the spread of pathogenic agents. Here the authors present SARSseq, which uses a dual indexing strategy in a multiplexed RT-PCR reaction to diagnose SARS-CoV-2 at scale.

Purpose The acute scrotum (AS) in the pediatric population is a medical emergency. The most common causes of AS include testicular torsion (TT) and torsion of the appendix testis (TAT). Their distinction may be clinically challenging. The purpose of our study was to compare demographic and clinical characteristics of the pediatric cases of TT and TAT and thus provide clinical evidence for distinguishing these two conditions. Methods We retrospectively analyzed all children ≤ 16 years who underwent surgical exploration for AS. The patients were divided into Group 1 or TT and Group 2 or TAT groups. Results Ninety patients were included in the study (24 with TT and 66 with TAT). Patients with TT were significantly older than those with TAT (p < 0.001). The peak incidence of TT was in the age of 12–16 years (p < 0.001), whereas the peak of TAT was in the age group of 7–11 years (p < 0.001). Scrotal pain was more prevalent in patients with TAT (p = 0.02), whereas systemic signs (nausea/vomiting and abdominal pain) affected more frequently the TT patients (p = 0.003 and p < 0.001, respectively). The mean duration of symptoms was significantly longer in the TAT group than in the TT group (p < 0.001). Color-Doppler Ultrasound (CDUS) findings of absent or decreased testicular blood flow in the affected testis strongly favored the diagnosis of TT (p < 0.001). Conclusion Our data indicate that the older age, shorter duration of symptoms, systemic signs (nausea/vomiting and abdominal pain), and characteristics CDUS findings can help distinguish between the two most common acute scrotum causes.

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Here we report four new patients carrying biallelic DNASE1L3 pathogenic variations, including two previously unreported mutations. Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

The application of electronic findings to biology and medicine has significantly impacted health and wellbeing [...]

Background: Pandemic caused by the COVID-19 virus brought tremendous changes in the lifestyle of adolescents, about which numerous studies have been published. Due to extended restrictions, long term impact should be investigated.Methods: This cross-sectional study enrolled 953 voluntary participants aged 14 to 21, from different regions of B&H. Participants were asked to complete an online 37-item survey, regarding socio-demographics, geographic, social characteristics, dietary and lifestyle habits, physical activity, including their consumption of dietary, vitamin and mineral supplements. They also needed to provide information about their weight, height and weight change during the entire period of the COVID-19 pandemic from March 2020 until the end of November when the study was completed. For data entry and analysis, SPSS (version 25) and Microsoft Excel were used.Results: At the time of completing the survey, a slightly lower BMI of participants was noticed compared to the time before the pandemic. A statistically significant difference was determined between males and females BMI, boys BMI was slightly higher. Females gained and men lost BW. Increased intake of unhealthy types of food was associated with weight change. Increased mental stress during the pandemic was associated with dietary changes, respectively with decreased as also increased food amount. High percent of participants (40.4%) who increased their physical activity did not alter their eating in the form of the food amount. This study reported use of some dietary supplements which have not been used before the pandemic by 63.5% participants.Conclusions: This paper presents a unique insight into the changing lifestyle and eating habits of adolescents in B&H during lockdown and post-lockdown period of research. Considering that pandemic is still ongoing, data from study like this may be useful to create further steps in battling the pandemic.

Advances in single-cell RNA sequencing (scRNAseq) technologies uncovered an unexpected complexity in tumors, underlining the relevance of intratumor heterogeneity to cancer progression and therapeutic resistance. Heterogeneity in the mutational composition of cancer cells is a result of distinct (sub)clonal expansions, each with a distinct metastatic potential and resistance to specific treatments. Unfortunately, due to their low read coverage per cell, scRNAseq datasets are too sparse and noisy to be used for detecting expressed mutations in single cells. Additionally, the large number of cells and mutations present in typical scRNAseq datasets are too large for available computational tools to, e.g., infer distinct subclones, lineages or trajectories in a tumor. Finally, there are no principled methods to assess distinct subclones inferred through single-cell sequencing data and the genomic alterations that seed and potentially cause them. Here we present Trisicell, a computational toolkit for scalable mutational intratumor heterogeneity inference and assessment from scRNAseq as well as single-cell genome or exome sequencing data. Trisicell allows reliable identification of distinct clonal lineages of a tumor, offering the ability to focus on the most important subclones and the genomic alterations that are associated with tumor proliferation. We comprehensively assessed Trisicell on a melanoma model by comparing distinct lineages and subclones it identifies on scRNAseq data, to those inferred using matching bulk whole exome (bWES) and transcriptome (bWTS) sequencing data from clonal sublines derived from single cells. Our results demonstrate that distinct lineages and subclones of a tumor can be reliably inferred and evaluated based on mutation calls from scRNAseq data through the use of Trisicell. Additionally, they reveal a strong correlation between aggressiveness and mutational composition, both across the inferred subclones, and among human melanomas. We also applied Trisicell to infer and evaluate distinct subclonal expansion patterns of the same mouse melanoma model after treatment with immune checkpoint blockade (ICB). After integratively analyzing our cell-specific mutation calls with their expression profiles, we observed that each subclone with a distinct set of novel somatic mutations is strongly associated with a specific developmental status. Moreover, each subclone had developed a unique ICB-resistance mechanism. These results demonstrate that Trisicell can robustly utilize scRNAseq data to delineate intratumor heterogeneity and help understand biological mechanisms underlying tumor progression and resistance to therapy.