Mucosal immunity to poliovirus in children 0-15 years of age: A community-based study in Karachi, Pakistan in 2019.

This study assesses poliovirus type 1 (PV1) immunity in children to inform the contribution of mucosal immunity in and preventing poliovirus circulation. A community-based study was conducted in peri-urban Karachi, Pakistan. Randomly selected children (0-15 years) received oral poliovirus vaccine (OPV) challenge dose. Blood and stool samples were collected at several time points and evaluated for polio-neutralizing antibodies and serotype-specific poliovirus, respectively. 81/589 (14%) children excreted PV1 7 days post-OPV-challenge; 70/81 (86%) were seropositive at baseline. 12/610 (2%) were asymptomatic Wild Poliovirus Type 1 (WPV1) excretors. Most poliovirus excretors had humoral immunity, suggesting mucosal immunity in these children likely waned or never developed. Without mucosal immunity, they are susceptible to poliovirus infection, shedding, and transmission. Asymptomatic WPV1 excretion suggests undetected poliovirus circulation within the community.

Two-Year Duration of Immunity of Inactivated Poliovirus Vaccine: A Follow-up Study in Pakistan in 2020.

This was a follow-up study conducted in 2020 assessing changes in levels of type 2 poliovirus-neutralizing antibodies 2 years postimmunization in children who received inactivated poliovirus vaccine (IPV) in Karachi, Pakistan. Unexpectedly, the findings revealed an increase in seroprevalence of type 2 antibodies from 73.1% to 81.6% 1 year and 2 years after IPV, respectively. The increase in type 2 immunity could result from the intensive transmission of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Karachi during the second year of IPV administration. This study suggests that the cVDPV2 outbreak detected in Pakistan infected large proportions of children in Karachi. Clinical Trials Registration . NCT03286803.

Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families.

BACKGROUND: Severe Combined Immunodeficiency (SCID) is an autosomal recessive inborn error of immunity (IEI) characterized by recurrent chest and gastrointestinal (GI) infections and in some cases associated with life-threatening disorders. METHODOLOGY AND RESULTS: This current study aims to unwind the molecular etiology of SCID and also extended the patients' phenotype associated with identified particular variants. Herein, we present 06 disease-causing variants identified in 07 SCID-patients in three different SCID related genes. Whole Exome Sequencing (WES) followed by Sanger Sequencing was employed to explore genetic variations. The results included identification of two previously reported heterozygous variants in homozygous form for the first time in RAG1gene [(p.Arg410Gln);(p.Arg737His)], followed by a recurrent variant (p.Trp959*) in RAG1, a novel variant in IL2RG (p.Asp48Lfs*24), a recurrent variant in IL2RG (p.Gly271Glu) and a recurrent variant in DCLRE1C (p.Arg191*) gene. CONCLUSION: To conclude, the immune-profiling and WES revealed two novel, two as homozygous state for the first time, and two recurrent disease causing variants contributing valuably to our existing knowledge of SCID.

Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country.

OBJECTIVES: Most biomarker studies of sepsis originate from high-income countries, whereas mortality risk is higher in low- and middle-income countries. The second version of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American PICUs for prognosis. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country. Due to uncertainty regarding how well PERSEVERE-II would perform, we also assessed the utility of other select biomarkers reflecting endotheliopathy, coagulopathy, and lung injury. DESIGN: Prospective cohort study. SETTING: PICU in Aga Khan University Hospital in Karachi, Pakistan. PATIENTS: Children (< 18 yr old) meeting pediatric modifications of adult Sepsis-3 criteria between November 2020 and February 2022 were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma was collected within 24 hours of admission and biomarkers quantified. The area under the receiver operating characteristic curve for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between survivors and nonsurvivors and between subjects with and without acute respiratory distress syndrome. In 86 subjects (20 nonsurvivors, 23%), PERSEVERE-II discriminated mortality (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.72-0.94) and stratified the cohort into low-, medium-, and high-risk of mortality. Biomarkers reflecting endotheliopathy (angiopoietin 2, intracellular adhesion molecule 1) increased across worsening risk strata. Angiopoietin 2, soluble thrombomodulin, and plasminogen activator inhibitor 1 were higher in nonsurvivors, and soluble receptor for advanced glycation end-products and surfactant protein D were higher in children meeting acute respiratory distress syndrome criteria. CONCLUSIONS: PERSEVERE-II performs well in septic children from Aga Khan University Hospital, representing the first validation of PERSEVERE-II in a low-middle income country. Patients possessed a biomarker profile comparable to that of sepsis from high-income countries, suggesting that biomarker-based enrichment strategies may be effective in this setting.

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

OBJECTIVES: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. RESULTS: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. CONCLUSIONS: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

Human semen quality as affected by SARS-CoV-2 infection: An up-to-date review.

Revealing the effect of SARS-CoV-2 infection on semen quality is a dynamic priority for many healthcare providers in the field as well as subfertile patients. Therefore, the collective summary in this research approach is still highly needed, especially with the continuous increase in original publications. Here, we provide an up-to-date review and discussion to collectively reveal the effect of SARS-CoV-2 infection on human semen quality. To do this, we reviewed all articles and abstracts published in Scopus and PubMed using the keywords 'SARS-CoV-2' and 'COVID' versus 'sperm' and 'semen'. In summary, it can be revealed that, at both symptomatic and recovery stages of infection, no investigational evidence of SARS-CoV-2 shedding in human semen. Also, the mainstream of the up-to-date published work reveals a negative impact of SARS-CoV-2 infection on semen quality parameters, particularly sperm count and motility. However, long-term post-recovery comparative studies seem very important in this particular setting.

Ranitidine decreases human sperm motility and vitality and increases the activity of seminal creatine kinase.

Ranitidine (brand name: Zantac), an acid reducer, belongs to histamine-2 receptor antagonists. Since 1981, even though several adverse effects of this drug were reported in the body, still, its effects on human sperm parameters have yet to be confirmed. In this work, we attempted to measure sperm motility, sperm vitality and activity of seminal creatine kinase in the ejaculated human semen (n = 31) in the presence of ranitidine at a range of concentrations (0.1, 0.3, 0.6, 0.9 and 1.2 µg/ml) compared with control (without ranitidine). Sperm motility was measured using the Makler counter, whilst sperm vitality was assessed using the Eosin test. Creatine kinase activity was measured using the kinetic spectrophotometric method. Sperm motility (total and progressive) as well as sperm vitality was significantly (p < .05) reduced in the presence of ranitidine in human semen, particularly at the higher tested concentrations (0.6-1.2 µg/ml) compared with the control. On the other hand, creatine kinase activity was significantly increased (p < .05) in the presence of ranitidine at 0.6, 0.9 and 1.2 µg/ml. In conclusion, ranitidine at 0.6-1.2 µg/ml reduced sperm motility and vitality, but increased the activity of creatine kinase in ejaculated human semen.

Perceptions towards sex selection among Jordanian population: A survey study.

Sex selection is becoming a more common practice in the society and worldwide. The current study aimed to examine the perceptions about sex selection options and possible association with sociodemographic factors and relevant characteristics. The study was a cross-sectional survey of adults in Jordan in January and February 2020 using a self-administered questionnaire. Results showed that 40.1% of respondents preferred male gender when having a child, 22.4% of respondents preferred the male gender when having a child, even if they have had children of both genders, and 71.3% preferred having children from both genders. On the other hand, 58.8% of participants preferred a male gender when there is one chance to conceive via assisted reproduction technologies. Also, among participants, 66% thought that sex selection is religiously acceptable, yet 78.0% did not support of the sex selection idea. The above factors were significantly associated with several sociodemographic variables such as gender, marital status, education, career, and place of residence, but not income. In conclusion, the current study shed a light on preferences towards sex selection in a large cohort to better understand the perception and attitude of the population towards this practice.

A descriptive case series of necrotising enterocolitis; occurrence at Aga Khan University Hospital.

The objective of this study was to determine the frequency and outcome of preterm infants diagnosed with Necrotising Enterocolitis (NEC). In a case series, 320 preterm infants were enrolled during a period of 12 months at Aga Khan University Hospital, Karachi, a tertiary care hospital. Diagnosis and staging was done as per Bell's staging criteria. Possible confounders were filtered. Analysis was based on the form of treatment and symptom progression. During the study, NEC was observed in 29(9.06%) babies of which stages I, II and III were 69%, 24% and 7%, respectively. Outcome analysis showed that among the 29 neonates diagnosed with NEC, 23 were discharged and 6 expired. A 9% prevalence observed during the study suggests this to be to be a major challenge in neonatology. Mortality outcome of 21% diagnosed with NEC recommends an early diagnosis coupled with prompt and appropriate treatment and preventive measures to reduce the burden of NEC in future.

New trends in immunocastration and its potential to improve animal welfare: a mini review.

Castration is frequently used to reduce aggressive behavior and improve the meat quality of animals. Traditionally, surgical and mechanical castration are used to sterilize the animals, but these approaches are associated with a high level of pain, stress, long recovery periods, and post-operative infections. Immunocastration is a new animal-friendly, painless alternative castration technique that is used to prevent undesired sexual behavior, reduce aggressive behavior, prevent unwanted pregnancy, control wildlife populations and wandering species, enhance growth performance, improve meat quality, and treat various sex hormone-dependent disorders. The mechanism of immunocastration includes the immunological block of the hypothalamic-pituitary-gonadal axis (HPG axis) which inhibits gonadotropin secretions, causes atrophy of gonadal tissues, and inhibits gametogenesis, resulting in infertility in both female and male mammals. By the mid-1990s, various immunocastration vaccines have been tested in different animal models to achieve successful castration effects. Recently, genetic immunocastration especially DNA vaccine has gained increasing attention due to its safety, being animal-friendly, and being easy to use. This review aims to evaluate the potential of traditional castration methods, as well as the current status of immunocastration vaccines, their effects, and future prospective.

Epidemiological, clinical, and radiological comparison of adult and pediatric features in COVID-19: A scoping review.

OBJECTIVE: To assess epidemiological, clinical, and radiological characteristics of the coronavirus disease in children and adults. METHODS: The scoping review comprised search on PubMed and Scopus Cochrane databases from January 2020 to April 2021 for English-language articles dealing with clinical and radiological manifestations amongst children and adults affected by coronavirus disease. Two reviewers independently screened the titles and abstracts. RESULTS: Of the 389 studies initially identified, 39(10%) were reviewed in detail. Data suggested that children were less frequently affected by the coronavirus disease. The affected children showed milder disease with low case fatalities compared to the adults. CONCLUSIONS: There exists significant gaps in knowledge of clinical and radiological aspects of coronavirus disease, but the available scientific data showed that the disease seems to be unusual in children.

One-Year Decline of Poliovirus Antibodies Following Fractional-Dose Inactivated Poliovirus Vaccine.

BACKGROUND: Fractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV. METHODS: A community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months. RESULTS: Seroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B. CONCLUSIONS: There was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing. CLINICAL TRIALS REGISTRATION: NCT03286803.

Effect of diclofenac on semen quality: A review.

Diclofenac is an effective nonsteroidal anti-inflammatory drug and one of the most prescribed medicines worldwide. So far, there are many published articles that directly link between diclofenac and semen quality; however, hitherto, there is no collective review or comprehensive discussion that reveal such imperative link. Therefore, this work reviews and judges the association between diclofenac administration and semen quality, henceforth male infertility. As a tool to accomplish this scientific input, Scopus, Embase and PubMed databases have been searched for all original articles using the keywords "diclofenac" versus "semen" and "sperm" since August 1987 through November 2020. In summary, diclofenac appears to induce negative effects on both qualitative and quantitative measures of sperm; however, this conclusion requires confirmation by human studies. The detected negative effects of diclofenac on semen quality measures may be owed to reduced levels of gonadal hormones, decreased antioxidant defence mechanism, increased oxidative stress, altered concentrations of nitric oxide that are required to maintain normal sperm physiology and reduced synthesis of prostaglandins.

Adaptive evolution of peptidoglycan recognition protein family regulates the innate signaling against microbial pathogens in vertebrates.

The innate immune system is the first line of defense in vertebrates against microbial pathogens. This defense system depends on the peptidoglycan pathogen recognition of receptors (PGRPs) existing in both invertebrates and vertebrates. Although some studies revealed the structural and functional differences between them, however, the evolutionary history and the selection pressures on these genes during adaptive evolution are poorly understood. In this study, we examined four (PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4) genes of 127 vertebrates' species, conserved across vertebrates to evaluate positive selection pressure drives by adaptive evolution. The codons under positive selection were recognized through likelihood tests by comparing different models based on ω ratios in these genes across the vertebrate species. The positive selection test used two sets of models M1a vs. M2a and M7 vs. M8. The results showed that the test of these genes in M1a vs. M2a was not significant with the likelihood value 2ΔlnL = 0, while the likelihood ratios (2ΔlnL) were 2ΔlnL = 12.386, 2ΔlnL = 4.9283, 2ΔlnL = 24.031, and 2ΔlnL = 103.39 for PGLYRP1, PGLYRP2, PGLYRP3, and PGLYRP4 in M7 vs. M8, respectively. Our study identified the evidence of robust positive selection for these four genes across the vertebrates. These protuberant changes in PGRPs evolution of vertebrates reveal their role in innate immunity. Our study provides an insight based on PGRP genes to understand the evolution of host and pathogens interaction that leads to the progress of the novel conducts for immune diseases that include proteins linked to the recognition of pathogens.

Effect of statin on semen quality characteristics.

Statins are lipid-lowering medications widely used to reduce the risk of cardiovascular diseases. Biochemically, they act by decreasing synthesis of cholesterol via inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Since 1992, various research studies have investigated the effect of statins on semen quality characteristics; however, to date, there is no collective summary to such effect. Here, we have systematically discussed and abridged all research studies published in Scopus, PubMed and Web of Science databases that are directly linking statin to semen fertility characteristics using the keywords "statin" versus "sperm" and "semen". In summary, considering the animal studies, statins, in general, were found to ameliorate semen quality characteristics in reproductive detrimental conditions, while, in human males or in in vivo systems with normal reproductive conditions, in general, statins showed negative to blunt effects against semen quality characteristics, mainly sperm motility. However, further research studies, in particular human studies, in this specific research setting is still needed to approve these effects.

Seminal plasma vitamin B6 levels in men with asthenozoospermia and men with normal sperm motility, a measurement using liquid chromatography with tandem mass spectrometry.

There is growing evidence that vitamin B6 has a valuable contribution in maintaining normal sperm parameters; however, this contribution has not yet well-identified. Here, we aimed to measure the level of seminal plasma vitamin B6 in men with asthenozoospermia compared to men with normal sperm motility. Ninety-seven human males with asthenozoospermia and eighty-eight human males with normal sperm motility (control) were recruited in this study. Collected semen samples were assessed for sperm motility, sperm count and semen volume. Liquid chromatography with tandem mass spectrometry was used to measure seminal plasma vitamin B6 concentrations. A highly significant difference (p < .0001) in concentrations of seminal plasma vitamin B6 was found between asthenozoospermic and control groups. Besides, no statistical correlations were found between seminal plasma vitamin B6 level and sperm motility, sperm count, semen volume and men age in both tested groups. In conclusion, men with asthenozoospermia have lower seminal plasma vitamin B6 level compared to men with normal sperm motility. Also, seminal plasma vitamin B6 was found not to be correlated with sperm motility and count, semen volume and men age in both tested groups. These results may provide new contribution in the management of male infertility.

Antimicrobial Stewardship - Do we need it in Pakistan?

In order to identify the literature and research available on development and implementation of Antimicrobial Stewardship Programme (ASP) in Pakistan, a systematic search of various electronic databases such as PubMed, Cochrane, CINAHL and PakMedinet from January 1, 2008 till November 2018 was conducted. Studies were included if they were focused around the development and implementation of the ASP within Pakistan. The search revealed that a significant knowledge gap exists regarding antimicrobial/antibiotic stewardship within Pakistan and not much is known about the current status of the development and implementation of antimicrobial stewardship programme. Only two research studies were found to be significant. Antimicrobial Stewardship Programme's development and implementation is highly essential and important. Currently, there exists a huge knowledge and systematic gap regarding ASP implementation at healthcare institutions.

Surgical-site infections in emergency abdominal paediatric surgeries at a tertiary-care hospital in Pakistan.

A retrospective chart review was carried out in children (neonates to 18 years) who underwent acute surgical abdominal exploration during 2012-2016 at the Aga Khan University Hospital, Karachi, to evaluate the postoperative surgical site infection rates in emergency paediatric abdominal surgery. Incidence of surgical site infection (SSI) was estimated. P-value was calculated, chisquare and non-parametric tests were performed by comparing pre-surgical and post-surgical procedure pathogen occurrence and pre-procedure wound status. Pathogen occurrence related to time-trend of 98 paediatric patients who underwent emergency abdominal surgery was plotted. Of the 94 who were discharged in stable condition, it was found that there was no significant difference between pre- and postsurgical pathogens. Escherichia coli (n=10) was found to be the most common pathogen. Contaminated wounds were associated with higher SSI (p=0.036, OR 1.95 95% CI 0.7-5.4). The study found that pre-surgery wound status could be an indicator for risk of SSI in a post-operative scenario.

Paediatric respiratory isolation: A challenge for a secondary care hospital! A service innovation project.

OBJECTIVE: The aim of this project was to broaden the secondary care hospital's scope of services and provide safe, effective and quality care for the patient presenting with measles. METHODS: Six Sigma DMAIC [define measure, analyze, improve, and control (DMAIC)] methodology was used in this quality improvement project. The quality project was started in October 2015 using a Gantt chart quality tool. RESULTS: The paediatric team with the support of administration of the hospital has established isolation rooms and devised a policy for the care and management of patient with airborne infection to avoid cross transmission. During six months period after establishment of isolation room there were sixty two suspected or confirmed measles cases who were admitted in our hospital, out of them only 4(6.4%) of patients were referred because of their sick condition and need of ventilator support. Further, the percentage of patient's satisfaction level also improved from 60 to 80%. CONCLUSIONS: After this clinical service innovation, there was significant reduction in referrals of measles patients to another hospital and consequently there was an increase in the patient's satisfaction.

Famotidine does not affect human sperm fertility characteristics (motility, viability and DNA integrity) in vitro.

Famotidine, a histamine-2 receptor antagonist, is commonly used to relieve the acid-related gastrointestinal diseases; however, its effect on human sperm parameters, and hence on sperm function, is still undetermined. Here, we intended to measure human sperm motility, viability, and DNA integrity of ejaculated human sperm in the presence of famotidine at 0, 0.1, 1 and 10 mM concentrations in vitro. Forty-nine semen samples of normal count, motility, and morphology were included in this study. Sperm motility was assessed using Makler counting chamber and a phase contrast optics (200× magnification), whereas sperm viability was assessed using eosin-nigrosin staining procedure. The effect of famotidine on sperm DNA integrity was measured using flow cytometry. Famotidine at 0.1, 1 or 10 mM had insignificant effect on human sperm motility (progressive, p = .9594; and total, p = .8420), sperm viability (p = .6471), and content of DNA breaks in sperm (p > .05) compared with the control. In conclusion, famotidine at 0.1, 1 or 10 mM did not alter human sperm motility, viability or DNA integrity in vitro. Although, these findings indicate safety of famotidine in human sperm, further in vivo studies are required to establish the drug's safety.