World Health Organization Reference Research Articles

Molecular characterization of Mumps virus genotype C detected from Dibrugarh district of Assam, India

Background & objectives Mumps, a contagious disease caused by the mumps virus (MuV) involves parotid gland inflammation, with potential complications affecting organs other than the parotid glands and central nervous system. Despite successful vaccination, a resurgence of mumps occurred, raising concerns about vaccine effectiveness. This study aimed to examine the entire genome of a representative MuV genotype C from Dibrugarh, Assam, and compare it with references to detect genetic variations in the circulating strain. Methods Representative MuV genotype C from our published study was subjected to whole genome sequencing. MuV genome was analyzed against the reference genome and vaccine strains before being subjected to mutational profiling, N-glycosylation site determination, and phylogenetic analysis. The Immune Epitope Database was used for epitope screening, and selected epitopes were mapped against Assam MuV for conservancy studies. Results Mutational analysis of Assam MuV with WHO (World health Organization) reference, vaccine strains Jeryl Lynn (Genotype A), and L Zagreb (Genotype N) showed variations in seven genes. Phylogenetic analysis established Assam MuV as genotype C. Epitope conservancy analysis highlighted subtle variations in experimentally determined T-cell epitopes for HN and F proteins, emphasizing overall epitope stability. Interpretation & conclusions Genome sequencing has evolved into a standard and potent method for investigating and recording circulating MuV as it provides information on surveillance, mutation analysis, and transmission dynamics. Despite mumps’ global effect, genomic studies are limited, particularly in north-east. Our study provides first comprehensive whole-genome report on circulating MuV genotype C in Assam. This research contributes vital genomic data, filling gaps in MuV genetic epidemiology, supporting global research, and assessing vaccine effectiveness.

The Influence of Treatment With Sofosbuvir/Velpatasvir on Children's Growth-Results of the PANDAA-PED Study.

The aim of this study was to evaluate the influence of treatment of hepatitis C with sofosbuvir and velpatasvir (SOF/VEL) on children's growth. Fifty children 6-18 years of age were successfully treated for hepatitis C with a 12-week course of SOF/VEL fixed dose adjusted to the body weight in the PANDAA-PED (Treatment of chronic hepatitis C in children aged 6-18 years of age using a pangenotypic direct-acting antiviral sofosbuvir/velpatasvir) project. Growth parameters were compared at 1 year after treatment with baseline (at the start of treatment) and 12-week-posttreatment values. Body mass index (BMI), weight and height Z scores adjusted to sex and age were calculated according to the World Health Organization reference data. Forty-nine participants (23 boys and 26 girls) completed all the visits. The mean age at 1 year after treatment was 10.9 ± 2.5 years, and all children had undetectable hepatitis C virus RNA at this point. Significant weight and height gains were observed after treatment irrespective of the patients' age and sex. Height Z scores did not vary significantly both at 12 weeks and 1 year after treatment, confirming a normal increase in participants' height. Weight Z scores for 16 children below 10 years of age decreased at 1 year after treatment. BMI Z score values decreased at 12 weeks after treatment compared to the baseline in boys, but no difference was found between 1-year posttreatment and baseline BMI Z scores in both girls and boys. Results of the PANDAA-PED study showed normal growth up to 1 year after successful treatment with SOF/VEL in children 6-18 years of age. Despite the decrease in BMI Z score in boys observed at 12 weeks after treatment, no differences were found between baseline and 1-year posttreatment values. Our observations confirm the long-term safety of the SOF/VEL treatment in children 6-18 years of age.

Sperm Quality in 1252 Adolescents and Young Adults (AYAs) Undergoing Fertility Preservation Due to Cancer or Nonmalignant Diseases.

Purpose: To investigate the quality of emergency-collected semen samples aimed at sperm cryopreservation provided by adolescents and young adults (AYAs) presenting with cancer or nonmalignant diseases. Methods: This is a prospective cohort study of postpubertal males referred for sperm cryopreservation who provided at least one semen sample for fertility preservation at the Reproductive Medicine Clinic of Karolinska University Hospital, Stockholm, Sweden, between January 2009 and January 2020. Sperm quality was assessed by total sperm count, concentration, and motility. Sperm quality by disease groups was compared with the reference population data of fertile men defined by the World Health Organization (WHO). Results: Among the 1252 patients who provided samples for cryopreservation, 1063 had cancer and 189 had nonmalignant diseases. The most common malignant indications included testicular cancers (n = 501) and Hodgkin lymphoma (n = 102). Among those with nonmalignant disease, 35% (n = 66) had testicular disease. Sperm quality was significantly lower in all groups of patients with cancer compared with the reference population. In total, azoospermia was found in 8% of the patients with cancer, in 9% of those with nonmalignant testicular disease, and in 3% of the remaining men with nonmalignant disease. Conclusion: Sperm quality in adult patients with cancer was significantly impaired compared with the WHO reference population standards for fertile men. For adolescent patients, standard reference values are lacking. AYAs wishing to preserve fertility should receive individualized counseling regarding sperm quality at the time of cryopreservation, and in selected cases, banking of additional samples should be recommended depending on the sperm quality parameters.

Unintended Consequences of Urban Expansion and Gold Mining: Elevated Indoor Radon Levels in Gauteng Communities’ Neighboring Gold Mine Tailings

The province of Gauteng in South Africa has a rich history of gold mining, which has driven economic growth and urbanization. Gold mining has also created over 270 gold mine tailings (GMT), now surrounded by human settlements due to a housing shortage. These GMT pose a health risk as they harbor elevated uranium, which over time undergoes radioactive decay to produce radon, a known lung carcinogen. This study aimed to investigate the potential correlation between the proximity to gold mine tailings (GMT) and indoor radon concentrations in Gauteng’s residential dwellings. Volume activity of radon (VAR) inside 330 residential dwellings was measured in residential dwellings located proximally (<2 km) and distally (>2 km) to gold mine tailings using AlphaE radon monitors during winter. An interviewer-administered questionnaire was utilized to obtain data on factors that may influence indoor radon activities. Descriptive statistics and bivariate logistic regression analyzed the influence of proximity to gold mine tailings and dwelling characteristics on VAR. Furthermore, VAR was compared to the World Health Organization (WHO) radon reference level of 100 Bq/m3. Residential dwellings near gold mine tailings had significantly higher average indoor radon concentrations (103.30 Bq/m3) compared to the control group (65.19 Bq/m3). Residential dwellings proximal to gold mine tailings were three times more likely to have VAR beyond the WHO reference level of 100 Bq/m3. Furthermore, they had estimated annual effective doses of 2.60 mSv/y compared to 1.64 mSv/y for the control group. This study highlighted a concerning association between proximity to gold mine tailings and elevated indoor radon levels. Public health interventions prioritizing residential dwellings near gold mine tailings are crucial. Educational campaigns and financial assistance for radon mitigation systems in high-risk dwellings are recommended. Residents near gold mine tailings are encouraged to ensure continuous natural ventilation through frequent opening of windows and doors.

Continued harmonization of the international normalized ratio across a large laboratory network: Evidence of sustained low interlaboratory variation and bias after a change in instrumentation.

Our objective was to maintain low interlaboratory variation and bias in international normalized ratio (INR) results following a network change in instrumentation and reagents, using a process of ongoing standardization and harmonization. Network-wide standardization to new common instrument and reagent platforms followed by network-wide application of a simple novel process of verification of international sensitive index and mean normal prothrombin time values for each new lot of prothrombin time (PT) reagent that does not require use of World Health Organization reference thromboplastin or INR calibration/certified plasma. The network transitioned from mechanical hemostasis detection instruments with associated PT reagent (Diagnostica Stago; NeoPTimal) to optical detection (ACL TOPs) with associated PT reagent (Werfen; RecombiPlasTin 2G). Comparing 3 years of data for each situation, the network (n=27 laboratories) maintained low INR variability and bias relative to general mechanical and optical groups and other laboratories. Harmonized support for patient management of vitamin K antagonists such as warfarin was continuously maintained in our geography, with potentially positive implications for other coagulation laboratories and geographies. For the United States in particular, paucity of US Food and Drug Administration-cleared INR certified plasmas potentially compromises INR test accuracy; our novel approach may provide workable alternatives for other laboratories/networks.

P-023 Gene expression in human sperm as biomarkers and tools for the assessment of male infertility

Abstract Study question Can gene expression as AURKA, HDAC4, and CARHSP1 be used for the diagnosis of sperm quality exploring male infertility? Summary answer The comprehensive outcome of gene expression involving AURKA, HDAC4, and CARHSP1 serves as a key to classifying sperm and predicting their functionality. What is known already Diagnostic male infertility is largely based on semen parameters according to the World Health Organization (WHO) reference values. While these parameters assess sperm quality, they do not provide insights into sperm quality and have a limited predictive value on natural fecundity, fertilization rates, and assisted reproductive technology (ART) outcomes. Study design, size, duration This prospective study investigates the gene expression involved in mitosis, epigenetic regulation, and early embryo development. From February to June 2023, we included all men aged from 20 to 60 years having sperm parameters analysis in our unit center. A total of 277 semen samples were collected, 129 (46.4%) exhibiting three normal sperm parameters according to WHO criteria. Among these, 32 samples showed oligo-astheno-teratozoospermia (OAT), while 116 samples had 1 or 2 abnormal parameters. Participants/materials, setting, methods The mRNA expression levels of three candidate genes (AURKA, HDAC4, and CARHSP1) were quantified in fresh ejaculate semen using real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The thresholds for the spermatozoa function index (SFI) were established by assessing the combined expression of these target genes, considering the morphology and the capability to reach a blastocyst stage. The sperm were ranked according to the concentration (million/ml), motility (%) and morphology (%). Main results and the role of chance We assess the quality of spermatozoa for three biomarkers by analyzing their mRNA expression levels. Receiver operator characteristics curves (ROC) indicate a combined index value expression. This model establishes an index threshold > 320 for an “over-index value,” distinguishing spermatozoa with a normal capacity, an index threshold < 290 for an “under-index value,” and 290 < index < 320 for an “intermediate-index value”. Among the 277, we find 112 (40.4%) have an over-expression index; 161 (58.1%) have an under-expressed index and 4 (1.4%) have an intermediate-index. Interestingly, among the 129 samples with the three normal WHO parameters, we show that 82 (63.5%) have an over-index value, 44 (34.1%) have an under-index value, and 3 (2.3%) display an intermediate-index value. In addition, all the 32 OAT samples have an under-index. These findings suggest that the OAT sperm population implies a potential epigenetic network connected with our three target genes. Furthermore, even in cases with normal sperm parameters, there may be an under-expressed index, indicating lower functionality in terms of fertilization and early embryo development. Limitations, reasons for caution The present method was validated only on ejaculate semen in men free of any chronic disease and any anti-oxidant treatment. This prospective study requires further validation in the largest population. Wider implications of the findings This study’s results could highlight understanding a chaotic early embryo development in ART and used to explore male infertility; particularly in unexplained infertility. Trial registration number not applicable

The Prevalence of Antibiotic Tolerance in Neisseria gonorrhoeae Varies by Anatomical Site.

Tolerance enables bacteria to survive intermittent antibiotic exposure without an increase in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone, azithromycin and ciprofloxacin, in clinical isolates and the WHO (World Health Organization) reference panel of Neisseria gonorrhoeae. We used the modified tolerance disk (TD test) to assess for tolerance to ceftriaxone, azithromycin and ciprofloxacin in 14 WHO reference strains and 62 N. gonorrhoeae clinical isolates-evenly divided between anorectal and urogenital infections. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disk for 20 h of incubation (Step I), followed by the replacement of the antibiotic disk with a nutrient disk for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). A total of 4 of the 62 clinical anorectal isolates and none of the urogenital isolates exhibited tolerance to azithromycin (p = 0.033). Tolerance to ceftriaxone and ciprofloxacin was observed in eight and four isolates, respectively, with no difference between infection sites. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO reference strains, with varying patterns of tolerance to ceftriaxone (n = 8), ciprofloxacin (n = 2) and azithromycin (n = 1). This study identified ceftriaxone, azithromycin and ciprofloxacin tolerance in clinical and WHO reference N. gonorrhoeae isolates. Azithromycin tolerance was more common in anorectal than urogenital infections.

Assessment of Adolescents' Overweight and Obesity Risk Factors Among Alabnaa Schools in Tabuk City, Saudi Arabia.

The prevalence of overweight and obesity among adolescents in Saudi Arabia has been progressively increasing. Obesity is associated with an increased risk of various morbidities and mortality. Identifying the factors that contribute to obesity in this age group is crucial for implementing targeted prevention measures. The aim of this study was to identify risk factors for overweight and obesity among adolescents aged nine to 17 years residing in Tabuk City, Saudi Arabia. A case-control study was conducted during the 2021-2022 academic year at Alabnaa Schools in Tabuk City, Saudi Arabia. The study included overweight/obese individuals (cases, n = 125) and normal-weight individuals (controls, n = 201) who were selected based on their body mass index and classified according to the World Health Organization's reference for defining overweight and obesity in individuals aged five to 19 years. Data were collected from both groups using a self-administered questionnaire. The study analyzed 125 overweight/obese students and 201 normal-weight students who were matched for sex and age (p > 0.05). Logistic regression analysis identified several risk factors for overweight or obesity among adolescents. A family history of obesity was found to be associated with a 5.735 times increased likelihood of obesity (95% CI: 3.318-9.912, p < 0.001). Another significant contributing risk factor for obesity was frequent consumption of four or more meals per day (adjusted odds ratio: 3.091, 95% CI: 1.094-8.736, p = 0.033). Students who used electronic devices for more than five hours were 2.422 times more likely to exhibit obesity (p = 0.006). Certain factors may increase the risk of overweight or obesity in adolescents aged nine to 17 years. These factors include frequent eating, prolonged use of electronic devices, family history of obesity, and the misconception that obesity is not an illness. Tailored school health programs are needed to improve students' healthy lifestyles and eating behaviors, minimize sedentary entertainment and use of electronic devices, and engage children in physical activity.

Measles in Poland in 2021.

Measles is one of the most contagious childhood diseases, and the behavior also occurs in adults. This is a multi-year vaccination covered by an elimination program coordinated by the World Health Organization (WHO). Elimination of measles in the country is conditional on a 95% incidence of infection with two victims, monitoring the epidemiological situation, registering all suspected cases of measles, and monitoring by the WHO Reference Laboratory. In our country, the Department of Virology of the NIZP PZH-PIB in Warsaw serves as the head of the Department of Virology. The aim of this study was to evaluate epidemiological indicators of measles in Poland in 2021 compared to previous years, taking into account the impact of the COVID-19 pandemic. The assessment of the epidemiological situation was based on a review of data from the bulletin, "Infectious Diseases and Poisons in Poland in 2021" (5), and the assessment of the immunization status of the population was based on data from the bulletin, "Immunization in Poland in 2021" (6). Classification of cases was made based on the definition used in the 2021 surveillance (7). Data from the epidemiological surveillance system "EpiBase" were also used. In 2021, 13 measles cases were registered in Poland (incidence 0.03 per 100,000), 44.8% less than in 2020 and 80% less than the median in 2014-2018. In 2021, the highest incidence was recorded at 0.32 per 100,000 children aged 0-4 years. 6 patients (46.2%) were hospitalized; no deaths due to measles were reported. 32 suspected measles cases were recorded, with over a hundred cases expected. Vaccination status of children aged 3 with the first dose was 90.8%, and the second dose was given to children at the age of 9. - 84.6%. Epidemiological indicators of measles in 2021 in Poland compared to 2020 have decreased. A similar trend observed throughout Europe. This is related to the extinguishment of outbreaks that occurred before the pandemic, mainly in 2019.

Assessing Disparities about Overweight and Obesity in Pakistani Youth Using Local and International Standards for Body Mass Index

Background/Objectives: Obesity is currently considered a public health problem in both developed and developing countries. Gender- and age-specific body mass index (BMI) growth standards or references are particularly effective in monitoring the global obesity pandemic. This study aimed to report disparities in age-, gender- and ethnic-specific statistical estimates of overweight and obesity for 2–18 years aged Pakistani children and adolescents using the World Health Organization (WHO), the Center for Disease Control (CDC) 2000 references, the International Obesity Task Force (IOTF) and Pakistani references for BMI. Methods: The study used secondary data of 10,668 pediatric population, aged 2–18 years. Demographic information like age (years), gender, city and anthropometric examinations, i.e., height (cm) and weight (kg) were used in this study. The recommended age- and gender-specific BMI cut-offs of the WHO, CDC 2000 and the IOTF references were used to classify the children sampled as overweight and obese. For the Pakistani reference, overweight and obesity were defined as BMI-for-age ≥ 85th percentile and BMI-for-age ≥ 95th percentile, respectively. Cohen’s κ statistic was used to assess the agreement between the international references and local study population references in the classification of overweight/obesity. Results: The statistical estimates (%) of the participants for overweight and obesity varied according to the reference used: WHO (7.4% and 2.2%), CDC (4.9% and 2.1%), IOTF (5.2% and 2.0%) and Pakistan (8.8% and 6.0%), respectively; suggesting higher levels of overweight and obesity prevalence when local study references are used. The Kappa statistic shows a moderate to excellent agreement (κ ≥ 0.6) among three international references when classifying child overweight and obesity and poor agreement between local references and the WHO (0.45, 0.52), CDC (0.25, 0.50) and IOTF references (0.16, 0.31), for overweight and obesity, respectively. Conclusions: The results of the study showed a visible difference in the estimates of excess body weight after applying the WHO, CDC, IOTF and local BMI references to the study population. Based on the disparity results and poor agreement between international references and the local study reference, this study recommends using local BMI references in identifying children with overweight and obesity.

Prevalence and associated factors of stunting and thinness among children and adolescents in Nasarawa State: comparison with World Health Organization reference

Prevalence and associated factors of stunting and thinness among children and adolescents in Nasarawa State: comparison with World Health Organization reference

Nutritional status assessment of 6-59 months age children in rural Yadgir, Karnataka state, India

Background: Childhood undernutrition contributes to childhood diseases and is a major cause of child mortality in India. According to National Family Health Survey (NFHS-5), 32% under-five children in India were under-weight, and 36% were stunted. In Karnataka, the prevalence of underweight among under-five children was 33% and stunting 35%. The objective of the study was to assess the nutritional status of under five-years children in rural communities. Methods: A community based cross sectional study was conducted among 1887 under-five children from rural Yadgir, Karnataka. Weight and height of children were measured using standard protocols. The World Health Organization (WHO) Anthro software version 3.2.2.1 was used for analyzing data. Children whose Z-scores on weight-for-age, height-for-age and weight-for-height indices were below -2SD from the median of the WHO reference population were considered as underweight, stunted, and wasted respectively. Results: The result revealed that 53.6% of children were stunted, 39.4% were underweight and 15.3% were wasted. Severe forms of underweight, stunting and wasting were observed among 9.4%, 24.2% and 4% children respectively. The frequency of being underweight and stunted has increased with age, which was accelerated after 6 months and about 34% and 52% of children were underweight and stunted by the age 12-23 months. While wasting was higher among children aged 6-11 (24.2%) months than their counterparts. Conclusions: Special attention is required to reduce nutrition vulnerability among young children (12-24 months). An appropriate strategy needs to be implemented to educate rural mothers on the importance of exclusive breastfeeding and complementary feeding practices.

Sibship Composition and BMI Z-Score Among Saudi Preschoolers: A Cross-Sectional Study.

Background and objective The association between sibship composition and child body mass index (BMI) has not been investigated in any Arab/Middle Eastern populations. In light of this, this study aimed to examine the association of the number of siblings, number of older siblings, and number of younger siblings with child BMI z-score (BMIz) among preschoolers in the Kingdom of Saudi Arabia (KSA). Methods A total of 209 mothers and their children were recruited from preschools in Jeddah, KSA. Mothers reported their responses to the study questionnaire via telephone. Child anthropometry was objectively measured; BMIz was calculated based on age- and sex-specific World Health Organization (WHO) growth standards and reference data. We used hierarchical multiple linear regression to examine the association between sibship composition variables and child BMIz, independent of the effect of potential confounders, and to evaluate changes in model fit. Results The number of siblings was negatively associated with child BMIz [b = -0.18, 95% confidence interval (CI) = -0.35, -0.06, p<0.01, adjusted R2= 0.16]. There was a negative association between the number of older siblings and child BMIz (b = -0.23, 95% CI = -0.38, -0.11, p<0.01, adjusted R2= 0.21) as well as between the number of older sisters and child BMIz (b = -0.18, 95% CI = -0.52, -0.09, p<0.01, adjusted R2= 0.19). However, there were no significant associations between the number of older brothers or the number of younger siblings and child BMIz. Conclusions Based on our findings, sibship composition was found to be associated with BMIz among a sample of preschoolers in KSA. More research is needed to further establish this association and to understand the underlying mechanism of the association of the greater number of older siblings and older sisters with lower BMIz.

Growth in height and its association with overweight and obesity in Mexican children: an evaluation based on a nationally representative sample (ENSANUT 2018).

Chronological age and height records (7,097 boys and 6,167 girls) were obtained from the Mexican National Survey of Health and Nutrition database. Height growth curves were fitted using the Preece-Baines 1 (PB1) model and the LMS method. Age at peak height velocity (APHV) was 12.4 and 12.7 years for overweight-obese and normal-weight boys, respectively, and was 9.6 and 10.4 years for overweight-obese and normal-weight girls, respectively. Growth velocity was higher at the age of take-off (TO) in overweight-obese children than in normal-weight children (5.2 cm/year vs. 5 cm/year in boys and 6.1 cm/year vs. 5.6 cm/year in girls); nevertheless, the growth velocity at APHV was higher for normal-weight children than for overweight-obese children (7.4 cm/year vs. 6.6 cm/year in boys and 6.8 cm/year vs. 6.6 cm/year in girls, respectively). Distance curves developed in the present study and by the World Health Organization (WHO) using LMS showed similar values for L and S parameters and a higher M value compared with the WHO reference values. This study concluded that overweight-obese children had earlier APHV and lower PHV than normal-weight children. Furthermore, Mexican children and adolescents were shorter than the WHO growth reference by age and sex.

Standardisation and harmonisation of thyroid-stimulating hormone measurements: historical, current, and future perspectives.

Thyroid-stimulating hormone (TSH) is an important clinical marker in the diagnosis and management of thyroid disease. TSH measurements are reported in milli-International Units per Litre (mIU/L), traceable to a World Health Organisation (WHO) reference material. There is a wide variety of commercial immunoassays for TSH measurements available, which have historically been poorly harmonised due to a lack of commutability of the WHO reference materials with patient samples. This led to the recent development of a serum-based reference panel for TSH, traceable to the WHO reference material, available via the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC), aimed at harmonisation of TSH immunoassays. This report describes recent developments in the TSH reference system, including establishment of the4th WHO International Standard for TSH, and aims to clarify the relationship between the available reference materials and their intended uses. This 4th WHO IS is widely available and defines the unit of TSH activity, therefore its continued existence is of paramount importance, however it continues to show a lack of commutability with patient in many TSH immunoassays. This makes the C-STFT TSH panel, albeit available in restricted numbers, a critical resource to ensure better TSH assay harmonisation.

Prevalence, risk factors, and clinical outcomes of vitamin C deficiency in adult hospitalized patients in high-income countries: a scoping review.

Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization. In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified. A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells. Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P = 0.015) and using excessive amounts of alcohol and tobacco (P = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33-13.86; P = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05-8.19, P = 0.031) (n = 160). VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted. Open Science Framework ( https://doi.org/10.17605/OSF.IO/AJGHX ).

Ramoplanin as a novel therapy for Neisseria gonorrhoeae infection: an in vitro and in vivo study in Galleria mellonella.

Neisseria gonorrhoeae is a bacterial pathogen that causes gonorrhoea, a sexually transmitted infection. Increasing antimicrobial resistance in N. gonorrhoeae is providing motivation to develop new treatment options. In this study, we investigated the effectiveness of the antibiotic ramoplanin as a treatment for N. gonorrhoeae infection. We tested the effectiveness of ramoplanin in vitro against 14 World Health Organization (WHO) reference strains of N. gonorrhoeae and found that it was active against all 14 strains tested. Furthermore, in a Galleria mellonella infection model of N. gonorrhoeae WHO P, we demonstrated that ramoplanin was active in vivo without any evidence of toxicity. This suggests that ramoplanin might be a new promising antibiotic treatment for gonorrhoea.

Recommendation to diagnose male factor infertility based on routine semen analysis results

It is apparent that sperm parameters like concentration, motility and morphology are not definitive/adequate fertility measures as sperm is a heterogeneous mixture, and sperm quality is determined by only what is visible in the microscopic field. Objective was to assess the quality variation among different aliquots of an ejaculate and present a concept that may allow interpreting the results in such a way as to determine the clinical usefulness of the semen analysis more accurately.A laboratory-based cross-sectional study was conducted at Teaching Hospital Jaffna’s Semiology laboratory from July to September 2023 after obtaining Institutional Ethical Review committee approval, analysing 102 semen ejaculates collected through masturbation. The sample was analysed using a Makler counting chamber, and Data was analysed using SPSS version 24, with statistical significance set at P&lt; 0.05.The three different aliquots obtained from the same ejaculate revealed no significant difference from each other for all three variables like Concentration (P=0.957), Progressive Motility (P=0.810) and Motility (P=0.832). Similarly, the mean and fifth percentile plus 95% confidence level were not significantly different (P= 0.782, P= 0.328, P= 0.370).When using the Makler counting chamber, the mean value calculated from one aliquot per ejaculate counted on three strips of ten squares should be acceptable, and at least two different ejaculates should be analysed when interpreting the results based on World Health Organization (WHO, 2021) reference limits.

Development and evaluation of a CRISPR-Cas13a system-based diagnostic for hepatitis E virus.

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. HEV RNA detection is the goldstandard for HEV infection diagnosis and PCR methods are commonly used but are usually time-consuming and expensive, resulting in low detection efficiency and coverage, especially in low-income areas. Here, we developed a simpler and more accessible HEV RNA detection method based on CRISPR-Cas13a system. A total of 265 samples of different types and sources, including 89 positive samples and 176 negative samples, were enrolled for evaluations. The sensitivity andspecificity of the Cas13a-crRNA detection system were evaluated. The World Health Organization reference panel for HEV genotypes was used to evaluate the capability for detecting different HEV genotypes. The validity of the assay was compared with RT-qPCR. The 95 % limits of detection (LOD) of Cas13a-crRNA-based fluorescence assay and strip assay were 12.5 and 200 IU/mL, respectively. They did not show cross-reactivity with samples positive for hepatitis A virus, hepatitis B virus, hepatitis C virus, coxsackievirus A16, rotavirus, enterovirus 71, norovirus or enteropathic Escherichia coli. Different HEV genotypes (HEV1-4) can be detected by the assay. Compared to RT-qPCR, the positive predictive agreements of Cas13a-crRNA-based fluorescence and strip assay were 98.9 % (95 % CI: 93.9-99.8 %) and 91.0 % (95 % CI: 83.3-95.4 %), respectively. The negative predictive agreements were both 100 % (95 % CI: 97.8-100 %). In conclusion, we established a rapid and convenient HEV RNA detection method with good sensitivity and specificity based on CRISPR-Cas13a system, providing anew option for HEV infection diagnosis.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to twoyears and to identify the critical exposure periods. A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first twoyears, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033kb).