COVID 19 Vaccine Breakthrough Infection among Health Care Workers.

Background Mass vaccination is considered the primary strategy for reducing the impact of COVID-19, and it has been implemented globally. Objective To study the extent of SARS-CoV-2 infection and breakthrough infection among the HCWs who were fully vaccinated for at least 14 days and investigated the relation between neutralizing antibody response and breakthrough infection. Method This study was a retrospective cohort study among health care workers at Dhulikhel Hospital Kathmandu University Hospital from December 2021 to October 2022. The interviews with semi structured questionnaire were conducted in person or over phone. Out of 1450 participants 137 fully vaccinated HCWs without breakthrough infection were randomly selected for the prospective serological cohort. Result Out of 1079 participants' majority (51.8%) were of age 25-34 years. Two thirds (66.7%) were females. More than half of participant (54.7%) had infection with SARS-CoV-2 at least once whereas more than one third people (35%) had reported SARS-CoV-2 infection 14 days after receiving full vaccination. Infection after vaccination had less moderate and sever/critical illness and less need for hospitalization as compared to infection before vaccination. Staffs who were directly involved in patient care had higher chance of breakthrough infection compared to those not involved directly in patient care. Those who had prior infection or booster dose had relatively higher antibody level and participants with low level of antibody had higher chance for breakthrough infection (35.3%) than participants with moderate to high level of antibody (11.9%). Conclusion Vaccinations significantly decreased severe diseases and the need for hospitalizations. Breakthrough infection was higher among the health care workers involved in direct patient care and with low level of antibody.

First Direct Detection Constraints on Planck-Scale Mass Dark Matter with Multiple-Scatter Signatures Using the DEAP-3600 Detector.

Dark matter with Planck-scale mass (≃10^{19} GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19} GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18} cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

Knowledge, Attitude and Practice towards COVID-19 among Private School Teachers of Chitwan, Nepal.

Background The coronavirus disease (COVID-19) pandemic has brought life to a standstill across the world, with nearly 178 countries reporting school closures. As the schools have started reopening slowly, precautions are utmost necessary to prevent the potential spread of COVID-19 in school and community settings. Objective To assess knowledge, attitude and practice towards COVID-19 among private school teachers. Method A web based cross-sectional analytical study design was undertaken. Currently working private school teachers of Chitwan District were included as a unit of analysis. The snowball sampling technique was employed to identify the eligible participant. Collected data was entered in SPSS version 20 and analyzed using the Chi-square test, Pearson correlation, and binary logistic regression. Result Of 344 participants, the majority were male (52.9%), most of the participants were from age group 26-30 years (38.4%). Regarding knowledge, attitude and practice, 57% had good knowledge, 53.2% had favorable attitude and 51.7% had good practice towards COVID-19. Logistic regression analysis demonstrated gender (OR 0.475, 95% CI: 0.256-0.818) and COVID-19 training (OR 25.687, 95% CI 5.354-123.226) were significant with good knowledge. Conclusion Knowledge about COVID-19 among private schools teacher was good, attitudes have been mostly favorable, and the practices were mostly adequate. However, good knowledge is not the only factor for better attitude and good practices. It is necessary to implement massive education campaigns, trainings and information via school authorities and health authorities by developing and adopting appropriate guidelines on COVID-19.

First Reported Death of a Postpartum Woman Due to Coronavirus Disease 2019 in Nepal: A Lesson Learnt.

The first case of coronavirus disease 2019 was reported on December 31, 2019 in Wuhan, China where the average case fatality rate was 6.1 ± 2.9%. There are 453 deaths as of September 24, 2020 in Nepal. We report the first death of a 29-years-old postpartum woman due to COVID-19 in Nepal who was referred from a rural health center to Dhulikhel Hospital. On arrival, she was taken to the acute respiratory zone of the emergency department to provide immediate lifesaving procedures. Despite the repeated resuscitative measures, return of spontaneous circulation could not be achieved. The real time polymerase chain reaction test was positive. Our case report highlights the importance of early clinical suspicion, importance of "safety first" in healthcare settings, and the chain of management in such patients. We consider the fact that a postpartum woman registered as the first case of COVID-19 related death in Nepal to be an area of further study.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis.

STUDY QUESTION: What is the role of SFRP2 in endometriosis? SUMMARY ANSWER: SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis, regulating endometriosis lesion growth and indicating endometriosis lesion borders together with CTNNB1 (also known as beta catenin). WHAT IS KNOWN ALREADY: Endometriosis is a common, chronic disease that affects women of reproductive age, causing pain and infertility, and has significant economic impact on national health systems. Despite extensive research, the pathogenesis of endometriosis is poorly understood, and targeted medical treatments are lacking. WNT signaling is dysregulated in various human diseases, but its role in extraovarian endometriosis has not been fully elucidated. STUDY DESIGN, SIZE, DURATION: We evaluated the significance of WNT signaling, and especially secreted frizzled-related protein 2 (SFRP2), in extraovarian endometriosis, including peritoneal and deep lesions. The study design was based on a cohort of clinical samples collected by laparoscopy or curettage and questionnaire data from healthy controls and endometriosis patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Global gene expression analysis in human endometrium (n = 104) and endometriosis (n = 177) specimens from 47 healthy controls and 103 endometriosis patients was followed by bioinformatics and supportive qPCR analyses. Immunohistochemistry, Western blotting, primary cell culture and siRNA knockdown approaches were used to validate the findings. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 220 WNT signaling and CTNNB1 target genes analysed, 184 genes showed differential expression in extraovarian endometriosis (P < 0.05) compared with endometrium tissue, including SFRP2 and CTNNB1. Menstrual cycle-dependent regulation of WNT genes observed in the endometrium was lost in endometriosis lesions, as shown by hierarchical clustering. Immunohistochemical analysis indicated that SFRP2 and CTNNB1 are novel endometriosis lesion border markers, complementing immunostaining for the known marker CD10 (also known as MME). SFRP2 and CTNNB1 localized similarly in both the epithelium and stroma of extraovarian endometriosis tissue, and interestingly, both also indicated an additional distant lesion border, suggesting that WNT signaling is altered in the endometriosis stroma beyond the primary border indicated by the known marker CD10. SFRP2 expression was positively associated with pain symptoms experienced by patients (P < 0.05), and functional loss of SFRP2 in extraovarian endometriosis primary cell cultures resulted in decreased cell proliferation (P < 0.05) associated with reduced CTNNB1 protein expression (P = 0.05). LIMITATIONS REASONS FOR CAUTION: SFRP2 and CTNNB1 improved extraovarian endometriosis lesion border detection in a relatively small cohort (n = 20), although larger studies with different endometriosis subtypes in variable cycle phases and under hormonal medication are required. WIDER IMPLICATIONS OF THE FINDINGS: The highly expressed SFRP2 and CTNNB1 improve endometriosis lesion border detection, which can have clinical implications for better visualization of endometriosis lesions over CD10. Furthermore, SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis and positively regulates endometriosis lesion growth, suggesting that the WNT pathway may be an important therapeutic target for endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Academy of Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no conflict of interest to declare.

Clinical and molecular characterization of neonatal diabetes and monogenic syndromic diabetes in Asian Indian children.

Mutations in the pancreatic ATP sensitive K(+) channel proteins [sulfonyluea receptor 1 (SUR1) and inward rectifier K(+) channel Kir6.2 (Kir6.2), encoded by ATP-binding cassette transporter subfamily C member 8 (ABCC8) and potassium channel J11 (KCNJ11), respectively], are the most common cause of neonatal diabetes. We describe the clinical presentation and molecular characterization of Asian Indian children with neonatal diabetes mellitus and monogenic syndromes of diabetes. We sequenced KCNJ11, ABCC8 and insulin (INS) genes in 33 unrelated Indian probands with onset of diabetes below one year of age. A total of 12 mutations were identified which included ABCC8 mutations in seven, KCNJ11 mutations in three and INS mutations in two children. The Asp212Tyr mutation in ABCC8 was novel. We also detected two novel mutations (Val67Met and Leu19Arg) in children with syndromic forms of diabetes like Berardinelli Seip syndrome [1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)] and Fanconi Bickel syndrome [solute carrier family 2A2 (SLC2A2)]. Children carrying the KCNJ11 (Cys42Arg, Arg201Cys) and ABCC8 (Val86Ala, Asp212Tyr) mutations have been successfully switched over from insulin therapy to oral sulfonylurea. Our study is the first large genetic screening study of neonatal diabetes in India.

Do geriatrics require dose titration for antidiabetic agents?

OBJECTIVE: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl). MATERIALS AND METHODS: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years) and nongeriatric (age <60 years). Patients' demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU) were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. RESULT: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01) and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42) was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06) was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01) and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45) and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. CONCLUSION: A substantial dose reduction of glibenclamide (25%), gliclazide (25%), glimepiride (22%), and metformin (5%) in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

Effects of protease enzyme supplementation and varying levels of amino acid inclusion on productive performance, egg quality, and amino acid digestibility in laying hens from 30 to 50 weeks of age.

An experiment was conducted to evaluate the effects of protease supplementation and reduced digestible amino acid (dAA)/ crude protein (CP) level on productive performance, AA digestibility, and egg quality parameters in Hy-Line W-36 laying hen from 30 to 50 wk of age. A total of 768 hens (12 replicates of 8 hens per treatment) were equally and randomly allocated into 8 experimental diets in a 4 × 2 factorial arrangement of dAA/CP level (100, 95, 90, and 85% of breeder recommendation) and protease (exclusion or inclusion). Protease was added at 60 g/metric ton of feed in the inclusion group. Hens were housed in raised-wire cages with a stocking density of 870 cm2/bird. The adequate (100%) diet was based on corn and soybean meal and formulated based on the digestible (d) Lys and dAAs (dMet, dThr, dTrp, dTSAA, dIle, and dVal) to meet 100% of the current management guide recommendation. Variations in dAA/CP (95, 90, and 85% diets) were accomplished by reducing the 100% dAA by 5, 10, and 15%, respectively. All diets were supplemented with phytase at 500 phytase units (FTU)/kg. Data were analyzed using PROC GLM of SAS 9.4. There was a main effect of dAA/CP level on 85% diet where it had a lower mean hen-day egg production (HDEP, P < 0.01), egg mass (EM, P < 0.01), and higher feed conversion ratio (FCR, P < 0.001). Higher egg weight (P < 0.01) was observed in 95 and 100% dAA/CP level diets. However, Haugh unit (P < 0.01) and albumen height (P < 0.01) were higher in 85 and 90% diets. The inclusion of protease reduced the feed consumption (P = 0.0247), FCR for dozens of eggs (P = 0.0049) from 30 to 49 wk of age without affecting the HDEP or EM. Protease supplementation and dAA/CP level had an effect on the apparent ileal digestibility (AID) of CP (P = 0.019), Lys (P < 0.01), Thr (P < 0.01), Trp (P = 0.017), and Val (P < 0.01). Addition of protease significantly increased egg income (P = 0.033) and return on investment (P = 0.00223) from 30 to 37 wk of age. At 38 to 50 wk of age, dAA/CP level had a significant effect on egg income (P < 0.001), feed cost (P < 0.001), and return on investment (P < 0.001). This experiment indicates that the inclusion of protease in 90 and 95% lower dAA/CP diets could help improve the digestibility of CP, and key amino acids and maintain productive performance of corn and soybean meal-based diets in Hy-Line W-36 laying hen from 30 to 50 wk of age.

Ocular morbidity in hearing impaired schoolchildren.

AIMS: To determine the pattern and prevalence of ocular morbidity in hearing impaired schoolchildren. METHODS: A cross-sectional descriptive study was conducted in the three different deaf schools of Kathmandu, Bhaktapur and Kavre districts. All children in the deaf school underwent complete ocular examination. Examination included visual acuity assessment, refraction, binocular vision assessment, and anterior and posterior segment evaluation. RESULTS: Ocular examination was carried out in 279 children with age range within 5 to 20 years (mean age 14.1 ± 3.14 years). Ocular morbidity was detected in 78 (28%) children with 46 (16.48%) having refractive errors. Seventy eight percent children did not have corrective lenses despite having refractive errors. Two children were found to have pigmentary retinopathy where electro-retinogram findings suggested Usher's Syndrome in one child. Another child was found to have Waardenburg Syndrome. CONCLUSIONS: Hearing impaired children are at an increased risk of having ocular morbidity. Hence, periodic eye examinations are important in deaf children.

Pulse-shape discrimination against low-energy Ar-39 beta decays in liquid argon with 4.5 tonne-years of DEAP-3600 data.

The DEAP-3600 detector searches for the scintillation signal from dark matter particles scattering on a 3.3 tonne liquid argon target. The largest background comes from 39 Ar beta decays and is suppressed using pulse-shape discrimination (PSD). We use two types of PSD estimator: the prompt-fraction, which considers the fraction of the scintillation signal in a narrow and a wide time window around the event peak, and the log-likelihood-ratio, which compares the observed photon arrival times to a signal and a background model. We furthermore use two algorithms to determine the number of photons detected at a given time: (1) simply dividing the charge of each PMT pulse by the mean single-photoelectron charge, and (2) a likelihood analysis that considers the probability to detect a certain number of photons at a given time, based on a model for the scintillation pulse shape and for afterpulsing in the light detectors. The prompt-fraction performs approximately as well as the log-likelihood-ratio PSD algorithm if the photon detection times are not biased by detector effects. We explain this result using a model for the information carried by scintillation photons as a function of the time when they are detected.

Pseudomembranous colitis in a pregnant woman.

Pseudomembranous colitis in association with pregnancy has not been well described in English literature. Recent studies show a drastic increase in the incidence and severity of Pseudomembranous colitis in pregnant women, who were once thought to be at low risk. We report here a case of Pseudomembranous colitis in a young healthy immunocompetent pregnant lady. An early suspicion of this entity with the characteristic appearance of pseudomembranes on colonoscopy and histology confirmed the diagnosis enabling prompt treatment and complete recovery without any serious consequences.

Fate of particle-bound polycyclic aromatic hydrocarbons in the river-influenced continental margin of the northern Gulf of Mexico.

This study utilizes suspended particles and seafloor sediments collected from the northern Gulf of Mexico (GOM) continental margin to study the fate, transport, residence times and accumulation rates of particle-bound polycyclic aromatic hydrocarbons (PAHs). Total particulate-PAHs and particulate organic carbon (POC) varied between 0.9 and 7.0 ng/L, and 4-131 µg/L, respectively. Particulate-PAHs were positively correlated with POC, while both particulate-PAHs and POC were negatively correlated with salinity (P-value < 0.05). These results show that the river-derived particle influx and associated POC are important vectors for transport and fate of particulate-PAHs in the river-dominated northern GOM continental ecosystems. The composition of underlying seafloor sediment-PAHs were not correlated to the water column particulate-PAHs, which is attributed to re-mineralization, sediment resuspension/redistribution and different timescales of comparison. The 210Pb-derived residence time of particles and associated particulate-PAHs in water column varied between 2 and 39 days. Residence times of particulate-PAHs were significantly correlated with seafloor sediment-PAHs accumulation rates, shorter water column residence times leading to higher PAHs accumulation rates.

Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance.

Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase is required to terminate Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short-lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body α/ß neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.

Changes in cecum microbial community in response to total sulfur amino acid (TSAA: DL-methionine) in antibiotic-free and supplemented poultry birds.

The effect of essential total sulfur amino acids (TSAA) like methionine and cysteine on the cecal microbiome of broilers was investigated at 2 different time points (days 21 and 42) of broiler rearing. A total of 360-day-old Cobb male broiler chicks were randomly distributed to 6 dietary treatments in a 2 × 3 factorial arrangement, with 2 levels of antibiotic growth promoters (AGP: 0 and 0.05%) and 3 levels of TSAA (DL-methionine) either for starter (0.7, 0.8, and 0.9%) or finisher chicks (0.52, 0.62, and 0.72%), labeled as diets 1 to 6. Cecal digesta from each replicate (n = 10) were sampled on days 21 and 42. DNA was extracted for the amplification of the V4 region of bacterial 16S rRNA genes and subjected to Illumina sequencing. Bioinformatic analyses were performed using QIIME, Mothur, and ad hoc tools and functional profiles of the inferred metagenome were analyzed using PICRUST. Statistical difference was determined by 2-way ANOVA and PERMANOVA. Clustering of cecal communities using PCoA showed clear separation of microbial communities based on age (P < 0.05) of birds and between low and medium/ high levels of TSAA (DL-methionine). At day 21, bacterial richness and diversity were higher than at day 42 where Clostridium cluster XI and Lactobacillus were found most abundant. No variability in taxonomic richness at the genus level was observed with AGP and DL-methionine supplementation. Interbird variation for richness was greater at day 42 compared to day 21. The mean fold difference of richness was greater (1.5 mean fold) with diets 1 and 6, suggesting interactive effects of AGP and TSAA (DL-methionine) in the diet. KEGG function profiles calculated by PICRUST suggest that the cecal microbiome increased glycolysis and energy generation correlated with increased dietary TSAA (DL-methionine) supplementation levels during the late broiler growth period (day 42). This study increases our knowledge of microbial dynamics and functions that are relevant to host nutrition and performance that may help us tailoring alternative strategies for raising poultry birds under antibiotic-free conditions.

Effect of probiotics on fecal excretion, colonization in internal organs and immune gene expression in the ileum of laying hens challenged with Salmonella Enteritidis.

A study was conducted to evaluate the supplementation of probiotics on Salmonella colonization in the ceca and various internal organs as well as immune response in laying hens challenged with Salmonella enterica serovar Enteritidis (SE). Thirty-two 46-wk-old White Leghorns (W-36) were housed individually in wired laying cages under 16L:8D lighting schedule. Hens were challenged individually with nalidixic acid resistant Salmonella Enteritidis (SENAR) after which time they were grouped into four treatments: T1 = SENAR unchallenged control, T2 = SENAR challenged control, T3 = SENAR challenged + 0.05% probiotics (Lactobacillus plantarum), and T4 = SENAR challenged + 0.1% probiotics. All hens, including T1, were euthanized and sampled for the liver with gall bladder (L/GB), ileum, ovary, spleen, and ceca on 7-days post-infection (dpi). Fecal screening was performed on individual hens at both 3 and 6 dpi. No difference was detected between the treatments in cecal SENAR enumeration, and the mean log 10 cfu/gm of SENAR in the ceca was 3.7 for all three treatments. The prevalence of SENAR was lowest for ovary in all treatments and was highest in the spleen. However, there were no significant differences among the treatments in the internal organs. There was no significant difference in the fecal shedding among the treatments on either 3 or 6 dpi, with incidence of positive feces higher at 3 dpi compared to 6 dpi (100 vs. 70% to 80%). SENAR challenge resulted in significant upregulation (P < 0.05) of interleukin (IL)-1ß, 6, 10, interferon gamma (IFN-γ), and toll-like receptor (TLR)-4 mRNA expression. Highest level of probiotics resulted in a significant decrease in IFN-γ and elevation of IL-6 and IL-10 gene expression in the ileum. However, IL-1B and TLR-4 gene expression were not different from the SENAR challenge control. This study reveals that there was important regulation of immune genes by probiotics supplementation.