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Introduction: Prematurity is a major cause of admission in the NICU in most hospitals. Premature babies are likely to face complications. Understanding the factors contributing to preterm mortality is needed to identify interventions required to reduce neonatal mortality rate. This study aims to determine the causes of mortality in preterm babies. Methods: A retrospective study was carried out in Paropakar Maternity and Women’s Hospital, Thapathali, Kathmandu, Nepal. All the preterm babies admitted in the sick newborn units were included. Descriptive statistics were performed using frequency and percentage. The bivariate and multivariate analyses were performed to determine the causes of mortality in preterm. Results: Total 205 (71.4%) admitted preterm babies had complications at the time of admission. LBW babies were three times more likely to have mortality among preterm admission (p – value < 0.0001). Co-morbidities such as sepsis (p - value < 0.05) and perinatal asphyxia (p – value < 0.0001) were significantly associated with preterm mortality. The duration of stay among preterm babies was higher compared to term babies. The mortality rate was higher among preterm admission compared to term admission (60% vs 40%). Conclusions: Preterm babies with LBW, neonatal sepsis and perinatal asphyxia are at greater risk of mortality. Improved antenatal and perinatal care, quality newborn care and appropriate infection prevention measures can help reduce preterm birth, prematurity related complications and mortality among these vulnerable group of newborns.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures in some countries to contain the spread of the disease has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (

BackgroundEvery year an estimated 7.9 million babies are born with birth defect. Of these babies, more than 3 million die and 3.2 million have disability. Improving nationwide information on prevalence of birth defect, risk factor and consequence is required for better resource allocation for prevention, management and rehabilitation. In this study, we assess the prevalence of birth defect, associated risk factors and consequences in Nepal.MethodThis is a prospective cohort study conducted in 12 hospitals of Nepal for 18 months. All the women who delivered in the hospitals during the study period was enrolled. Independent researchers collected data on the social and demographic information using semi-structured questionnaire at the time of discharge and clinical events and birth outcome information from the clinical case note. Data were analyzed on the prevalence and type of birth defect. Logistic regression was done to assess the risk factor and consequences for birth defect.ResultsAmong the total 87,242 livebirths, the prevalence of birth defects was found to be 5.8 per 1000 live births. The commonly occurring birth defects were anencephaly (3.95%), cleft lip (2.77%), cleft lip and palate (6.13%), clubfeet (3.95%), eye abnormalities (3.95%) and meningomyelocele (3.36%). The odds of birth defect was higher among mothers with age ConclusionMaternal age younger than 20 years and advantaged ethnicity were risk factors of birth defects. Babies with birth defect have high risk for birth asphyxia, neonatal infection and pre-discharge mortality at birth. Further evaluation on the care provided to babies who have birth defect is warranted.FundingSwedish Research Council (VR).

Introduction: The paediatric intensive care unit (PICU) takes care of critically ill paediatric patients. Regular evaluation of the outcomes of patients admitted to PICU is important to assess the effectiveness of various interventions. This study aimed to find the morbidity and mortality pattern of patients admitted to PICU of tertiary level Paediatric hospital of Nepal. Methods: We conducted a retrospective, cross sectional observational study using the records of all the patients admitted to PICU of a tertiary level hospital from January 2017 to August 2017. We collected data on age, sex, geographical distribution, duration of PICU stay and the morbidity and mortality outcomes. Outcome is classified as transfer to ward, leave against medical advice (LAMA) and death. Data were analysed descriptively using SPSS version 23. Results: Out of 358 patients admitted to PICU, the mean age was 1.83 years. Majority were infants (54.5%) with male:female ratio of 1.8:1. The major causes of PICU admission were respiratory disease (27.7%) followed by CNS disease (19.6%) and infections (17.3%). The average length of stay was 6.27 days. Overall mortality was 22.7%. Conclusion: Respiratory infections were the primary cause of PICU admission and overall mortality rate was high at 22.7%. However, mortality rate was even worse for patients with multi-system involvement. We need prospective studies to examine the underlying reasons for mortality among patients with multi-system involvement.

The corona virus disease 19 pandemic has affected the whole world with pregnant ladies being more vulnerable population. This study aimed to evaluate characteristics of corona virus disease 19 infection in pregnancy and neonates and whether close proximity to the mother increases the incidence of corona virus disease infection in neonates..This is a hospital based prospective cross sectional observational study done among pregnant women presenting to Paropakar maternity and womens hospital from 1st September 2020 to 31st march 2021 with confirmed corona virus disease 19 infection.The total 160 cases were included in study. Most of the women (33.8%) were of 20- 25 years of age, 55 % were multigravida and 77.6 % were full term. Around 74 % of cases were symptomatic with predominant symptoms being cough, fever and sore throat present in 33.1 %, 18% and 14% respectively. Out of 125 deliveries 71 % of cases underwent cesarean section of which fetal distress was most common indication. Six newborns were positive for corona virus disease 19 infection within 48 hours of life. Mortality was seen in four mothers and three neonates.The clinical presentation of corona virus disease infection in pregnant ladies is similar to general population. There is no increased risk of vertical transmission to the baby.

Aim The aim of this study was to identify the incidence, risk factors and outcome associated with meconium aspiration syndrome (MAS). Methods An observational study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. All babies born within the study period were included in the study. Babies who were diagnosed as MAS were designated as outcome. Data were analysed with bivariate analysis followed by multiple regression analysis. Results The overall incidence of MAS was 2.0 per 1000 livebirths. Babies born at post-term gestation (adjusted odds ratio (AOR) = 2.41; 95% confidence interval (CI): 1.05-5.55), nulliparity (AOR = 2.26; 95% CI: 1.20-4.28), instrumental delivery (AOR = 4.79; 95% CI: 2.52-9.10) and caesarean delivery (AOR = 3.67; 95% CI: 2.29-5.89) were significantly associated with MAS. Babies with MAS had a 10-fold risk for pre-discharge mortality (odds ratio = 9.87; 95% CI: 5.81-16.76). Conclusions The findings in this study are consistent with that reported in other studies. MAS has a high risk of neonatal mortality. Thus, monitoring during pregnancy and labour is necessary for early identification of high-risk conditions associated with MAS. Strengthening of newborn care services is essential to curtail mortality.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the Spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures to contain the spread of the disease in many countries has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread and whether they can cause a more severe disease remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (KD) values using surface plasmon resonance (SPR) assays of three fastspreading SARS-CoV-2 variants, Alpha, Beta and Gamma ones, as well as genetic factors in the host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased Spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN and TMPRSS2), may have few contributions to the SARS-CoV-2 variants infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than wild-type.Abstract Figure

Background Timely initiation of breastfeeding can reduce neonatal morbidities and mortality. We aimed to study predictors for timely initiation of breastfeeding (within 1 h of birth) among neonates born in hospitals of Nepal. Method A prospective observational study was conducted in four public hospitals between July and October 2018. All women admitted in the hospital for childbirth and who consented were included in the study. An independent researchers observed whether the neonates were placed in skin-to-skin contact, delay cord clamping and timely initiation of breastfeeding. Sociodemographic variables, obstetric and neonate information were extracted from the maternity register. We analysed predictors for timely initiation of breastfeeding with Pearson chi-square test and multivariate logistic regression. Results Among the 6488 woman-infant pair observed, breastfeeding was timely initiated in 49.5% neonates. The timely initiation of breastfeeding was found to be higher among neonates who were placed skin-to-skin contact (34.9% vs 19.9%, p - value p - value Conclusions The rate of timely initiation of breastfeeding practice is low in the health facilities of Nepal. Multiparity, no obstetric complication at admission, neonates placed in skin-to-skin contact and delay cord clamping were strong predictors for timely initiation of breastfeeding. Quality improvement intervention can improve skin-to-skin contact, delayed cord clamping and timely initiation of breastfeeding.

Background Perinatal events which result in compromised oxygen delivery to the fetus can lead to Birth Asphyxia (BA). While the incidence, risk factors and outcomes of BA have been characterized, less is known in low resource settings. Aim To determine the incidence of Birth Asphyxia (BA) in Nepal and to evaluate associated risk factors and outcomes of this condition. Methods A nested observational study was conducted in 12 hospitals of Nepal for a period of 14 months. Babies diagnosed as BA at ≥37 weeks of gestation were identified and demographics were reviewed. Data were analyzed using binary logistic regression followed by multiple logistic regression analysis. Results The incidence of BA in this study was 6 per 1000 term livebirths and was higher among women 35 years and above. Predictors for BA were instrumented vaginal delivery (aOR:4.4, 95% CI, 3.1–6.1), fetal distress in labour (aOR:1.9, 95% CI, 1.0–3.6), malposition (aOR:1.8, 95% CI, 1.0–3.0), birth weight less than 2500 g (aOR:2.0, 95% CI, 1.3–2.9), gestational age ≥ 42 weeks (aOR:2.0, 95% CI, 1.3–3.3) and male gender (aOR:1.6, 95% CI, 1.2–2.0). The risk of pre-discharge mortality was 43 times higher in babies with BA (aOR:42.6, 95% CI, 32.2–56.3). Conclusion The incidence of Birth asphyxia in Nepal higher than in more resourced setting. A range of obstetric and neonatal risk factors are associated with BA with an associated high risk of pre-discharge mortality. Interventions to improve management and decrease rates of BA could have marked impact on outcomes in low resource settings.

Background-Every year an estimated 7.9 million babies are born with birth defects. Of these, more than 3 million die and a further 3.2 million suffer from a disability. In order to address this, countries require data to enable better resource allocation for prevention, management and rehabilitation of babies born with birth defects. This paper contributes to this evidence base, assessing the prevalence of birth defects, associated risk factors and health consequences in Nepal. Method-This is a prospective observational study conducted in 12 hospitals in Nepal for 18 months. All the women who delivered in the hospitals during the study period were enrolled. Independent researchers collected social and demographic data using semi-structured questionnaires at the time of discharge. Clinical events and birth outcome information were extracted from clinical case notes. Data were analysed to determine the prevalence and type of birth defect. Logistic regression was performed to assess risk factors and health outcomes of babies born with a birth defect. Results-Among the total 87,242 livebirths, the prevalence of birth defects was found to be 5.8 per 1000 live births. The most common birth defects observed were anencephaly (3.95%), cleft lip (2.77%), cleft lip and palate (6.13%), clubfeet (3.95%), eye abnormalities (3.95%) and meningomyelocele (3.36%). The odds of having a baby with a birth defect was higher for mothers younger than 20 years (adjusted Odds ratio (aOR) 1.64; 95% CI, 1.18-2.28) and those from disadvantaged ethnicity (aOR 1.78; 95% CI, 1.46-2.18). The odds of birth asphyxia was almost double for babies with birth defect (aOR 1.88; 95% CI, 1.41-2.51) when compared to babies without a birth defect. The odds of neonatal infection was nearly double for babies with birth defect (aOR 1.82; 95% CI, 1.12-2.96) compared to babies without a defect. Babies with a birth defect had three-fold risk of pre-discharge mortality (aOR 3.00; 95% CI, 1.93-4.69). Conclusion- Babies with birth defect have a higher risk of birth asphyxia, neonatal infection and pre-discharge mortality at birth. A portion of birth defect could have been prevented through micro-nutrient supplementation, a portion can be managed through surgery and rehabilitation. Funding-Swedish Research Council (VR)

Background: Preterm birth is a worldwide epidemic and a leading cause of neonatal mortality. In this study, we aimed to evaluate the incidence, risk factors and consequences of preterm birth in Nepal.Methods: This was an observational study conducted in 12 public hospitals of Nepal. All the babies born during the study period were included in the study. Babies born Results: The incidence of preterm was found to be 93 per 1000 live births. Mothers aged less than 20 years (aOR 1.26 ;1.15-1.39) had a high risk for preterm birth. Similarly, education of the mother was a significant predictor for preterm birth: illiterate mothers (aOR 1.41; 1.22-1.64), literate mothers (aOR 1.21; 1.08-1.35) and mothers having basic level of education (aOR 1.17; 1.07-1.27). Socio-demographic factors such as smoking (aOR 1.13; 1.01-1.26), use of polluted fuel (aOR 1.26; 1.17-1.35) and sex of baby (aOR 1.18; 1.11-1.26); obstetric factors such as nulliparity (aOR 1.33; 1.20-1.48), multiple delivery (aOR 6.63; 5.16-8.52), severe anemia during pregnancy (aOR 3.27; 2.21-4.84), antenatal visit during second trimester (aOR 1.13; 1.05-1.22) and third trimester (aOR 1.24; 1.12-1.38), Conclusion: In this study, we found high incidence of preterm birth. Various socio-demographic, obstetric and neonatal risk factors were associated with preterm birth. Risk factor modifications and timely interventions will help in the reduction of preterm births and associated mortalities. Trial registration: ISRCTN30829654

Background Every year, neonatal infections account for approximately 750,000 neonatal deaths globally. It is the third major cause of neonatal death, globally and in Nepal. There is a paucity of data on clinical aetiology and outcomes of neonatal infection in Nepal. This paper aims to assess the incidence and risk factors of neonatal infection in babies born in public hospitals of Nepal. Methods This is a prospective cohort study conducted for a period of 14 months, nested within a large-scale cluster randomized control trial which evaluated the Helping Babies Breathe Quality Improvement package in 12 public hospitals in Nepal. All the mothers who consented to participate within the study and delivered in these hospitals were included in the analysis. All neonates admitted into the sick newborn care unit weighing > 1500 g or/and 32 weeks or more gestation with clinical signs of infection or positive septic screening were taken as cases and those that did not have an infection were the comparison group. Bivariate and multi-variate analysis of socio-demographic, maternal, obstetric and neonatal characteristics of case and comparison group were conducted to assess risk factors associated with neonatal infection. Results The overall incidence of neonatal infection was 7.3 per 1000 live births. Babies who were born to first time mothers were at 64% higher risk of having infection (aOR-1.64, 95% CI, 1.30–2.06, p-valuep-valuep-value Conclusion Antepartum factors, such as antenatal care attendance, and intrapartum factors such as mode of delivery and birth asphyxia, were risk factors for neonatal infections. These findings highlight the importance of ANC visits and the need for proper care during resuscitation in babies with birth asphyxia.

Aim To test and refine a performance‐based management system to improve health worker performance in Nepal. Methods A mixed‐methods implementation research in three districts. The study assessed health workers’ job satisfaction at the start and end of the study. Qualitative techniques were used to document processes, and routine health service data were analysed to measure outcomes. Results Job satisfaction significantly increased in six of nine key areas, and the proportion of staff absenteeism significantly declined in the study districts. It demonstrated an increase in immunisation coverage, the proportion of women who had a first antenatal check‐up also having a fourth check‐up and the proportion of childbirth in a health facility. The greatest perceived strengths of the system were its robust approach to performance planning and evaluation, supportive supervision, outcome‐based job descriptions and a transparent reward system. A functional health facility environment, leadership and community engagement support successful implementation. Conclusion The performance‐based management system has the potential to increase health workers’ job satisfaction, and it offers a tool to link facility‐wide human resource management. A collaborative approach, ownership and commitment of the health system are critical to success. Considering the Nepal context, a management system that demonstrates a positive improvement has potential for improved health care delivery.

Background: Preterm birth is a worldwide epidemic and a leading cause of neonatal mortality. In this study, we aimed to evaluate the incidence, risk factors and consequences of preterm birth in Nepal. Methods: This was an observational study conducted in 12 public hospitals of Nepal. All the babies born during the study period were included in the study. Babies born

Additional file 2. STROBE flow figure.

Introduction The third Sustainable Development Goal, focused on health, includes two targets related to the reduction in maternal, newborn and under-five childhood mortality. We found it imperative to examine the equity and coverage of reproductive, maternal, newborn and child health (RMNCH) interventions from 2001 to 2016 in Nepal; and the death aversion that will take place during the SDG period. Methods We used the datasets from the Nepal Demographic Health Surveys (NDHS) 2001, 2006, 2011 and 2016. We calculated the coverage and equity for RMNCH interventions and the composite coverage index (CCI). Based on the Annualized Rate of Change (ARC) in the coverage for selected RMNCH indicators, we projected the trend for the RMNCH interventions by 2030. We used the Lives Saved Tools (LiST) tool to estimate the maternal, newborn, under-five childhood deaths and stillbirths averted. We categorised the interventions into four different patterns based on coverage and inequity gap. Results Between 2001 and 2016, a significant improvement is seen in the overall RMNCH intervention coverage-CCI increasing from 46 to 75%. The ARC was highest for skilled attendance at birth (11.7%) followed by care seeking for pneumonia (8.2%) between the same period. In 2016, the highest inequity existed for utilization of the skilled birth attendance services (51%), followed by antenatal care (18%). The inequity gap for basic immunization services reduced significantly from 27.4% in 2001 to 5% in 2016. If the current ARC continues, then an additional 3783 maternal deaths, 36,443 neonatal deaths, 66,883 under-five childhood deaths and 24,024 stillbirths is expected to be averted by the year 2030. Conclusion Nepal has experienced an improvement in the coverage and equity in RMNCH interventions. Reducing inequities will improve coverage for skilled birth attendants and antenatal care. The current annual rate of change in RMNCH coverage will further reduce the maternal, neonatal, under-five childhood deaths and stillbirths.

Additional file 1.

Background Neonatal sepsis is one of the major causes of death during the first month of life and early empirical treatment with injectable antibiotics is a life-saving intervention. Adherence to World Health Organisation guidelines on first line antibiotics is crucial to mitigate the risks of increased antimicrobial resistance. The aim of this paper was to evaluate if treatment of early onset neonatal sepsis in a low-income facility setting observe current guidelines and if compliance is influenced by contextual factors. Methods This cohort study used data on antimicrobial treatment of neonatal sepsis onset within 72 h of life from 12 regional hospitals participating in a scale-up trial of a neonatal resuscitation quality improvement package intervention in Nepal. Infants treated according to guidelines were compared with those receiving other antimicrobials. A multiple logistic regression analysis adjusted for the intervention and time trend was applied. Results 1564 infants with a preliminary diagnosis of early onset sepsis were included. A majority (74.9%) were treated according to guidelines and adherence was increasing over time. Infants born at larger facilities (adjusted Odds Ratio 5.6), those that were inborn (adjusted Odds Ratio 1.97) or belonging to a family of dis-advantaged caste (adjusted Odds Ratio 2.15) had higher odds for treatment according to guidelines. A clinical presentation of lethargy or tachypnoea was associated with adherence to guidelines. Conclusion Adherence to guidelines for antibiotic treatment of early neonatal sepsis was moderately high in this low-income setting. Odds for observing guidelines increased with facility size, for inborn infants and if the family belonged to a dis-advantaged caste. Cefotaxime was a common alternative choice when guidelines were not followed, highly relevant for the risk of increased antimicrobial resistance. Trial registration ISRCTN, ISRCTN30829654, registered 17th of May, 2017.

Additional file 1. Estimated deliveries at the selected hospital 2015.

Additional file 3. Indepth interview questionnaires.

Additional file 1. SPIRINT checklist filled.

Background Simulation-based training in neonatal resuscitation is more effective when reinforced by both practice and continuous improvement processes. We aim to evaluate the effectiveness of a quality improvement program combined with an innovative provider feedback device on neonatal resuscitation practice and outcomes in a public referral hospital of Nepal. Methods A pre- and post-intervention study will be implemented in Pokhara Academy of Health Sciences, a hospital with 8610 deliveries per year. The intervention package will include simulation-based training (Helping Babies Breathe) enhanced with a real-time feedback system (the NeoBeat newborn heart rate meter with the NeoNatalie Live manikin and upright newborn bag-mask with PEEP) accompanied by a quality improvement process. An independent research team will collect perinatal data and conduct stakeholder interviews. Discussion This study will provide further information on the efficiency of neonatal resuscitation training and implementation in the context of new technologies and quality improvement processes. Trial registration 10.1186/ISRCTN18148368, date of registration-31 July 2018

Additional file 2.

Objective To identify the prevalence, risk factors and health impacts associated with small for gestational age (SGA) births in Nepal. Methods A cross-sectional study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. A total of 60 695 babies delivered in these hospitals during the study period were eligible for inclusion. Clinical information of mothers and newborns was collected by data collectors using a data retrieval form. A semistructured interview was conducted at the time of discharge to gather sociodemographic information from women who provided the consent (n=50 392). Babies weighing less than the 10th percentile for their gestational age were classified as SGA. Demographic, obstetric and neonatal characteristics of study participants were analysed for associations with SGA. The association between SGA and likelihood of babies requiring resuscitation or resulting in stillbirth and neonatal death was also explored. Results The prevalence of SGA births across the 12 hospitals observed in Nepal was 11.9%. After multiple variable adjustment, several factors were found to be associated with SGA births, including whether mothers were illiterate compared with those completing secondary and higher education (adjusted OR (AOR)=1.73; 95% CI 1.09 to 2.76), use of polluted fuel compared with use of clean fuel for cooking (AOR=1.51; 95% CI 1.16 to 1.97), first antenatal care (ANC) visit occurring during the third trimester compared with first trimester (AOR=1.82; 95% CI 1.27 to 2.61) and multiple deliveries compared with single delivery (AOR=3.07; 95% CI 1.46 to 6.46). SGA was significantly associated with stillbirth (AOR=7.30; 95% CI 6.26 to 8.52) and neonatal mortality (AOR=5.34; 95% CI 4.65 to 6.12). Conclusions Low literacy status of mothers, use of polluted fuel for cooking, time of first ANC visit and multiple deliveries are associated with SGA births. Interventions encouraging pregnant women to attend ANC visits early can reduce the burden of SGA births.

Background Each year, 2.2 million intrapartum-related deaths (intrapartum stillbirths and first day neonatal deaths) occur worldwide with 99% of them taking place in low- and middle-income countries. Despite the accelerated increase in the proportion of deliveries taking place in health facilities in these settings, the stillborn and neonatal mortality rates have not reduced proportionately. Poor quality of care in health facilities is attributed to two-thirds of these deaths. Improving quality of care during the intrapartum period needs investments in evidence-based interventions. We aim to evaluate the quality improvement package—Scaling Up Safer Bundle Through Quality Improvement in Nepal (SUSTAIN)—on intrapartum care and intrapartum-related mortality in public hospitals of Nepal. Methods We will conduct a stepped wedge cluster randomized controlled trial in eight public hospitals with each having least 3000 deliveries a year. Each hospital will represent a cluster with an intervention transition period of 2 months in each. With a level of significance of 95%, the statistical power of 90% and an intra-cluster correlation of 0.00015, a study period of 19 months should detect at least a 15% change in intrapartum-related mortality. Quality improvement training, mentoring, systematic feedback, and a continuous improvement cycle will be instituted based on bottleneck analyses in each hospital. All concerned health workers will be trained on standard basic neonatal resuscitation and essential newborn care. Portable fetal heart monitors (Moyo®) and neonatal heart rate monitors (Neobeat®) will be introduced in the hospitals to identify fetal distress during labor and to improve neonatal resuscitation. Independent research teams will collect data in each hospital on intervention inputs, processes, and outcomes by reviewing records and carrying out observations and interviews. The dose-response effect will be evaluated through process evaluations. Discussion With the global momentum to improve quality of intrapartum care, better understanding of QI package within a health facility context is important. The proposed package is based on experiences from a similar previous scale-up trial carried out in Nepal. The proposed evaluation will provide evidence on QI package and technology for implementation and scale up in similar settings. Trial registration number ISRCTN16741720. Registered on 2 March 2019.

Degradation of glyphosate in the presence of manganese oxide and UV light was analyzed using phosphate oxygen isotope ratios and density function theory (DFT). The preference of C–P or C–N bond cleavage was found to vary with changing glyphosate/manganese oxide ratios, indicating the potential role of sorption-induced conformational changes on the composition of intermediate degradation products. Isotope data confirmed that one oxygen atom derived solely from water was incorporated into the released phosphate during glyphosate degradation, and this might suggest similar nucleophilic substitution at P centers and C–P bond cleavage both in manganese oxide- and UV light-mediated degradation. The DFT results reveal that the C–P bond could be cleaved by water, OH– or •OH, with the energy barrier opposing bond dissociation being lowest in the presence of the radical species, and that C–N bond cleavage is favored by the formation of both nitrogen- and carbon-centered radicals. Overall, these results highlight th...

Significance Ubiquitination is an important posttranslational modification that regulates almost every aspect of cellular functions. Ubiquitin can form chains of different topology; each has a distinctive role in dictating the function and fate of the modified proteins. Deubiquitinases (DUBs) reverse ubiquitination. How DUBs recognize ubiquitin chains is a topic of immense interest due to the therapeutic potentials of human DUBs. We obtained the atomic details of the USP9X catalytic core, a DUB involved in cancers and developmental disorders, and revealed its unusual mechanisms of action using a set of activity-based ubiquitin probes. These probes will propel future investigation of how DUBs recognize and process ubiquitin chains and identify potential new sites on DUBs for drug discovery., USP9X is a conserved deubiquitinase (DUB) that regulates multiple cellular processes. Dysregulation of USP9X has been linked to cancers and X-linked intellectual disability. Here, we report the crystal structure of the USP9X catalytic domain at 2.5-Å resolution. The structure reveals a canonical USP-fold comprised of fingers, palm, and thumb subdomains, as well as an unusual β-hairpin insertion. The catalytic triad of USP9X is aligned in an active configuration. USP9X is exclusively active against ubiquitin (Ub) but not Ub-like modifiers. Cleavage assays with di-, tri-, and tetraUb chains show that the USP9X catalytic domain has a clear preference for K11-, followed by K63-, K48-, and K6-linked polyUb chains. Using a set of activity-based diUb and triUb probes (ABPs), we demonstrate that the USP9X catalytic domain has an exo-cleavage preference for K48- and endo-cleavage preference for K11-linked polyUb chains. The structure model and biochemical data suggest that the USP9X catalytic domain harbors three Ub binding sites, and a zinc finger in the fingers subdomain and the β-hairpin insertion both play important roles in polyUb chain processing and linkage specificity. Furthermore, unexpected labeling of a secondary, noncatalytic cysteine located on a blocking loop adjacent to the catalytic site by K11-diUb ABP implicates a previously unreported mechanism of polyUb chain recognition. The structural features of USP9X revealed in our study are critical for understanding its DUB activity. The new Ub-based ABPs form a set of valuable tools to understand polyUb chain processing by the cysteine protease class of DUBs.

DOI: https://doi.org/10.3126/jnhrc.v16i3.21435 Background: Nepal has made a significant progress in reducing child mortality. However, the annual rate of reduction in neonatal mortality is not satisfactory. As safeguarded by constitution of Nepal and to address neonatal mortality due to poverty and inequity, government has introduced free newborn care (FNC) package. This study aims to assess the status of FNC services in all the public hospitals. Methods: Child Health Division organized 5 workshops region-wise with the theme of newborn care services in March/April 2018 to cover all the public hospitals in the country. A template was designed comprising of duration of FNC implementation, number of newborns admitted since implementation, morbidities pattern, and number of babies served. It was circulated and all hospitals were advised to fill it and present in the review. Later, the data were compiled and analyzed. Results: Only 58 presentations out of 93 participated hospitals were included in this study. The total admitted cases were 8564 newborns. The common causes of admission were neonatal sepsis (44.5%) followed by asphyxia (14.29%) and hyperbilirubinemia (11.4%). A total of 1573 neonates received services of FNC package C, 3722 package B, 3081 received package A. The main challenges faced in implementation reported were lack of infrastructure and human resources to provide services and the reimbursement is not enough. Conclusions: Free newborn care is a new initiative taken to reduce neonatal mortality. This package is very helpful to serve sick newborns. However, the package should be revised taking into consideration the appropriate reimbursement and extra staffs to provide this service. Keywords: Free newborn care, government efforts, health services

Phytate, the salt of myo-inositol hexakisphosphate, and its partially dephosphorylated products are commonly present in the environment, but their origins and bioavailability are not well understood. This research applied phosphate O isotope ratios (δ¹⁸OP) in combination with nuclear magnetic resonance (NMR) and high-performance liquid chromatography (HPLC) methods to characterize the kinetics and pathways of phytate degradation by wheat phytase and the O isotopic composition during progressive degradation of phytate. Our results show that phytate degradation undertakes two pathways: d-inositol-1,2,3,5,6-pentakisphosphate, d-inositol-1,2,5,6-tetrakisphosphate, d-inositol-1,2,6-trisphosphate, d-inositol-1,2-bisphosphate, d-inositol-1-phosphate; and d-inositol-1,2,4,5,6-pentakisphosphate, d-inositol-1,2,5,6-tetrakisphosphate, d-inositol-1,5,6-trisphosphate. The first pathway is similar to that previously known, while the other one is a new pathway. Isotope results show that the cleavage of the P–O bond during phytate degradation is accompanied by the introduction of one O atom solely from water to the released inorganic orthophosphate. Interestingly, isotopic compositions of all phosphate moieties in K phytate used in this study were found to be the same. This means that the original source of phytate can be tracked from its partially dephosphorylated products. Overall, these results provide improved insights into the mechanisms and pathways of phytate degradation and highlight the importance of an isotopic tool that can potentially be used for tracking phytate source and its degradation products in the environment.

The essential oil from the parasitic vine Cuscuta reflexa Roxb., collected from Kirtipur, Kathmandu, Nepal, was obtained by hydrodistillation and analysed by gas chromatography-mass spectrometry. From a total of 62 peaks, 61 compounds were identified in the oil, accounting for 99.6% of the oil. The majority of the essential oil was dominated by the relatively rare component cis-3-butyl-4-vinylcyclopentane (26.4%). The oil also contained substantial amounts of limonene (5.1%) and (E)-nerolidol (9.5%). Biological screening for antimicrobial activities did not show appreciable activity against either Gram-positive (Bacillus cereus and Staphylococcus aureus) or Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. However, marginal activity against Aspergillus niger was observed (minimum inhibitory concentration = 313 μg/mL).

The leaf essential oil of Momordica charantia was obtained by hydrodistillation and analyzed by gas chromatography- mass spectrometry. The leaf oil was rich in geijerene (11.2 %), pregeijerene (27.1 %), α-pinene (14.0 %), β-pinene (7.1 %), (E)-caryophyllene (4.6 %), and germacrene D (8.6 %); remarkably different from previous reports of this plant.

The essential oil from the leaf of Kyllinga brevifolia Rottb., collected from Biratnagar, Nepal, was obtained by hydrodistillation and analyzed by GC-MS. A total of 22 compounds were identified in the oil accounting for 96.1 % of the oil composition. The majority of the essential oil was identified to be occadinol (40.3 %),’L-τ-muurolol (19.5 %), and germacrene D-4-ol (12.5 %). The oil also contained smaller amounts of δ-cadinene (2.9 %), and germacrene D (4.0 %). Reports on the essential oil composition of K. brevifolia from Nepal were compared with a sample from Brazil, which showed that 13-epi-manoyl oxide (26.1 %) and manoyl oxide derivatives constituted the majority of composition with a-cadinol comprising only 0.4 %. However germacrene D was found in similar percentages between Nepal and Brazil samples (4.0 %and 4.2 %, respectively).