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Flooding and drought are serious constraints that reduce crop productivity worldwide. Previous studies identified genes conferring tolerance to both water extremes in various plants. However, overlapping responses to flooding and drought at the genome-scale remain obscure. Here, we defined overlapping and stress-specific transcriptomic and hormonal responses to submergence, drought and recovery from these stresses in soybean (Glycine max). We performed comparative RNA-sequencing and hormone profiling, identifying genes, hormones and biological processes that are differentially regulated in an overlapping or stress-specific manner. Overlapping responses included positive regulation of trehalose and sucrose metabolism and negative regulation of cellulose, tubulin, photosystem II and I, and chlorophyll biosynthesis, facilitating the economization of energy reserves under both submergence and drought. Additional energy-consuming pathways were restricted in a stress-specific manner. Downregulation of distinct pathways for energy saving under each stress suggests energy-consuming processes that are relatively unnecessary for each stress adaptation are turned down. Our newly developed transcriptomic-response analysis revealed that abscisic acid and ethylene responses were activated in common under both stresses, whereas stimulated auxin response was submergence-specific. The energy-saving strategy is the key overlapping mechanism that underpins adaptation to both submergence and drought in soybean. Abscisic acid and ethylene are candidate hormones that coordinate transcriptomic energy-saving processes under both stresses. Auxin may be a signaling component that distinguishes submergence-specific regulation of the stress response.

Objectives Deficiency as well as excess dietary iodine is associated with several thyroid disorders including Grave’s disease and goitre. Previously, cross sectional studies conducted among school children in Nepal showed high prevalence of iodine deficiency. In contrast, recently, few studies have revealed emerging trends of excess urinary iodine concentration in children. This paper, reports excess urinary iodine excretion and thyroid dysfunction among school age children from eastern Nepal. Results It was a community based cross sectional study in which we measured urinary iodine excretion levels among school age children at baseline and after educational program. The educational program consisted of audio-visual and pamphlets on thyroid health. We also screened them for thyroid function status by physical examination and measuring serum thyroid hormones. Our results show that 34.4% of the children had excess urinary iodine concentration above the WHO recommended levels. Overall, 3.2% of the children were identified to have thyroid dysfunction. Urinary iodine concentration was significantly different between types of salt used and between salt iodine content categories.

Background The third Sustainable Development Goal for 2030 development agenda aims to reduce maternal and newborn deaths. Pregnant women’s understanding of danger signs is an important factor in seeking timely care during emergencies. We assessed knowledge of obstetric danger signs using both recall and understanding of appropriate action required during obstetric emergencies. Methods This was a cross-sectional study among pregnant women attending antenatal clinic at Bhutan’s largest hospital in Thimphu. Recall was assessed against seven obstetric danger signs outlined in the Mother and Child Health Handbook (7 points). Understanding of danger signs was tested using 13 multiple choice questions (13 points). Knowledge was scored out of 20 points and reported as ‘good’ (≥80%), ‘satisfactory’ (60–79%) and ‘poor’ (p Results Four hundred and twenty-two women responded to the survey (response rate = 96.0%). Mean (±SD) knowledge score was 12 (±2.5). Twenty women (4.7%) had ‘good’ knowledge, 245 (58.1%) had ‘satisfactory’ knowledge and 157 (37.2%) had ‘poor’ knowledge. The median number of danger signs recalled was 2 (IQR 1, 3) while 68 women (20.3%) could not recall any danger signs. Most women were knowledgeable about pre-labour rupture of membranes (96.0%) while very few women were knowledgeable about spotting during pregnancy (19.9%). Both knowledge score and number of danger signs recalled had significant correlation with the period of gestation. Women with previous surgery on the reproductive tract had higher odds of having ‘good’ level of knowledge. Conclusions Most pregnant women had ‘satisfactory’ knowledge score with poor explicit recall of danger signs. However, women recognized obstetric emergencies and identified the appropriate action warranted.

The Mygalomorphae includes tarantulas, trapdoor, funnel-web, purse-web and sheet-web spiders, species known for poor dispersal abilities. Here, we attempted to compile all the information available on their long-distance dispersal mechanisms from observations that are often spread throughout the taxonomic literature. Mygalomorphs can disperse terrestrially, and in some tarantulas, for example, spiderlings walk together in single files away from their maternal burrow, a mechanism limited in distance covered. Conversely, at least eight species disperse aerially, via dropping on drag lines from elevated positions and being passively blown off (‘suspended ballooning’). The first record of this behaviour is 135 years old, but we still know very little about it. Phylogeographic studies suggest several occurrences of transcontinental dispersal in the evolutionary history of mygalomorphs, but these might result from contingent rafting events, rather than regular dispersal mechanisms. We use occurrence data to show that suspended ballooning increases the species ranges in Australian mygalomorph families where this behaviour has been recorded. We also identified Anamidae, Idiopidae, and especially Atracidae, as families that might employ suspended ballooning or another efficient but undiscovered dispersal mechanism. Finally, we suggest that molecular studies with mitochondrial genes will help disentangle behavioural limitations of dispersal from ecological or physical ones.

Chronic otitis media with anterior perforation is a challenging condition to treat with a microscope especially if the canal is narrow or has overhang. The endoscope provides the advantage of wide-angle view and transcanal access avoiding postauricular approach and canaloplasty.To compare the anatomical, functional outcomes, and surgical duration between endoscopic and microscopic type-I tympanoplasty performed for anterior perforation.A comparative study was conducted. The two groups, the microscopic (MT) and the endoscopic (ET) were created with 50 cases each and underwent type-I tympanoplasty. Results were evaluated at a minimum follow-up of 12 months.The graft uptake rate in MT and ET was 81.8% and 91.3% respectively and was not statistically significant. The mean operative time for MT and ET was 68.68 ± 18.79 min and 61.24 ± 11.18 min respectively which was significant (The endoscopic tympanoplasty offered superior visualization avoiding postauricular incision and canaloplasty, with morphological and functional outcomes comparable to microscopic tympanoplasty. It offers significantly faster completion of procedure and provides minimally invasive surgery.

Spot blotch of wheat caused by Bipolaris sorokiniana appears at all growth stages, though susceptibility increases with increase in plant age. Every year disease causes high yield losses even up to 60% depending on the wheat variety and weather factors. The cultivation of wheat in North Eastern Plains Zone (NEPZ) of India is increasing, but the crop yield is low due to warm and humid climate which increase diseases like spot blotch. Considering significant impact of the spot blotch on crop yield, an experiment was conducted during rabi seasons of 2015–2016 and 2016–2017 to evaluate the effect of different abiotic factors on spread of the disease, as well as development of a predictive model to predict the disease severity in a set of 12 wheat varieties. Statistical analysis proved that all the thermic variables like temperature (maximum and minimum) and soil temperature are significantly correlated with diseases initiation across growth stages of the crop. Step-wise regression showed high R2 values like, 0.99, 0.97, 0.96, 0.96, 0.98, 0.96, 0.99, 0.98, 0.96, 0.98, 0.98, 0.98 for the predicative model of spot blotch in PBW 343, HD 2733, PBW154, Raj4015, KALYAN SONA, SONALIKA, LERMA RAJO, DBW39, UP301, HD2009, NP114, NP718 respectively.

Lactobacillus plantarum DMR17 was isolated from homemade cow dahi of Sikkim Himalayan region of India. Here, we report the draft genome sequence of this strain. A total of 21,176,638 paired-end reads were obtained which were assembled into 65 contigs. The reference genome used was L. plantarum WCFS1. The genome size of DMR17 was 3,228,341 bp with G + C content of 46.25%. 3302 coding sequences were predicted including 68 tRNA and 67 rRNA genes. More than 88% of the total pre-processed reads from the sample were mapped to the reference genome. The identified coding proteins were classified into 27 functional categories based on COG classification. The genome was found to possess genes for lactate and mixed acid fermentation. The genome also showed the presence of genes for catabolism of aromatic compounds, phosphorous, and other metabolism. The genome information of L. plantarum DMR17 provides the basis for understanding the functional properties and to consider its use as a potential component of functional foods especially dahi.

In 2011, Bhutan’s Royal Centre for Disease Control began Japanese encephalitis (JE) surveillance at 5 sentinel hospitals throughout Bhutan. During 2011–2018, a total of 20 JE cases were detected, indicating JE virus causes encephalitis in Bhutan. Maintaining JE surveillance will help improve understanding of JE epidemiology in this country.

Introduction The study was conducted to evaluate the efficacy of arthroscopic debridement, microfracture and plasma rich in growth factor (PRGF) injection in the management of type V (Scranton) osteochondral lesions of talus and its role in healing the subchondral cyst and cessation of progression of ankle osteoarthritis. Material and methods This is a prospective case series conducted on patients who were diagnosed with type V osteochondral lesions of talus. All the cases were treated with arthroscopic debridement, microfracture, and PRGF injections. The patients were evaluated for the healing of subchondral cysts and progression of osteoarthritis with radiography (plain radiographs and computerised tomography Scan). Also, the patients' outcome was evaluated with Quadruple Visual Analogue Scale, Ankle Range of Motion, Foot and Ankle Disability Index, Foot and Ankle Outcome Instrument and a Satisfaction Questionnaire. Results Five male patients underwent arthroscopic debridement, microfracture and PRGF injection for type V osteochondral lesion of talus. The mean age of patients was 27.4 years (19-47 years). All the patients gave history of minor twisting injury. Subchondral cyst healing was achieved in all patients by six months post-surgery. However, four out of five patients had developed early osteoarthritic changes of the ankle by their last follow-up [mean follow-up 29 months (ranged 15-36 months)]. Despite arthritic changes, all the patients reported 'Good' to 'Excellent' results on satisfaction questionnaire and Foot and Ankle Disability Index and could perform their day to day activities including sports. Conclusion Arthroscopic debridement, microfracture, and PRGF causes healing of the subchondral cyst but does not cause cessation of progression to osteoarthritis of ankle in type V osteochondral defects of talus. However, despite progress to osteoarthritis, patient satisfaction post-procedure is good to excellent at short-term follow-up.

Despite representing a sizeable fraction of the canopy, very little is known about leaf sheath gas exchange in grasses. Specifically, estimates of sheath stomatal conductance, transpiration and photosynthesis along with their responses to light, CO2 and vapour pressure deficit (VPD) are unknown. Furthermore, the anatomical basis of these responses is poorly documented. Here, using barley as a model system, and combining leaf-level gas exchange, whole-plant gravimetric measurements, transpiration inhibitors, anatomical observations, and biophysical modelling, we found that sheath and blade stomatal conductance and transpiration were similar, especially at low light, in addition to being genotypically variable. Thanks to high abaxial stomata densities and surface areas nearly half those of the blades, sheaths accounted for up to 17% of the daily whole-plant water use, which -surprisingly- increased to 45% during the nighttime. Sheath photosynthesis was on average 17-25% that of the blade and was associated with lower water use efficiency. Finally, sheaths responded differently to the environment, exhibiting a lack of response to CO2 but a strong sensitivity to VPD. Overall, these results suggest a key involvement of sheaths in feedback loops between canopy architecture and gas exchange with potentially significant implications on adaptation to current and future climates in grasses.

Background Anemia is the commonest hematological complications in HIV patients, and has a significant impact on quality of life, morbidity, and mortality. However, little is known about the epidemiology of anemia in this population in a Nepalese setting. Therefore, the present study aimed at assessing the prevalence of anemia in patients living with HIV and further to determine the independent predictors associated with it. Methods This cross-sectional study was conducted in patients diagnosed with HIV at Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu from November 2016 to August 2017. Anemia was considered a core variable, and covariates used for analysis were age, sex, CD4 count, antiretroviral therapy regimen, history of intravenous drug use, marital status, religion, geography, employment status, hypertension, and diabetes mellitus. Prevalence of anemia and its independent predictors were evaluated. Fisher's exact and χ 2 tests were performed to determine the significance of differences among categorical variables and t-tests for continuous variables. Binary logistic regression was modeled to assess predictors associated with anemia. Results Of the total 210 patients analyzed, median age was 37.50±10.57 years, and 110 (52.6%) were male. The estimated prevalence of anemia overall was 66.7% (95% CI 60.64%-73.35%): mild anemia 14.3% (95% CI 8.25%-19.74%), moderate anemia 40.5% (95% CI 31.88%-48.11%), and severe anemia 11.9% (95% CI 6.61%-17.30%). Prevalence of anemia increased significantly with decreasing CD4 count: 5.71%, 12.85%, and 48.09% among patients with CD4 counts >500, 200-499, and 500; P=0.048). Female sex was significantly associated with increased odds of anemia (OR 2.27, P=0.007). Conclusion The present study demonstrated a high rate of anemia in a substantial number of HIV individuals. Therefore, early detection and timely management of anemia, especially in females and those with decreased immunostatus, are crucial to prevent anemia progression and improve quality of life.

Patients with mucopolysaccharidosis type IIIA (MPS IIIA) lack the lysosomal enzyme sulfamidase (SGSH), which is responsible for the degradation of heparan sulfate (HS). Build-up of undegraded HS results in severe progressive neurodegeneration for which there is currently no treatment. The ability of the vector adeno-associated virus (AAV)rh.10-CAG-SGSH (LYS-SAF302) to correct disease pathology was evaluated in a mouse model for MPS IIIA. LYS-SAF302 was administered to 5-week-old MPS IIIA mice at three different doses (8.6E+08, 4.1E+10, and 9.0E+10 vector genomes [vg]/animal) injected into the caudate putamen/striatum and thalamus. LYS-SAF302 was able to dose-dependently correct or significantly reduce HS storage, secondary accumulation of GM2 and GM3 gangliosides, ubiquitin-reactive axonal spheroid lesions, lysosomal expansion, and neuroinflammation at 12 weeks and 25 weeks post-dosing. To study SGSH distribution in the brain of large animals, LYS-SAF302 was injected into the subcortical white matter of dogs (1.0E+12 or 2.0E+12 vg/animal) and cynomolgus monkeys (7.2E+11 vg/animal). Increases of SGSH enzyme activity of at least 20% above endogenous levels were detected in 78% (dogs 4 weeks after injection) and 97% (monkeys 6 weeks after injection) of the total brain volume. Taken together, these data validate intraparenchymal AAV administration as a promising method to achieve widespread enzyme distribution and correction of disease pathology in MPS IIIA.

The COVID-19 pandemic is rapidly growing and has been a major challenge for the health system globally. As of 27 April 2020, 213 country around the world are struggling to combat the spreading the virus with 28,58,635 confirmed cases and 1,96,295 confirmed deaths. The first case in South Korea was identified on 20 Jan 2020 but the number of confirmed cases started to increase rapidly on end of February with total of 7,513 cases reported as of 10 March 2020, second country to have experience outbreak. South Korea’s effort to control the virus combined many approaches, such as organized and no negligence in response, extensive screening, provision of improved information and the use of technology. This experience could provide some valuable lessons for countries on response to control the spread of pandemic disease like COVID-19 or any other outbreak situation in coming days or for those who are yet to face the COVID-19 outbreak so that they can control the disease spread in early phase.

Artificial miRNA technology enables the generation of siRNAs to regulate the expression of targeted genes. However, the application of siRNAs to alter gene expression is challenging due to their instability and requires a means to efficiently deliver siRNAs into the host. Here, we report that the siRNAs targeted to animal mRNAs can be heterologously expressed and stably produced in lettuce. We have modified rice miRNA precursors to produce siRNAs in lettuce with the potential to target mRNAs of mouse complement 3 ( C3) and coagulation factor 7 ( CF7). Expression of primary and mature siRNAs in the transgenic lettuce lines was confirmed via Sanger sequencing. Our study demonstrates an applicable tool to alter gene expression in the targeted host and has potential utility in siRNA-based oral therapeutics.

Continuous monitoring in the intensive care setting has transformed the capacity to rapidly respond with interventions for patients in extremis. Noninvasive monitoring has generally been limited to transdermal or intravascular systems coupled to transducers including oxygen saturation or pressure. Here it is hypothesized that gastric fluid (GF) and gases, accessible through nasogastric (NG) tubes, commonly found in intensive care settings, can provide continuous access to a broad range of biomarkers. A broad characterization of biomarkers in swine GF coupled to time‐matched serum is conducted . The relationship and kinetics of GF‐derived analyte level dynamics is established by correlating these to serum levels in an acute renal failure and an inducible stress model performed in swine. The ability to monitor ketone levels and an inhaled anaesthetic agent (isoflurane) in vivo is demonstrated with novel NG‐compatible sensor systems in swine. Gastric access remains a main stay in the care of the critically ill patient, and here the potential is established to harness this establishes route for analyte evaluation for clinical management., Nasogastric tube placement in intensive care settings is a mainstay in the management of critical conditions. The authors demonstrate that systemic biomarkers are present in gastric fluid and that nasogastric tubes can be leveraged to monitor systemic disturbances through evaluation of these biomarkers. Real‐time biomarker monitoring can help improve responsiveness of clinical teams and improve critical care.

IntroductionunCoVer—Unravelling data for rapid evidence-based response to COVID-19—is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic.Methods and analysisFrom the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients’ baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded.Ethics and disseminationAfter strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer’s activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications.

Objective:To translate and validate the velopharyngeal insufficiency (VPI) effects on life outcomes (VELO) instrument into Nepali, and test its internal consistency and validity.Design:Quality-of-life instrument translation and validation.Setting:Community served by Nepal’s craniofacial referral hospital.Participants:Twenty-three postpalatoplasty children with VPI, 19 family guardians of VPI cases, and 29 non-VPI controls.Interventions:The VELO instrument was translated to Nepali by 2 independent bilingual translators, reconciled, backward-translated, compared, and modified using patient cognitive interviews. All VPI children, guardians, and controls completed the VELO-Nepali.Main Outcome Measure(s):The VELO internal consistency was evaluated using Cronbach α coefficient. Concurrent validity and discriminant validity were assessed using 2-sample t test: assuming unequal variances.Results:The VELO was translated and optimized using cognitive interviews. The VELO-Nepali demonstrated excellent internal consistency, with Cronbach α coefficients of 0.93, 0.94, and 0.90 for VPI cases, guardians of VPI cases, and non-VPI controls, respectively. The VELO-Nepali exhibited strong discriminant validity between VPI cases ([Formula: see text] = 45.4, standard deviation [SD] = 22.1) and non-VPI controls ([Formula: see text] = 84.9, SD = 12.3), ( P < .001). The VELO-Nepali showed strong concurrent validity with similarities in VPI case scores ([Formula: see text] = 45.4, SD = 22.1), and guardian scores ([Formula: see text] = 52.9, s = 22.8; P = .473).Conclusion:The translated VELO-Nepali demonstrates strong internal consistency, discriminant validity, and concurrent validity, and can assess quality of life for Nepali VPI patients. This instrument represents the first VPI quality of life assessment validated in Nepali, and supports the feasibility of its implementation in other low- and low-middle-income countries.

Background In 2017, measles elimination was verified in Bhutan, and the country appears to have sufficiently high vaccination coverage to achieve rubella elimination. However, a measles and rubella serosurvey was conducted to find if any hidden immunity gaps existed that could threaten Bhutan’s elimination status. Methods A nationwide, three-stage, cluster seroprevalence survey was conducted among individuals aged 1–4, 5–17, and >20 years in 2017. Demographic information and children’s vaccination history were collected, and a blood specimen was drawn. Serum was tested for measles and rubella immunoglobulin G (IgG). Frequencies, weighted proportions, and prevalence ratios for measles and rubella seropositivity were calculated by demographic and vaccination history, taking into account the study design. Results Of the 1325 individuals tested, 1045 (81%, 95% CI 78%–85%) were measles IgG seropositive, and 1290 (97%, 95% CI 95%–99%) were rubella IgG seropositive. Rubella IgG seropositivity was high in all three age strata, but only 47% of those aged 5–17 years were measles IgG seropositive. Additionally, only 41% of those aged 5–17 years who had documented receipt of two doses of measles– or measles-rubella–containing vaccine were seropositive for measles IgG, but almost all these children were rubella IgG seropositive. Conclusions An unexpected measles immunity gap was identified among children 5–17 years of age. It is unclear why this immunity gap exists; however, it could have led to a large outbreak and threatened sustaining of measles elimination in Bhutan. Based on this finding, a mass vaccination campaign was conducted to close the immunity gap.

Objectives Most population-based cancer databases lack information on metastatic recurrence. Electronic medical records (EMR) and cancer registries contain complementary information on cancer diagnosis, treatment and outcome, yet are rarely used synergistically. To construct a cohort of metastatic breast cancer (MBC) patients, we applied natural language processing techniques within a semisupervised machine learning framework to linked EMR-California Cancer Registry (CCR) data. Materials and Methods We studied all female patients treated at Stanford Health Care with an incident breast cancer diagnosis from 2000 to 2014. Our database consisted of structured fields and unstructured free-text clinical notes from EMR, linked to CCR, a component of the Surveillance, Epidemiology and End Results Program (SEER). We identified de novo MBC patients from CCR and extracted information on distant recurrences from patient notes in EMR. Furthermore, we trained a regularized logistic regression model for recurrent MBC classification and evaluated its performance on a gold standard set of 146 patients. Results There were 11 459 breast cancer patients in total and the median follow-up time was 96.3 months. We identified 1886 MBC patients, 512 (27.1%) of whom were de novo MBC patients and 1374 (72.9%) were recurrent MBC patients. Our final MBC classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.917, with sensitivity 0.861, specificity 0.878, and accuracy 0.870. Discussion and Conclusion To enable population-based research on MBC, we developed a framework for retrospective case detection combining EMR and CCR data. Our classifier achieved good AUC, sensitivity, and specificity without expert-labeled examples.

Idiopathic dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. The aim of this study was to assess the role of mitochondrial DNA (mtDNA) variations and haplogroups in Indian DCM patients. Whole mtDNA analysis of 221 DCM patients revealed 48 novel, 42 disease-associated and 97 private variations. The frequency of reported variations associated with hearing impairment, DEAF, SNHL and LHON are significantly high in DCM patients than controls. Haplogroups H and HV were over represented in DCM than controls. Functional analysis of two private variations (m.8812A>G & m.10320G>A) showed decrease in mitochondrial functions, suggesting the role of mtDNA variations in DCM.

Introduction Oral steroids currently represent the standard treatment for idiopathic sudden sensorineural hearing loss The aim of this study is to assess the effectiveness of intratympanic dexamethasone injection for treating ‘Idiopathic sudden sensori-neural hearing loss’ (ISSNHL) not improved with conventional oral steroid. Materials and Methods A prospective study was conducted on 30 patients refractory to oral steroid therapy between June 2017 to May 2018. ‘Intratympanic dexamethasone injection’ (ITDI) was given every week for 3 consecutive weeks. Hearing was assessed by performing pure tone audiogram before every ITDI and also 1 week after the completion of treatment. Results Hearing improvement was found in 19 out of the 30 cases (63.3%). Conclusions Intratympanic dexamethasone significantly improves the prognosis of ISSNHL and is a safe, inexpensive and effective treatment.

Background Primary purpose of this study is to compare the clinical outcomes of patients undergoing arthroscopic arthrolysis in posttraumatic and non-traumatic elbow stiffness. Secondary aims are to compare the level of satisfaction and complications. Methods We retrospectively evaluated the patients undergoing arthroscopic elbow arthrolysis between January 2008 and September 2015 and have completed a minimum 2-year follow-up. Total of 141 patients (male = 90; female = 51) with 143 elbows (posttraumatic, n = 75; non-traumatic, n = 68) with an average age of 33 years were available for final evaluation. The average follow-up period was 44 months. We used the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), Visual Analogue Scale (VAS) to measure clinical outcomes. The level of satisfaction was measured by a self-constructed questionnaire. Results All parameters were significantly improved postoperatively (P

Breast cancer (BC) is a common malignant tumour for the adult female and its relative incidence has increased continuously in recent years. The primary molecular mechanisms of breast tumourigenesis remain unclear. With the sequencing technology, we found that coatomer protein complex subunit beta 2 (COPB2) gene is overexpressed in breast cancer tissues. However, the biological function of COPB2 in BC has yet to be determined. This current research demonstrates, significant up‐regulation of COPB2 in tissues of breast cancer while comparing the adjacent normal tissue both invalidated cohort and TCGA cohort. Up‐regulated expression of COPB2 was correlated with lymph node metastasis (LNM) and oestrogen receptor (ER) in the TCGA cohort and a high level of COPB2 was associated with age and lymph node metastasis in the validated cohort. Besides, logistic analysis illustrated in BC patient COPB2 expression, tumour size, age, ER and disease stage were independent high‐risk factors of LNM. Loss of function experiments revealed that down‐regulation of COPB2 could inhibit capacities of proliferation and cell invasion in MDA‐MB‐231 and BT‐549 cell lines. Moreover, underexpression of COPB2 could decrease the EMT‐related protein N‐cadherin and vimentin which may lead to cell invasion. This current research provides new shreds of evidence that COPB2 overexpression shows significant character in the progression of breast cancer. To best of our knowledge, our findings indicated that COPB2 was vital oncogene which was associated with breast cancer.

Nationally representative population data on zinc status in Nepal is lacking at present. This study analyzed data from the recent Nepal National Micronutrient status survey 2016 to determine the prevalence of zinc deficiency and associated risk factors among children aged 6–59 months (n = 1462) and non-pregnant women aged 15–49 years (n = 1923). Venous blood was collected from the participants to measure micronutrients such as zinc, markers of anemia, RBP (vitamin A), and markers of inflammation. Stool samples were collected to assess soil-transmitted helminths and Helicobacter pylori infection. Socio-demographic, household, and other relevant factors were collected by a structured questionnaire. Serum zinc concentration was measured by Microwave Plasma Atomic Emission Spectrometry, and zinc deficiency was defined according to the International Zinc Nutrition Consultative Group’s guidelines. Logistic regression was used to examine the predictors of zinc deficiency among the participants. The overall zinc deficiency in children was 22.9%, while it was higher in non-pregnant women (24.7%). The prevalence of anemia among zinc-deficient children was higher (21.3%) than the zinc non-deficit children (18.7%). The prevalence of anemia was 18% among zinc-deficient non-pregnant women compared to 22% non-deficit non-pregnant women. Predictors associated with zinc deficiency among the study children were living in rural areas (AOR = 2.25, 95% CI, [1.13, 4.49]), the occurrence of diarrhea during the two weeks preceding the survey (AOR = 1.57, 95% CI, [1.07, 2.30]), lowest household wealth quintile (AOR = 0.48, 95% CI, [0.25, 0.92]) and lower vitamin A status (AOR = 0.49, 95% CI, [0.28, 0.85]. The predictors associated with zinc deficiency among non-pregnant women were: being underweight (AOR = 1.55, 95% CI, [1.12, 2.15]), fever occurrence during two weeks preceding the survey (AOR = 1.43, 95% CI, [1.04, 1.98]), H. pylori in the stool (AOR = 1.33, 95% CI, [1.04, 1.71]), lowest household wealth quintile (AOR = 0.62, 95% CI,[0.40, 0.94]) and being at risk of folate deficiency (AOR = 0.58, 95% CI,[0.36, 0.94]). We conclude that community-level intervention programs focused on rural children and women to prevent diarrhea, improve nutrition counseling, and provide economic opportunities in rural communities may help to lower zinc deficiency and other micronutrient deficiencies in the Nepalese population. We believe that intervention programs to address zinc deficiency should not be isolated. Instead, integrated approaches are beneficial to improve overall micronutrient status, such as encouraging dietary diversity, providing livelihood opportunities to the unemployed, micronutrient supplementation to vulnerable populations, and consumption of zinc-rich animal-based foods.

Astragalus root (Huang Qi) and Shiitake mushrooms (Lentinus edodes) are both considered medicinal foods and are frequently used in traditional Chinese medicine due to their anticancer and immunomodulating properties. Here, the scientific literatures describing evidence for the anticancer and immunogenic properties of Shiitake and Astragalus were reviewed. Based on our experimental data, the potential to develop medicinal food with combined bioactivities was assessed using Shiitake mushrooms grown over Astragalus beds in a proprietary manufacturing process, as a novel cancer prevention approach. Notably, our data suggest that this new manufacturing process can result in transfer and increased bioavailability of Astragalus polysaccharides with therapeutic potential into edible Shiitake. Further research efforts are required to validate the therapeutic potential of this new Hengshan Astragalus Shiitake medicinal food.

Since the beginning of the COVID-19 pandemic, pharmaceutical treatment hypotheses have abounded, each requiring careful evaluation. A randomized controlled trial generally provides the most credible evaluation of a treatment, but the efficiency and effectiveness of the trial depend on the existing evidence supporting the treatment. The researcher must therefore compile a body of evidence justifying the use of time and resources to further investigate a treatment hypothesis in a trial. An observational study can provide this evidence, but the lack of randomized exposure and the researcher’s inability to control treatment administration and data collection introduce significant challenges. A proper analysis of observational health care data thus requires contributions from experts in a diverse set of topics ranging from epidemiology and causal analysis to relevant medical specialties and data sources. Here we summarize these contributions as 10 rules that serve as an end-to-end introduction to retrospective pharmacoepidemiological analyses of observational health care data using a running example of a hypothetical COVID-19 study. A detailed supplement presents a practical how-to guide for following each rule. When carefully designed and properly executed, a retrospective pharmacoepidemiological analysis framed around these rules will inform the decisions of whether and how to investigate a treatment hypothesis in a randomized controlled trial. This work has important implications for any future pandemic by prescribing what we can and should do while the world waits for global vaccine distribution.

Background The maize inbred line A188 is an attractive model for elucidation of gene function and improvement due to its high embryogenic capacity and many contrasting traits to the first maize reference genome, B73, and other elite lines. The lack of a genome assembly of A188 limits its use as a model for functional studies. Results Here, we present a chromosome-level genome assembly of A188 using long reads and optical maps. Comparison of A188 with B73 using both whole-genome alignments and read depths from sequencing reads identify approximately 1.1 Gb of syntenic sequences as well as extensive structural variation, including a 1.8-Mb duplication containing the Gametophyte factor1 locus for unilateral cross-incompatibility, and six inversions of 0.7 Mb or greater. Increased copy number of carotenoid cleavage dioxygenase 1 (ccd1) in A188 is associated with elevated expression during seed development. High ccd1 expression in seeds together with low expression of yellow endosperm 1 (y1) reduces carotenoid accumulation, accounting for the white seed phenotype of A188. Furthermore, transcriptome and epigenome analyses reveal enhanced expression of defense pathways and altered DNA methylation patterns of the embryonic callus. Conclusions The A188 genome assembly provides a high-resolution sequence for a complex genome species and a foundational resource for analyses of genome variation and gene function in maize. The genome, in comparison to B73, contains extensive intra-species structural variations and other genetic differences. Expression and network analyses identify discrete profiles for embryonic callus and other tissues.

Background The high burden of chronic conditions, coupled with various physical, mental, and psychosocial changes that accompany the phenomenon of aging, may limit the functional ability of older adults. This study aims to assess the prevalence of poor functional status and investigate factors associated with poor functional status among community-dwelling older adults in rural communities of eastern Nepal. Methods Data on 794 older adults aged ≥ 60 years from a previous community-based cross-sectional study was used. Participants were recruited from rural municipalities of Morang and Sunsari districts of eastern Nepal using multi-stage cluster sampling. Functional status was assessed in terms of participants’ ability to perform activities of daily living using the Barthel Index. Covariates included sociodemographic characteristics, lifestyle factors, and self-reported chronic conditions. A binary logistic regression model was used to investigate factors associated with poor functional status. Results The overall prevalence of poor functional status was 8.3 % (male: 7.0 % and female: 9.6 %), with most dependence noted for using stairs (17.3 %), followed by dressing (21.9 %) on Barthel Index. In the adjusted model, oldest age group (odds ratio [OR] = 2.83, 95 %CI: 1.46, 5.50), those unemployed (OR = 2.41, 95 %CI: 1.26, 4.65), having memory/concentration problems (OR = 2.32, 95 %CI: 1.30, 4.13), depressive symptoms (OR = 2.52, 95 %CI: 1.28, 4.95), and hypertension (OR = 1.78, 95 %CI: 1.03, 3.06) had almost or more than two times poor functioning. Conclusions One in 12 older adults had poor functional status as indicated by their dependency on the items of the Barthel Index; those in the oldest age bracket were more likely to exhibit poor functional status. We suggest future studies from other geographies of the country to supplement our study from the rural setting for comprehensive identification of the problem, which could guide the development of prevention strategies and comprehensive interventions for addressing the unmet needs of the older adults for improving functional status.

Drought stress is a major constraint in global maize production, causing almost 30–90% of the yield loss depending upon growth stage and the degree and duration of the stress. Here, we report that ectopic expression of Arabidopsis glutaredoxin S17 (AtGRXS17) in field grown maize conferred tolerance to drought stress during the reproductive stage, which is the most drought sensitive stage for seed set and, consequently, grain yield. AtGRXS17-expressing maize lines displayed higher seed set in the field, resulting in 2-fold and 1.5-fold increase in yield in comparison to the non-transgenic plants when challenged with drought stress at the tasseling and silking/pollination stages, respectively. AtGRXS17-expressing lines showed higher relative water content, higher chlorophyll content, and less hydrogen peroxide accumulation than wild-type (WT) control plants under drought conditions. AtGRXS17-expressing lines also exhibited at least 2-fold more pollen germination than WT plants under drought stress. Compared to the transgenic maize, WT controls accumulated higher amount of proline, indicating that WT plants were more stressed over the same period. The results present a robust and simple strategy for meeting rising yield demands in maize under water limiting conditions.

Summary box As of April 2021, COVID-19 cases continue to rise globally and in the South Asia region causing devastating morbidity, mortality and disruption of socioeconomic life. Apart from public health measures to prevent spread of COVID-19, significant investment has been made to develop, test and roll out vaccines. Modelling studies predict significant reduction in overall attack rates by SARS-CoV-2 through use of effective COVID-19 vaccines, with the highest relative reduction among older adults (aged 65 years and older), reduction of intensive care admissions and deaths.1 As of 18 April 2021, 14 vaccines have been approved for human use by at least one country2 and 890 million doses of COVID-19 vaccines have been administered globally.3 In the South Asia region, the Oxford-AstraZeneca (COVISHIELD) vaccine manufactured in India has been made available through the COVAX Facility.2 As of 18 April 2021, 122 million doses (7.9% of the …

Cervical cancer is preventable and also curable when detected early and treated adequately, yet it remains a leading cause of morbidity and mortality among women. In Bhutan, cervical cancer is the most common cancer among women. Bhutan was the first country among the low- and middle-income economies to have instituted a national HPV vaccination program, in 2010, and has achieved >90% coverage. In 2019, Bhutan launched a cervical cancer elimination flagship program well ahead of WHO's launch of the global strategy for accelerated elimination of cervical cancer. Bhutan initiated vaccination of adolescent boys and adopted a gender-neutral vaccination program beginning September 2020 through its well-established network of primary healthcare centres. The flagship program aims to screen women aged 30-69 years with HPV testing using liquid-based cytology (LBC) as triaging for screen positive women. For women aged 25-29 years, LBC will be continued as per American Society of Colposcopy and Cervical Pathology guidelines. Colposcopy and treatment will be performed in camps to decrease loss of follow up of screen positive women. This program is also expected to improve early diagnosis of cervical cancer and provide timely and adequate cancer treatment and palliative care services. This article reviews the progress made and the challenges facing the 2030 cervical cancer elimination targets in Bhutan.

Objectives The primary aim of this study was to compare the clinical outcomes of patients undergoing arthroscopic Bankart repair and the open Latarjet procedure for recurrent dislocation of the shoulder. The secondary aims were to assess and compare the surgical cost, patient satisfaction, and complications, including recurrence and infection. Methods We retrospectively compared the clinical outcomes of all consecutive patients undergoing either arthroscopic Bankart repair or the open Latarjet procedure from May 2015 to May 2018 with a minimum 2-year follow-up. Forty-one patients (32 men, 9 women) in the Bankart group and 40 patients (34 men, 6 women) in the Latarjet group were available for the final follow-up. Results There were no statistically significant differences in the demographic parameters or clinical outcomes between the two groups. Functional satisfaction was higher with the Latarjet procedure. Bankart repair had a significantly higher operating cost than the Latarjet procedure. Three patients in the Bankart group and no patients in the Latarjet group developed recurrence. Conclusion Both procedures provided satisfactory clinical outcomes. However, the Latarjet group had a higher rate of functional satisfaction and lower operating cost, and there was a trend toward higher recurrence in the arthroscopic Bankart group.

ObjectivesThis study aimed to investigate whether child marriage had causal effects on unmet needs for modern contraception, and unintended pregnancy, by estimating the marginal (population-averaged) treatment effect of child marriage.DesignThis study used secondary data from the Nepal Demographic and Health Survey 2016. Applying one-to-one nearest-neighbour matching with replacement within a calliper range of ±0.01, 15–49 years old women married before the age of 18 were matched with similar women who were married at 18 or above to reduce selection bias.SettingNationally representative population survey data.ParticipantsThe sample consisted of 7833 women aged 15–49 years who were married for more than 5 years.Outcome measuresUnmet needs for modern contraception and unintended pregnancy.ResultsThe matching method achieved adequate overlap in the propensity score distributions and balance in measured covariates between treatment and control groups with the same propensity score. Propensity score matching analysis showed that the risk of unmet needs for modern contraception, and unintended pregnancy among women married as children were a 14.3 percentage point (95 % CI 10.3 to 18.2) and a 10.1 percentage point (95 % CI 3.7 to 16.4) higher, respectively, than among women married as adults. Sensitivity analysis indicated that the estimated effects were robust to unmeasured covariates.ConclusionsChild marriage appears to increase the risk of unmet needs for modern contraception and unintended pregnancy. These findings call for social development and public health programmes that promote delayed entry into marriage and childbearing to improve reproductive health and rights.

Background Coronavirus disease 2019 (COVID-19) has affected all age groups worldwide, but older adults have been affected greatly with an increased risk of severe illness and mortality. Nepal is struggling with the COVID-19 pandemic. The normal life of older adults, one of the vulnerable populations to COVID-19 infection, has been primarily impacted. The current evidence shows that the COVID-19 virus strains are deadly, and non-compliance to standard protocols can have serious consequences, increasing fear among older adults. This study assessed the perceived fear of COVID-19 and associated factors among older adults in eastern Nepal. Methods A cross-sectional study was conducted between July and September 2020 among 847 older adults (≥60 years) residing in three districts of eastern Nepal. Perceived fear of COVID-19 was measured using the seven-item Fear of COVID-19 Scale (FCV-19S). Multivariate logistic regression identified the factors associated with COVID-19 fear. Results The mean score of the FCV-19S was 18.1 (SD = 5.2), and a sizeable proportion of older adults, ranging between 12%-34%, agreed with the seven items of the fear scale. Increasing age, Dalit ethnicity, remoteness to the health facility, and being concerned or overwhelmed with the COVID-19 were associated with greater fear of COVID-19. In contrast, preexisting health conditions were inversely associated with fear. Conclusion Greater fear of the COVID-19 among the older adults in eastern Nepal suggests that during unprecedented times such as the current pandemic, the psychological needs of older adults should be prioritized. Establishing and integrating community-level mental health support as a part of the COVID-19 preparedness and response plan might help to combat COVID-19 fear among them.

Background The proportion of incident cases of HPV-attributable cancers is highest in the low- and middle-income countries (LMICs) but many are yet to initiate HPV vaccination programs. This meta-analysis was performed to assess the uptake of HPV vaccination in LMICs at the beginning of the global strategy to eliminate cervical cancer and describes the gaps and challenges. Methods A systematic search was conducted in PubMed, EMBASE, Scopus, Web of Science, and CENTRAL databases for observational studies that reported the uptake of HPV vaccination until October 2020. The meta-analysis was done using a random-effects model to assess the pooled estimate of HPV uptake. CRD42021218429 Findings During 2008–2020, an estimated 3.3 million females received at least one dose of HPV vaccine with 61.69% of the target population vaccinated. In countries with high uptake, the pooled estimate of uptake was higher in females than males (45.48% vs 8.45%) and showed significant decline in 2015–2020 compared to 2006–2014 (89.03% vs 41.48%). In countries with low uptake, the estimate of uptake was low in both males and females (5.31% vs 2.93%) and showed increase in uptake in 2015–2020 compared to 2006–2014 (0.76% vs 5.22%). In countries with high uptake, compared to routine programs, the estimate was higher when delivered through demonstration programs (89.94% vs 59.74%). Interpretation The major concern was a significant drop in the uptake in countries that started with high uptake, challenges in the maintenance of vaccine uptake, sustainability of funding and the lack of standard monitoring and reporting.

Barley is an important cereal crop worldwide because of its use in the brewing and distilling industry. However, adequate supplies of quality malting barley are threatened by global climate change due to drought in some regions and excess precipitation in others, which facilitates epidemics caused by fungal pathogens. The disease net form net blotch caused by the necrotrophic fungal pathogen Pyrenophora teres f. teres (Ptt) has emerged as a global threat to barley production and diverse populations of Ptt have shown a capacity to overcome deployed genetic resistances. The barley line CI5791 exhibits remarkably effective resistance to diverse Ptt isolates from around the world that maps to two major QTL on chromosomes 3H and 6H. To identify genes involved in this effective resistance, CI5791 seed were γ-irradiated and two mutants, designated CI5791-γ3 and CI5791-γ8, with compromised Ptt resistance were identified from an M2 population. Phenotyping of CI5791-γ3 and -γ8 × Heartland F2 populations showed three resistant to one susceptible segregation ratios and CI5791-γ3 × -γ8 F1 individuals were susceptible, thus these independent mutants are in a single allelic gene. Thirty-four homozygous mutant (susceptible) CI5791-γ3 × Heartland F2 individuals, representing 68 recombinant gametes, were genotyped via PCR genotype by sequencing. The data were used for single marker regression mapping placing the mutation on chromosome 3H within an approximate 75 cM interval encompassing the 3H CI5791 resistance QTL. Sequencing of the mutants and wild-type (WT) CI5791 genomic DNA following exome capture identified independent mutations of the HvWRKY6 transcription factor located on chromosome 3H at ∼50.7 cM, within the genetically delimited region. Post transcriptional gene silencing of HvWRKY6 in barley line CI5791 resulted in Ptt susceptibility, confirming that it functions in NFNB resistance, validating it as the gene underlying the mutant phenotypes. Allele analysis and transcript regulation of HvWRKY6 from resistant and susceptible lines revealed sequence identity and upregulation upon pathogen challenge in all genotypes analyzed, suggesting a conserved transcription factor is involved in the defense against the necrotrophic pathogen. We hypothesize that HvWRKY6 functions as a conserved signaling component of defense mechanisms that restricts Ptt growth in barley.

BackgroundThe aim of this study was to determine the knowledge, attitude and practice (KAP) regarding the COVID-19 among frontline healthcare workers (F-HCWs) working at different hospitals in Nepal and to identify the factors significantly associated with KAP.MethodsWe used a web-based survey, and a convenience sampling method was adopted to collect data from 603 F-HCWs working at different hospitals in Nepal during the first week of June 2020. A self-administered questionnaire was utilized to assess the KAP perceived by the F-HCWs. It was divided into 4-parts consisting of 30-items, demographic characteristics (10-items), knowledge (10-items), attitude (5-items), and practice (5-items). It consisted of both multiple-choice questions and Likert scale items questionnaire.ResultsAmong the participants, 76% reported adequate knowledge, 54.7% reported positive attitude, and 78.9% reported appropriate practice. Statistically significant differences regarding the perceived level of knowledge among F-HCWs were observed among independent variables, including age, gender, level of education, marital status, profession, work experience, source of information, infection prevention and control (IPC) training, and online course(p p p p = 0.01. The factors significantly associated with adequate knowledge were male gender, nurse and doctor, websites and IPC training. Similarly, factors significantly associated with positive attitude were online course related to COVID-19 only. Moreover, factors significantly associated with appropriate practice were master’s degree or above and online course related to COVID-19.ConclusionsF-HCWs reported adequate overall knowledge with a positive attitude and adopted the appropriate practice. The experienced F-HCWs with higher education and who received IPC training and online course regarding COVID-19 had better KAP. So, the stakeholders must arrange the educational programs and training for F-HCWs for better preparedness tackling with COVID-19.

PURPOSE: The prevalence of breast cancer survivors has increased due to dissemination of population-based mammographic screening and improved treatments. Recent changes in anti-hormonal therapies for breast cancer may have modified the risks of subsequent urological and genital cancers. We examine the risk of subsequent primary urological and genital cancers in patients with incident breast cancer compared with risks in the general population.METHODS: Using population-based Danish medical registries, we identified a cohort of women with primary breast cancer (1990-2017). We followed them from one year after their breast cancer diagnosis until any subsequent urological or genital cancer diagnosis. We computed incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as the observed number of cancers relative to the expected number based on national incidence rates (by sex, age, and calendar year).RESULTS: Among 84,972 patients with breast cancer (median age 61 years), we observed 623 urological cancers and 1397 genital cancers during a median follow-up of 7.4 years. The incidence rate per 100,000 person-years was stable during follow-up (83 for urological cancers and 176 for genital cancers). The SIR was increased for ovarian cancer (1.37, 95% CI 1.23-1.52) and uterine cancer (1.37, 95% CI 1.25-1.50), but only during the pre-aromatase inhibitor era (before 2007). Moreover, the SIR of kidney cancer was increased (1.52, 95% CI 1.15-1.97), but only during 2007-2017. The SIR for urinary bladder cancer was marginally increased (1.15, 95% CI 1.04-1.28) with no temporal effects. No associations were observed for cervical cancer.CONCLUSION: Breast cancer survivors had higher risks of uterine and ovarian cancer than expected, but only before 2007, and of kidney cancer, but only after 2007. The risk of urinary bladder cancer was moderately increased without temporal effects, and we observed no association with cervical cancer.

The Himalayan people prepare dry and oval to round-shaped starter cultures to ferment cereals into mild-alcoholic beverages, which contain lactic acid bacteria (LAB) as one of the essential microbiota. There is no report on probiotic characters of LAB isolated from dry starters. Hence, we screened the probiotic and some functional properties of 37 LAB strains isolated from dry starters of the Eastern Himalayas viz. marcha, phab, paa, pee and phut. About 38% of the LAB strains showed high survival rate (> 50%) at pH 3 and 0.3% bile salts. Enterococcus durans BPB21 and SMB7 showed the highest hydrophobicity percentage of 98%. E. durans DMB4 and SMB7 showed maximum cholesterol assimilation activity. About 65% of the LAB strains showed the ability to produce β galactosidase. Majority of the strains showed phytase activity, whereas none of the strain showed amylase activity. About 86% of LAB strains showed an optimum tolerance of 10% ethanol concentration. Genetic screening of some probiotic and functional marker genes have also been analysed. The occurrence of clp L gene, agu A gene (survival of gastrointestinal tract conditions), apf, mub1 and map A gene (adhesion genes) was higher compared to other genes. The occurrence of bsh gene (bile salt tolerance) was detected in Pediococcus pentosaceus SMB13-1 and Enterococcus faecium BPB11. Gene ped B for pediocin with amplicon size of 375 bp was detected in E. durans DMB13 and Pediococcus acidilactici AKB3. Detection of nutritional marker gene rib A and fol P in some strains showed the potential ability to synthesize riboflavin and folic acid. LAB with probiotic and functional properties may be explored for food industry in future.

Commensal non-pathogenicNeisseriaspp. live within the human host alongside the pathogenicNeisseria meningitidisandNeisseria gonorrhoeaeand due to natural competence, horizontal gene transfer within the genus is possible and has been observed. Four distinctNeisseriaspp. isolates taken from the throats of two human volunteers have been assessed here using a combination of microbiological and bioinformatics techniques. Three of the isolates have been identified asNeisseria subflavabiovarperflavaand one asNeisseria cinerea. Specific gene clusters have been identified within these commensal isolate genome sequences that are believed to encode a Type VI Secretion System, a newly identified CRISPR system, a Type IV Secretion System unlike that in otherNeisseriaspp., a hemin transporter, and a haem acquisition and utilization system. This investigation is the first to investigate these systems in either the non-pathogenic or pathogenicNeisseriaspp. In addition, theN. subflavabiovarperflavapossess previously unreported capsule loci and sequences have been identified in all four isolates that are similar to genes seen within the pathogens that are associated with virulence. These data from the four commensal isolates provide further evidence for aNeisseriaspp. gene pool and highlight the presence of systems within the commensals with functions still to be explored.

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.

The lesser-known traditionally processed meat products such as beef kargyong, pork kargyong, satchu, and khyopeh are popular food items in the Himalayan state of Sikkim in India. The present study aimed to assess the microbiological safety of traditional meat products by identifying the potential spoilage or pathogenic bacteria, detecting the enterotoxins, and screening the antibiotic susceptibility patterns. The pH and moisture contents of the meat products varied from 5.3 to 5.9 and from 1.5 to 18%, respectively. The microbial loads of aerobic bacteria were 105 to 107 cfu/g, Staphylococcus 103 to 106 cfu/g, Bacillus 104 to 106 cfu/g, and total coliform 102 to 107 cfu/g, respectively. Based on 16S rRNA gene sequencing, the bacterial species isolated from traditionally processed meat products were Staphylococcus piscifermentans, Citrobacter freundii, Enterococcus faecalis, Salmonella enterica, Staphylococcus aureus, Citrobacter werkmanii, Klebsiella pneumoniae, Macrococcus caseolyticus, Klebsiella aerogenes, Staphylococcus saprophyticus, Pseudocitrobacter anthropi, Citrobacter europaeus, Shigella sonnei, Escherichia fergusonii, Klebsiella grimontii, Burkholderia cepacia, and Bacillus cereus. The enzyme-linked immunosorbent assay (ELISA) tests detected Salmonella spp. and enterotoxins produced by B. cereus well as Staphylococcus in a few tested samples. However, the PCR method did not detect the virulence genes of B. cereus and Salmonella in the isolates. Virulence gene (sea) was detected in S. piscifermentans BSLST44 and S. piscifermentans BULST54 isolated from beef kargyong and in S. aureus PSST53 isolated from pork kargyong. No enterotoxins were detected in khyopeh samples. The antibiotic sensitivity test showed that all bacterial strains were susceptible toward gentamicin, cotrimoxazole, norfloxacin, and trimethoprim. Gram-positive bacteria showed 100% sensitivity against clindamycin and erythromycin; however, 50% of the resistance pattern was observed against oxacillin followed by penicillin (33%) and ampicillin (27%).

Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the small intestine, given its role in drug and nutrient absorption, and identified catalase as an essential enzyme with the potential to catalyze polymerization and growth of synthetic biomaterial layers. We demonstrated that the polymerization of dopamine by catalase yields strong tissue adhesion. We characterized the mechanism and specificity of the polymerization in segments of the gastrointestinal tracts of pigs and humans ex vivo. Moreover, we demonstrated proof-of-concept for application of these gastrointestinal synthetic epithelial linings (GSELs) for drug delivery, enzymatic immobilization for digestive supplementation, and nutritional modulation through transient barrier formation in pigs. This catalase-based approach to in situ biomaterial generation may have broad indications for gastrointestinal applications.

Objectives: Management of radiation-induced ureteral stricture (RIUS) is complex, requiring chronic drainage or morbid definitive open reconstruction. Herein, we report our multi-institutional comp...

Purpose: New therapies are needed to treat immune checkpoint inhibitor–resistant non–small cell lung cancer (NSCLC) and identify biomarkers to personalize treatment. Epigenetic therapies, including histone deacetylase inhibitors, may synergize with programmed cell death-1 (PD-1) blockade to overcome resistance. We report outcomes in patients with anti-programmed cell death ligand-1 [PD-(L)1]–resistant/refractory NSCLC treated with pembrolizumab plus entinostat in ENCORE 601. Patients and Methods: The expansion cohort of ENCORE 601 included patients with NSCLC who previously experienced disease progression with immune checkpoint inhibitors. The primary endpoint for the phase II expansion cohort is overall response rate (ORR); safety, tolerability, and exploratory endpoints are described. Results: Of 76 treated patients, 71 were evaluable for efficacy. immune-regulated RECIST–assessed ORR was 9.2% [95% confidence interval (CI): 3.8–18.1], which did not meet the prespecified threshold for positivity. Median duration of response was 10.1 months (95% CI: 3.9–not estimable), progression-free survival (PFS) at 6 months was 22%, median PFS was 2.8 months (95% CI: 1.5–4.1), and median overall survival was 11.7 months (95% CI: 7.6–13.4). Benefit was enriched among patients with high levels of circulating classical monocytes at baseline. Baseline tumor PD-L1 expression and IFNγ gene expression were not associated with benefit. Treatment-related grade ≥3 adverse events occurred in 41% of patients. Conclusions: In anti–PD-(L)1–experienced patients with NSCLC, entinostat plus pembrolizumab did not achieve the primary response rate endpoint but provided a clinically meaningful benefit, with objective response in 9% of patients. No new toxicities, including immune-related adverse events, were seen for either drug. Future studies will continue to evaluate the association of monocyte levels and response.

Alternative means for drug delivery are needed to facilitate drug adherence and administration. Microneedles (MNs) have been previously investigated transdermally for drug delivery. To date, drug loading into MNs has been limited by drug solubility in the polymeric blend. We designed a highly drug-loaded MN patch to deliver macromolecules and applied it to the buccal area, which allows for faster delivery than the skin. We successfully delivered 1-mg payloads of human insulin and human growth hormone to the buccal cavity of swine within 30 s. In addition, we conducted a trial in 100 healthy volunteers to assess potential discomfort associated with MNs when applied in the oral cavity, identifying the hard palate as the preferred application site. We envisage that MN patches applied on buccal surfaces could increase medication adherence and facilitate the painless delivery of biologics and other drugs to many, especially for the pediatric and elderly populations.

Based on epidemiological data provided by the World Health Organization (2018), cancer is the second most prevalent cause of death worldwide. Several factors are thought to contribute to the high mortality rate in cancer patients, including less-than-optimal diagnostic and therapeutic strategies. Thus, there is an urgent need to identify accurate biomarkers with diagnostic, prognostic, and potential therapeutic applications. In this regard, long noncoding RNAs (lncRNAs) hold immense potential due to their regulatory roles in cancer development and associated cancer hallmarks. Recently, CASC9 transcripts have attracted significant attention due to their altered expression during the pathogenesis of cancer and their apparent contributions to various cancer-associated phenotypes involving a broad spectrum of molecular mechanisms. Here, we have provided an in-depth review describing the known functions of the lncRNA CASC9 in cancer development and progression.

Radio stations particularly those of local FM have an influential role in disseminating environmental concerns among the wide populace. This study provides the first nationwide assessment of FM radio coverage of environmental issues in Nepal by using data collected from a web-based questionnaire survey from 102 radio stations. We found that environmental programs were covered in 57% of radio stations, but they were among the least popular ones. Among various categories of environmental programs, the general category was the most common and popular, followed by forest and wildlife conservation and water resource management. Surprisingly, environmental pollution and disaster risk management were ranked as being less popular in comparison to their coverage. Environmental programs were mostly broadcasted weekly (73%) during prime time (morning and evening). Although there were agreements among respondents on the importance of environment program for radio stations (agreement = 0.74), nearly 22% of all radio stations terminated such programs in the past and only a few of them were interested to relaunch them in the foreseeable future. Limited funding was the most reported challenge followed by difficulty in finding environmental experts and radio journalists. We recommend the Government of Nepal to formulate a media engagement strategy to strengthen environmental campaigns in the face of rapid environmental change in Nepal., Social science; FM radio; Mass media; Environmental communication; Community awareness; Online survey; Media strategy

Purpose Glutamate (Glu) is the most abundant neurotransmitter in the human central nervous system and glutamatergic neurotransmission has been implicated in many common and severe neuropsychiatric disorders. In vivo MRS techniques have been developed to measure brain Glu concentration to investigate the pathophysiology of various brain disorders. However, it is difficult to interpret Glu signal changes because Glu plays multiple roles in the brain and is found in multiple microenvironments including cytosolic, vesicular, and extracellular. Methods In vivo diffusion-weighted MRS (DW-MRS) with low to very high b-values was performed on the rat prefrontal cortex at 9.4T under both light and deep anesthetic conditions to examine Glu diffusion properties. Results Significant alterations in Glu diffusion as well as reduced Glu concentration were observed under deep anesthesia compared with superficial anesthesia in the absence of similar changes in NAA or creatine. Conclusion The modifications in Glu diffusion under deep anesthesia might reflect changes in Glu microenvironment. The present work shows that Glu DW-MRS could be an important tool to explore Glu physiology with changing levels of neuronal activity and synaptic function.