Better Social-emotional Behavior in Young Nepali Children is Associated with Household Wealth, Child Age, and Family Participation in a Community Development Intervention.

Background Mental health and behavior problems are under-recognized in low- and middleincome countries, especially in young children. Early identification of these problems could encourage governments to address the shortages of child mental health professionals and promote early intervention programs to help children achieve their full developmental potential. Objective Describe the social-emotional development of young rural Nepali children; explore risk factors for poor development. Method The study was embedded in a longitudinal intervention trial comparing control households with those who received training in family nutrition+livestock management (Partial Package) or family nutrition+livestock management+community mobilization (Full Package). At midline, enumerators completed a 145-item household questionnaire, child anthropometry, and Administered the Ages and Stages Questionnaire-Social-Emotional (ASQ-SE) to all enrolled children age 33-47 months (n=310). Bivariate and regression analyses examined the relationship of child and household risk factors to administered the Ages and Stages QuestionnaireSocial-Emotional scores. Result Administered the Ages and Stages Questionnaire-Social-Emotional scores were below age cutoffs in 24% of children, suggesting worse social-emotional development. In bivariate analyses and the adjusted linear regression model, older child age, greater household wealth, and Full Package Intervention status were all associated with better social-emotional development scores. Partial Package Intervention status was associated with worse scores. Conclusion The Administered the Ages and Stages Questionnaire-Social-Emotional is a potential tool to assess child social-emotional development in the context of household and community level interventions. Further work is necessary to validate the administered the Ages and Stages Questionnaire-Social-Emotional and similar tools in Nepal, and to better understand the prevalence of challenges to optimal socialemotional development in young children in order to use this information to design and monitor needed interventions.

First-Generation SARS-CoV-2 Vaccines: A Comparative Analysis between Vaccinated and Unvaccinated Hospitalized Patients Infected with SARS-CoV-2.

Background Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variants, which have emerged due to several mutations in spike protein, have a potential to escape immune protection provided by the first-generation vaccines, thereby resulting in breakthrough infections. Objective To identify the socio-demographic factors, clinical features, and outcomes in both vaccinated and unvaccinated hospitalized patients infected with SARS-CoV-2. Method Socio-demographic details, clinical features, and the outcomes among fully vaccinated (double for Covishield/AstraZeneca and BBIBP-CorV and single for Janssen), partially vaccinated, and unvaccinated hospitalized patients with coronavirus disease of 2019 (COVID-19) were collected and analyzed using SPSS version 17. Result Among the hospitalized COVID-19 patients (n=299), 175 (58.5%) patients received a single-dose, 82 (27.4%) double-dose, and 124 (41.5%) did not receive any dose of the COVID-19 vaccines. The risk of SARS-CoV-2 infection when compared between vaccinated and unvaccinated patients was found to be associated among professional degree holders (23.4% versus 9.7%) (p<0.05), professional workers (43.4% vs. 25.0%) (p<0.05), hospitalization to general ward (76.6% vs. 72.6%) (p<0.05), and presence of multiple symptoms (> or equel 3) (86.8% vs. 75.0%) (p>0.05) and comorbidities (> or equal 2) (15.5% vs. 13.7%) (p>0.05). Despite such approximate incidences, the risk of in-hospital mortality among the vaccinated patients was reduced (0.6% vs. 3.2%) (p>0.05), when compared to the unvaccinated patients. The risk of in-hospital mortality was associated with the older age and the presence of multiple comorbidities including bronchial asthma, diabetes, and hypertension. Conclusion Full or partial vaccination against the SARS-CoV-2 variants of concerns might be effective in preventing in-hospital mortality among COVID-19 patients.

Flower colour and size signals differ depending on geographical location and altitude region.

Bees are major pollinators of angiosperms and have phylogenetically conserved colour vision but differ in how various key species use achromatic information that is vital for both flower detection and size processing. We modelled green contrast and colour contrast signals from flowers of different countries where there are well established differences in availability of model bee species along altitudinal gradients. We tested for consistency in visual signals as expected from generalization in pollination principles using phylogenetically informed linear models. Patterns of chromatic contrast, achromatic green contrast and flower size differed among the three floras we examined. In Nepal there is a significant positive correlation between flower size and colour contrast in the subalpine region, but a negative correlation at the lower altitudes. At high elevations in Norway, where pollinators other than bees are common, flower size was positively correlated with colour contrast. At low and medium altitudes in Norway and in Australia, we did not observe a significant relationship between size and colour contrast. We thus find that the relationship between size, green and colour contrast cannot be generalized across communities, thus suggesting that flower visual signal adaptations to local pollinators are not limited to chromatic contrast.

Rewardlessness in orchids: how frequent and how rewardless?

About one-third of orchid species are thought to offer no floral reward and therefore attract pollinators through deception. Statements of this idea are common in the botanical literature, but the empirical basis of the estimate is rarely mentioned. We traced citation pathways for the one-third estimate in a sample of the literature and found that the paths lead to empirical foundations that are surprisingly narrow. Moreover, recent measurements have detected minute quantities of sugar available to insect visitors in some orchids thought to be rewardless, raising the possibility of a pollination strategy that is largely deceitful but different to absolute rewardlessness. The orchids are a well-studied group and there is no doubt that rewardlessness is common in the family. However, greater empirical effort is needed to verify rewardlessness in orchids and to explore geographic and environmental variation in the proportion of rewardless species.

Gaming Disorder among Medical College Students during COVID-19 Pandemic Lockdown.

Background The frequent lockdown in Nepal during COVID-19 pandemic had brought various kinds of complexities such as stress among college students. This situation had created uncertainty of future academic career of undergraduate students in medical colleges. Some previously published literature showed gaming as a coping mechanism against stress. Objective To assess the gaming behavior of Medical college students during lockdown in COVID-19 pandemic. Method A cross-sectional study was conducted during lockdown period of July to August 2020. A total of 412 college students were enrolled. Online Google forms were shared to all the eligible students through email, viber and messenger with the help of class representative. Collected data were analyzed in SPSS version 20.0. Result The prevalence of gaming disorder was 8.5% among 260 internet gaming users. About 69.2% of the participants reported that their gaming behavior had increased due to stress of COVID-19 pandemic. Gender and spending more time online per day showed significant associations with greater scores on the internet gaming disorder. Conclusion During lockdown period of COVID-19 pandemic, the gaming behavior of medical college students has increased.

Colour evolution within orchids depends on whether the pollinator is a bee or a fly.

Orchids are a classic angiosperm model for understanding biotic pollination. We studied orchid species within two species-rich herbaceous communities that are known to have either hymenopteran or dipteran insects as the dominant pollinators, in order to understand how flower colour relates to pollinator visual systems. We analysed features of the floral reflectance spectra that are significant to pollinator visual systems and used models of dipteran and hymenopteran colour vision to characterise the chromatic signals used by fly-pollinated and bee-pollinated orchid species. In contrast to bee-pollinated flowers, fly-pollinated flowers had distinctive points of rapid reflectance change at long wavelengths and a complete absence of such spectral features at short wavelengths. Fly-pollinated flowers also had significantly more restricted loci than bee-pollinated flowers in colour space models of fly and bee vision alike. Globally, bee-pollinated flowers are known to have distinctive, consistent colour signals. Our findings of different signals for fly pollination is consistent with pollinator-mediated selection on orchid species that results from the distinctive features of fly visual systems.

Prevalence of Nonalcoholic Fatty Liver Disease in a Tertiary Care Teaching Hospital: A Cross Sectional Study in Province 4 of Nepal.

Background Nonalcoholic fatty liver disease (NAFLD) is collection of lipids in hepatic tissues excluding other hepatic diseases and chronic alcohol intake. It may advance to nonalcoholic steatohepatitis or cirrhosis. Ultrasonography has high sensitivity and specificity for detecting nonalcoholic fatty liver disease. Objective Lack of sufficient information in this region on sonological prevalence of nonalcoholic fatty liver disease, lead us to design the survey and may also serve as reference for further researches. Method This is a cross sectional study with 600 participants, conducted at Gandaki Medical College Teaching Hospital, Province 4 of Nepal, from September to October 2017. Ethical approval is taken from the Institutional review board. The study group includes the participants referred for abdominal sonography from outpatient department. Result In present survey, 367 (61.2%) are female and 233 (38.8%) are male participants. The mean age is 41.6 years and median age is 38 years. The prevalence of nonalcoholic fatty liver in our observation is 229 cases (38.2%) of which, 102 cases (44.5%) are male and 127 cases (55.4%) are female participants. Normal liver was seen in 61.8%, Grade one fatty liver was discovered in 24.8%, Grade one in 12.6% and Grade three in 0.6%. The mean liver size in those with fatty liver was 14.1 cm. Conclusion Province 4 of Nepal is not exempt from the growing epidemic of nonalcoholic fatty liver disease with prevalence of 38.2%. The study shows that with higher grades of fatty liver, the size of liver is also increased and the mean age of the participants involved is also in the higher side of the spectrum.

Implementation research to assess a health workers performance-based management system in Nepal.

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.

Abnormalities in Protocol Graft Kidney Biopsy 6 Months Posttransplantation in a Tertiary Care Center Hospital of Nepal.

BACKGROUND: Increasing graft survival is the prime focus of every transplantation program. Detection of subclinical abnormalities with the help of protocol renal graft biopsies performed at predetermined intervals after transplantation has been one of the approaches. The objective was to study the abnormalities in protocol renal graft biopsy specimens at 6 months posttransplantation. METHODS: This was a hospital-based observational descriptive study. It included the recipients who underwent kidney transplantation between October 2014 and September 2015. The recipients were followed up postoperatively on an outpatient basis, as per the institution protocol. At 6 months posttransplantation, protocol graft biopsy was performed in all patients with normal functioning allograft without proteinuria after obtaining informed written consent. RESULTS: A total of 57 patients with chronic kidney disease underwent renal transplantation during the study period. Protocol biopsy was performed in 47 recipients. Subclinical rejection was found in 4 (8.5%) recipients. Two recipients had significant tubulitis and interstitial inflammation. One of them showed features of Banff Type IA cellular rejection (t2, i2) and another showed Banff Type IB cellular rejection (t3, i2). Biopsy specimen of 1 recipient showed significant glomerulitis and peritubular capillaritis (g3, ptc1). Another recipient showed significant peritubular capillaritis (ptc2) with C4d positivity. IgA nephropathy was present in 6 (12.8%) recipients. BK virus nephropathy was found in 2 (4.3%) recipients. CONCLUSION: This study demonstrates that abnormal histologic findings occur in protocol graft biopsy specimens at 6 months post renal transplantation in patients without any clinical or laboratory abnormalities.

Spectrum of Infections in Living Donor Kidney Transplant Recipients: An Experience From a Tertiary Center in Nepal.

BACKGROUND: Kidney transplant recipients are always at risk of infections because they are on lifelong immunosuppressive medications. The spectrum of infections in this special population is not the same as in the general population. Post-transplant infections are extensively studied in the developed world. Publications about post-transplant infections from Nepal are scarce. This study was carried out to study the spectrum of infections, the trends in treatment, and the incidence of tuberculosis in kidney transplant recipients. METHODS: This is a retrospective analysis of the patient data in Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Follow-up data from the first 100 kidney transplant recipients was recorded in a Microsoft Excel worksheet and descriptive analysis was done. RESULTS: In the first 100 transplants done until 21 September 2011, 92 patients' data were recorded and 8 patients' data were missing. The mean follow-up period was 61.03 months. The population was 76.09% male (n = 70) and 23.91% female (n = 22). A total of 641 episodes of infections were recorded. Urinary tract infections were the most common type of infection. Escherichia coli was the most common organism isolated (36% of all cultures). There were 17 (2.65%) episodes of viral and 42 (6.6%) episodes of fungal infections. Tuberculosis was diagnosed in 6 (6.5%) patients. CONCLUSION: Urinary tract infection is the most common type of infection in post-kidney transplant patients. Quinolones were the most common agents used to treat urinary tract infections. The incidence of tuberculosis in kidney transplant recipients is 6.5% in 5 years' follow-up.

Preoperative serum uric acid predicts incident acute kidney injury following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) following cardiac surgery is a frequent complication and several risk factors increasing its incidence have already been characterized. This study evaluates the influence of preoperative increased serum uric acid (SUA) levels in comparison with other known risk factors on the incidence of AKI following cardiac surgery. METHODS: During a period of 5 month, 247 patients underwent elective coronary artery bypass grafting, valve replacement/ repair or combined bypass and valve surgery. Datas were prospectively analyzed. Primary endpoint was the incidence of AKI as defined by the AKI criteria comparing patients with preoperative serum uric acid (SUA) levels below versus above the median. Multivariate logistic regression analysis was used to identify independent predictors of postoperative AKI. RESULTS: Thirty (12.1%) of the 247 patients developed postoperative AKI, 24 of 30 (80%) had preoperative SUA- levels above the median (≥373 µmol/l) (OR: 4.680, CI 95% 1.840; 11.904, p = 0.001). In the multivariate analysis SUA levels above the median (OR: 5.497, CI 95% 1.772; 17.054, p = 0.003), cardiopulmonary bypass (CPB) time > 90 min (OR: 4.595, CI 95% 1.587; 13.305, p = 0.005), cardiopulmonary bypass (CPB) > 30 kg/m2 (OR: 3.208, CI 95% 1.202; 8.562; p = 0.02), and preoperative elevated serum-creatinine levels (OR: 1.015, CI 95% 1.001; 1.029, p = 0.04) were independently associated with postoperative AKI. CONCLUSIONS: Serum uric acid is an independent risk marker for AKI after cardiac surgery. From all evaluated factors it showed the highest odds ratio.

Tissue inhibitor of metalloproteinase-1 promotes cell proliferation through YAP/TAZ activation in cancer.

Tissue inhibitor of metalloproteinase-1 (TIMP-1), a member of the TIMP family (TIMP-1 to 4), is highly expressed in various types of cancer and forms a complex with its receptor CD63 and Integrin ß1. However, the precise oncogenic mechanism of TIMP-1 remains unclear. Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) are transcription co-activators enhancing the transcription of specific genes related to cell proliferation. But the mechanism of aberrant YAP/TAZ activation in cancer is not fully understood. Here, we showed that TIMP-1 activates YAP/TAZ as novel downstream targets to promote cell proliferation. The TIMP-1-CD63-Integrin ß1 axis activates Src and promotes RhoA-mediated F-actin assembly, leading to LATS1/2 inactivation. This results in under-phosphorylation, protein stabilization and nuclear translocation of YAP/TAZ (YAP/TAZ activation); CTGF production; and cell proliferation. Furthermore, the TIMP-1-YAP/TAZ axis is aberrantly activated in various types of cancer cells or tissues. TIMP-1 knockdown inhibits cell proliferation through YAP/TAZ inactivation in cancer cells. This study found that TIMP-1 accelerates cell proliferation through YAP/TAZ activation in cancer, and suggests the TIMP-1-YAP/TAZ axis may be a novel potential drug target for cancer patients.

Transcription Factors in Breast Cancer-Lessons From Recent Genomic Analyses and Therapeutic Implications.

Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways. A notable observation is that DB-TFs that mediate major oncogenic signaling (e.g., WNT, receptor tyrosine kinase (RTK), NOTCH, and HIPPO), which switch from default repression (signal OFF) to transcriptional activation (signal ON), are not altered in breast cancer. Instead, corepressors (e.g., pRb for E2F1 downstream of various proliferation signals) or upstream factors (e.g., APC and AXIN for TCF, downstream of canonical WNT signaling) are lost, or coactivators (e.g., NOTCH1/2 for CSL/RBPJk) are induced. In contrast, constitutive (MYC, TBX3) and signal-induced (TP53, FOXA1) DB-TFs that do not mediate default repression are directly altered in breast cancer. Some of these TFs have been implicated in the establishment of super-enhancers and positive transcriptional elongation. In addition, oncogenic transcription is induced by mutations affecting regulatory elements or chromatin conformation that create new TF-binding sites in promoters and enhancers of oncogenic genes to promote tumorigenesis. Here we review these diverse oncogenic alterations in TFs in BC and discuss implications for therapy.

Protease-activated receptor-1 inhibits proliferation but enhances leukemia stem cell activity in acute myeloid leukemia.

Eradication of leukemia stem cells (LSCs) is the ultimate goal of treating acute myeloid leukemia (AML). We recently showed that the combined loss of Runx1/Cbfb inhibited the development of MLL-AF9-induced AML. However, c-Kit+/Gr-1- cells remained viable in Runx1/Cbfb-deleted cells, indicating that suppressing RUNX activity may not eradicate the most immature LSCs. In this study, we found upregulation of several hemostasis-related genes, including the thrombin-activatable receptor PAR-1 (protease-activated receptor-1), in Runx1/Cbfb-deleted MLL-AF9 cells. Similar to the effect of Runx1/Cbfb deletion, PAR-1 overexpression induced CDKN1A/p21 expression and attenuated proliferation in MLL-AF9 cells. To our surprise, PAR-1 deficiency also prevented leukemia development induced by a small number of MLL-AF9 leukemia stem cells (LSCs) in vivo. PAR-1 deficiency also reduced leukemogenicity of AML1-ETO-induced leukemia. Re-expression of PAR-1 in PAR-1-deficient cells combined with a limiting-dilution transplantation assay demonstrated the cell-dose-dependent role of PAR-1 in MLL-AF9 leukemia: PAR-1 inhibited rapid leukemic proliferation when there were a large number of LSCs, while a small number of LSCs required PAR-1 for their efficient growth. Mechanistically, PAR-1 increased the adherence properties of MLL-AF9 cells and promoted their engraftment to bone marrow. Taken together, these data revealed a multifaceted role for PAR-1 in leukemogenesis, and highlight this receptor as a potential target to eradicate primitive LSCs in AML.

Floral colours in a world without birds and bees: the plants of Macquarie Island.

We studied biotically pollinated angiosperms on Macquarie Island, a remote site in the Southern Ocean with a predominately or exclusively dipteran pollinator fauna, in an effort to understand how flower colour affects community assembly. We compared a distinctive group of cream-green Macquarie Island flowers to the flora of likely source pools of immigrants and to a continental flora from a high latitude in the northern hemisphere. We used both dipteran and hymenopteran colour models and phylogenetically informed analyses to explore the chromatic component of community assembly. The species with cream-green flowers are very restricted in colour space models of both fly vision and bee vision and represent a distinct group that plays a very minor role in other communities. It is unlikely that such a community could form through random immigration from continental source pools. Our findings suggest that fly pollination has imposed a strong ecological filter on Macquarie Island, favouring floral colours that are rare in continental floras. This is one of the strongest demonstrations that plant-pollinator interactions play an important role in plant community assembly. Future work exploring colour choices by dipteran flower visitors would be valuable.

UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO.

The t(8;21) rearrangement, which creates the AML1-ETO fusion protein, represents the most common chromosomal translocation in acute myeloid leukemia (AML). Clinical data suggest that CBL mutations are a frequent event in t(8;21) AML, but the role of CBL in AML1-ETO-induced leukemia has not been investigated. In this study, we demonstrate that CBL mutations collaborate with AML1-ETO to expand human CD34+ cells both in vitro and in a xenograft model. CBL depletion by shRNA also promotes the growth of AML1-ETO cells, demonstrating the inhibitory function of endogenous CBL in t(8;21) AML. Mechanistically, loss of CBL function confers hyper-responsiveness to thrombopoietin and enhances STAT5/AKT/ERK/Src signaling in AML1-ETO cells. Interestingly, we found the protein tyrosine phosphatase UBASH3B/Sts-1, which is known to inhibit CBL function, is upregulated by AML1-ETO through transcriptional and miR-9-mediated regulation. UBASH3B/Sts-1 depletion induces an aberrant pattern of CBL phosphorylation and impairs proliferation in AML1-ETO cells. The growth inhibition caused by UBASH3B/Sts-1 depletion can be rescued by ectopic expression of CBL mutants, suggesting that UBASH3B/Sts-1 supports the growth of AML1-ETO cells partly through modulation of CBL function. Our study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETO-induced leukemia, and identifies UBASH3B/Sts-1 as a potential target for pharmaceutical intervention.

Assessment of knowledge and practice of community pharmacy personnel on diabetes mellitus management in Kathmandu district: a cross sectional descriptive study.

BACKGROUND: Pharmacists are the most reachable healthcare professionals to many chronically ill patients. It has been found that pharmacists see patients with diabetes up to five times more often than any other healthcare provider. Therefore, to provide quality health care to patients it is important that they have appropriate knowledge and practice on diabetes mellitus management. Thus, this study was conducted to assess the knowledge and practice of diabetes mellitus management among community pharmacy personnel involved in retail community pharmacies of Kathmandu. METHODS: Three hundred and fifteen community pharmacies, selected by systematic random sampling were surveyed by using pre-validated self-administered questionnaires. The first set of questionnaire evaluated the community pharmacy personnel's diabetes knowledge based on a pre-validated 20-item questionnaire. The second set of questionnaire documented about the practice of community pharmacy personnel on diabetes mellitus management which contained 22 questions. Data was entered in EPI Data and analyzed by using SPSS version 20. RESULTS: This survey demonstrated that 76.5 % respondents had poor knowledge and 86.4 % had negative practice on diabetes mellitus (DM) management. Only 26.2 % respondents had good knowledge as well as good practice. 31.4 % of respondents had poor knowledge as well as poor practice on DM management. CONCLUSIONS: Laws and regulations regarding community pharmacy personnel need to be implemented. There should be more advanced and experiment based training. Additionally, the provision for further education curriculum in pharmacy education should be implemented which should intensively include disease and proper management. Guidelines covering diabetes care should be distributed and implemented throughout community pharmacies.

Difficult journey from delivery to discharge, case of congenital diaphragmatic hernia.

We report a case of congenital diaphragmatic hernia which was diagnosed prenatally for which surgical correction was done on second day of life. The child was discharged in 17 days and has resulted in good post repair condition of patient.