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Cascading hazards are becoming more prevalent in the central Himalayas. Primary hazards (e.g., earthquakes, avalanches, and landslides) often trigger secondary hazards (e.g., landslide dam, debris flow, and flooding), compounding the risks to human settlements, infrastructures, and ecosystems. Risk management strategies are commonly tailored to a single hazard, leaving human and natural systems vulnerable to cascading hazards. In this commentary, we characterize diverse natural hazards in the central Himalayas, including their cascading mechanisms and potential impacts. A scientifically sound understanding of the cascading hazards, underlying mechanisms, and appropriate tools to account for the compounding risks are crucial to informing the design of risk management strategies. We also discuss the need for an integrated modeling framework, reliable prediction and early warning system, and sustainable disaster mitigation and adaptation strategies.

Nepal exhibits a tuberculosis (TB) incidence rate that is comparable to neighbouring high TB incidence countries. In addition, it records >500 cases of multi-drug resistant (MDR) TB each year. The objective of this study was to perform whole-genome bioinformatic analysis on MDR-TB isolates from Nepal (n = 19) to identify the specific mutations underlying their phenotypic resistance. In addition, we examined the dominant genotype among the Nepal MDR-TB isolates, the East-Asian Beijing sub-lineage, to determine its relatedness to a panel of 1274 genomes of international strains available from public databases. These analyses provided evidence that the XDR-TB isolates in our collection were not derived from importation of primary XDR-TB to Nepal but were more likely the result of acquisition of second-line drug resistance in Nepal. Resistance to fluoroquinolones was detected among a high proportion of the Nepal isolates. This has implications for the management of TB, including appropriate antimicrobial stewardship and susceptibility testing for fluoroquinolones and other second-line TB drugs, to minimise the development of XDR-TB among Nepal TB cases.

Extensively drug-resistant (XDR) Mycobacterium tuberculosis has become a challenge to the treatment of tuberculosis (TB) in several countries, including Nepal. Here, we report for the first time the draft genome sequence of an isolate of XDR-TB collected in Nepal and describe single-nucleotide variations associated with its extensively drug-resistant phenotype.

The essential oils (EOs) of three Caprifoliaceae species, the Eurasiatic Valeriana officinalis (Vo), the Himalayan Valeriana jatamansi (Vj) and Nardostachys jatamansi (Nj), are traditionally used to treat neurological disorders. Roots/rhizomes micromorphology, DNA barcoding and EOs phytochemical characterization were carried out, while biological effects on the nervous system were assessed by acetylcholinesterase (AChE) inhibitory activity and microelectrode arrays (MEA). Nj showed the highest inhibitory activity on AChE (IC50 67.15 µg/mL) followed by Vo (IC50 127.30 µg/mL) and Vj (IC50 246.84 µg/mL). MEA analyses on rat cortical neurons, carried out by recording mean firing rate (MFR) and mean bursting rate (MBR), revealed stronger inhibition by Nj (IC50 18.8 and 11.1 µg/mL) and Vo (16.5 and 22.5 µg/mL), compared with Vj (68.5 and 89.3 µg/mL). These results could be related to different EO compositions, since sesquiterpenes and monoterpenes significantly contribute to the observed effects, but the presence of oxygenated compounds such as aldehydes and ketones is a discriminating factor in determining the order of potency. Our multidisciplinary approach represents an important tool to avoid the adulteration of herbal drugs and permits the evaluation of the effectiveness of EOs that could be used for a wide range of therapeutic applications.

BACKGROUND: Tuberculosis (TB) is a major public health problem in low and middle-income countries. Early detection and enrolment of TB cases is a challenge for National TB Programs. OBJECTIVE: To understand the performance and feasibility for scale-up of Xpert MTB/RIF assay for the TB diagnosis in Nepal. DESIGN: Implementation research employed mixed-method sequential explanatory design. The results of Xpert MTB/RIF assay were analysed in 26 TB diagnostic centres where Xpert machines had been installed before 2015. In-depth interviews and focus group discussions were conducted with stakeholders, purposively selected to represent experiences in centres that were functioning well, poorly or not functioning. RESULTS: During a one-year period in 2015/16, 23,075 Xpert MTB/RIF assays were performed in 21 diagnostic centres with 22,288 people also tested by sputum microscopy. Among these, 77% had concordant (positive or negative) results, demonstrating fair agreement (Kappa score, 0.3) between test results. Test failure and positivity rates in diagnostic centres ranged from 2.6% to 13.4% and 6.5% to 49%, respectively. The number of cartridges per positive result varied from 2.3 to 10.2. Xpert assay was positive in 3314 (15% of all cases) sputum smear microscopy negative cases. Of 4280 bacteriologically confirmed cases by Xpert assay, 355 (8%) were rifampicin resistant. Xpert machines were no longer functioning regularly throughout the year in 5 diagnostic centres. The main barriers for effective implementation of Xpert in Nepal were the lack of: timely supply of cartridges; replacement of damaged modules; maintenance of Xpert machines; and stock verification for timely procurement of cartridges. Inadequate laboratory infrastructure for maintaining functional Xpert equipment further challenges implementation and scale-up. CONCLUSION: The implementation of Xpert MTB/RIF assay has increased case-finding of TB and MDR-TB in Nepal. However, there is a need to improve laboratory

Introduction: Relapse cases of pulmonary tuberculosis (PTB) and drug resistance is increasing in National Tuberculosis Centre (NTC), National Tuberculosis Control Programme, Nepal (NTP) and the predictors of relapse PTB is multi-factorial. Initial drug resistant was found to be associated with high relapse cases, so public awareness for regularity of drug intake is highly recommended. Age, sex, occupation, smoking, alcoholism may be important risk factor for relapse. The study aims to determine the prevalence, anti-tubercular drug resistance and predictors of relapse pulmpnary tuberculosis (PTB) cases. Materials and methods: Suspected relapse PTB patients were enrolled and microscopy, culture and drug susceptibility testing were done for all culture positive cases. Result and conclusion: Prevalence of relapse PTB was 45.5% (n=127). M. tuberculosis isolates resistant to at least one anti-TB drug were 25.4% (n=31), 35.5% (n=11) were mono resistant and 64.5% (n=20) were poly resistant. Multi-drug resistance were 14% (n=17). The farmer (OR=1.96), who rest at home (OR=1.12), smokers (OR=1.48), alcoholics (OR=1.73) and those who were on irregular drugs (OR=4.10) were at high risk of relapse PTB. Almost half of patients studied had relapse PTB and drug resistance was noteworthy. Close monitoring and follow up, adherence of treatment and risk factors identified should be addressed to reduce relapses and emergence of drug resistance.

Introduction: Relapse cases of pulmonary tuberculosis (PTB) and drug resistance is increasing in National Tuberculosis Centre (NTC), National Tuberculosis Control Programme, Nepal (NTP) and the predictors of relapse PTB is multi-factorial. Initial drug resistant was found to be associated with high relapse cases, so public awareness for regularity of drug intake is highly recommended. Age, sex, occupation, smoking, alcoholism may be important risk factor for relapse. The study aims to determine the prevalence, anti-tubercular drug resistance and predictors of relapse pulmpnary tuberculosis (PTB) cases. Materials and methods: Suspected relapse PTB patients were enrolled and microscopy, culture and drug susceptibility testing were done for all culture positive cases. Result and conclusion: Prevalence of relapse PTB was 45.5% (n=127). M. tuberculosis isolates resistant to at least one anti-TB drug were 25.4% (n=31), 35.5% (n=11) were mono resistant and 64.5% (n=20) were poly resistant. Multi-drug resistance were 14% (n=17). The farmer (OR=1.96), who rest at home (OR=1.12), smokers (OR=1.48), alcoholics (OR=1.73) and those who were on irregular drugs (OR=4.10) were at high risk of relapse PTB. Almost half of patients studied had relapse PTB and drug resistance was noteworthy. Close monitoring and follow up, adherence of treatment and risk factors identified should be addressed to reduce relapses and emergence of drug resistance.

Pulmonary hypertension is a common but complex clinical problem. When suspected in an appropriate clinical setting or detected incidetally, an array of investigative tools are employed with an intent to confirm the diagnosis, define aetiology, evaluate the functional and haemodynamic impairment, define treatment options, monitor the therapy, and establish long-term prognosis. However, no single tool provides comprehensive information that encompasses the aforementioned aims. Therefore, judicious use of these tools is of paramount importance, in order to maximise outcome and cost-effectiveness, while minimising risks and redundancies. Furthermore, a number of promising tools and techniques are emerging rapidly in the arena of pulmonary hypertension. These tools augment our understanding of pathophysiology and natural history of pulmonary hypertension. There is, therefore, increasing need for validating these emerging paradigms in multicentre trials. In this review, we focus on the tools commonly used to evaluate pulmonary arterial hyertension and also define some of the new approaches to pulmonary arterial hypertension., Journal Article, Research Support, N.I.H. Extramural, Review, SCOPUS: re.j, info:eu-repo/semantics/published

Pulmonary hypertension is a common but complex clinical problem. When suspected in an appropriate clinical setting or detected incidetally, an array of investigative tools are employed with an intent to confirm the diagnosis, define aetiology, evaluate the functional and haemodynamic impairment, define treatment options, monitor the therapy, and establish long-term prognosis. However, no single tool provides comprehensive information that encompasses the aforementioned aims. Therefore, judicious use of these tools is of paramount importance, in order to maximise outcome and cost-effectiveness, while minimising risks and redundancies. Furthermore, a number of promising tools and techniques are emerging rapidly in the arena of pulmonary hypertension. These tools augment our understanding of pathophysiology and natural history of pulmonary hypertension. There is, therefore, increasing need for validating these emerging paradigms in multicentre trials. In this review, we focus on the tools commonly used to evaluate pulmonary arterial hyertension and also define some of the new approaches to pulmonary arterial hypertension., Journal Article, Research Support, N.I.H. Extramural, Review, SCOPUS: re.j, info:eu-repo/semantics/published