Application of Skimmed-Milk Flocculation Method for Wastewater Surveillance of COVID-19 in Kathmandu, Nepal.

Wastewater surveillance (WS) has been used globally as a complementary tool to monitor the spread of coronavirus disease 2019 (COVID-19) throughout the pandemic. However, a concern about the appropriateness of WS in low- and middle-income countries (LMICs) exists due to low sewer coverage and expensive viral concentration methods. In this study, influent wastewater samples (n = 63) collected from two wastewater treatment plants (WWTPs) of the Kathmandu Valley between March 2021 and February 2022 were concentrated using the economical skimmed-milk flocculation method (SMFM). The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was tested by qPCR using assays that target the nucleocapsid (N) and envelope (E) genes. Overall, 84% (53/63) of the total samples were positive for SARS-CoV-2 according to at least one of the tested assays, with concentrations ranging from 3.5 to 8.3 log10 gene copies/L, indicating the effectiveness of the SMFM. No correlation was observed between the total number of COVID-19 cases and SARS-CoV-2 RNA concentrations in wastewater collected from the two WWTPs (p > 0.05). This finding cautions the prediction of future COVID-19 waves and the estimation of the number of COVID-19 cases based on wastewater concentration in settings with low sewer coverage by WWTPs. Future studies on WS in LMICs are recommended to be conducted by downscaling to sewer drainage, targeting a limited number of houses. Overall, this study supports the notion that SMFM can be an excellent economical virus-concentrating method for WS of COVID-19 in LMICs.

An atypical heterotrimeric Gα and its interactome suggest an extra-large role in overcoming abiotic and biotic stress.

Canonical heterotrimeric G-proteins (G-proteins) are comprised of Gα, Gß, and Gγ subunits. G-proteins regulate multiple crucial plant growth and development processes, incorporating environmental responses. Besides Gα, Gß and Gγ, the discovery of atypical Gα subunits termed as extra-large G-proteins or extra-large GTP-binding proteins (XLGs) makes G-protein signaling unique in plants. The C-terminus of XLG shares similarities with the canonical Gα subunits; the N-terminus harbors a nuclear localization signal (NLS) and is rich in cysteine. The earlier explorations suggest XLG's role in flowering, the development of embryos and seedlings, root morphogenesis, stamen development, cytokinin-induced development, stomatal opening and regulation of rice grain filling. The XLGs are also known to initiate signaling cascades that prime plants against a variety of abiotic and biotic stresses. They are also engaged in controlling several agronomic parameters such as rice panicle length, grain filling, grain size, and biomass, highlighting their potential contribution to crop improvement. The present review explores the remarkable properties of non-canonical Gα subunits (XLGs) and reflects on the various developmental, abiotic and biotic stress signaling pathways controlled by them. Moreover, the bottleneck dilemma of how a tiny handful of XLGs control a multiplicity of stress-responsive activities is partially resolved in this review by addressing the interaction of XLGs with different interacting proteins. XLG proteins presented in this review can be exploited to gain access to highly productive and stress-tolerant plants.

Is structural hybridization invoking new dimensions for antimalarial drug discovery research?

Despite effective prevention methods, malaria is a devastating, persistent infection caused by protozoal parasites that result in nearly half a million fatalities annually. Any progress made thus far in the eradication of the disease is jeopardized by the expansion of malaria parasites that have evolved to become resistant to a wide range of drugs, including first-line therapy. To surmount this significant obstacle, it is necessary to develop newly synthesized drugs with multiple modes of action that may have a novel target in various stages of Plasmodium parasite development and this is made possible by the hybridization concept. Hybridization is the combination of at least two diverse pharmacophore units with some linkers bringing about a single molecule with a diverse mode of action. It intensifies a drug's physiological and chemical characteristics, such as absorption, cellular target contact, metabolism, excretion, distribution, and toxicity. This review article outlines the currently published most potent hybrid drugs against the Plasmodium species.

Study of Fine Needle Aspiration Cytology (FNAC) of Thyroid Gland According to the Bethesda System.

BACKGROUND:  Fine needle aspiration cytology (FNAC) of thyroid gland is a powerful diagnostic tool for thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) classifies thyroid FNAC findings into six categories. It is a standardized, simple, and convenient method of reporting which also provides guidelines for management. AIMS AND OBJECTIVES:  To study the cytomorphology of thyroid lesions and classify them as per TBSRTC. Determine the epidemiology and distribution of various thyroid lesions in our tertiary care hospital. Correlation of cytopathology with histopathological diagnosis in cases which were operated in our hospital. METHODS AND MATERIAL:  This is a prospective analytical study of 105 patients with clinically enlarged thyroid gland presenting at G.K. General Hospital, Bhuj during July 2018 to August 2020. FNAC smears of these patients were studied and correlated with histopathology wherever available. RESULTS:  Out of a total 105 cases, 94 were non-neoplastic, eight were neoplastic, and three were unsatisfactory for evaluation. There were 94 cases in the benign category (category II), with colloid goiter being the most common cytological diagnosis (38 cases). There were no cases in categories III and V, respectively. On cytology, two cases in category IV were diagnosed as follicular neoplasm. Category VI had six cases comprising papillary carcinoma of thyroid (five cases) and medullary carcinoma of thyroid (one case). Out of a total 105 cases, 55 patients were operated in our center and hence their cytopathological findings were correlated with histopathological findings. Out of 55 operated cases, 45 cases (81.8%) had benign lesion and 10 cases (18.2%) were malignant. The sensitivity of FNAC was 70% and specificity was 100%. CONCLUSIONS:  Thyroid cytology proves to be a reliable, simple, and cost-effective first-line diagnostic procedure with high patient acceptance and with rare, usually easily treated and not life-threatening complications. The Bethesda system is very useful for a standardized and reproducible system of reporting thyroid FNAC. It satisfactorily correlates with the histopathological diagnosis and helps in comparing results amongst various institutes.

Emerging role of small GTPases and their interactome in plants to combat abiotic and biotic stress.

Plants are frequently subjected to abiotic and biotic stress which causes major impediments in their growth and development. It is emerging that small guanosine triphosphatases (small GTPases), also known as monomeric GTP-binding proteins, assist plants in managing environmental stress. Small GTPases function as tightly regulated molecular switches that get activated with the aid of guanosine triphosphate (GTP) and deactivated by the subsequent hydrolysis of GTP to guanosine diphosphate (GDP). All small GTPases except Rat sarcoma (Ras) are found in plants, including Ras-like in brain (Rab), Rho of plant (Rop), ADP-ribosylation factor (Arf) and Ras-like nuclear (Ran). The members of small GTPases in plants interact with several downstream effectors to counteract the negative effects of environmental stress and disease-causing pathogens. In this review, we describe processes of stress alleviation by developing pathways involving several small GTPases and their associated proteins which are important for neutralizing fungal infections, stomatal regulation, and activation of abiotic stress-tolerant genes in plants. Previous reviews on small GTPases in plants were primarily focused on Rab GTPases, abiotic stress, and membrane trafficking, whereas this review seeks to improve our understanding of the role of all small GTPases in plants as well as their interactome in regulating mechanisms to combat abiotic and biotic stress. This review brings to the attention of scientists recent research on small GTPases so that they can employ genome editing tools to precisely engineer economically important plants through the overexpression/knock-out/knock-in of stress-related small GTPase genes.

Delivering hypertension care in private-sector clinics of urban slum areas of India: the Mumbai Hypertension Project.

In India, the private sector provides 70% of the total outpatient medical care. This study describes the Mumbai Hypertension Project, which aimed to deliver a standard hypertension management package in private sector clinics situated in urban slums. The project was conducted in two wards (one "lean" and one "intensive") with 82 private providers in each. All hypertensive patients received free drug vouchers, baseline serum creatinine, adherence support, self-management counseling and follow-up calls. In the intensive-ward, project supported hub agents facilitated uptake of services. A total of 13,184 hypertensive patients were registered from January 2019 to February 2020. Baseline blood pressure (BP) control rates were higher in the intensive-ward (30%) compared with the lean-ward (13%). During the 14-month project period, 6752 (51%) patients followed-up, with participants in the intensive-ward more likely to follow-up (aOR: 2.31; p < 0.001). By project end, the 3-6-month cohort control rate changed little from baseline-29% for intensive ward and 14% for lean ward. Among those who followed up, proportion with controlled BP increased 13 percentage points in the intensive ward and 16 percentage points in the lean ward; median time to BP control was 97 days in the intensive-ward and 153 days in lean-ward (p < 0.001). Despite multiple quality-improvement interventions in Mumbai private sector clinics, loss to follow-up remained high, and BP control rates only improved in patients who followed up; but did not improve overall. Only with new systems to organize and incentivize patient follow-up will the Indian private sector contribute to achieving national hypertension control goals.

N-sulfonylpiperidinedispiro-1,2,4,5-tetraoxanes exhibit potent in vitro antiplasmodial activity and in vivo efficacy in mice infected with P. berghei ANKA.

The artemisinin resistance has posed a serious threat against malaria elimination lately. Past few years have seen important development of several peroxide based medicinal compounds and their derivatives such as trioxanes and tetraoxanes. Here, we report a rapid, one-pot method for synthesizing a new series of N-sulfonylpiperidine dispiro-1,2,4,5-tetraoxane analogs with diverse substitution on the tetraoxane ring i.e., various substituted alkyl and aryl sulfonyl chlorides, as well as cyclic, acyclic and aryl substituted ketones. All the synthesized tetraoxanes were characterized by spectroscopic (1H NMR,13C NMR), and spectrometric (High-resolution mass spectrometry) techniques and quantify by High Performance Liquid Chromatography (HPLC) analysis. The structure of compound 19 was confirmed by single crystal XRD. From the overall preliminary in vitro data, analogs 14, 16, 19, 20, 24, 41, and 44 exhibited potential IC50 values in the nanomolar range between 4.7 ± 0.3 to 12.9 ± 1.1 nM against P. falciparum (Pf3D7) strains of human malaria parasite. Furthermore, these selective analogs were evaluated in vivo for their antimalarial potential against P. berghei and results revealed that analogue 24 rapidly kills the infected cell at asexual erythrocytic stage, with activity comparable to positive control chloroquine.

A case report of retrograde intubation as rescue procedure in unanticipated difficult airway: an old technique still relevant in low resource settings.

In cases with an unanticipated difficult airway, retrograde intubation can be used as an alternative procedure for airway management when a fiber optic bronchoscope is unavailable. We here report a case of successful management of an unanticipated difficult airway following a failed intubation in a 34-year-old 54 kg male patient with carcinoma lateral border of tongue using retrograde intubation guided technique. Maintaining oxygenation and minimizing airway trauma should be the priority following a failed intubation. Decisions seeking alternative techniques following failed intubation are easy, if valid and applicable techniques (as per anesthesiologist's skills and available resources) are discussed before induction of anesthesia.

Cost of wastewater-based environmental surveillance for SARS-CoV-2: Evidence from pilot sites in Blantyre, Malawi and Kathmandu, Nepal.

Environmental surveillance of rivers and wastewater for SARS-CoV-2 detection has been explored as an innovative way to surveil the pandemic. This study estimated the economic costs of conducting wastewater-based environmental surveillance for SARS-CoV-2 to inform decision making if countries consider continuing these efforts. We estimated the cost of two SARS-CoV-2 environmental surveillance pilot studies conducted in Blantyre, Malawi, and Kathmandu, Nepal. The cost estimation accounted for the consumables, equipment, and human resource time costs used for environmental surveillance from sample selection until pathogen detection and overhead costs for the projects. Costs are reported in 2021 US$ and reported as costs per month, per sample and person per year. The estimated costs for environmental surveillance range from $6,175 to $8,272 per month (Blantyre site) and $16,756 to $30,050 (Kathmandu site). The number of samples processed per month ranged from 84 to 336 at the Blantyre site and 96 to 250 at the Kathmandu site. Consumables costs are variable costs influenced by the number of samples processed and are a large share of the monthly costs for ES (ranging from 39% to 72%). The relatively higher costs per month for the Kathmandu site were attributable to the higher allocation of dedicated human resources and equipment to environmental surveillance for SARS-CoV-2 compared to the Blantyre site where these resources were shared with other activities. The average cost per sample ranged from $25 to $74 (Blantyre) and $120 to $175 (Kathmandu). There were associated economies of scale for human resources and equipment costs with increased sample processing and sharing of resources with other activities. The cost per person in the catchment area per year ranged from $0.07 to $0.10 in Blantyre and $0.07 to $0.13 in Kathmandu. Environmental surveillance may be a low-cost early warning signal for SARS-CoV-2 that can complement other SARS-CoV2 monitoring efforts.

Advancement of chimeric hybrid drugs to cure malaria infection: An overview with special emphasis on endoperoxide pharmacophores.

Emergence and spread of Plasmodium falciparum resistant to artemisinin-based combination therapy has led to a situation of haste in the scientific and pharmaceutical communities. Sincere efforts are redirected towards finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. Extensive research yielded the concept of "Chimeric Bitherapy (CB)" which involves the linking of two molecules with individual pharmacological activity and exhibit dual mode of action into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next-generation antimalarial drugs and are more effective compared to the multi-component drugs because of the lower occurrence of drug-drug adverse effects. This review is an attempt to congregate complete survey on endoperoxide based hybrid antiplasmodial molecules that will give glimpse on the future directions for successful development and discovery of useful antimalarial hybrid drugs.

Lipid-rich carcinoid of the appendix: A case report with review of literature.

The carcinoids are the most frequent tumors arising from the appendix, in majority of the cases, these are asymptomatic and are discovered after appendectomy. The lipid-rich carcinoid, also known as clear cell carcinoid; is histologically characterized by the presence of clear vacuoles in the cytoplasm of tumor cells. Only 24 cases of lipid-rich carcinoid of the appendix are described in the English literature, and there is no report of this entity in the Indian literature. In this report we describe a first case of lipid-rich carcinoid of the appendix in India and also present a review of the literature.

Adjunctive Brivaracetam in Indian Patients with Uncontrolled Focal Epilepsy: Results from a Pooled Analysis of Two Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Nearly one-third of patients don't achieve seizure control with existing antiepileptic drugs. Brivaracetam (BRV) is a new member of the racetam class of drug, designed to selectively target SV2A, with binding affinity 15- to 30-fold greater than that of levetiracetam. OBJECTIVE: This pooled analysis reports efficacy and tolerability data of adjunct BRV (50, 100, and 200 mg/day) compared with placebo in Indian patients with uncontrolled focal epilepsy. METHODS: Data of 104 patients (aged 16-80 years) from 2 studies (N01252 and N01358) were pooled for this analysis. The studies comprised an 8-week prospective baseline period, and a 12-week treatment period. The study endpoints included median percent reduction from baseline in focal seizure frequency/28-days, ≥50% responder rate, and seizure freedom (all seizure types). The safety analysis included treatment-emergent adverse events (TEAEs). RESULTS: The efficacy population comprised 101 patients. In the Indian sub-group population, median percent reduction from baseline in focal seizure frequency/28-days was greater in the BRV dose groups: 39.7% (p = 0.00868), 46.8% (p = 0.00180) and 48.2% (p = 0.05224), for BRV 50, 100, 200 mg/day, respectively, compared with 20.6% for placebo. Responder rates (≥50%) were 38.1%, 45.7%, and 45.5% for BRV 50, 100, and 200 mg/day, respectively, compared with 11.7% for placebo. Complete seizure freedom was reported by 4.8% (1/21) and 2.9% (1/35) of patients on BRV50 and 100 mg/day, respectively, and none out of the 11 and 34 patients on BRV200 mg/day and placebo, respectively. In the safety population (n = 104), most commonly reported TEAEs (reported by ≥5% of patients taking brivaracetam) were headache and cough; most TEAEs were mild or moderate in intensity. CONCLUSION: This pooled analysis has provided evidence that adjunct brivaracetam, was effective and well-tolerated in Indian patients with uncontrolled focal epilepsy.

Interaction between the Antimalarial Drug Dispiro-Tetraoxanes and Human Serum Albumin: A Combined Study with Spectroscopic Methods and Computational Studies.

Dispiro-tetraoxanes, a class of fully synthetic peroxides which can be used as an antiplasmodial remedy for multiple drug-resistant strains of Plasmodium falciparum, were selected for the interaction study with human serum albumin (HSA). The insight into the interaction of the two chemically synthesized, most potent antimalarial tetraoxane analogues (TO1 and TO2) and HSA has been scrutinized using distinct spectroscopic techniques such as. UV-visible absorption, fluorescence, time-resolved fluorescence, and circular dichroism (CD). Fluorescence quenching experiments divulged the static mode of quenching and binding constants obtained (∼104) indicated the moderate affinity of the analogues to HSA. CD confirmed the conformational changes in the serum albumin upon interaction with these analogues. Molecular docking validated the empirical results as these two analogues bind through hydrophobic interactions and hydrogen bonding with HSA. Present work first defined the binding mechanism of dispiro-tetraoxanes with HSA and thus provides a fresh insight into the drug transportation and metabolism. The present study could direct toward designing more potent tetraoxane analogues for their use in the biomedical field.

Tinospora cordifolia protects from skeletal muscle atrophy by alleviating oxidative stress and inflammation induced by sciatic denervation.

ETHANOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (TC) is widely being used as immunomodulatory and re-juvenile drug and well described in Indian Ayurveda system of medicine. Rejuvenation also means the fine tuning of the skeletal muscles. Skeletal muscle related disorder, i.e. atrophy is major problem which arise due to cachexia, sarcopenia and immobilization. However, despite of the great efforts, there is scarcity of FDA approved drugs in the market to treat skeletal muscle atrophy. AIM OF THE STUDY: The current study was aimed to explore the in-vitro and in-vivo efficacy and mechanism of TC in myogenic differentiation and skeletal muscle atrophy to establish the possibility of its usage to counteract skeletal muscle atrophy. MATERIALS AND METHODS: C2C12 cell lines were used to determine myogenic potential and anti-atrophic effects of T. cordifolia water extract (TCE). Its in-vitro efficacy was re-validated in vivo by supplementation of TCE at a dose of 200 mg/kg/p.o. for 30 days in denervated mice model of skeletal muscle atrophy. Effects of TCE administration on levels of oxidative stress, inflammatory markers and proteolysis were determined. RESULTS: TCE supplementation displayed increased lymphocyte proliferation and induced myogenic differentiation of C2C12 myoblasts by significantly increasing myocytes length and thickness, in comparison to control (p < 0.05). TCE supplementation decreased oxidative stress and inflammatory response by significantly modulating activities of catalase, glutathione peroxidase, lipid peroxidase, superoxide dismutase and ß-glucuronidase (p < 0.05). It increased MF-20c expression and ameliorated degradation of muscle protein by down-regulating MuRF-1 and calpain activity. CONCLUSION: TCE supplementation promotes myogenic differentiation in C2C12 cell lines and prevents denervation induced skeletal muscle atrophy by antagonizing the proteolytic systems (calpain and UPS) and maintaining the oxidative defense mechanism of the cell. Hence, TCE can be used as a protective agent against muscle atrophy.

Interaction of coumarin triazole analogs to serum albumins: Spectroscopic analysis and molecular docking studies.

The interaction of triazole substituted 4-methyl-7-hydroxycoumarin derivatives (CUM1-4) with serum albumin (bovine serum albumin [BSA] and human serum albumin [HSA]) have been studied employing ultraviolet-visible (UV-Vis), fluorescence, circular dichroism (CD) spectroscopy, and molecular docking methods at physiological pH 7.4. The fluorescence quenching occurred with increasing concentration of CUMs, and the binding constant of CUM derivatives with BSA and HSA obtained from fluorescence quenching experiment was found to be ~ 104 L mol-1 . CD study showed conformational changes in the secondary structure of serum albumin upon titration of CUMs. The observed experimental results were further validated by theoretical studies involving density functional theory (DFT) and molecular docking.

Role of Pro-inflammatory Cytokines in Regulation of Skeletal Muscle Metabolism: A Systematic Review.

BACKGROUND: Metabolic pathways perturbations lead to skeletal muscular atrophy in the cachexia and sarcopenia due to increased catabolism. Pro-inflammatory cytokines induce the catabolic pathways that impair the muscle integrity and function. Hence, this review primarily concentrates on the effects of pro-inflammatory cytokines in regulation of skeletal muscle metabolism. OBJECTIVE: This review will discuss the role of pro-inflammatory cytokines in skeletal muscles during muscle wasting conditions. Moreover, the coordination among the pro-inflammatory cytokines and their regulated molecular signaling pathways which increase the protein degradation will be discussed. RESULTS: During normal conditions, pro-inflammatory cytokines are required to balance anabolism and catabolism and to maintain normal myogenesis process. However, during muscle wasting their enhanced expression leads to marked destructive metabolism in the skeletal muscles. Proinflammatory cytokines primarily exert their effects by increasing the expression of calpains and E3 ligases as well as of Nf-κB, required for protein breakdown and local inflammation. Proinflammatory cytokines also locally suppress the IGF-1and insulin functions, hence increase the FoxO activation and decrease the Akt function, the central point of carbohydrates lipid and protein metabolism. CONCLUSION: Current advancements have revealed that the muscle mass loss during skeletal muscular atrophy is multifactorial. Despite great efforts, not even a single FDA approved drug is available in the market. It indicates the well-organized coordination among the pro-inflammatory cytokines that need to be further understood and explored.

Interactions of a medicinal climber Tinospora cordifolia with supportive interspecific plants trigger the modulation in its secondary metabolic profiles.

Tinospora cordifolia (TC) is scientifically proven immunomodulatory drug being used for centuries. Ancient literature reported that inter-specific interactions change medicinal properties of TC. Thus, the current study is aimed to understand the influence of interspecific biotic interactions on chemo-profiles of TC. To explore it, TC samples collected from six co-occurring plants, i.e. Azarditchita indica, Acacia nilotica, Albezia lebbeck, Ficus benghalensis, Tamarandus indica and Acacia leucophloea were analyzed by HPLC-ESI-QTOF-MS. Mass data were subjected to multivariate analysis. Support vector machines (SVMs) was found to be best classifier (r2 < 0.93). Data analysis showed the specific compounds in all TC due to inter-specific interactions. Data were further analyzed with SNK post-hoc test followed by permutative (n = 50) Bonferroni FDR multiple testing correction. The compound without any missing values reduced the number of variables to 133 (p < 0.01). Statistical analysis revealed that TC having interactions with A.lebbeck and A. nilotica formed the most distant groups. However, TC co-occurred with A. indica showed the highest number of up-regulated metabolites, including jatrorrhizine, chrysin, peonidin, 6-methylcoumarin and some terpenoids. Some metabolites, including jatrorrhizine and magnoflorine were quantified to confirm the accuracy of qualitative analysis. Results demonstrated the influence of inter-specific biotic interactions on TC chemo-profiles, hence its medicinal properties.

Women's empowerment and use of contraception in India: Macro and micro perspectives emerging from NFHS-4 (2015-16).

BACKGROUND AND OBJECTIVE: Based on the four-corner stone of population and development programmes recognized by ICPD (1994) this paper envisages the relationship between the recent waves of women's empowerment anduse of contraceptive methods in India. DATA AND METHODS: Findings are based on two rounds of NFHS (3 & 4). Liberson's Diversity Index has been used to assess the inequality in women's empowerment. Multiple regression analysis is used to portray the relationship and logistic regression is used to access the adjusted effects of various dimensions of women's empowerment on use of contraception. RESULTS: Varying degrees of equity in women's empowerment across different states of India builds a combative relationship with uptake of contraceptive methods. Results portray a positive association between inequality in household decision making, engaged in paid work in last 12 months and having 10 years of schooling with use of any modern method. Women who participated in household decision making (OR = 1.17 p < 0.005), using mobile phone (OR = 1.23 p < 0.005) and working and were paid in cash in last 12 months (OR = 1.37 p < 0.005) are significantly more likely to use any method of contraception. CONCLUSIONS: Status of women in India has improved in different dimensions, yet the patriarchal norms influence the decision of using contraception. The current women-centric bottom-top approach in implementation of family planning programme should focus at the women's right to decision on their own life and health. Such efforts should hinge at strengthening inter personal counseling and capacity building sessions by outreach workers, which may empower women with enhanced knowledge about their health and bodily rights.

Depth of soil compaction predominantly affects rice yield reduction by reproductive-stage drought at varietal screening sites in Bangladesh, India, and Nepal.

AIMS: Drought is the major constraint to rainfed rice productivity in South Asia, but few reports provide detailed characterization of the soil properties related to drought stress severity in the region. The aim of the study was to provide a compilation of drought breeding network sites and their respective levels of drought stress, and to relate soil parameters with yield reduction by drought. METHODS: This study characterized levels of drought stress and soil nutrient and physical properties at 18 geographically distributed research station sites involved in rice varietal screening in Bangladesh, India, and Nepal, as well as at farmers' fields located near the research stations. RESULTS: Based on soil resistance to penetration profiles, a hardpan was surprisingly absent at about half of the sites characterized. Significant relationships of depth of compaction and yield reduction by drought indicated the effects of soil puddling on susceptibility to cracking, rather than water retention by hardpans, on plant water availability in this region. The main difference between research stations and nearby farmers' fields was in terms of soil compaction. CONCLUSIONS: These results present an initiative for understanding the range of severities of reproductive-stage drought stress in drought-prone rainfed lowland rice-growing areas in South Asia.

Guduchi Sawras (Tinospora cordifolia): An Ayurvedic drug treatment modulates the impaired lipid metabolism in alcoholics through dopaminergic neurotransmission and anti-oxidant defense system.

Tinospora cordifolia (Guduchi Sawras) though has been clearly demonstrated in literature for its hypolipidemic and anti-alcoholism properties but its anti-hyperlipidemia mechanistic approach is still missing. Moreover, its direct implication with alcohol induced hyperlipidemia has also not been reported till date. In order to explore the answers of these questions, phytochemicals of Tinospora cordifolia water extract "Guduchi Sawras" (GS) was analyzed using HPLC-Q-TOF-MS. On the basis of relative peak volumes 110 compounds were selected and identified in GS. Besides that, protein targets of most abundant compounds present in GS were fetched from ChEMBL and protein interaction network (PIN) was constructed. GO enrichment analysis showed that GS targets various pathways including dopamine metabolism, cAMP-dependent signaling pathway, and glycolytic process. Biological processes obtained via PIN were correlated with hyperlipidemia markers and dopamine metabolism in moderate alcohol consumers (n=25) and healthy volunteers (n=27) of age 41±3.8years. Metabolic analysis demonstrated the increased serotonin (1.9-fold) and decreased dopamine (-2.3-fold) levels in alcoholics. Further data analysis revealed a significant increase in urinary BCAAs (>2.0-fold), pantothenic acid (1.8-fold), carnitines (>2-fold) levels, and decrease in PPARα activation markers levels i.e. nicotinamide-1-oxide (-1.7-fold), and N-methylnicotinamide (-1.6-fold) in alcoholics. Biochemical analysis showed the increased AST/ALT ratio (1.91), along with triglycerides (20%), and MDA (34%) and GSH (56%) levels in alcoholics. GS treatment significantly reverted the most of the discussed metabolites levels (p<0.05) and enzymes activities (p<0.05) in alcoholics. The data depict that moderate chronic alcohol consumption lead to hyperlipidemia and oxidative burden; whereas GS treatment ameliorates hyperlipidemia by decreasing oxidative stress, activating PPARα, CREB and SREBP-1 through stimulation of dopamine D1 receptors mediated signalling molecules i.e. cAMP and protein kinase A.