Spatiotemporal variability identification and analysis for non-stationary climatic trends for a tropical river basin of India.

The non-stationary behavior of climatic variables has been increasingly recognized as a challenge that disrupts the equilibrium of human-defined climate-based stationary processes, including hydrological and agricultural practices, and irrigation systems. This study aims to investigate long-term trends and non-stationarity in climatic variables across 23 stations of the Krishna River basin, India. Prominent trends in rainfall, temperature, and their extreme indices were identified using the Modified Mann-Kendall (MMK), Bootstrapped Mann-Kendall (BMK), and Sen's Slope Estimator tests, while the Innovative Trend Analysis (ITA) test uncovered hidden trends and potential shifts in climatic patterns. This study addresses a critical research gap by exploring both significant and hidden trends in climatic variables, providing a better understanding of future dynamics. Traditional methods like MMK and Sen's Slope were insufficient to reveal these hidden trends, but ITA offered a more comprehensive analysis. The findings revealed an increase in total annual rainfall for almost 50% of the basin, which aligns with rising maximum temperatures, suggesting enhanced evaporation rates and subsequent fluctuations in rainfall patterns. Seasonal analysis indicated a shift towards decreased rainfall during winter and pre-monsoon seasons, contrasted by increased precipitation during the monsoon and post-monsoon periods, highlighting a clear alteration in rainfall distribution. The Simple Daily Intensity Index (SDII) and other indices suggest intensified rainfall events despite a decrease in the number of rainy days, indicating fewer but more intense events. Temperature analysis showed an overall increase in maximum temperatures, with the Diurnal Temperature Range (DTR) significantly increasing across all stations, implying greater daily temperature variations and potential for intensified water cycles and extreme climatic events. Furthermore, the study simplifies these trends by classifying them into two attributes: intensity and frequency, aiding policymakers in site-specific management of water resources and planning for future climatic scenarios. The presence of non-stationarity in extreme rainfall was confirmed by the Augmented Dickey-Fuller (ADF), Phillips-Perron (PP), and Kwiatkowski-Phillips-Schmidt-Shin (KPSS) tests. These findings are significant as they conclude how climate change is altering hydrological patterns at each station. The study emphasizes the necessity for adaptive management strategies to mitigate the adverse impacts on agriculture, infrastructure, and human safety.

SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy.

Cancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after anticancer therapies. This study illuminates the role and efficacy of smac mimetic compound BV6 alone and in co-treatment with death ligands such as TRAIL and TNFα in the regulation of cell death mechanisms, i.e., apoptosis and autophagy. In this study, MTT assays, wound healing assays, and cellular and nuclear morphological studies were done. DAPI staining, AO/EtBr staining and AnnexinV/PI FACS was done to study the apoptosis. The expression of IAPs and autophagy biomarkers was analyzed using Real time-PCR and western blotting. Meanwhile, TEM demonstrated autophagy and cellular autophagic vacuoles in response to the BV6. The result shows a promising anti-cancer effect of BV6 alone as well as in combinational treatment with TRAIL and TNFα, compared to the lone treatment of TRAIL and TNFα in both breast cancer cell lines. The smac mimetic compound might provide an alternative combinational therapy with conventional anticancer therapies to tackle their inefficiency at the advanced stage of cancer, cancer resistance, and reoccurrence. Also, IAPs and autophagic proteins could act as potent target molecules for the development of novel anti-cancer drugs in pathogenesis and the betterment of regimens for cancer.

Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus.

BACKGROUND: Chronic inorganic arsenic (iAs) exposure induces deleterious effects on CNS including oxidative stress, cognitive deficits and altered brain neurochemistry. Little is known about the association between iAs and estrogen receptor expression in brain regions. AIMS AND OBJECTIVES: Owing to the neuroprotective and estrogenic activities of resveratrol (RES), we examined the combined effects of arsenic trioxide (As2O3) and RES on neurobehavioural functions, estrogen signalling and associated neurochemical changes in mouse hippocampus. MATERIALS AND METHODS: As2O3 alone (2 and 4 mg/kg bw) or along with RES (40 mg/kg bw) was administered orally for 45 days to adult female mice. From days 33 to 45, open field, elevated plus maze and Morris water maze tests were conducted to evaluate locomotion, anxiety and learning and memory. On day 46, animals were euthanized and brain tissue and hippocampi obtained therefrom were processed for atomic absorption spectrophotometry and western blotting respectively. RESULTS: As2O3 alone exposure resulted in enhanced anxiety levels, reduced locomotion and impaired learning and memory. As2O3-induced behavioural deficits were accompanied by downregulation of estrogen receptor (ERα) expression with a concomitant reduction of BDNF and NMDAR 2B levels in the hippocampus. However, the behavioural alterations and expression of these markers were restored in RES-supplemented mice. Moreover, a dose-dependent iAs accumulation was observed in serum and brain tissues of mice receiving As2O3 alone whereas simultaneous administration of As2O3 with RES facilitated iAs efflux. CONCLUSIONS: These results suggest that reduced ERα expression with associated downregulation of BDNF and NMDAR 2B levels could be a mechanism by which iAs induces cognitive impairment; hence, the modulation of estrogen-NMDAR-BDNF pathway by RES represents a potential avenue to recover behavioural deficits induced by this neurotoxin.

Autophagy Paradox of Cancer: Role, Regulation, and Duality.

Autophagy, a catabolic process, degrades damaged and defective cellular materials through lysosomes, thus working as a recycling mechanism of the cell. It is an evolutionarily conserved and highly regulated process that plays an important role in maintaining cellular homeostasis. Autophagy is constitutively active at the basal level; however, it gets enhanced to meet cellular needs in various stress conditions. The process involves various autophagy-related genes that ultimately lead to the degradation of targeted cytosolic substrates. Many factors modulate both upstream and downstream autophagy pathways like nutritional status, energy level, growth factors, hypoxic conditions, and localization of p53. Any problem in executing autophagy can lead to various pathological conditions including neurodegeneration, aging, and cancer. In cancer, autophagy plays a contradictory role; it inhibits the formation of tumors, whereas, during advanced stages, autophagy promotes tumor progression. Besides, autophagy protects the tumor from various therapies by providing recycled nutrition and energy to the tumor cells. Autophagy is stimulated by tumor suppressor proteins, whereas it gets inhibited by oncogenes. Due to its dynamic and dual role in the pathogenesis of cancer, autophagy provides promising opportunities in developing novel and effective cancer therapies along with managing chemoresistant cancers. In this article, we summarize different strategies that can modulate autophagy in cancer to overcome the major obstacle, i.e., resistance developed in cancer to anticancer therapies.

Curcumin supplementation shows modulatory influence on functional and morphological features of hippocampus in mice subjected to arsenic trioxide exposure.

Since, oxidative stress has been suggested as one of the mechanisms underlying arsenic-induced toxicity, the present study focused on the role of antioxidant (curcumin) supplementation on behavioral, biochemical, and morphological alterations with context to mice hippocampus (CA1) following arsenic trioxide (As2O3) administration. Healthy male Swiss albino mice were divided into control and experimental groups. As2O3 (2 mg/kg bw) alone or along with curcumin (100 mg/kg bw) was administered to experimental groups by oral route for 45 days whereas the control groups received either no treatment or vehicle for curcumin. Animals were subjected to behavioral study towards the end of the experimental period (day 33-45). On day 46, the brain samples were obtained and subjected either to immersion fixation (for morphometric observations) or used afresh for biochemical test. Behavioral tests (open field, elevated plus maze, and Morris water maze) revealed enhanced anxiety levels and impairment of cognitive functions in As2O3 alone treated groups whereas a trend of recovery was evident in mice simultaneously treated with As2O3 and curcumin. Morphological observations showed noticeable reduction in stratum pyramidale thickness (CA1), along with decrease in density and size of pyramidal neurons in As2O3 alone exposed group as compared to As2O3+Cu co-treated group. Hippocampal glutathione levels were found to be downregulated in animals receiving As2O3 as against the levels of controls and curcumin supplemented animals, thereby, suggestive of beneficial role of curcumin on As2O3 induced adverse effects.

Protein purification from Arachis hypogaea in one step: stability studies and anticarcinogenic analysis.

The study involved purification of trypsin inhibitor from the seeds of Indian peanuts (Arachis hypogaea), a member of leguminosae family. The inhibitor was purified to homogeneity via three sequential step procedure i.e., salt precipitation to anion-exchange chromatography. The purity and molecular mass was detected using SDS PAGE analysis i.e. ~ 16 kDa. The purified inhibitor termed as Peanut Trypsin Inhibitor (PTI) which inhibits trypsin belonging to serpins family. Anti- neoplastic potential on breast cancer cells (MCF-7) and normal Human Embryonic Kidney cells (HEK) was determined using MTT assay. PTI exhibited IC50 value of ~ 18.412 µg/mL in HEK cells compared to ~ 9.635 µg/mL in MCF-7 cells. The values were quite comparable to curcumin, the standard anticancer drug demonstrating IC50 values of ~ 21.581 µg/mL and ~ 7.135 µg/mL in HEK and MCF-7 respectively. Therefore, we conclude that PTI may be used as supplement along with the conventional drugs for increased efficacy in the treatment of cancer.

Factors affecting outcomes of individualised treatment for drug resistant tuberculosis in an endemic region.

BACKGROUND: Individualised treatment regimens for drug resistant tuberculosis have improved outcomes. This retrospective observational study examined potential factors that affect individualised treatment in an endemic region, and highlighted predictors of a successful outcome. METHODS: We examined records of proven MDR, pre-XDR and XDR TB patients diagnosed and started on treatment between 2010 and 2014, and collected the following data for each patient: age, gender, comorbidities, past history of TB, diagnosis, site of disease, drug susceptibility testing (DST) results, treatment, adverse reactions to anti-tubercular drugs, treatment changes and outcomes, which were recorded as positive, negative or neutral. Tests of association were carried out between factors and outcomes, following which multiple logistic regression analysis was done to determine the predictors of a positive outcome such as patient cured after completion of treatment at 18 months or longer. RESULTS: Fifty-nine patients completed treatment at our centre. The median age was 26 years (range 8-65 years). There were 31 (52.5%) female patients. Forty-four (74.6%) were successfully treated over a median treatment period of 23 months (range 18-30 months). Successful outcomes were associated with age less than 45 years (P=0.01, OR=6.67, 95% CI=1.73-23.47), resistance to fewer than five drugs (P=0.001, OR=9.51, 95% CI=2.50-38.18) and susceptibility to Group 4 drugs (P=0.04, OR=4.71, 95% CI=1.03-16.83). CONCLUSIONS: Age and drug susceptibility were important predictors of treatment outcome.

Assessment of topsoil contamination in an urbanized interfluve region of Indo-Gangetic Plains (IGP) using magnetic measurements and spectroscopic techniques.

The magnetic susceptibility (MS) measurements are used for rapid and cost-effective soil surveys and for accessing heavy metal contamination worldwide. In the sub-Himalayan plains of India, nearly 6.05 × 104 km2 area of most the fertile land occurs as interfluve of Late Quaternary age between the two major glacier-fed rivers (Ganga and Yamuna). The vast areal expanse of interfluve terminates at the rivers' confluence in Sangam (25°25'13″N-81°53'22″E), Allahabad. This is the first study of MS soil survey of the interfluve region at the confluence comprising 490 samples from 49 locations. The MS values are between 8.84 and 261.25 × 10-8 m3 kg-1 and the change is more pronounced (8.84-312.65 × 10-8 m3 kg-1) with increasing depth. A sudden increase in the MS between 12- (11.28-303.32 × 10-8 m3 kg-1) and 14-cm (11.21-238.45 × 10-8 m3 kg-1) depth is observed similar to observations worldwide. The high MS hotspots are aligned parallel to major traffic networks of the city suggesting a major contribution emanating from the anthropogenic load. A significant difference has been noted in the MS values of present-day mid-channel bar sediments of Ganga (25.24 × 10-8 m3 kg-1) and Yamuna (116.47 × 10-8 m3 kg-1) Rivers. The laser-induced breakdown spectroscopy (LIBS) data showed the presence of heavy (Fe, Ti, Cr, Cu, Cd, Zn, and Pb) and light (H, C, N, and O) elements supporting MS data. The concentration of toxic elements predicted by partial least squares regression (PLSR) approach concurs with magnetic measurements. The topsoil MS values increase up to a depth of ~ 6.25 cm suggesting the dominant role of anthropogenic source for the increased heavy metal concentration compared with basement contributions.

Inconsistency in the reporting of antitubercular drug susceptibility tests in an endemic region.

BACKGROUND: Individualized treatment for multidrug-resistant tuberculosis (MDR TB) is associated with improved outcomes. Therapy needs to be tailored to drug susceptibility testing (DST) results. We present our observations on the inconsistency in DST reporting in an endemic region with a high prevalence of MDR TB. METHODS: We retrospectively analyzed 118 DST reports from 10 different laboratories. OBSERVATIONS: Of 118 patients, only 79 (67%) had DST reports with results to all first-line drugs, a fluoroquinolone (excluding ciprofloxacin), all aminoglycosides, and a polypeptide. Twenty-one (18%) isolates did not have DST reports for all first-line drugs; 4 (3%) did not have DST reports for any second-line drugs; 9 (8%) did not have DST reports for a fluoroquinolone; and 31 (26%) did not have DST reports for all second-line aminoglycosides and polypeptide. CONCLUSION: Inconsistencies were observed in several of the 118 DST reports. A case is made for sensitization toward standardization and completeness in TB DST reporting in India.

Utility of Transcutaneous Capnography for Optimization of Non-Invasive Ventilation Pressures.

INTRODUCTION: Nocturnal Non-invasive Positive Pressure Ventilation (NPPV) is the treatment of choice in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous oxygen saturation measured with a pulse oximeter provides a surrogate measure of arterial oxygen saturation but does not completely reflect ventilation. Currently, Partial Pressure of Arterial (PaCO2) measured by arterial blood analysis is used for estimating the adequacy of ventilatory support and serves as the gold standard. AIM: To examine the safety, feasibility and utility of cutaneous capnography to re-titrate the non-invasive positive pressure ventilation settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. MATERIALS AND METHODS: Twelve patients with chronic hypercapnic respiratory failure prospectively underwent complete polysomnography and cutaneous capnography measurement on the ear lobe. Non-invasive ventilation pressures were adjusted with the aim of normalizing cutaneous carbon dioxide or at least reducing it by 10 to 15 mmHg. Sensor drift for cutaneous carbon dioxide of 0.7 mmHg per hour was integrated in the analysis. RESULTS: Mean baseline cutaneous carbon dioxide was 45.4 ± 6.5 mmHg and drift corrected awake value was 45.1 ± 8.3 mmHg. The correlation of baseline cutaneous carbon dioxide and the corrected awake cutaneous carbon dioxide with arterial blood gas values were 0.91 and 0.85 respectively. Inspiratory positive airway pressures were changed in nine patients (75%) and expiratory positive airway pressures in eight patients (66%). Epworth sleepiness score before and after the study showed no change in five patients, improvement in six patients and deterioration in one patient. CONCLUSION: Cutaneous capnography is feasible and permits the optimization of non-invasive ventilation pressure settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous cutaneous capnography might serve as an important additional tool to complement diurnal arterial carbon dioxide tension values.

Who will teach the teachers: An analysis of the inhaler technique of Indian patients and health care providers in a tertiary health care centre.

INTRODUCTION: The proper use of inhalers is essential for ensuring proper control of the disease. Various studies have shown high levels of improper use and lack of knowledge of the correct technique among patients with asthma. However, less data are available on how health care workers (HCW's) use inhalers. MATERIALS AND METHODS: The study was conducted at a Tertiary Care Hospital in Mumbai. We evaluated the pMDI technique in 141 consecutive adult asthmatics and 100 HCW's. All patients and HCW's were graded out of 10 points for following 10 steps. These were derived from Melani et al.'s study on inhaler mishandling. RESULTS: Techniques of 141 patients and 100 HCW's (55 nurses and 45 doctors) were analyzed. The average technique score among patients ranged from 0 to 10 with a mean of 4.65 ± 2.00. The combined score for health workers ranged from 3 to 9 with a mean of 5.45 ± 1.47. Doctors had a higher score of 6.35 ± 1.33 as opposed to the nurses' score of 4.70 ± 1.13 (P < 0.05). There was no significant difference between scores of nurses and patients (P > 0.05). CONCLUSIONS: Our study highlights the need for better education of not only patients but also health care providers regarding the appropriate use of inhaler devices in order to achieve optimal control of obstructive airway diseases.

Bronchoscopic and surgical management of rare endobronchial tumors.

Pure endobronchial neoplasms are a rare entity, and they may present with diverse pathological findings. Malignant diseases are more common than benign ones, and they mostly originate from the surface epithelium. Endobronchial tumors usually present with symptoms such as cough, hemoptysis, recurrent pneumonia, wheezing, and chest pain. Flexible bronchoscopy is necessary for diagnosis and evaluation of these endobronchial tumors. Advance bronchoscopy or definitive surgery is the modality of treatment for these tumors based on the presentation. We present a case series of patients suffering from different rare endobronchial tumors and their management along with the review of literature.

Diagnostic value of core biopsy histology and cytology sampling of mediastinal lymph nodes using 21-gauge EBUS-TBNA needle.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the initial modality of choice in sampling mediastinal lymphadenopathy. It is possible to obtain both cytological and histological samples using both 21-gauge and 22-gauge EBUS-TBNA needles. The current study was undertaken to compare the diagnostic yield of cytology and histology samples obtained by the same EBUS-TBNA 21-gauge needle. PATIENTS AND METHODS: One hundred sixty-six consecutive patients who underwent EBUS-TBNA with a 21-gauge EBUS-TBNA needle over a period of 3 years were included in this retrospective analysis. The diagnostic yields of EBUS-TBNA histology (EBUS-TBNA-H) and EBUS-TBNA cytology (EBUS-TBNA-C) specimens were compared using the McNemar test. RESULTS: The overall sensitivity and specificity of EBUS-TBNA were 89% and 100%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of EBUS-TBNA were 100% and 53%, respectively. The overall sensitivity and specificity of EBUS-TBNA-H were 85% and 100%, respectively. The PPV and NPV of EBUS-TBNA-H were 100% and 43%, respectively. The overall sensitivity and specificity of EBUS-TBNA-C were 65% and 100%, respectively. The PPV and NPV of EBUS-TBNA-C were 100% and 14%, respectively. The diagnostic yield of EBUS-TBNA-H over EBUS-TBNA-C was statistically significant (P < 0.0001). CONCLUSION: EBUS-TBNA-H with 21-gauge needle significantly improves the diagnostic yield of EBUS-TBNA. EBUS-TBNA-H improves the NPV of EBUS-TBNA. The combination of EBUS-TBNA-H and EBUS-TBNA-C improves the overall diagnostic yield of EBUS-TBNA.

Management of Amavata with 'Amrita Ghrita': A clinical study.

Amavata is a disease caused due to the vitiation or aggravation of Vayu associated with Ama. Vitiated Vayu circulates the Ama all over the body through Dhamanies, takes shelter in the Shleshma Sthana (Amashaya, Sandhi, etc.), producing symptoms such as stiffness, swelling, and tenderness in small and big joints, making a person lame. The symptoms of Amavata are identical to rheumatism, which include rheumatoid arthritis and rheumatic fever. It is observed that rheumatism is an autoimmune disorder, which is among the collagen disorders having strong and significant parlance with Amavata. Various drug trials were already carried out on Amavata, yet there is a lacuna in the management of Amavata. Hence, in the present clinical study, 28 patients were selected and kept on 'Amrita Ghrita'. All the patients were investigated for complete blood count (CBC), rheumatoid arthritis (RA) titer, Antistreptolysin O (ASO) titer, C-reactive protein (CRP) titer, platelet count, urine routine, and microscopic, before and after treatment. The collected data was distributed according to age, sex, and prakruti, and a t-test was applied for the clinical assessment of the subjective and objective parameters of 'Amrita Ghrita,' and it has shown significant reduction in the positivity of the RA titer (t > 5.09, at the 0.001% level), ASO titer (t > 4.08, at the 0.001% level), and CRP titer (t > 4.82, at the 0.001% level), and weight gain (t > 5.12, at the 0.001% level), as also an increase in Hb% (t >9.22, at the 0.001% level), and platelet count (t> 5.90, at the 0.001% level), and decrease in ESR (t > 9.70, at the 0.001% level).