Smoking blunts sertraline response in depression: A prospective observational cohort study.

Background: Smoking is common in patients of depression and is known to affect response to antidepressants. This study was undertaken to evaluate the effect of smoking on the antidepressant effect of sertraline. Method: Patients with depression were divided into smoker and nonsmoker cohorts and followed up for 8 weeks. Serum sertraline levels were estimated using the high-performance liquid chromatography system. Response to treatment was evaluated with the Hamilton Depression Rating Scale (HAM-D). Results: Serum sertraline levels did not differ between smokers and nonsmokers at 4 and 8 weeks. Nonsmokers responded better to sertraline than smokers after 8 weeks. Adverse drug reaction profile did not vary between the two groups and was not impacted by serum sertraline levels. Nonsmokers showed a greater fall in the HAM-D score than smokers. Conclusion: This study found depression among smokers to be less responsive to sertraline. This was not explained by serum sertraline levels. Treatment of depression in smokers with sertraline might require higher doses and duration, with more frequent reviews.

Assessment of thermal and temporal stability of SARS-CoV-2 samples using real-time qRT-PCR.

BACKGROUND: As per the guidelines of the Indian Council of Medical Research, nasopharyngeal and oropharyngeal swabs in viral transport medium (VTM) are to be stored at 4 °C for less than 5 days and for more than 5 days at -70 °C. Samples are not transported or stored as per prescribed conditions because of the limitations, resulting in an apprehensive diagnosis. The aim of the study was to test the stability of the SARS-CoV-2 sample stored in VTM at different temperatures. METHODS: In this study, the stability of 21 positive and 9 negative samples for SARS-CoV-2 was evaluated in commercial VTM at different temperatures (-80 °C, -20 °C, 4 °C, and 25 to 30 °C). Stability was checked for up to 50 days in the above storage conditions at different intervals. PathoDetect™ and Hi-PCR® kits were used for the detection of the four genes of SARS-CoV-2. The Cycle Threshold (Ct) value for determining the positivity of samples for PathoDetect™ was < 40 and for Hi-PCR® was < 38. RESULTS: The SARS-CoV-2 confirmatory genes (RdRp and E genes) and the internal housekeeping gene remained detectable even on the 50th day of the study. The Ct of the RdRp and E genes were found to increase with storage duration, but all positive samples remained positive till the end of the study, or the Ct value remained below the cut-off level. The negative samples gave consistent results until the end of the study. When the differences in Ct values were compared between the days in a set of experiments, they were not significantly different except in a few samples. CONCLUSION: The SARS-CoV-2 genetic materials in commercial VTM were stable at room temperature to -80 °C for 50 days.

Emergence of Mycobacterium orygis-Associated Tuberculosis in Wild Ruminants, India.

Tuberculosis caused by Mycobacterium orygis was detected in 2 spotted deer from a wildlife sanctuary in western India and an Indian bison from a national park in central India. Nationwide surveillance is urgently required to clarify the epidemiology of the Mycobacterium tuberculosis complex at the human-livestock-wildlife interface.

Metabolism of aceclofenac to diclofenac in the domestic water buffalo Bubalus bubalis confirms it as a threat to Critically Endangered Gyps vultures in South Asia.

Vulture declines in South Asia were caused by accidental poisoning by the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Although veterinary use of diclofenac has been banned, other vulture-toxic NSAIDs are legally available, including aceclofenac, which has been shown to metabolise into diclofenac in domestic cattle. We gave nine domestic water buffalo the recommended dose of aceclofenac (2 mg kg-1 body weight), collected blood at intervals up to 48 h, and carried out a pharmacokinetic analysis of aceclofenac and its metabolite diclofenac in plasma. Aceclofenac was rapidly converted to diclofenac, and was barely detectable in plasma at any sampling time. Diclofenac was present within 20 min, and peaked 4-8 h after dosing. Aceclofenac is a prodrug of diclofenac, and behaves similarly in domestic water buffalo as it did in domestic cattle, posing the same risk to vultures. We recommend an immediate ban on the veterinary use of aceclofenac across vulture-range countries.

Tuberculosis in free-ranging and captive wild animals: Pathological and molecular diagnosis with histomorphological differentiation of granulomatous lesions.

Tuberculosis (TB) is a serious zoonotic threat, impacting the human-livestock-wildlife interface globally. Here, we evaluated the status and histomorphological differentiation of TB lesions in 89 morbid cases of wild animals (bovids, cervids, carnivores, non-human primates, and pachyderms) in India. Histomorphological and molecular studies were done using Ziehl-Neelsen (ZN) staining, immunohistochemistry, and polymerase chain reaction (PCR), whereas cultural isolation was performed on selected samples. A total of 32 (35.95%) cases were confirmed as TB, comprising of 12 carnivores, 09 bovids, 06 cervids, 04 non-human primates, and a pachyderm. The TB lesions in the lungs, liver, and lymph nodes varied from the large-sized caseous nodules filled with dry cheesy material in bovids and cervids to variable-sized cavitations containing liquefied caseum in carnivores' lungs. The lungs, livers, and spleens of non-human primates exhibited small to medium-sized nodules. Histologically, lesions were divided into four categories (Types I, II, III, and IV) based on the extent of necrosis, the presence of mineralization, giant cells, and fibrous encapsulation. Extensive caseous necrosis with calcification, abundant giant cells, and thick fibroblastic encapsulation were consistent findings in the lungs, livers, and lymph nodes of bovids and cervids, whereas airway impaction with cellular exudate containing a teeming number of acid-fast bacilli and, at times, alveolar rupture leading to cavity formation was present in the lungs of carnivores. Absence of calcification and fibrous encapsulation was recorded in lungs of non-human primates. Immunohistochemical labelling with anti-early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) antibodies showed mild, moderate, and intense positive reactions in type II and III, type I, and type IV granulomatous lesions, respectively. Molecular detection by PCR revealed Mycobacterium tuberculosis (12 carnivores, 02 non-human primates and 01 pachyderm), M. bovis (02 cervids and 01 bovid) and M. orygis (02 cervids and 01 bovid). Cultural isolation confirmed M. tuberculosis in 03 carnivores and M. orygis in 02 cervids and 01 bovid. Our findings imply that TB is quite prevalent in the wildlife of India and there are considerable differences in the histomorphological lesions induced by distinct Mycobacterium species in different wild animals. The circulation of TB organisms in wild animals warrants a strict surveillance programme to identify the carrier status of these animals so that effective TB control strategies can be formulated to prevent spillover and spillback incidences at the human-livestock-wildlife interface.

A study to investigate the chemical potency, physical stability, and efficacy of analgesic agents over a period of two years post their expiry date.

Background: As per regulations, drugs have to be used within their shelf life and must be discarded after their expiry date. The present study was conducted in commonly used analgesic agents to investigate the change in the physical, chemical, and efficacy parameters of the drugs over a period of two years after their expiry date. Methods: The drugs studied were Tab Ibuprofen, Tab Diclofenac, Tab Piroxicam, Inj Diclofenac, and Inj Piroxicam. The parameters investigated were chemical potency, physical stability, and analgesic efficacy. Testing for these parameters was carried out once before expiry to establish the baseline followed by at expiry, and then every six months for two years post expiry date. Results: The active ingredient in all the drugs were within the accepted range as per IP during the study period indicating that they retained their potency up to a period of two years post expiry. The analgesic efficacy as determined by the "Radiant Heat Tail flick" and "Acetic acid-induced writhing" model also showed no significant difference in the Maximum Possible Efficacy and Percent protection, indicating that the drugs retained their efficacy. There was a slight difference in the dissolution times at expiry as compared to different time periods in the case of Ibuprofen and Diclofenac, while there are was no statistical difference in the disintegration times during the study period. Conclusion: The analgesic drugs in our study retained their chemical potency, physical stability and analgesic efficacy up to a period of two years after expiry. The expiry date of a drug, as estimated currently, is not an accurate reflection of its actual shelf life.

SITE-SPECIFIC DRY AND WET DEPOSITION VELOCITIES USING 7BE AND MASS INTERCEPTION FACTOR FOR VARIOUS TYPES OF PLANT LEAVES AT NARORA SITE, INDIA.

Comprehensive studies were carried out during the period 2016-19 on the estimation of site-specific wet and dry deposition velocities and the mass interception factor for Narora site based on the concentrations of 7Be in air, air deposits, rain water and vegetation samples. Mean wet and dry deposition velocities for Narora site were found to be 1.64E-2 and 1.58E-3 m s-1, respectively. Mass interception factors for vegetation found to be 0.34-2.51 m2 kg-1 dry weight with a mean of 0.97 m2 kg-1 dry weight. The obtained parameters shall be used for estimation of impact due to radionuclide related to Narora Atomic Power station.

Epigenetic Modification: A Key Tool for Secondary Metabolite Production in Microorganisms.

Microorganisms are stupendous source of secondary metabolites, having significant pharmaceutical and industrial importance. Genome mining has led to the detection of several cryptic metabolic pathways in the natural producer of secondary metabolites (SMs) such as actinobacteria and fungi. Production of these bioactive compounds in considerable amount is, however, somewhat challenging. This led to the search of using epigenetics as a key mechanism to alter the expression of genes that encode the SMs toward higher production in microorganisms. Epigenetics is defined as any heritable change without involving the changes in the underlying DNA sequences. Epigenetic modifications include chromatin remodeling by histone posttranslational modifications, DNA methylation, and RNA interference. Biosynthetic gene cluster for SMs remains in heterochromatin state in which the transcription of constitutive gene is regulated by epigenetic modification. Therefore, small-molecule epigenetic modifiers, which promote changes in the structure of chromatin, could control the expression of silent genes and may be rationally employed for discovery of novel bioactive compounds. This review article focuses on the types of epigenetic modifications and their impact on gene expression for enhancement of SM production in microorganisms.

Socio-demographic features and quality of life post burn injury.

Introduction: Burn injury is a highly devastating injury accounting for the major cause of disability-adjusted life years (DALYs) lost mostly in developing countries. Physical trauma, body disfigurement, the social stigma associated with injury completely shatter an individual's life. Aim: To study the quality of life among burn injury patients. Methodology: A cross-sectional hospital-based descriptive study was done on 150 burn injury patients. During the initial recruitment from Burns and Plastic Surgery Ward, socio-demographic profile and burn incident-related data were collected, whereas the WHO QoL-BREF tool was applied after 3 months of discharge during a follow-up visit in the outpatient department of Burns and Plastic Surgery to assess the quality of life among subjects. Data were compiled in MS Excel and statistical analysis was done using SPSS 20 version. Results: The study revealed poor quality of life among four domains of QoL; it was most inferior in the psychological domain followed by the physical health domain, environment domain, and social relationship domain. Conclusion: Advancement in the medical field has improved the survival rate in victims although the patients recover from the acute painful phase of physical trauma. However, the psychological and social impacts of injury remain unaddressed leading to a poor QoL. There is a need for an integrated approach for prevention and enhancement of the quality of care for the victims in all four domains of life. More emphasis is needed on rehabilitative care for long-term improvement in the QoL of the affected person.

Molecular and pathological screening of canine distemper virus in Asiatic lions, tigers, leopards, snow leopards, clouded leopards, leopard cats, jungle cats, civet cats, fishing cat, and jaguar of different states, India.

The present investigation was conducted to rule out canine distemper (CD) diseases in Indian wild felids (Asiatic lions, tigers, leopards, snow leopards, clouded leopards, leopard cats, jungle cats, civet cats, fishing cat, and jaguar). The collected samples were screened for CD virus (CDV) by histopathology (HP), immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) targeting H gene and N gene. The HP and IHC of suspected samples portrayed that 22 [11 leopards, 6 lions, 3 tigers, 1 snow leopard and 1 civet cat] out of 129 (17.05%) wild felids were positive for CD. The major pathological consequences were observed in spleen, lung, kidney and brain. The syncytia and intranuclear as well as intracytoplasmic eosinophilic inclusion bodies were seen in CDV infected cells. Although the histopathological lesions in spleen were more specific and consistent, however, the severe demyelinated leukoencephalitis (usually expected in CD infected dog) was not observed in the brain of any Indian wild felids. Conversely, the CDV antigen has been portrayed via IHC in pancreatic islets of Langerhans of tiger species for the first time in this study. Moreover, the concurrent CD and babesiosis has also been observed in a lioness without a usual coffee-coloured urine. The N gene and H gene of CDV isolates were amplified, sequenced and subsequently constructed the phylogenetic tree. The phylogenetic analysis of H gene revealed that the CDV isolates from Indian lion formed separate clade with CDV isolates from Indian dog and Indian palm civet cat. Furthermore, two CDV isolates from Indian tigers formed clade with Onderstepoort vaccine strain and CDV isolates from dogs of Uttar Pradesh, USA and UK. Evidently, CDV is circulating in Indian wild felids and causing diseases in them.

Pre-COVID-19 pandemic: effects on air quality in the three cities of India using fuzzy MCDM model.

Due to urbanization and industrialization pollution level increases. Air pollution directly affects to human health. Air Quality Indices (AQI) method is related to measuring the concentration of different pollutants PM10, NO2, SO2 and other pollutants. The fuzzy Logic air quality index calculates in single value of AQI defines limits 0 to 1. In this study, a comparison of air quality data of three cities was conducted with the help of fuzzy logic algorithm. It used to evaluating Indices through fuzzy multi criteria decision making (MCDM) framework in which linguistic terms of experts opinion and perception, accordingly computing matrix is constructed for sub criteria. There are five linguistic terms used in this framework to create membership functions such as high significant, significant, average significant, low significant and not significant. The three cities, Bangalore, Mysore, and Hubli-Dharwad air quality datas was taken for analysis and evaluating indices during pre-COVID years (2017, 2018, and 2019). The AQI value shows that Bangalore has the highest pollution level while Mysore has the lowest. Using the fuzzy theory, results show that Bangalore and Hubli-Dharwad decrease in pollution level by -0.074921% and -0.04797%. Negative sign shows the decrease pollution level while Mysore increase pollution level by 0.011792%. Overall the results show that AQI of Mysore city is low compared to Bangalore and Hubli-Dharwad. Also, this study reveals air quality disseminated through industrial processes and automobile emissions in India cities during pre-COVID pandemic years.

Experimental safety testing shows that the NSAID tolfenamic acid is not toxic to Gyps vultures in India at concentrations likely to be encountered in cattle carcasses.

Population declines of Gyps vultures across the Indian subcontinent were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Subsequently, a number of other NSAIDs have been identified as toxic to vultures, while one, meloxicam, is safe at concentrations likely to be encountered by vultures in the wild. Other vulture-safe drugs need to be identified to reduce the use of those toxic to vultures. We report on safety-testing experiments on the NSAID tolfenamic acid on captive vultures of three Gyps species, all of which are susceptible to diclofenac poisoning. Firstly, we estimated the maximum level of exposure (MLE) of wild vultures and gave this dose to 40 Near Threatened Himalayan Griffons G. himalayensis by oral gavage, with 15 control birds dosed with benzyl alcohol (the carrier solution for tolfenamic acid). Two birds given tolfenamic acid died with elevated uric acid levels and severe visceral gout, while the remainder showed no adverse clinical or biochemical signs. Secondly, four G. himalayensis were fed tissues from water buffaloes which had been treated with double the recommended veterinary dose of tolfenamic acid prior to death and compared to two birds fed uncontaminated tissue; none suffered any clinical effects. Finally, two captive Critically Endangered vultures, one G. bengalensis and one G. indicus, were given the MLE dose by gavage and compared to two control birds; again, none suffered any clinical effects. The death of two G. himalayensis may have been an anomaly due to i) the high dose level used and ii) the high ambient temperatures at the time of the experiment. Tolfenamic acid is likely to be safe to Gyps vultures at concentrations encountered by wild birds and could therefore be promoted as a safe alternative to toxic NSAIDs. It is manufactured in the region, and is increasingly being used to treat livestock.

Primary malignant melanoma of the gastroesophageal junction: A rare and unusual disease.

Malignant melanoma, an aggressive tumor of skin, is also seen rarely in extra cutaneous sites like the gastrointestinal tract (GIT). Primary melanoma of the GIT by itself is a rare tumor; often metastatic at presentation and if found non-metastatic, it is rarely resectable. We are reporting a histopathologically confirmed case of primary malignant melanoma affecting the 'gastroesophageal junction', which we operated on.

Multi-drug resistant (MDR), extended spectrum beta-lactamase (ESBL) producing and carbapenem resistant Escherichia coli in rescued Sloth bears (Melursus ursinus), India.

The study reports the multi-drug resistant (MDR), extended spectrum beta-lactamase (ESBL) producing and carbapenem resistant Escherichia coli (CRE) isolated from rescued sloth bear (Melursus ursinus), India. Non-duplicate faecal samples from 21 adult rescued sloth bears were collected at once during 2015-2016 and processed for isolation of E. coli and antibacterial susceptibility pattern. From 21 samples, 45 E. coli were isolated and on phenotypic screening, 23 were MDR, 17 were ESBL producers, and five were carbapenem-resistant (CR). Three E. coli isolates (6.67%, 3/45) showed no resistance, however 42 isolates (93.33%, 42/45) exhibited resistant to at least one antibiotics. The MDR isolates carried beta-lactamase, chloramphenicol, aminoglycosides, tetracycline, fluroquinolone, and sulphadimidine resistance genes. All the phenotypic ESBL producing isolates harbored blaCTX-M genes. On genotypic screening, three CRE (60.0%, 3/5) were positive for blaNDM carbapenemase gene and efflux pump-mediated carbapenem resistance was detected in two CRE isolates (40.0%, 2/5) which were negative for carbapenemase genes. The CRE isolates (n = 5) also co-harbored AMR genes like blaTEM-1, blaAmpC, qnrA, qnrB, qnrS, tetA, tetB and sulI. Virulence screening of the resistant isolates detected the presence of Stx1(n = 1), Stx2 (n = 3), eaeA (n = 4) and hlyA (n = 3) genes. Plasmid incompatibility (Inc) typing revealed that two isolates harboured blaNDM-5 gene on Incl1 and one isolate on IncF plasmid. Apart from the NDM gene, the plasmids also carried tetracycline, beta-lactamase and quinolone resistance genes. The plasmid multilocus sequence typing (pMLST) of the E. coli Incl1 plasmid showed the Sequence Type (ST) 297. This appears to be the first report of MDR, ESBL producing and blaNDM-5 genes on Incl1 and IncF plasmids from rescued sloth bear.

An evaluation of medication appropriateness in pregnant women with coexisting illness in a tertiary care hospital.

AIM: Prescribing drugs during pregnancy needs careful consideration of benefit to the mother and risk to the fetus. Therefore, this study was conducted to evaluate the appropriateness of medications among pregnant women with coexisting illness in a tertiary care hospital, Western India. MATERIALS AND METHODS: It was a hospital-based cross-sectional study conducted in the obstetrics and gynecology department of a tertiary care hospital. The study was conducted over a period of 12 months wherein data from 800 pregnant women suffering from any co-existing illness and being prescribed any medication apart from routine supplementation were analyzed. The Medication Appropriateness Index (MAI) was used to assess the appropriateness of medications. Higher MAI scores indicate more inappropriate prescribing. RESULTS: Drugs which were most inappropriately prescribed with the highest average MAI scores were albendazole, itraconazole, injection amikacin, oxcarbazepine, warfarin, domperidone, propylthiouracil, and combiflam (ibuprofen + paracetamol). Diseases with the highest average MAI scores were anemia, Grave's disease, umbilical hernia, urinary tract infection, urticaria, allergic rhinitis, and preeclampsia. The MAI criteria which had the highest percentage of inappropriately prescribed medications were "cost of drugs," "duration of therapy," and "indication." CONCLUSION: Potentially inappropriate prescribing was seen in the study with some of the common coexisting illness being treated with drugs which fared poorly on the MAI. The study has also highlighted areas in drug prescribing where scope for improvement exists. Further, it can act as a benchmark for comparison of future studies to evaluate medication appropriateness in pregnant women.

Dual trace inter-pulse interferometer for measurement of phase stability of ultra short laser pulse train.

A dual trace intra-pulse and inter-pulse spatio-spectral interferometer has been set up to study the temporal stability of a ∼200 fs duration laser pulse train from a cw mode-locked laser oscillator. Simultaneous recording of twin interferograms helps identify the phase error in inter-pulse interferograms due to the diagnostic setup kept in a standard laboratory environment. Applicability of inter-pulse tilted pulse-front interferograms has been demonstrated to constitute an alternative inexpensive method for visual detection and estimation of phase slippage and pulse repetition frequency of an ultra short pulse train. The effect of pump beam intensity on the repetition rate of pulses due to accumulated intra-cavity non-linear phase shifts is also presented.

Use of knotless barbed sutures for closure of intraoral incisions for maxillofacial trauma: a randomised controlled trial.

The objective of this study was to assess the efficacy of knotless barbed sutures in intraoral wound closure for maxillofacial trauma in comparison with conventional (vicryl) sutures. This was a randomised controlled clinical trial involving 40 patients with isolated mandibular angle fractures who required intraoral incisions for open reduction and internal fixation (ORIF). The sample was randomised into the study group (20 patients) and control group (20 patients). Following fracture fixation by a standardised surgical protocol, the wound closure was done with bidirectional knotless barbed suture and vicryl for the study and control groups, respectively. The wounds were closed in layers (periosteum and mucosa). All operations were performed by a single surgeon. Outcome parameters measured were intraoperative wound closure time and wound healing using 'Landry's wound healing index' on the first, third, and seventh postoperative days. Statistically significant difference in suturing time was noted between the study and control group (p value <0.001). The study group demonstrated a mean (SD) suturing time of 9.46 (2.01) minutes, compared with the 17.61 (2.57) minutes in the control group. Wound healing was found to be better and statistically significant in the study group than the control group (p value<0.001). Knotless barbed suture is a promising alternative to vicryl for intraoral wound closure.

Efficacy and safety of a single-tablet regimen containing tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and efavirenz 400 mg as a switch strategy in virologically suppressed HIV-1-infected subjects on nonnucleoside reverse transcriptase inhibitor-containing first-line antiretroviral therapy in Pune, India.

OBJECTIVES: As per National AIDS Control Organization (NACO) estimates, there are 2.1 million people living with HIV (PWH) in India, of whom 1.2 million are on first-line antiretroviral therapy (ART). This study explored the use of a single-tablet regimen containing tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + efavirenz 400 mg (TLE400 STR) as a first-line switch strategy in PWH in Pune, India. METHODS: This retrospective cohort study was conducted in private sector ART clinics in three tertiary-level hospitals in Pune, India. PWH > 12 years of age (n = 502) who initiated first-line ART (predominantly TLE600 STR), completed ≥ 6 months of follow-up and achieved virological suppression [plasma viral load (VL) < 1000 HIV-1 RNA copies/mL] were identified and switched to TLE400 STR. The virological and immunological efficacy of TLE400 STR at 6 and 12 months of follow-up were noted. Grade 3/4 adverse events (especially efavirenz-related neuropsychiatric adverse events) leading to regimen discontinuation were also noted. RESULTS: Of 502 PWH who switched to TLE400 STR, complete virological suppression (VL < 20 copies/mL) was maintained in more than 97% of patients at follow-up. TLE400 STR was successful in maintaining CD4 counts within the range observed at the start of the regimen. Grade 3/4 adverse events leading to TLE400 STR discontinuation were seen in 11 (2.2%) patients. Virological failure (VL > 1000 copies/mL) and treatment regimen failure were seen in six (1.2%) and 49 (9.8%) subjects, respectively. CONCLUSIONS: TLE400 STR exhibits excellent efficacy and safety as a switch strategy and should be introduced in the Indian National ART Program, especially for PWH who are virologically suppressed on TLE600 STR.