Impact of comorbidities and inflammatory markers on mortality of COVID-19 patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes coronavirus disease 2019 (COVID-19) is a serious global health concern. The severity of the disease can be determined by serologic indicators such as C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6. (IL-6). Patients with preexisting conditions such as respiratory, cardiovascular, and pulmonary disease could be at risk of adverse outcomes. It is crucial to provide adequate medical care to manage these patients and increase their chances of survival. AIM: The study examined the impact of comorbidity and inflammatory markers on the severity and mortality of hospitalised COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 101 COVID-19 patients who had comorbidities and were hospitalised from April 2021 to April 2022. RESULTS: Patients with a severe COVID-19 infection could be anticipated to have higher levels of inflammatory markers in their blood. Patients with chronic kidney and coronary artery disease have a worse prognosis than those with other comorbidities (P value <0.001). However, tuberculosis had no statistically significant effect on mortality and showed a minimal chance of death (P value = 0.303). In addition, tocilizumab performed poorly and was ineffective against the COVID-19 treatment. However, ivermectin exhibited a statistically significant probability of survival in COVID-19 patients. CONCLUSION: The inflammatory markers D-dimer, ferritin, and IL-6 were identified as valuable indicators of disease severity. Further, chronic kidney disease and coronary artery disease were identified as risk factors for mortality, while tuberculosis showed potential protective effects. The study showed that higher neutrophil levels were linked to mortality in tocilizumab-treated patients, while ivermectin showed promise in increasing survival rates.

Factors associated with unexplained sudden deaths among adults aged 18-45 years in India - A multicentric matched case-control study.

BACKGROUND OBJECTIVES: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study. METHODS: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). RESULTS: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. INTERPRETATION CONCLUSIONS: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.

Mitotic DNA Synthesis in Untransformed Human Cells Preserves Common Fragile Site Stability via a FANCD2-Driven Mechanism That Requires HELQ.

Faithful genome duplication is a challenging task for dividing mammalian cells, particularly under replication stress where timely resolution of late replication intermediates (LRIs) becomes crucial prior to cell division. In human cancer cells, mitotic DNA repair synthesis (MiDAS) is described as a final mechanism for the resolution of LRIs to avoid lethal chromosome mis-segregation. RAD52-driven MiDAS achieves this mission in part by generating gaps/breaks on metaphase chromosomes, which preferentially occur at common fragile sites (CFS). We previously demonstrated that a MiDAS mechanism also exists in untransformed and primary human cells, which is RAD52 independent but requires FANCD2. However, the properties of this form of MiDAS are not well understood. Here, we report that FANCD2-driven MiDAS in untransformed human cells: 1) requires a prerequisite step of FANCD2 mono-ubiquitination by a subset of Fanconi anemia (FA) proteins, 2) primarily acts to preserve CFS stability but not to prevent chromosome mis-segregation, and 3) depends on HELQ, which potentially functions at an early step. Hence, FANCD2-driven MiDAS in untransformed cells is built to protect CFS stability, whereas RAD52-driven MiDAS in cancer cells is likely adapted to prevent chromosome mis-segregation at the cost of CFS expression. Notably, we also identified a novel form of MiDAS, which surfaces to function when FANCD2 is absent in untransformed cells. Our findings substantiate the complex nature of MiDAS and a link between its deficiencies and the pathogenesis of FA, a human genetic disease.

Rhino-orbito-cerebral mucormycosis during Covid-19 pandemic- a prospective observational study.

OBJECTIVE: An unprecedented rise in mucormycosis cases; apparently called 'an epidemic within a pandemic' was seen worldwide. Therefore, the following study was conducted to know the epidemiology, underlying risk factors, diagnostic approach, and possible outcome of mucormycosis during the Covid-19 pandemic. METHODS: A prospective observational study was conducted on patients with a high index of clinical suspicion of mucormycosis Data about demographics, co-morbidities, laboratory investigations, radiology, management, and outcomes were collected. RESULTS: We got 45 cases of proven Rhino-orbital-cerebral-mucormycosis (ROCM) from clinically suspected cases. Covid-19 was the most common underlying risk factor (n â€‹= â€‹41, 91.11%) followed by Diabetes mellitus (DM) (n â€‹= â€‹39; 86.67%). Steroids and oxygen usage were noted in 53.66% (n â€‹= â€‹22) and 41.46% (n â€‹= â€‹17) respectively. Among the 51 suspected cases of mucormycosis, 47 were supported by radiodiagnosis. Histopathology diagnosed the highest number of mucormycosis cases (n â€‹= â€‹44; 97.78%), followed by KOH examination (n â€‹= â€‹36; 80%) and Culture (n â€‹= â€‹28; 62.22%). The most common species isolated from the tissue samples was Rhizopus species (n â€‹= â€‹17; 60.71%), followed by Mucor species (n â€‹= â€‹7; 25%). The mortality rate was 17.14%. CONCLUSION: DM, Covid-19, and corticosteroids are the chief underlying risk factor for ROCM. Rhizopus spp. was the most dominant etiological agent. Early diagnosis and management with combined medical & surgical intervention have a better survival rate.

Mitochondria-targeted metformin (mitomet) inhibits lung cancer in cellular models and in mice by enhancing the generation of reactive oxygen species.

Lung cancer is the leading cause of cancer-related mortality in the United States. Although some epidemiological studies have shown an inverse relationship between the use of metformin, a widely used antidiabetic drug, and the incidence of lung cancer, the real benefits of the drug are unclear as the efficacy is low and the outcomes are quite heterogeneous. To develop a more potent form of metformin, we synthesized mitochondria-targeted metformin (mitomet) and tested its efficacy in in vitro and in vivo models of lung cancer. Mitomet was cytotoxic to transformed bronchial cells and several non-small cell lung cancer (NSCLC) cell lines but relatively safe to normal bronchial cells, and these effects were mediated mainly via induction of mitochondrial reactive oxygen species. Studies using isogenic A549 cells showed that mitomet was selectively toxic to those cells deficient in the tumor suppressor gene LKB1, which is widely mutated in NSCLC. Mitomet also significantly reduced the multiplicity and size of lung tumors induced by a tobacco smoke carcinogen in mice. Overall, our findings showed that mitomet, which was about 1000 and 100 times more potent than metformin, in killing NSCLC cells and reducing the multiplicity and size of lung tumors in mice, respectively, is a promising candidate for the chemoprevention and treatment of lung cancer, in particular against LKB1-deficient lung cancers which are known to be highly aggressive.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Secondary infections in critically ill patients with COVID-19: A retrospective single-center study.

Background: Patients infected with COVID-19 admitted to the intensive care unit (ICU) may have a higher incidence of developing secondary infections. These infections can further deteriorate the hospital course and increase mortality. Therefore, the objectives of this study were to investigate the incidence, associated risk factors, outcomes, and pathogens associated with secondary bacterial infections in critically ill patients with COVID-19. Methods: All adult COVID-19 patients admitted to the intensive care unit requiring mechanical ventilation from October 1, 2020 until December 31, 2021 were screened for inclusion in the study. A total of 86 patients were screened and 65 who met the inclusion criteria were prospectively entered into a customized electronic database. The database was then retrospectively analyzed to investigate secondary bacterial infections. Results: Of the 65 patients included, 41.54% acquired at least one of the studied secondary bacterial infections during the course of their ICU stay. The most common secondary infection (59.26%) seen was hospital-acquired pneumonia followed by acquired bacteremia of unknown origin (25.92%) and catheter-related sepsis (14.81%). Diabetes mellitus (P = <.001), cumulative dose of corticosteroids (P = 0.001), were associated with an increased risk of secondary bacterial infection. The most commonly isolated pathogen in patients with secondary pneumonia was Acinetobacter baumannii. Staphylococcus aureus was the most common organism associated with a bloodstream infection and catheter-related sepsis. Conclusion: The incidence of secondary bacterial infections was high in critically ill patients with COVID-19 and was associated with a longer duration of admission to the hospital and ICU and a higher mortality. Diabetes mellitus and cumulative dose of corticosteroids were associated with significantly increased risk of secondary bacterial infection.

Inhibition of lung adenocarcinoma by combinations of sulfasalazine (SAS) and disulfiram-copper (DSF-Cu) in cell line models and mice.

Sulfasalazine (SAS) is a repurposed antitumor drug which inhibits the proliferation and survival of cancer cells by inhibiting the xCT cellular antioxidant system. Recent clinical studies have shown that, due to poor bioavailability, the antitumor effects of SAS monotherapy are minimal. Therefore, we hypothesized that DSF, another repurposed drug that has demonstrated anticancer effects, or its complex with copper (DSF-copper, DSF-Cu) could potentiate the antilung cancer effects of SAS. Exposure of non-small cell lung cancer cells to therapeutically achievable concentrations of SAS-induced low-to-moderate cytotoxic effects (20-40% reduction in cell viability) and, unexpectedly, induced the antioxidant protein NRF2 and its downstream effectors xCT and ALDH1A1. However, combinations of SAS and DSF-Cu, but not SAS and DSF, induced a significantly higher cytotoxic effect (64-88% reduction in cell viability), apoptosis and generation of mitochondrial reactive oxygen species as compared with SAS or DSF-Cu alone. Moreover, DSF-Cu abrogated SAS-induced NRF2, xCT and ALDH1A1 expression. In a mouse model of lung tumor, SAS + DSF-Cu showed a higher efficacy than the individual drugs in reducing the number and size of tumors as well as the incidence and multiplicity of lung adenocarcinoma. Taken together, our findings indicate that the observed antilung cancer effects of SAS plus DSF-Cu are mediated, at least in part, via impairment of reactive oxygen species defense and -enhancement of oxidative stress and provide evidence for the preventive/therapeutic potential of this combinatorial approach against lung cancer.

Prevalence of bronchial asthma in school going children: A cross-sectional study from Uttar Pradesh.

Background: Asthma is coined as a chronic inflammatory disorder and disarrays of the airways and respiratory tract which manifests as recurrent episodes of wheezing, breathlessness, chest tightness, and cough. The World Health Organization recognizes asthma as a major health problem. Although asthma can occur at any age, children and young adults are the age groups which are affected more commonly. Objectives: The objective of this study is to find the prevalence of bronchial asthma in school-going children (6-16 years) and its associated factors. Materials and Methods: A cross-sectional study among the school-going children in the age group of 6-16 years was done in the field practice areas of urban health and training center and rural health and training center of the Department of Community Medicine, JNMCH, A. M. U., Aligarh, U.P. the study done for a period of one year. The validated questionnaire (International Study on Allergy and Asthma in Childhood) was used. The sample size was taken as 902. The data were entered and analyzed in the SPSS statistical software version 20.0. Chi-square was used. Results: The prevalence of asthma among the study population was found to be 26.9%. Family history of smoking and history of allergy in an individual came out to be a significant factor associated with asthma. The association is also significant between asthma and the diet of an individual. Conclusions: Asthma among school children is a public health problem in urban and rural areas. There was a rising pattern in the prevalence of asthma at national and subnational levels.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Withania somnifera (L.) Dunal as Add-On Therapy for COPD Patients: A Randomized, Placebo-Controlled, Double-Blind Study.

Background: The current gold-standard therapies for chronic obstructive pulmonary disease (COPD) lack disease-modifying potential and exert adverse side effects. Moreover, COPD patients are at a higher risk of severe outcomes if they get infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of the current epidemic. This is the first study to document clinical research on an adaptogenic and steroidal activity-containing herb as a complementary medicine for COPD treatment. Objective: We aimed to evaluate the efficacy of Withania somnifera (L.) Dunal [Solanaceae] (WS) as an add-on therapy for COPD patients. Methods: A randomized, placebo-controlled, and double-blind clinical study was conducted. A total of 150 patients were randomly assigned to three groups: control, placebo, and WS group. In addition to conventional medicines, WS root capsules or starch capsules were given twice a day to the WS group and the placebo group, respectively. Their lung functioning, quality of life, exercise tolerance, systemic oxidative stress (OS), and systemic inflammation were assessed before and after 12 weeks of intervention. WS root phytochemicals were identified by LC-ESI-MS. The inhibitory activity of these phytochemicals against angiotensin-converting enzyme 2 (ACE-2); the SARS-CoV-2 receptor; myeloperoxidase (MPO); and interleukin-6 (IL-6) was evaluated by in silico docking to investigate the mechanism of action of WS. Results: The pulmonary functioning, quality of life, and exercise tolerance improved, and inflammation reduced notably the most in the WS group. Systemic oxidative stress subsided significantly only in the WS group. Although a minor placebo effect was observed in the SGRQ test, but it was not present in other tests. Withanolides found in the WS roots demonstrated substantial inhibitory activity against the proteins ACE-2, MPO, and IL-6, compared to that of a standard drug or known inhibitor. Moreover, FEV1% predicted had significant correlation with systemic antioxidative status (positive correlation) and malondialdehyde (MDA, negative correlation), suggesting that the antioxidative potential of WS has significant contribution to improving lung functioning. Conclusion: Our study clinically demonstrated that WS root when given along with conventional drugs ameliorated COPD significantly more in comparison to the conventional drugs alone, in GOLD 2 and 3 categories of COPD patients. In silico, it has potent inhibitory activity against SARS-CoV-2 receptor, ACE-2, MPO, and IL-6.

OPTCLOUD: An Optimal Cloud Service Selection Framework Using QoS Correlation Lens.

Cloud computing has grown as a computing paradigm in the last few years. Due to the explosive increase in the number of cloud services, QoS (quality of service) becomes an important factor in service filtering. Moreover, it becomes a nontrivial problem when comparing the functionality of cloud services with different performance metrics. Therefore, optimal cloud service selection is quite challenging and extremely important for users. In the existing approaches of cloud service selection, the user's preferences are offered by the user in a quantitative form. With fuzziness and subjectivity, it is a hurdle task for users to express clear preferences. Moreover, many QoS attributes are not independent but interrelated; therefore, the existing weighted summation method cannot accommodate correlations among QoS attributes and produces inaccurate results. To resolve this problem, we propose a cloud service framework that takes the user's preferences and chooses the optimal cloud service based on the user's QoS constraints. We propose a cloud service selection algorithm, based on principal component analysis (PCA) and the best-worst method (BWM), which eliminates the correlations between QoS and provides the best cloud services with the best QoS values for users. In the end, a numerical example is shown to validate the effectiveness and feasibility of the proposed methodology.

Impaired GABAergic and glutamatergic neurometabolic activity in aged mice brain as measured by 1 H-[13 C]-NMR spectroscopy.

Healthy aging is associated with a decline in cognitive function, and is a major risk factor for many neurodegenerative diseases. Although, there are several evidence that brain mitochondrial function is altered with aging its significance at the cellular level is elusive. In this study, we have investigated mitochondrial TCA cycle and neurotransmitter cycle fluxes associated with glutamatergic, GABAergic neurons and astroglia in the cerebral cortex and hippocampus of young (6 months) and aged (24 months) C57BL6 mice by using 1 H-[13 C]-NMR spectroscopy together with timed infusion of 13 C-labeled glucose and acetate. The ratio VCyc /VTCA was determined from a steady-state [2-13 C]acetate experiment. Metabolic fluxes were obtained by fitting a three-compartment metabolic model to 13 C turnover of amino acids from glucose. Levels of glutamate, aspartate and taurine were reduced in the cerebral cortex, while glutamine and choline were elevated in the hippocampus of aged mice. Interestingly, the rate of acetate oxidation increased in the cerebral cortex, while the flux of mitochondrial TCA cycle of glutamatergic neurons decreased in the cerebral cortex (P < .0001) and hippocampus (P = .025) of aged mice. The glutamate-glutamine neurotransmitter cycle flux was reduced in the cerebral cortex (P < .0001). The GABAergic TCA cycle flux was reduced in the cerebral cortex (P = .0008), while GABA-glutamine neurotransmitter cycling flux was also reduced in the cerebral cortex (P = .011) and hippocampus (P = .042) of aged brain. In conclusion, the reduction in excitatory and inhibitory neurotransmitter activity of glutamatergic and GABAergic neurons in the cerebral cortex and hippocampus correlates qualitatively with declined cognitive function in aged mice.

Effect of Obstructive Sleep Apnea on Bone Mineral Density.

OBJECTIVE: Various studies have suggested that obstructive sleep apnea (OSA) affects bone metabolism. One of the most significant factors is hypoxia which induces certain transcription factors that stimulate bone osteoclastic activity. It also induces respiratory acidosis and oxidative stress which enhances bone resorption. Leptin and melatonin secretions are regulated by the circadian system which is affected due to sleep fragmentation in OSA. Other comorbidities associated with OSA such as vitamin D deficiency, hypogonadism, obesity, and insulin resistance are indirect mechanisms that affect bone mineral density (BMD). MATERIAL AND METHODS: This is a prospective case-control study. All patients having symptoms of sleep-related breathing disorder (excluding post-menopausal females or patients with known case of osteoporosis or any other clinical illness which is a direct cause of osteoporosis) attending the Sleep Out Patient Department (OPD) were screened for OSA as per the STOPBANG questionnaire scoring system. Participants having score >2 constituted the final study population and were subjected to the polysomnography test. Participants with an apnea-hypopnea index (AHI) > 5 in polysomnography were considered as cases and those with AHI <5 were considered as controls. Both the groups were then subjected for dual-energy X-ray absorptiometry (DEXA) scan and vitamin D to establish a comparison. RESULTS: Out of 93 participants, 59 were taken as cases (OSA group), whose mean age was 48.02 (±8.435) years, mean body mass index (BMI) was 33.73 (±7.48) kg/m2, mean neck circumference was 37.8 cm (±5.08) as compared with the age, sex, and BMI matched non-OSA control group (n = 34). Mean BMD in the case group was found to be significantly on the lower side as compared with the control group (-2.02 ± 1.09 vs. -1.03 ± 0.97) (P < .001) when compared in Z score, while (0.885 ± 0.535 vs. 0.933 ± 0.616) when compared in g/cm2 (P < .001), with negative correlation between AHI and BMD (r = -0.507, P < .001). Mean vitamin D level in the case group was at a lower level as compared to the control group (21.02 ± 7.27 vs. 24.48 ± 6.92, P < .05), with negative correlation between AHI and serum vitamin D level (P < .001, r = -0.286). CONCLUSION: OSA affects BMD by various pathophysiologic mechanisms. The AHI is inversely correlated with BMD; that is, with increasing severity of OSA, there is a decrease in BMD.

Profile of drug-resistant-conferring mutations among new and previously treated pulmonary tuberculosis cases from Aligarh region of Northern India.

Background: The prevalence of multidrug-resistant-tuberculosis (MDR-TB) among new and previously treated cases is increasing worldwide as well as in India. Rapid detection of MDR-TB allows the establishment of an effective treatment regimen; minimizes the risk of further resistance, and limits the spread of drug-resistant strains. Early diagnosis of MDR-TB is the need of the hour in high-TB burden countries like India, and GenotypeMTBDRplus is quite sensitive and specific in determining the molecular resistance in drugs such as rifampicin and isoniazid. Methods: The present study was done for molecular detection of rifampicin and isoniazid resistance and resistance patterns among MDR-TB suspects and comparison of resistance patterns among new and previously treated cases by GenoType® MTBDRplus Line Probe Assay. A total of 1268 sputum samples of MDR-TB suspects were subjected to fluorescent microscopy. Fluorescent microscopy positive samples were subjected to GenoType® MTBDRplus (HAIN Lifescience) assay. Results: MDR-TB was detected 11.02%, 20.03% in new and previously treated cases. Among MDR-TB patients S531 L was the most common mutation detected in rpoB gene; 71.43% in new, and 72.17% in previously treated cases. S315T1 was the most common mutation noted in katG gene; 100% in new and 81.74% in previously treated. While in hA gene, it was C15T (7.8%) among previously treated cases. Conclusion: MDR-TB has high prevalence in the western part of Uttar Pradesh, India. Previously treated cases have even more high rate of MDR-TB than new TB cases. The most dominant gene mutations associated with resistance to INH and RIF were observed in codon 315 of the katG gene and codon 531 of the rpoB gene. While comparing the mutation patterns by Genotype MTBDRplus assay, previously treated cases showed more diversity of mutations and had greater number of unknown mutations.

Comparing the profile of respiratory fungal pathogens amongst immunocompetent and immunocompromised hosts, their susceptibility pattern and correlation of various opportunistic respiratory fungal infections and their progression in relation to the CD4+T-cell counts.

INTRODUCTION: Invasive fungal infections are increasingly common in the nosocomial setting. MATERIALS AND METHODS: The patients were divided into two groups immunocompetent and immunocompromised that is, patients with significant neutropenia <500 neutrophils/µl for longer than 10 days. microscopy, culture, identification of isolates were done and some specilised tests on serum and BAL for antigen detection were performed. RESULTS: Majority of the patients were young adult males in this study. A higher prevalence of 26.7% was seen in immunocompromised patients. Amongst yeasts, Candida albicans was the predominant species followed by the National AIDS Control that is, Candida glabrata, Candida dubliniensis, Candida parapsilosis and Candida tropicalis in the same order. Amongst moulds, Aspergillus fumigatus was the most common species followed by Aspergillus flavus and Aspergillus niger. Mucor and Penicillium marneffei were seen in a lower prevalence. By Broth microdilution method, isolates of Candida spp. were most sensitive to caspofungin, amphotericin B, ketoconazole and fluconazole in the same order. Isolates of Aspergillus spp. were most sensitive to caspofungin, amphotericin B and itraconazole in the same order. By disc diffusion method, resistance to fluconazole was observed in 6.9% isolates of C. albicans. 50% of C. dubliniensis and 20% of C. glabrata showed resistance to fluconazole. A total mortality of 27.7% was observed during this study. This was distributed as 24.1%, 26.7%, 50%, 50%, 100% and 0% among by patients of candidiasis, aspergillosis, cryptococcosis, pneumocystosis, mucormycosis and penicilliosis. Fifteen per cent were lost to follow-up. CONCLUSION: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.

Correlation of exhaled carbon monoxide level with disease severity in chronic obstruction pulmonary disease.

INTRODUCTION: Amplification of airway inflammation and its destruction due to oxidative stress is a major step in the pathogenesis of chronic obstruction pulmonary disease (COPD). Exhaled carbon monoxide (eCO) may be quantified to evaluate the airway inflammation and oxidative stress in such patients. OBJECTIVES: To assess the disease severity of COPD and treatment response by measuring eCO as a biomarker. MATERIALS AND METHODS: COPD patients diagnosed according to the global initiative for chronic obstructive lung disease guidelines and healthy individuals as controls were selected. One hundred and fifty patients with COPD and 125 controls were included in the study. Participants were further subdivided on the basis of their smoking habits. Clinical examinations and spirometry were done to diagnose COPD by following the standard protocol. eCO was measured using a piCO + Smokerlyzer (Breath CO Monitor, Bedfont Scientific Ltd., Kent, UK). It was a single-center cross-sectional study. RESULTS: Mean (± standard error of mean) CO levels in ex-smokers with COPD were higher (5.21 ± 1.546 ppm; P < 0.05) than in nonsmoking controls (1.52 ± 0.571 ppm) but were lower than in current smokers with COPD (12.55 ± 4.514 ppm; P < 0.05). eCO levels were higher in current smokers with COPD (12.55 ± 4.514 ppm; P < 0.05) compared to healthy smokers (9.71 ± 5.649). There was a negative correlation between eCO and forced expiratory volume in 1 s (FEV1) in COPD (r = -0.28; P < 0.05). The mean eCO level was decreased (6.291-4.332; P < 0.001) with improvement in lung function (FEV1 38.75%-50.65%: P < 0.05) after treatment with inhaled steroid. CONCLUSION: Our study concludes that quantification of eCO level in COPD varies with different grades of airway obstruction and to measure the treatment response. Measuring the level of eCO can be used to assess the indirect assessment of airway inflammation, oxidative stress, and severity of airway obstruction in COPD patients.

A Novel Benzocoumarin-Stilbene Hybrid as a DNA ligase I inhibitor with in vitro and in vivo anti-tumor activity in breast cancer models.

Existing cancer therapies are often associated with drug resistance and toxicity, which results in poor prognosis and recurrence of cancer. This necessitates the identification and development of novel therapeutics against existing as well as novel cellular targets. In this study, a novel class of Benzocoumarin-Stilbene hybrid molecules were synthesized and evaluated for their antiproliferative activity against various cancer cell lines followed by in vivo antitumor activity in a mouse model of cancer. The most promising molecule among the series, i.e. compound (E)-4-(3,5-dimethoxystyryl)-2H-benzo[h]chromen-2-one (19) showed maximum antiproliferative activity in breast cancer cell lines (MDA-MB-231 and 4T1) and decreased the tumor size in the in-vivo 4T1 cell-induced orthotopic syngeneic mouse breast cancer model. The mechanistic studies of compound 19 by various biochemical, cell biology and biophysical approaches suggest that the compound binds to and inhibits the human DNA ligase I enzyme activity that might be the cause for significant reduction in tumor growth and may constitute a promising next-generation therapy against breast cancers.