Optimization of phytase production by Penicillium oxalicum in solid-state fermentation for potential as a feed additive.

The study aims to statistically optimize the phytase production by Penicillium oxalicum PBG30 in solid-state fermentation using wheat bran as substrate. Variables viz. pH, incubation days, MgSO4, and Tween-80 were the significant parameters identified through the Plackett-Burman design (PBD) that majorly influenced the phytase production. Further, central composite design (CCD) method of response surface methodology (RSM) defined the optimum values for these factors i.e., pH 7.0, 5 days of incubation, 0.75% of MgSO4, and 3.5% of Tween-80 that leads to maximum phytase production of 475.42 U/g DMR. Phytase production was also sustainable in flasks and trays of different sizes with phytase levels ranging from 394.95 to 475.42 U/g DMR. Enhancement in phytase production is 5.6-fold as compared to unoptimized conditions. The in-vitro dephytinization of feed showed an amelioration in the nutritive value by releasing inorganic phosphate and other nutrients in a time-dependent manner. The highest amount of inorganic phosphate (33.986 mg/g feed), reducing sugar (134.4 mg/g feed), and soluble protein (115.52 mg/g feed) was achieved at 37 °C with 200 U of phytase in 0.5 g feed for 48 h. This study reports the economical and large-scale production of phytase with applicability in enhancing feed nutrition.

JB Sharma's white cotton ball sign: A new laparoscopic sign in abdominopelvic tuberculosis.

BACKGROUND: Abdominopelvic tuberculosis (TB) is a variant of extrapulmonary TB causing significant morbidity, including infertility. MATERIALS AND METHODS: Results of 87 cases of diagnostic laparoscopy in cases of abdominopelvic TB diagnosed on composite reference standard (CRS) for demonstration of new laparoscopic white cotton ball sign are presented. RESULTS: Mean age, parity and duration of infertility were 27.2 years, 0.21 and 3.1 years, respectively. Oligomenorrhoea and hypomenorrhea were seen in 35 (40.22%) and 32 (36.78%) cases, while infertility was seen in all 87 (100%) cases while abdominal mass was seen in 27 (31.03%) cases and pelvic mass in 37 (42.58%) cases. Positive acid fast bacilli on microscopy and culture of endometrial biopsy was seen in 3.34% and 6.89% cases while epithelioid granuloma was seen in 12.64% cases on endometrial biopsy and in 13.79% cases on peritoneal biopsy. Positive polymerase chain reaction was seen in all cases while definitive abdominal pelvic TB was seen in 35 (40.1%) cases and probable findings in 42 (48.27%) cases. A new laparoscopic white cotton ball sign (resembling a large white cotton ball) was observed in 5 (5.74%) cases and biopsy from 3 showed it to be epithelioid granulomas positive. CONCLUSION: Demonstration of a new white cotton ball sign on laparoscopy seems to be a useful finding in abdominal pelvic TB.

Comparative study on complications and difficulties in laparoscopy in female genital tuberculosis cases versus non-tuberculosis cases.

BACKGROUND AND OBJECTIVE: Female genital tuberculosis (FGTB) is an important type of extrapulmonary tuberculosis (TB) associated with morbidity especially infertility in developing countries. Laparoscopy may be difficult and hazardous in FGTB. The aim of the study was to observe the difficulties and complications of laparoscopy in FGTB cases. MATERIALS AND METHODS: It was a prospective study over 12 years' period on 412 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling for acid-fast bacilli (AFB) microscopy, culture, polymerase chain reaction (PCR), gene Xpert (last 212 cases) and histopathological evidence of epithelioid granuloma. Another 412 cases of diagnostic laparoscopy in the absence of FGTB performed during same time were taken as controls from the pool of non-TB cases. Various difficulties and complications were noted in both groups and statistical analysis was done. RESULTS: Mean age, parity, body mass index and duration of infertility were 26.8 versus 25.4 years, 0.32 versus 0.28, 23.15 versus 25.28 Kg/m 2 and 4.15 versus 5.12 years, respectively. Primary and secondary infertility was seen in 78.6% and 20.38% of cases in the study group and 74.75% and 25.24% in the control group, respectively. Endometrial biopsy showed AFB microscopy in 5.3%, culture in 6.3%, epithelioid granuloma in 15.77% and on peritoneal biopsy granuloma in 6.55%, positive PCR in 368 (89.32%) and positive gene Xpert in 38 out of 212 (17.92%, out of last 212 cases). Definite findings of FGTB were seen in 171 (41.50%) cases. Probable findings of FGTB were seen in 241 (58.49%) cases. Various complications were difficulty in the creation of pneumoperitoneum or insertion of trocar and cannula in 16.74% and 13.10% of cases as compared to 1.94% and 1.69% in the control group. Excessive bleeding was seen in 5.09% versus 0.97% cases, respectively. Various injuries observed were bowel injury in 1.69% versus 0.24% cases (small bowel in 1.21% vs. 0.24%, large bowel in 0.48% vs. 0.1%), while bladder injury was seen in 0.97% versus 0.24% cases, subacute intestinal obstruction was seen in 5.8% versus 0.72% cases respectively while flare up of TB was seen in 5.09% versus 0% in cases and controls, respectively. Wound infection was seen in 8.48% versus 1.25% cases, respectively. INTERPRETATION AND CONCLUSION: FGTB is associated with increased complications and difficulties as compared to laparoscopy in other cases.

To assess the analgesic efficacy of adjuvant magnesium sulfate added with ropivacaine over ropivacaine alone as a continuous infiltration in total abdominal hysterectomy wound: A randomized controlled trial.

Background and Aims: Magnesium sulfate (MgSO4) has been demonstrated to have analgesic property in various clinical settings. This study explores if addition of MgSO4 to ropivacaine increases its analgesic efficacy when infiltrated continuously in the postsurgical wound following total abdominal hysterectomy. Material and Methods: This randomized controlled trial was conducted at a tertiary care referral hospital in New Delhi, India. Fifty-two patients were randomized into two groups to receive the intervention of which 48 were able to complete the study. The first group (n = 26) received 0.25% ropivacaine infiltration and the second group (n = 26) received 0.25% ropivacaine with 5% MgSO4 at the incision site for 48 h postoperatively. Primary objective was to compare the total postoperative opioid (morphine) consumption by the study participants in both the groups and the secondary objectives were pain scores at rest and at movement, patient satisfaction score, and wound quality of life on the 7th postoperative day among the two groups. Results: Both the groups were comparable in their demographic characteristics. The median morphine consumed at 48 h postoperatively was 16.5 [0-77] mg in the ropivacaine group and 13[1-45] mg in the ropivacaine with MgSO4 group and the difference was statistically insignificant (P = 0.788). There was no statistical difference between the groups with respect to the pain scores, patient satisfaction, or wound quality of life at 7 days. Conclusion: The addition of MgSO4 to ropivacaine does not confer any additional postoperative analgesic benefits over ropivacaine alone in continuous wound infiltration following total abdominal hysterectomy.

Laparoscopic evaluation of female genital tuberculosis in infertility: An observational study.

Background & objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB. Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB. Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases. Interpretation & conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.

Unveiling the Significance of FGF8 Overexpression in Orchestrating the Progression of Ovarian Cancer.

The asymptomatic nature, high rate of disease recurrence, and resistance to platinum-based chemotherapy highlight the need to identify and characterize novel target molecules for ovarian cancer. Fibroblast growth factor 8 (FGF8) aids in the development and metastasis of ovarian cancer; however, its definite role is not clear. We employed ELISA and IHC to examine the expression of FGF8 in the saliva and tissue samples of epithelial ovarian cancer (EOC) patients and controls. Furthermore, various cell assays were conducted to determine how FGF8 silencing influences ovarian cancer cell survival, adhesion, migration, and invasion to learn more about the functions of FGF8. In saliva samples, from controls through low-grade to high-grade EOC, a stepped overexpression of FGF8 was observed. Similar expression trends were seen in tissue samples, both at protein and mRNA levels. FGF8 gene silencing in SKOV3 cells adversely affected various cell properties essential for cancer cell survival and metastasis. A substantial reduction was observed in the cell survival, cell adhesion to the extracellular matrix, migration, and adhesion properties of SKOV3 cells, suggesting that FGF8 plays a crucial role in the development of EOC. Conclusively, this study suggests a pro-metastatic function of FGF8 in EOC.

Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus.

In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer's results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes.

Insights into microbial diversity on plastisphere by multi-omics.

Plastic pollution is a major concern in marine environment as it takes many years to degrade and is one of the greatest threats to marine life. Plastic surface, referred to as plastisphere, provides habitat for growth and proliferation of various microorganisms. The discovery of these microbes is necessary to identify significant genes, enzymes and bioactive compounds that could help in bioremediation and other commercial applications. Conventional culture techniques have been successful in identifying few microbes from these habitats, leaving majority of them yet to be explored. As such, to recognize the vivid genetic diversity of microbes residing in plastisphere, their structure and corresponding ecological roles within the ecosystem, an emerging technique, called metagenomics has been explored. The technique is expected to provide hitherto unknown information on microbes from the plastisphere. Metagenomics along with next generation sequencing provides comprehensive knowledge on microbes residing in plastisphere that identifies novel microbes for plastic bioremediation, bioactive compounds and other potential benefits. The following review summarizes the efficiency of metagenomics and next generation sequencing technology over conventionally used methods for culturing microbes. It attempts to illustrate the workflow mechanism of metagenomics to elucidate diverse microbial profiles. Further, importance of integrated multi-omics techniques has been highlighted in discovering microbial ecology residing on plastisphere for wider applications.

India's Opportunities and Challenges in Establishing a Twin Registry: An Unexplored Human Resource for the World's Second-Most Populous Nation.

Nature and nurture have always been a prerogative of evolutionary biologists. The environment's role in shaping an organism's phenotype has always intrigued us. Since the inception of humankind, twinning has existed with an unsettled parley on the contribution of nature (i.e. genetics) versus nurture (i.e. environment), which can influence the phenotypes. The study of twins measures the genetic contribution and that of the environmental influence for a particular trait, acting as a catalyst, fine-tuning the phenotypic trajectories. This is further evident because a number of human diseases show a spectrum of clinical manifestations with the same underlying molecular aberration. As of now, there is no definite way to conclude just from the genomic data the severity of a disease or even to predict who will get affected. This greatly justifies initiating a twin registry for a country as diverse and populated as India. There is an unmet need to set up a nationwide database to carefully curate the information on twins, serving as a valuable biorepository to study their overall susceptibility to disease. Establishing a twin registry is of paramount importance to harness the wealth of human information related to the biomedical, anthropological, cultural, social and economic significance.

Assessment of preoperative and postoperative cardiac function in children with adenotonsillar hypertrophy: a prospective cohort study.

PURPOSE: Chronic upper airway obstruction caused by adenotonsillar hypertrophy is one of the major cause of morbidity in children. It can lead to Obstructive Sleep Apnoea Syndrome, Pulmonary Hypertension, Cor Pulmonale and right heart failure. The study aimed to evaluate and compare various parameters of cardiac function with the help of echocardiography preoperatively and postoperatively in children undergoing adenotonsillectomy. METHODOLOGY: A prospective cohort study was conducted on 23 patients at an apex care institute, under the age group of 4-12 years, who were diagnosed with adenotonsillar hypertrophy. Preoperative symptom analysis and Echocardiographic examination were done. After the assessment, all patients underwent surgery in the form of adenotonsillectomy. Follow-up symptom analysis and echocardiographic examination was done after 3 months postoperatively. RESULTS: Significant improvement in the obstructive symptoms were noted in postoperative group as expected (p = < 0.001) and also in parameters such as mPAP (p = < 0.001), TAPSE (p = < 0.001), TAV (p = 0.001), Ejection fraction (p = 0.027) and RVMPI (p = 0.044) were improved in postoperative group. 4 patients had Grade 1 Right ventricular diastolic dysfunction, which disappeared in three patients postoperatively. CONCLUSION: We have concluded that there can be subclinical cardiac dysfunctions which occurs as a result of chronic upper airway obstruction due to untreated adenotonsillar hypertrophy. Routine cardiac screening in children presenting with sleep disordered breathing associated with adenotonsillar hypertrophy may be helpful in identifying and preventing the development of cardiopulmonary complication. These changes can be reversed by performing adenotonsillectomy.

On Admission, Microcirculation Abnormality is an Independent Predictor of Sepsis and Sepsis-related Mortality: A Hospital-based Study.

Background: Microcirculatory derangement is the primary cause of organ dysfunction in patients with sepsis. Assessment of the microcirculation is usually done by means of indirect parameters (SvO2 transcutaneous PO2 serum lactate.) The aim of our study is to understand microcirculatory abnormalities in patients with sepsis by directly visualizing the tiny vessels using hand-held video microscopes (HVMs) and determining the role of this modality in the prediction of sepsis-related mortality. Methods: A longitudinal prospective hospital-based study was carried out in medical ward and ICU of a tertiary care hospital. Patients admitted with the presumed infectious disease were included. Evaluation of sublingual microcirculation was done in these patients from Day 1 to Day 5 Clinical and laboratory variables and microcirculation variables were compared between patients with or without sepsis and between survivors and non-survivors of sepsis. Chi-square test for categorical and Student's t-test or Wilcoxon rank-sum test for continuous variables were applied. Univariate and multivariate regression analyses were performed using the Cox-proportional hazard model. Results and discussion: On admission, microcirculation assessment measure, PPV (small), was significantly reduced in those with sepsis, as compared to those without sepsis. Multivariable models indicate the inverse relationship of PPV small with mortality. How to cite this article: Panda A, Revadi G, Sharma JP, Pakhare A, Singhai A, Joshi R, et al. On Admission, Microcirculation Abnormality is an Independent Predictor of Sepsis and Sepsis-related Mortality: A Hospital-based Study. Indian J Crit Care Med 2022;26(3):294-301.

Weaning Outcomes and 28-day Mortality after Tracheostomy in COVID-19 Patients in Central India: A Retrospective Observational Cohort Study.

BACKGROUND: Tracheostomy is integral in long-term intensive care of coronavirus disease-2019 (COVID-19) patients. There is a paucity of studies on weaning outcomes and mortality after tracheostomy in COVID-19 in Indian scenario. MATERIALS AND METHODS: We conducted a retrospective, single-center, observational study of severe COVID-19 patients who underwent elective tracheostomy (n = 65) during critical care in a tertiary care institute in Central India from May 1, 2020, to April 30, 2021. Data were collected from Medical records, ICU charts, and follow-up visits by patient. A primary objective was to study the clinical characteristics, tracheostomy complications, weaning outcomes, and mortality at 28 and 60 days of ICU admission. We categorized the cohort into two groups (deceased and survivor) and studied association of clinical parameters with 28-day mortality. Cox Proportional regression analysis was applied to calculate the hazard ratio among the predictors of mortality with p value <0.05 as significant. RESULTS: Elective tracheostomy was done in 69 of 436 (15.8%) patients on invasive mechanical ventilation, of which 65 were included. Tracheostomy was percutaneous in 45/65 (69%) and surgical in 20/65 (31%) with timing from intubation as early in 41/65 and late in 24/65 with most common indication as weaning failure followed by anticipated prolonged ventilation. Tracheostomy complications were present in 29/65 (45%) patients with no difference in complication rates between timing and type of tracheostomy. Downsizing, decannulation, and weaning were successful in 22%, 32 (49%), and 35/65 (54%) patients after tracheostomy. The 28-day mortality was 30/65 (46%). The fractional inspired oxygen concentration (FiO2) requirement in survivors was lower (0.4-0.6, p = 0.015) with a higher PaO2/FiO2 ratio (118-200, p = 0.033). Early tracheostomy within 7 days of intubation was not associated with weaning or survival benefit. CONCLUSIONS: We suggest that tracheostomy should be delayed to after 7 days of intubation, especially till FiO2 reduces to 0.5 with improvement in PaO2/FiO2 for better outcomes and avoiding a wasted procedure (CTRI/2021/07/034768). STUDY HIGHLIGHTS: Tracheostomy is integral in care of COVID-19 patients needing prolonged ventilation. There is no difference in complications in early/late or percutaneous dilatational/surgical technique. We observed successful weaning post-tracheostomy in 54% patients. Mortality at 28 days was 46%. Early tracheostomy within 7 days of intubation did not improve weaning or survival. HOW TO CITE THIS ARTICLE: Karna ST, Trivedi S, Singh P, Khurana A, Gouroumourty R, Dodda B, et al. Weaning Outcomes and 28-day Mortality after Tracheostomy in COVID-19 Patients in Central India: A Retrospective Observational Cohort Study. Indian J Crit Care Med 2022;26(1):85-93.

Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India.

Background: The outcomes in critical illness depend on disease severity, practice protocols, workload, and access to care. This study investigates the factors affecting outcomes in mechanically ventilated coronavirus disease-2019 acute respiratory distress syndrome (COVID-19 ARDS) patients admitted in a tertiary teaching hospital intensive care unit (ICU) in Central India with reference to different time periods in pandemic. This is one of the largest series of mechanically ventilated COVID-19 ARDS patients, globally. Methods: This retrospective cohort study classified the entire data into four time periods (Period 1: April 2020 to June 2020; Period 2: July 2020 to September 2020; Period 3: October 2020 to December 2020; and Period 4: January 2021 to April 2021). We performed a multivariable-adjusted analysis to evaluate predictors of mortality, adjusted for baseline-severity, sequential organ failure assessment (SOFA score) and time period. We applied mixed-effect binomial logistic regression to model fixed-effect variables with incremental complexity. Results: Among the 56 survivors (19.4%) out of 288 mechanically ventilated patients, there was an up-gradient of survival proportion (0, 18.2, 17.4, and 28.6%) in four time periods. Symptom-intubation interval (OR 1.16; 95% CI 1.03-1.31) and driving pressures (DPs) (OR 1.17; 95% CI 1.07-1.28) were significant predictors of mortality in the model having minimal AIC and BIC values. Patients aged above 60 years also had a larger effect, but statistically insignificant effect favoring mortality (OR 1.99; 95% CI 0.92-4.27). The most complex but less parsimonious model (with higher AIC/BIC) indicated the protective odds of high steroid on mortality (OR 0.59; 95% CI 0.59-0.82). Conclusion: The outcomes in mechanically ventilated COVID-19 ARDS patients are heterogeneous across time windows and may be affected by the complex interaction of baseline risk and critical care parameters. How to cite this article: Saigal S, Joshi A, Panda R, Goyal A, Kodamanchili S, Anand A, et al. Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India. Indian J Crit Care Med 2022;26(9):1022-1030.

Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.

PURPOSE: To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS: Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS: Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS: Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.

Frequency and Impact of Preadmission Digestive Symptoms on Outcome in Severe COVID-19: A Prospective Observational Cohort Study.

BACKGROUND: Coronavirus disease-2019 (COVID-19) commonly presents with respiratory symptoms. However, symptoms involving the digestive system may be present, significance of which is not well studied in the Indian scenario. METHODS: This prospective observational cohort study included consecutive patients with severe COVID-19 admitted to intensive care unit of our tertiary care hospital from September 9, 2020, to March 14, 2021. We evaluated the frequency of preadmission digestive symptoms and compared the demographic, clinical, laboratory parameters, and organ failure at admission and during intensive care along with mortality between those with and without digestive symptoms. In the digestive group, we sought to find predictors of mortality. RESULTS: Digestive symptoms were present in 76/234 (32.4%) with severe COVID-19 infection. In comparison to nondigestive group, digestive patients had higher need for noninvasive ventilation (p 0.028), invasive lines (68%, p 0.003), vasopressors (64%, p 0.01), blood product transfusion (21.1%, p <0.001), and heart failure (55.4%, p 0.041). Confounding factors of alcohol abuse, smoking, sedentary lifestyle as a causative agent for heart failure could not be ruled out. Proportional mortality rate is higher in the digestive group (65.8%, p = 0.015). Mortality is multifactorial with preadmission abdominal pathologies (HR 4.3) or central nervous system (CNS)-related comorbidities (HR 2.829), presentation with multiple digestive symptoms (HR 6.9), higher sequential organ failure assessment score (SOFA) score at admission (HR 1.258) and discharge (HR 1.162), and presence of acute kidney injury (AKI) Grade 3 (HR 2.95) as predictors of mortality. After adjusting for all confounders, need for vasopressor was observed to be associated with 11.58 times higher risk of mortality. CONCLUSION: Preadmission digestive symptoms may be associated with a turbulent illness with invasive interventions, heart failure, and greater proportional mortality in severe COVID-19. AKI Grade 3 is identified as a preventable risk factor predicting mortality. CTRI/2021/03/032325. HOW TO CITE THIS ARTICLE: Karna ST, Singh P, Revadi G, Khurana A, Shivhare A, Saigal S, et al. Frequency and Impact of Preadmission Digestive Symptoms on Outcome in Severe COVID-19: A Prospective Observational Cohort Study. Indian J Crit Care Med 2021;25(11):1247-1257.

Endometrial stromal cell inflammatory phenotype during severe ovarian endometriosis as a cause of endometriosis-associated infertility.

RESEARCH QUESTION: Do endometrial stromal cells from primary infertile patients with severe ovarian endometriosis display differential secretory profiles of inflammation-associated cytokines during the implantation window that may cause infertility? DESIGN: Forty-eight cytokines were measured in conditioned medium of isolated endometrial stromal cells obtained from primary infertile patients without endometriosis (control group, n = 12) or with stage IV ovarian endometriosis (ovarian endometriosis group, n = 14) using multiplex assays. Key cytokines showing differential secretory profiles were validated using Western immunoblotting. Cellular phenotypic validation was carried out in vitro by comparing proliferation and migration capacity between control (n = 6) and ovarian endometriosis (n = 7) groups. RESULTS: CCL3, CCL4, CCL5, CXCL10, FGF2, IFNG, IL1RN, IL5, TNFA, and VEGF could be detected only in the conditioned media of stromal cells obtained from the ovarian endometriosis group. Among other cytokines detected in the conditioned media of both groups, CCL2 (P = 0.0018), CSF3 (P = 0.0017), IL1B (P = 0.0066), IL4 (P = 0.036), IL6 (P = 0.0039) and IL13 (P = 0.036) were found to be higher, whereas the concentration of IL18 was lower (P = 0.023) in the ovarian endometriosis group. Concentrations of CCL2, IL1B, IL4 and IL13 in conditioned medium reflected significant diagnostic performance for predicting ovarian endometriosis. Cellular phenotypic validation in vitro revealed an enhanced proliferative phenotype (P = 0.046) with no change in cell migratory capacity of endometrial stromal cells from the ovarian endometriosis group. CONCLUSIONS: Endometrial stromal cells derived from severe ovarian endometriosis samples displayed a hyperinflammatory and hyperproliferative bias in the endometrial stroma during the 'window of implantation' putatively causing loss of fecundability.

Diagnostic utility of mitral annular displacement by speckle tracking echocardiography in predicting significant coronary artery disease in suspected chronic stable angina pectoris.

BACKGROUND: More than 50% of patients currently referred for coronary angiography (CAG) with suspected chronic stable angina pectoris (CSAP) shows normal or nonobstructive CAD. Mitral annular displacement (MAD) is a function of global shortening deformation of left ventricle (LV) and mirrors sub-endocardial ischemia in CAD. The aim of this study was to ascertain if MAD can predict the presence of CAD in patient presenting with suspected CSAP. METHODS: This cross-sectional study was conducted on patients with suspected CSAP (n = 140) and preserved LV function without apparent wall motion abnormalities during the study period. We excluded patients with prior heart disease (valvular, ischemic), presenting with acute coronary syndrome, arrhythmia, heart failure, and poor imaging. All the patients were subjected to speckle tracking echocardiography (STE) and CAG. Average MAD and normalized MAD were calculated by automated function imaging (AFI), and receiver operating characteristic (ROC) curve was plotted for presence of significant CAD considering CAG as gold standard. RESULTS: The results showed that both average MAD (4 segment) and normalized MAD were significantly reduced (P = <.001) in patients with significant CAD (n = 81). In ROC analysis, area under curve (AUC) for predicting significant CAD in patients of CSAP was better for normalized MAD (0.88) compared to average MAD (4 segment, 0.85).The optimal cutoff of normalized MAD and average MAD for detection of significant CAD were ≤15.3% (sensitivity 90.1%, specificity 79.7%) and ≤11.19 (sensitivity 84%, specificity 69.5%), respectively. Normalized MAD showed week inverse correlation with SYNTAX score (-0.24, R2  = 0.058) and Hs CRP (-0.23, R2  = 0.057). CONCLUSION: MAD is a simple and rapid noninvasive diagnostic tool which accurately predicted the presence of significant CAD in patients with CSAP.

Aerobic biodegradation of high explosive hexahydro-1,3,5- trinitro-1,3,5-triazine by Janibacter cremeus isolated from contaminated soil.

OBJECTIVE: To evaluate the ability of Janibacter cremeus a soil bacterium isolated from explosive contaminated site in degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and to study enzyme responsible for degradation. RESULTS: The isolate exhibited 88% degradation of RDX in 30 days of incubation. The biodegradation process followed the first order kinetics. The half- life of RDX was calculated to be 11.088 days. The RDX degradation process was complemented by concomitant release of nitrite ions with 0.78 mol of nitrite released per mole of RDX. The metabolites; Trinitroso- RDX, diamino-RDX, trimino-RDX, bis- (hydroxymethyl) nitramine and methylenedintramine derivative, viz, methylene- N- (hydroxy- methyl)- hydroxylamine- N-(hydroxymethyl) nitroamine corresponding to the molecular weights 174, 162, 132, 122 and 167 Da respectively were also detected. Nitroreductase enzyme was found to be responsible for RDX degradation. CONCLUSION: J. cremeus could degrade RDX as sole source of nitrogen, via three different pathways wherein, Nitroreductase enzyme was found to play a major role. The efficient degradation of RDX makes J. cremeus suitable in treatment of contaminated water and soil at field scale levels.

Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility.

BACKGROUND: Previous studies, which were primarily based on the fluorescent in-situ hybridisation (FISH) technique, revealed conflicting evidence regarding male foetal microchimerism in endometriosis. FISH is a relatively less sensitive technique, as it is performed on a small portion of the sample. Additionally, the probes used in the previous studies specifically detected centromeric and telomeric regions of Y chromosome, which are gene-sparse heterochromatised regions. In the present study, a panel of molecular biology tools such as qPCR, expression microarray, RNA-seq and qRT-PCR were employed to examine the Y chromosome microchimerism in the endometrium using secretory phase samples from fertile and infertile patients with severe (stage IV) ovarian endometriosis (OE) and without endometriosis. METHODS: Microarray expression analysis followed by validation using RNA-seq and qRT-PCR experiments at the RNA levels and further validation at the DNA level by qPCR of target inserts for selected targets in eutopic endometrium samples obtained from control (CON) and stage IV ovarian endometriosis (OE), either from fertile (FCON and FOE; n = 30/each) or infertile (ICON and IOE; n = 30/each) women, were performed. RESULTS: Six coding (AMELY, PCDH11, SRY, TGIF2LY, TSPY3, and USP9Y) and 10 non-coding (TTTY2, TTTY4C, TTTY5, TTTYY6, TTTY8, TTTY10, TTTY14, TTTY21, TTTY22, and TTTY23) genes exhibited a bimodal pattern of expression characterised by low expression in samples from fertile patients and high expression in samples from infertile patients. Seven coding MSY-linked genes (BAGE, CD24, EIF1AY, NLGN4Y, PRKY, VCY and ZFY) exhibited differential regulation in microarray analysis, and this change was validated by RNA-seq or qRT-PCR. DNA inserts for 7 genes in various samples were validated by qPCR. The prevalence and concentration of PCR-positive target inserts for BAGE, PRKY, TTTY9A and ZFY displayed higher values in the fertile, control (FCON) patients compared with the fertile, endometriosis patients (FOE). CONCLUSION: Several coding and non-coding MSY-linked genes displayed microchimerism as evidenced by the presence of their respective DNA inserts, along with their differential transcript expression, in the endometrium during endometriosis and in cases of infertility.

An assessment of the multifactorial profile of steroid-metabolizing enzymes and steroid receptors in the eutopic endometrium during moderate to severe ovarian endometriosis.

BACKGROUND: Previous studies of expression profiles of major endometrial effectors of steroid physiology in endometriosis have yielded markedly conflicting conclusions, presumably because the relative effects of type of endometriosis, fertility history and menstrual cycle phases on the measured variables were not considered. In the present study, endometrial mRNA and protein levels of several effectors of steroid biosynthesis and action in patients with stage III-IV ovarian endometriosis (OE) with known fertility and menstrual cycle histories were compared with the levels in control endometrium to test this concept. METHODS: Endometrial samples were collected from patients without endometriosis (n = 32) or OE stages III-IV (n = 52) with known fertility and cycle histories. qRT-PCR and immunoblotting experiments were performed to measure levels of NR5A1, STAR, CYP19A1, HSD17Bs, ESRs and PGR transcripts and proteins, respectively. Tissue concentrations of steroids (P4, T, E1 and E2) were measured using ELISAs. RESULTS: The levels of expression of aromatase and ERß were lower (P < 0.0001) and 17ß-HSD1 (P < 0.0001) and PRA (P < 0.01) were higher in OE endometrium. Lower aromatase levels and higher 17ß-HSD1 levels were detected in fertile (aromatase: P < 0.05; 17ß-HSD1: P < 0.0001) and infertile (aromatase: P < 0.0001; 17ß-HSD1: P < 0.0001) OE endometrium than in the matched control tissues. Both proliferative (PP) and secretory (SP) phase OE samples expressed aromatase (P < 0.0001) and ERß (PP: P < 0.001; SP: P < 0.01) at lower levels and 17ß-HSD1 (P < 0.0001) and PRA (PP: P < 0.01; SP: P < 0.0001) at higher levels than matched controls. Higher 17ß-HSD1 (P < 0.01) and E2 (P < 0.05) levels and a lower (P < 0.01) PRB/PRA ratio was observed in infertile secretory phase OE endometrium than in control. CONCLUSIONS: We report that dysregulated expression of 17ß-HSD1 and PGR resulting in hyperestrogenism and progesterone resistance during the secretory phase of the menstrual cycle, rather than an anomaly in aromatase expression, was the hallmark of eutopic endometrium from infertile OE patients. Furthermore, the results provide proof of concept that the fertility and menstrual cycle histories exerted relatively different effects on steroid physiology in the endometrium from OE patients compared with the control subjects.