Immune disturbances in female genital tuberculosis and latent genital tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. AIMS: This review tries to elucidates the role of various immune factors in FGTB and LGTB. CONTENT: Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. IMPLICATIONS: Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.

Establishment of Normative Data for Autonomic Function Tests in Indian Population.

Background: Normative data for autonomic function tests (AFT) is not available for Indian population. Objective: The aim of the study was to establish normative data in AFT and its correlation with age, gender, and body mass index. Material and Methods: The study was done on 254 healthy subjects of age ≥18 years. All AFTs were done in autonomic laboratory at the Department of Neurology, Christian Medical College and Hospital, Ludhiana. Cardiovascular tests (heart rate response to deep breathing, HR changes in Valsalva maneuver and head-up tilt test (HUT)) and quantitative sudomotor axon reflex testing (QSART) were performed in all the subjects. Fifty subjects underwent thermoregulatory sweat test (TST). Results: The mean age (SD) of study participants was 43 (16.0) years (range 20-84), and 129 (50.8%) were men. The normative value range (2.5-97.5 percentile) for HR difference, E: I ratio, and Valsalva ratio (VR) was 3.5-47.0, 1.05-1.93, and 1.11-2.64, respectively, for all the subjects. HR difference and E: I ratio showed an significant inverse relation with age (r = -0.623 and r = -0.584, respectively). VR also showed an inverse relation with age (r = -0.575, P =< 0.001), and female had a lower value than male (1.63 vs 1.78, P =< 0.001). In QSART, mean (SD) sweat volume was higher in males 0.630 (0.230) compared to females 0.513 (0.132) for all sites, P < 0.001, and similar trend was noticed for sweat area in TST. Discussion and Conclusion: Normative AFT data has been established for Indian population for the first time. The values are comparable to previously published studies.

Prognostic Factors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Advanced Breast Cancer: A Systematic Literature Review.

PURPOSE: Advanced breast cancer is a heterogeneous disease with several well-defined subtypes, among which, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) is most prevalent. Determination of HR and HER2 status influences prognosis and, thus, disease management. Although literature on these prognostic factors exist, especially in the early breast cancer setting, it remains unclear to what extent these factors can guide clinical decision-making in the advanced disease setting. Therefore, we sought to identify the strength and consistency of evidence for prognostic factors in patients with HR+/HER2- advanced breast cancer. METHODS: A systematic literature review (SLR) of the major electronic databases was conducted in November 2018 for primary research studies published since 2010. Endpoints of interest were tumor response, progression-free survival (PFS), overall survival (OS), and breast cancer-specific survival (BCSS). RESULTS: Seventy-nine studies were included wherein all patients were diagnosed with advanced breast cancer and ≥50% of the population were HR+/HER2-. OS was the most commonly assessed endpoint (n=67) followed by PFS (n=33), BCSS (n=5) and tumor response (n=3). The prognostic factors with strongest evidence of association with worse OS were negative progesterone receptor status, higher tumor grade, higher circulating tumor cell (CTC) count and higher Ki67 level, number of metastatic sites (eg multiple vs single) and sites of metastases (eg presence of liver metastases vs absence), shorter time to recurrence or progression to advanced breast cancer, poor performance status, prior therapy attributes in the early or metastatic setting (type of therapy, treatment line, response of prior therapy), and race (black vs white). The prognostic factors that had strongest evidence of association with PFS included CTC count, number and sites of metastases, and absence of prior therapy or higher lines of therapy in the early or metastatic setting. The directionality of association was consistent for all prognostic factors except between lymph node and OS, and de novo metastatic breast cancer and PFS. CONCLUSION: Multiple disease, treatment, and patient-related prognostic factors impact survival, particularly OS, in patients with HR+/HER2- advanced breast cancer. Treatment outcomes can vary considerably due to these factors. Understanding poorer prognostic factors for patients can result in improved clinical decision-making.

Investigating transportation research based on social media analysis: a systematic mapping review.

Social media is a pool of users' thoughts, opinions, surrounding environment, situation and others. This pool can be used as a real-time and feedback data source for many domains such as transportation. It can be used to get instant feedback from commuters; their opinions toward the transportation network and their complaints, in addition to the traffic situation, road conditions, events detection and many others. The problem is in how to utilize social media data to achieve one or more of these targets. A systematic review was conducted in the field of transportation-related research based on social media analysis (TRR-SMA) from the years between 2008 and 2018; 74 papers were identified from an initial set of 703 papers extracted from 4 digital libraries. This review will structure the field and give an overview based on the following grounds: activity, keywords, approaches, social media data and platforms and focus of the researches. It will show the trend in the research subjects by countries, in addition to the activity trends, platforms usage trend and others. Further analysis of the most employed approach (Lexicons) and data (text) will be also shown. Finally, challenges and future works are drawn and proposed. Supplementary Information: The online version contains supplementary material available at 10.1007/s11192-021-04046-2.

Construct validity and predictive utility of internal assessment in undergraduate medical education.

BACKGROUND: Internal assessment is a partial requirement of all medical college examinations in India. It can help teachers provide remedial action and guide learning. But its utility and acceptability is doubted because, with no external control, internal assessment is considered prone to misuse. It is therefore not used as a tool for learning. There is no study on the validity of internal assessment from India. METHODS: We use multiple methods and multiple teachers to assess students and our records are well maintained. We analysed the internal assessment scores at our institute. We correlated the internal assessment marks with the university marks obtained by students in one of the subjects in each of the four professional examinations. RESULTS: There was a positive correlation of university marks with internal assessment marks. The r values ranged from +0.426 to +0.685 and were statistically significant (p<0.01). The percentage of internal assessment marks was higher than the university percentage in all professional examinations except the first. CONCLUSIONS: Internal assessment marks correlate well with marks in university examinations. This provides evidence for construct validity and predictive utility of internal assessment. Internal assessment can predict performance at summative examinations and allow remedial action.

Assessment of the quality of life in patients with bronchial asthma, before and after yoga: a randomised trial.

Yoga which is used as an adjunct treatment for bronchial asthma is gaining popularity throughout the world. The objective of this study was to assess the effect of yoga on quality of life in patients with bronchial asthma. 120 non-smoking male and female patients of asthma in the age group of 17-50 years were randomized into two groups i.e. Group A (Yoga group) and Group B (control group). All patients remained on their prescribed medication, but Group A patients practiced yoga breathing exercises for 8 weeks. Asthma Quality of Life Questionnaire (AQLQ) and diary record was used to assess quality of life, number and severity of asthmatic attacks, and the dosage of the medication required at baseline and after 8 weeks. Group A subjects showed a statistically significant improvement in "symptoms", "activities" and "environmental" domains of AQLQ at 8 weeks (p<0.01) and significant reduction in daily number and severity of attacks, and the dosage of medication required at 4 and 8 weeks (p<0.01) compared to the baseline. Yoga breathing exercises used adjunctively with standard pharmacological treatment significantly improved quality of life in patients with bronchial asthma.

Alcohol education provided to opioid treatment program patients: results of a nationwide survey.

Alcohol-related problems are especially common among opioid treatment program (OTP) patients, suggesting that educating OTP patients about alcohol and its harmful effects needs to be a priority in OTPs. Using data collected in interviews with a nationwide U.S. sample of OTP directors (N = 200) in 25 states, we identified factors that differentiate OTPs that provided this education to all OTP patients from those that did not. Findings indicate that these factors include (1) providing this education in a greater variety of ways, (2) having a larger percent of staff knowledgeable about alcohol-related issues, (3) having a director who views alcohol issues as a high priority, and (4) having a written OTP policy.

Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin.

Candida albicans is the leading fungal pathogen of humans, causing life-threatening disease in immunocompromised individuals. Treatment of candidiasis is hampered by the limited number of antifungal drugs whose efficacy is compromised by host toxicity, fungistatic activity, and the emergence of drug resistance. We previously established that the molecular chaperone Hsp90, which regulates the form and function of diverse client proteins, potentiates resistance to the azoles in C. albicans and in the model yeast Saccharomyces cerevisiae. Genetic studies in S. cerevisiae revealed that Hsp90's role in azole resistance is to enable crucial cellular responses to the membrane stress exerted by azoles via the client protein calcineurin. Here, we demonstrate that Hsp90 governs cellular circuitry required for resistance to the only new class of antifungals to reach the clinic in decades, the echinocandins, which inhibit biosynthesis of a critical component of the fungal cell wall. Pharmacological or genetic impairment of Hsp90 function reduced tolerance of C. albicans laboratory strains and resistance of clinical isolates to the echinocandins and created a fungicidal combination. Compromising calcineurin function phenocopied compromising Hsp90 function. We established that calcineurin is an Hsp90 client protein in C. albicans: reciprocal co-immunoprecipitation validated physical interaction; Hsp90 inhibition blocked calcineurin activation; and calcineurin levels were depleted upon genetic reduction of Hsp90. The downstream effector of calcineurin, Crz1, played a partial role in mediating calcineurin-dependent stress responses activated by echinocandins. Hsp90's role in echinocandin resistance has therapeutic potential given that genetic compromise of C. albicans HSP90 expression enhanced the efficacy of an echinocandin in a murine model of disseminated candidiasis. Our results identify the first Hsp90 client protein in C. albicans, establish an entirely new role for Hsp90 in mediating resistance to echinocandins, and demonstrate that targeting Hsp90 provides a promising therapeutic strategy for the treatment of life-threatening fungal disease.

Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease.

Invasive fungal infections are a leading cause of mortality among immunocompromised individuals. Treatment is notoriously difficult with the limited armamentarium of antifungal drugs, whose efficacy is compromised by host toxicity, a limited activity spectrum, or the emergence of drug resistance. We previously established that the molecular chaperone Hsp90 enables the emergence and maintenance of fungal drug resistance. For the most prevalent fungal pathogen of humans, Candida albicans, Hsp90 mediates resistance to azoles, which inhibit ergosterol biosynthesis and are the most widely deployed antifungals in the clinic. For the emerging opportunistic pathogen Aspergillus terreus, Hsp90 is required for basal resistance to echinocandins, which inhibit beta(1, 3)-glucan synthesis and are the only new class of antifungals to reach the clinic in decades. Here, we explore the therapeutic potential of Hsp90 inhibitors in fungal disease using a tractable host-model system, larvae of the greater wax moth Galleria mellonella, and a murine model of disseminated disease. Combination therapy with Hsp90 inhibitors that are well tolerated in humans and an azole rescued larvae from lethal C. albicans infections. Combination therapy with an Hsp90 inhibitor and an echinocandin rescued larvae from infections with the most lethal mold, Aspergillus fumigatus. In a murine model of disseminated candidiasis, genetic compromise of C. albicans HSP90 expression enhanced the therapeutic efficacy of an azole. Thus, harnessing Hsp90 provides a much-needed strategy for improving the treatment of fungal disease because it enhances the efficacy of existing antifungals, blocks the emergence of drug resistance, and exerts broad-spectrum activity against diverse fungal pathogens.

A study of the effect of yoga training on pulmonary functions in patients with bronchial asthma.

The role of yoga breathing exercises, as an adjunct treatment for bronchial asthma is well recognized. One hundred twenty patients of asthma were randomized into two groups i.e Group A (yoga training group) and Group B (control group). Each group included sixty patients. Pulmonary function tests were performed on all the patients at baseline, after 4 weeks and then after 8 weeks. Majority of the subjects in the two groups had mild disease (34 patients in Group A and 32 in Group B). Group A subjects showed a statistically significant increasing trend (P < 0.01) in % predicted peak expiratory flow rate (PEFR), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced mid expiratory flow in 0.25-0.75 seconds (FEF25-75) and FEV1/FVC% ratio at 4 weeks and 8 weeks as compared to Group B. Thus, yoga breathing exercises used adjunctively with standard pharmacological treatment significantly improves pulmonary functions in patients with bronchial asthma.