Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13 000 autologous cycles reported to SART CORS.

STUDY QUESTION: After an IVF cycle cancellation, does changing the stimulation protocol affect the odds of live birth and recurrent cancellation in the subsequent cycle? SUMMARY ANSWER: After IVF cycle cancellation, compared to those who repeated the same stimulation protocol, those who changed their protocol had higher odds of live birth and lower odds of recurrent cycle cancellation. WHAT IS KNOWN ALREADY: There is limited data addressing the effect of changing the stimulation protocol after an IVF cycle is cancelled during initial stimulation. The odds of live birth outcomes are not known so far in studies addressing the effect of changing the protocol. STUDY DESIGN, SIZE, DURATION: Retrospective Cohort Study using the 2014-2017 Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. PARTICIPANTS/MATERIALS, SETTING, METHODS: The data included 13 135 patients with a first autologous IVF cycle that resulted in a cycle cancellation and was followed by a second autologous cycle within the study period. We excluded fertility preservation cycles, supernumerary cycle attempts after the second IVF cycle attempt, and cycles with more than one stimulation protocol documented per cycle start. Patients who received the same protocol for both cycles (n = 6434) were compared to those who changed their protocol in the second cycle (n = 6701). Multivariable logistic regression analyses were performed to estimate the adjusted odds of live birth and recurrent cancellation. MAIN RESULTS AND THE ROLE OF CHANCE: Changing the protocol in the second cycle resulted 14% lower odds of recurrent cycle cancellation (P = 0.01) and 17% higher odds of live birth after fresh transfers (P = 0.04). When stratifying the data by specific combinations of protocol change (agonist flare, agonist suppression, antagonist), there was an increase in live birth when switching from antagonist to agonist suppression (odds ratio (OR) = 1.36, P = 0.03) and from agonist suppression to antagonist (OR = 1.73, P = 0.01) compared to those who repeated their same stimulation protocol. Specifically in poor responders, outcomes were worse when using the agonist flare protocol and significantly improved with the agonist suppression protocol. LIMITATIONS, REASONS FOR CAUTION: Comparison of response to stimulation between first and second cycles cannot be made in this study because the index IVF cycle was cancelled during ovarian stimulation, and thus there is no reportable outcome data for that cycle. Additionally, SART only tracks the three stimulation protocols addressed in this study and does not have data on more contemporary protocols that are used in poor responders thus limiting the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Using the SART CORS database, which includes >90% of all reported IVF cycles in the USA, provides generalizability to the demographically diverse IVF populations found here. In agreement with prior studies assessing change in IVF protocols, the agonist flare protocol seems to result in worse IVF outcomes, and based on our results, we believe that there is no role for the agonist flare protocol in patients with a prior poor response to stimulation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: N/A.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Live birth rate from euploid blastocysts is not associated with infertility etiology or oocyte source following frozen-thawed embryo transfer (FET): analysis of 4148 cycles reported to SART CORS.

PURPOSE: To investigate whether live birth rates from euploid blastocyst frozen-thawed embryo transfer (FET) cycles are associated with infertility diagnosis or oocyte source. DESIGN: Retrospective analysis of FET cycles reported to SART CORS in 2014. METHODS: Data from fresh IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A), linked to the first FET cycles, were collected from the 2014 SART CORS database for autologous and donor oocyte cycles. Inclusion criteria were patients undergoing FET with euploid embryos (n = 4148). Demographic data including age, BMI, prior fertility, and etiology of infertility were collected from the retrieval cycle and analyzed. Patients with uterine anomalies, preimplantation genetic testing-mutation (PGT-M) for genetic diseases, gender selection, HLA determination, or systemic and immunologic disorders were excluded. The primary outcome measure was live birth (LB) rate. Potential confounders such as age, prior fertility, and maximum baseline FSH values were analyzed with regression models as indicated. RESULTS: Though age, maximum baseline FSH, and infertility diagnosis were significantly different, LB was similar between patients undergoing autologous or donor oocyte FET cycles. Etiology of infertility was not significantly associated with LB in autologous cycles (p = 0.95). Potential confounders such as maternal age, prior fertility, and maximum baseline FSH were not associated with outcomes; however, maternal BMI was inversely related to LB in autologous cycles, with an odds ratio of 0.97 (95% CI: 0.96-0.98 (rho = - 0.08, p < 0.01)). CONCLUSIONS: After controlling for confounding variables, a euploid embryo derived from a donor or autologous oocyte results in similar LB in women with different infertility diagnoses.

Molecular expression of caprine estrogen receptor gene 1 in reproductive and non-reproductive tissues.

During the last decades, physiological effects of oestrogens have been increasingly explored by scientists and biotechnologists. Estrogens exert a wide range of effects on a large variety of cell types. Oestrogen and its receptors are essential for sexual development and reproduction. Estrogen receptor alpha is a nuclear receptor activated by the hormone oestrogen. In male, ERα is encoded by the gene estrogen receptor gene 1 (ESR1), responsible for better fertility. The ESR1 is involved in the reabsorption of luminal fluid during the transit of spermatozoa from the testis to the head of the epididymis which is important for their survival and maturation during epididymal storage. The absence of ESR1 leads to reduced epididymal sperm content, reduced sperm motility and fertilizing ability. Therefore, this is a good startby to study the expression pattern of estrogen receptor 1 gene in high-fertile (G1) and low-fertile (G2) bucks of Jamunapari and Barbari breeds identified on the basis of seminal quality traits and fertility trials. RNA was extracted from the tissues by TRIzol method. The identification and expression pattern of caprine ESR1 gene was analysed by real-time PCR (Roche LC-480). Our work shows that the relative quantification by RT-PCR indicates more fold in head of epididymis as compared to spleen of caprine ESR1 gene. Furthermore, the RT-PCR indicated that fertile bucks of Jamunapari breed have more fold value as compared to Barbari breed in respect of reproductive organ.

Association of growth related seedling traits in Acacia senegal under arid environment of western Rajasthan.

Climatic models and predictions indicate increase in aridity world over due to global warming. Arid environments occupy about one third land area of the world. A. senegal is the most important dryland resource of western Rajasthan desert ecosystem. The seeds of 13 low and high seed yielding exotic and indigenous provenances were evaluated for diversity and interrelationship among growth related seedling traits targeting establishment and end use of this species. Under the present study most of the growth related seedling traits varied within and amongst provenances. Highly significant correlation of dry biomass per plant of more than 72% with root length (73.3%), collar diameter (72.2%), shoot dryweight (99.7%), root dry weight (95.7%) and seedling length (79.9%) under the present study may be used for early selection. Similarly, highly significant positive correlation of seedling length with seven out of 12 growth related seedling traits validate strong inherent association of these traits under strong genetic control and are amenable for selection. Significant negative correlation in number of nodules per plant with root/shoot length ratio (-57.6%) and no correlation with 10 out of 12 growth related seedling traits tested advocate emphasis on other growth related seedling traits in selection of elite A. senegal genotypes for afforestation. The non significant associations suggest that per cent germination was independent of other characters and could be selected separately.

Role of TLR4 C>1196T (Thr399Ile) and TLR4 A>896G (Asp299Gly) polymorphisms in a North Indian population with asthma: a case-control study.

Toll-like receptor 4 (TLR4) is the most important TLR among the pattern recognition receptors which recognizes lipopolysaccharide of gram-negative bacteria. They identify a highly conserved structure of microbes called pathogen-associated molecular patterns and activate immune and inflammatory responses that have been shown to be involved in the pathogenesis of asthma. The role of TLR4 gene polymorphisms in asthma was detected in a total of 964 individuals, including 483 healthy controls and 481 asthma patients from a North Indian population. The genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis revealed that the heterozygous genotype as well as the mutant (T) allele of the TLR4 C>1196T (Thr399Ile) polymorphism shows resistance towards asthma with OR = 0.70, 95% CI (0.49-0.99), P corrected value = 0.046 and OR = 0.72, 95% CI (0.52-0.98), P corrected value = 0.039, respectively. However, no association was found between the TLR4 A>896G (Asp299Gly) polymorphism and asthma patients (P > 0.05). This is the first study conducted in India conferring TLR4 (Thr399Ile) polymorphism resistance towards asthma, while lack of association was found between TLR4 (Asp299Gly) polymorphism and asthma in the studied North Indian population.

Embryo quality but not pronuclear score is associated with clinical pregnancy following IVF.

PURPOSE: The association between pronuclear (PN) scoring of embryos from assisted reproductive technology (ART) and clinical pregnancy remains controversial. We hypothesized that embryos with PNs scored on the day of fertilization check offer better embryo selection on day 3 and higher CPR compared to non-PN scored embryos. METHODS: Patients (19-46 years) undergoing IVF/ICSI cycles at Montefiore's Institute for Reproductive Medicine and Health between January 2006 and December 2009 were included in our study. We analyzed fresh day 3 cycles only with autologous oocytes and partner's fresh sperm (n = 344). A total of 1,899 embryos were included. We compared CPR from non-PN scored embryos (Group 1, n = 835) with PN scored embryos (Group 2, n = 1,064). Composite scores by patient were developed based on embryo disposition. We also assessed traditional embryo grading derived from cell number, fragmentation and cell symmetry. Data analysis included chi square and t test to determine if PN scoring was associated with improved CPR, and to compare the additional variables. RESULTS: CPR between Group 1 and Group 2 were not different (p = 0.91). CPR was significantly associated with female age, number of mature oocytes retrieved, number of day 3 embryos and grade of embryos transferred on day 3 (p < 0.05). CONCLUSION: PN scoring was not associated with improved CPR in day 3 embryo transfers. Mean grade of transferred embryos continues to be a well-established, independent predictor of CPR. We conclude that further refinement of embryo grading by PN scoring is not beneficial.

Guidelines for diagnosis and management of chronic obstructive pulmonary disease: joint recommendations of Indian Chest Society and National College of Chest Physicians (India).

Chronic obstructive pulmonary disease (COPD) is a major public health problem in India. Although several International guidelines for diagnosis and management of COPD are available, yet there are lot of gaps in recognition and management of COPD in India due to vast differences in availability and affordability of healthcare facilities across the country. The Indian Chest Society and the National College of Chest Physicians (India) have joined hands to come out with these evidence-based guidelines to help the physicians at all levels of healthcare to diagnose and manage COPD in a scientific manner. Besides the International literature, the Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (a) definition, epidemiology and disease burden, (b) disease assessment and diagnosis, (c) pharmacologic management of stable COPD, (d) management of acute exacerbations; and (e) non-pharmacologic and preventive measures.

Effects of smoking on asthma.

Tobacco smoking has several adverse associations with asthma.The odds ratios for prevalence of asthma are high for both active smoking and ETS exposures. In-utero exposure of foetus from maternal smoking, as well as its tertiary exposure from maternal passive-smoking are also known to be responsible for development of asthma in childhood. Smoking adversely affects the health and treatment-outcomes of asthma. There are increased requirements of drugs for smoker and ETS exposed asthmatics. Smoking is also an important factor in the development of airway remodelling, fixed airway obstruction and an exaggerated lung function decline.

Effect of co-inoculations of native PGPR with nitrogen fixing bacteria on seedling traits in Prosopis cineraria.

Prosopis cineraria significantly contribute to sand dune stabilization, soil fertility rejuvenation and is an integral component of agro-forestry systems in arid regions of India. Effect of different rhizobacterial seed treatments on seed germination and seedling traits in two genotypes of P. cineraria (HPY-1) and (FG-1) were tested. Observations on seed germination (%) and seedling traits viz., root length (cm), shoot length (cm), seedling weight (g) and seedling length of different treatments were recorded. Whereas, germination index (GI), seedling vigour index (SVI) and root/shoot length ratio were derived from the observed data. The scarification treatment with sulphuric acid for 10 minutes substantially enhanced germination from < 20% to 80-82% in control treatments. Treatments with co-inoculations of Bacillus licheniformis and Sinorhizobium kostiense or S. saheli supported the maximum seed germination and seedling growth and vigour. The maximum germination per cent (92.5%), seedling length (10.94 cm), seedling vigour index (10.12) and germination index (7.97) were recorded with treatment (V2T6) wherein seeds of high pod yielding genotype were co-inoculated with Bacillus licheniformis and S. kostiense. The higher positive correlations of seedling length v/s shoot length followed by SVI v/s seedling length, SVI v/s root length and seedling length v/s root length is a fair indicative of inter dependency of these characteristics. Higher R2 values of root length v/s shoot length followed by that of SVI v/s GI indicates that a regression line fits the data well and future outcomes of observed seedling traits are likely to be predicted by the model.

Leptin suppresses anti-Mullerian hormone gene expression through the JAK2/STAT3 pathway in luteinized granulosa cells of women undergoing IVF.

STUDY QUESTION: Do the adipocytokines, leptin and adiponectin affect the granulosa cell expression of anti-Mullerian hormone (AMH) and its receptor (AMHR-II)? SUMMARY ANSWER: Leptin suppresses AMH mRNA levels in human luteinized granulosa cells through the JAK2/STAT3 pathway, while adiponectin has no such effect. WHAT IS KNOWN ALREADY: AMH is one of the most reliable markers of ovarian reserve. Serum AMH levels decline with obesity. Obesity is associated with elevated leptin and reduced adiponectin levels. STUDY DESIGN, SIZE AND DURATION: This prospective study included 60 infertile women undergoing fresh IVF and ICSI cycles utilizing autologous oocytes at Montefiore's Institute for Reproductive Medicine and Health between July 2010 and April 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was collected from small (SFs; <14 mm) and large follicles (LFs; ≥14 mm) from 38 participants. Total RNA was extracted separately from mural and cumulus granulosa cells and mRNA levels were measured by RT-PCR. In an additional group of participants (N = 22), primary cumulus and mural granulosa cells (pooled SFs and LFs) were cultured in media alone or with addition of either leptin (N = 7), adiponectin (N = 8) or JAK2/STAT3 inhibitor + leptin (N = 7), and AMH and AMHR-II mRNA levels measured. Levels of AMH, leptin and adiponectin protein were measured in follicular fluid. MAIN RESULTS AND THE ROLE OF CHANCE: AMH and AMHR-II mRNA and follicular fluid AMH protein levels were inversely correlated with age. AMH mRNA expression was six times higher in cumulus compared with mural granulosa cells in SFs (P< 0.05) and eight times higher in cumulus compared with mural granulosa cells in LFs (P < 0.001). In follicular fluid, leptin protein level positively correlated (r = 0.7, P = 0.03), while adiponectin protein level inversely correlated (r = -0.46, P = 0.02) with BMI. Leptin treatment suppressed AMH and AMHR-II mRNA in both cumulus and mural granulosa cells (all P < 0.05). In the presence of JAK2/STAT3 inhibitor, leptin treatment did not alter AMH but continued to suppress AMHR-II mRNA in cumulus cells (P = 0.02). Adiponectin treatment did not alter AMH or AMHR-II mRNA levels. LIMITATIONS, REASONS FOR CAUTION: This study included a luteinized granulosa cell model as these cells were collected from women who were hyperstimulated with gonadotrophins. The results obtained may not fully extrapolate to non-luteinized granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS: Leptin may program abnormal AMH signaling, thereby resulting in ovarian dysfunction. This study opens a new perspective for understanding the low ovarian reserve seen in obese women and provides new insights into potential mechanisms that explain the lower AMH seen in obese women. Whether our findings explain the worse response to ovulation induction observed in obese women needs to be further elucidated.

Effect of sesamol on the pathophysiological changes induced by surgical menopause in rodents.

OBJECTIVE: Estrogen deprivation after menopause is associated with increased oxidative stress. The present study was designed to study the role of sesamol (3,4-methylenedioxyphenol), a phenolic antioxidant and anti-inflammatory molecule, in oxidative stress-induced changes in three major affected organ systems, the central nervous system, the cardiovascular system and the skeletal system in ovariectomized rats, a widely used animal model of menopause. DESIGN: Animals were divided into eight different groups (n = 6-8). Five groups underwent ovariectomy; starting from the 2nd day of ovariectomy, three of these groups received sesamol (2, 4, 8 mg/kg) and the fourth group was administered α-tocopherol (100 mg/kg) orally for 7 weeks. The fifth ovariectomized group did not receive any drug treatment. Rats in the naïve (non-operated) and sham-operated groups did not receive any drug treatment, while the eighth group consisted of naïve animals which were treated for 7 weeks with only sesamol 8 mg/kg orally daily. After 7 weeks, animals were subjected to testing of behavioral paradigms (elevated plus maze and Morris water maze for assessment of anxiety and memory, respectively) 24 h after the last dose. After behavioral studies, animals were sacrificed for various biochemical estimations. RESULT: Administration of sesamol (2, 4, 8 mg/kg orally) to ovariectomized rats for 7 weeks significantly and dose-dependently improved memory, attenuated anxiety, decreased oxidative stress in brain, improved the serum lipid profile and reduced serum tumor necrosis factor-α levels when compared with ovariectomized control rats. Similar protective effects were observed in the case of the skeletal system studies. Sesamol increased the bone ash content and the mechanical stress parameters in treated groups. CONCLUSION: The results emphasize the involvement of oxidative stress and inflammation in the development of ovariectomy-induced pathophysiological changes and point towards the therapeutic potential of sesamol in menopausal pathologies.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Incidence of occult cleft palate on prenatal magnetic resonance images obtained for non-cleft indications.

Prenatal diagnosis of craniofacial anomalies has improved family education and preparedness. Isolated cleft palate, however, remains difficult to identify sonographically. The aim of this study was to investigate the rate of incidental cleft palate identified on fetal magnetic resonance imaging (MRI) following the ultrasound detection of non-cleft abnormalities. This was a retrospective study of pregnant women who had fetal MRI performed between 2003 and 2017. To be included, the woman had to have been referred for fetal imaging for a non-cleft indication, with subsequent identification of an isolated cleft palate on MRI. Fetuses with a postnatal diagnosis of Robin sequence were excluded. The study sample included 30 women. Mean gestational age at MRI was 24 weeks 4 days± 38 days. Most referrals (76.7%) were for non-cleft craniofacial anomalies, of which micrognathia was the most common (63.3%). The annual incidence of occult cleft palate diagnosis was 0.4%, and a genetic syndrome was suspected based on imaging findings in 76.7%. Although rare, isolated cleft palate found incidentally on fetal imaging led to concern for a genetic syndrome in a high percentage of cases. This suggests that early referral for fetal MRI may provide critical information when sonographic fetal anomalies have been identified.

Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.

Validity Assessment of an Automated Brain Morphometry Tool for Patients with De Novo Memory Symptoms.

BACKGROUND AND PURPOSE: Automated volumetric analysis of structural MR imaging allows quantitative assessment of brain atrophy in neurodegenerative disorders. We compared the brain segmentation performance of the AI-Rad Companion brain MR imaging software against an in-house FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. MATERIALS AND METHODS: T1-weighted images of 45 participants with de novo memory symptoms were selected from the OASIS-4 database and analyzed through the AI-Rad Companion brain MR imaging tool and the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. Correlation, agreement, and consistency between the 2 tools were compared among the absolute, normalized, and standardized volumes. Final reports generated by each tool were used to compare the rates of detection of abnormality and the compatibility of radiologic impressions made using each tool, compared with the clinical diagnoses. RESULTS: We observed strong correlation, moderate consistency, and poor agreement between absolute volumes of the main cortical lobes and subcortical structures measured by the AI-Rad Companion brain MR imaging tool compared with FreeSurfer. The strength of the correlations increased after normalizing the measurements to the total intracranial volume. Standardized measurements differed significantly between the 2 tools, likely owing to differences in the normative data sets used to calibrate each tool. When considering the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline as a reference standard, the AI-Rad Companion brain MR imaging tool had a specificity of 90.6%-100% and a sensitivity of 64.3%-100% in detecting volumetric abnormalities. There was no difference between the rate of compatibility of radiologic and clinical impressions when using the 2 tools. CONCLUSIONS: The AI-Rad Companion brain MR imaging tool reliably detects atrophy in cortical and subcortical regions implicated in the differential diagnosis of dementia.

Development and evaluation of a multiplex polymerase chain reaction for the detection of Mycobacterium tuberculosis from pulmonary specimens.

BACKGROUND: The diagnosis of pulmonary tuberculosis is still a major challenge. Using a polymerase chain reaction (PCR), one can detect Mycobacterium tuberculosis in clinical samples within a few hours. However, single gene targets may result in false negativity due to the absence of target DNA in some M. tuberculosis isolates. The objective of this study was to develop and evaluate a multiplex PCR (M-PCR) using IS6110 and devR primers for the detection of M. tuberculosis in sputum samples. METHODS: Sputum samples were collected from: (1) 200 confirmed cases of tuberculosis; (2) 100 suspected cases of tuberculosis diagnosed on the basis of clinical and radiological findings; (3) 200 non-tubercular patients suffering from respiratory diseases other than tuberculosis, in whom tuberculosis had been excluded. All 500 sputum samples were subjected to PCR using IS6110 primers, and M-PCR using IS6110 and devR primers; results were compared with conventional techniques. RESULTS: It was found that M-PCR was 97.5% successful in detecting the presence of tuberculosis in the confirmed tuberculosis group as compared to 84.5% by IS6110-based PCR. In the suspected tuberculosis group, M-PCR could detect 45% of cases as compared to 40% by IS6110-based PCR. Overall, the specificities of both the PCR and M-PCR were found to be 96.5%. CONCLUSIONS: This study demonstrated that the M-PCR assay is more sensitive than the IS6110-based PCR for the detection of M. tuberculosis in sputum specimens and could be applied in situations of highly suspected tuberculosis when all others tests including IS6110 PCR are negative.

Research in clinical sciences.

The scope and spectrum of medical research, including that in clinical sciences has tremendously expanded. It now extends from simple clinical observations to gathering of epidemiological data to the study of molecular mechanisms of diseases to evaluation of effects of therapeutic interventions. It is more meaningful to engage in multi-disciplinary and collaborative arrangements for the better achievements in health research. Translational approach involves the direct application of results of laboratory experiments to clinical use for benefit of patients. Besides clinical and experimental research, it is equally important to strengthen operational research for efficient implementation of health programmes and policies in the hospitals as well as in the community. There are several difficulties and constraints related to ethical principles, patient's safety, confidentiality and costs. It is critically important to adhere to ethical principles and guidelines to maintain the moral and social perspectives. It is equally important to follow the scientific research methodology for the maximum gains from research experiments and projects. Interpretation of results of clinical experiments are hardly ever unequivocal, hence, there is a need for repetitive studies, systematic reviews and meta-analyses to reach definitive conclusions. It is important for busy physicians to adopt a scientific temper of logic and engage themselves in searching for answers to different research questions. It is always gainful to spare some time and resources for research out of a busy clinical practice. It is also worthwhile to go through a formal training programme in research methodology to improve capacity and competence to conduct meaningful research.

Genetic polymorphisms among Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in northern India.

Restriction fragment length polymorphism (RFLP) based on IS6110 is considered the gold standard for Mycobacterium tuberculosis molecular typing. It is useful to discriminate among M. tuberculosis strains, investigate outbreaks and distinguish between reactivation and re-infection. We studied polymorphisms among M. tuberculosis isolates from northern India using RFLP to determine the presence of a correlation between IS6110 based fingerprints and drug resistance and to look for relapse and transmission among patients and their contacts. RFLP patterns of PvuII digested genomic DNA of 100 M. tuberculosis isolates were analyzed using southern blotting with a 245 bp IS6110 probe. Drug sensitivity testing (DST) was conducted for rifampicin (40 microg/ml), isoniazid (1 microg/ml), ethambutol (2 microg/ml) and streptomycin (4 microg/ml) using the proportion method. A high degree of polymorphism was seen among the M. tuberculosis isolates and the number of IS6110 copies varied from 0 to 14, with a predominance of isolates with 11 bands. Seventy-five isolates had a high number of bands, 9 had an intermediate number, 6 isolates had a low number and 10 isolates had no bands. No correlation between IS6110 band numbers and RFLP banding patterns was found with drug resistance or for any particular geographical area, although clustering was seen amongst MDR-TB cases. No cases of relapses or transmissions were seen.