Recent trends in the immunopathogenesis of tuberculosis

Tuberculosis kills about 500,000 Indians every year, ie, one person every minute. For every patient who dies of the disease, there are at least two individuals who develop disability. Further, the advent of infection by the human immunodeficiency virus and drug resistant forms of Mycobacterium tuberculosis have made the management and control of tuberculosis more difficult. Although the genome of M. tuberculosis has been sequenced, diagnosis of the infectious sputum positive case is straightforward, simple and inexpensive and effective short course chemotherapy is available, morbidity and mortality due to the disease have not appreciably decreased. Among the several reasons cited for this failure are the inadequacy of the BCG vaccine in preventing post primary tuberculosis and the relatively long duration (six months) of chemotherapy which encourages irregularity and incomplete treatment. Furthermore, two more aspects which deserve consideration are a) lack of appropriate tests to identify the individual who is likely to develop clinical illness and b) disability caused by the disease process. This presentation will limit itself to two major areas of the immunopathology of the disease. These are a) host immune mechanisms underlying the varied clinical and pathological manifestations and b) events that lead to tissue damage and disability

Methyl 3-[(E,E)-3-phenyl­prop-2-enyl­idene]dithio­carbazate

In the title compound, C11H12N2S2, the dithio­carbazate group adopts an EE configuration with respect to the C=C and C=N bonds of the propenyl­idene group. The atoms of the propenyl­idene and dithio­carbazate unit are essentially co-planar, with a maximum deviation of 0.058 (1) Å; the phenyl ring forms a dihedral angle of 18.3 (1)° with this fragment. In the crystal, mol­ecules form inversion dimers via pairs of N—H⋯S hydrogen bonds involving the terminal S atom

Effectiveness of intrapartum fetal surveillance to improve maternal and neonatal outcomes: a systematic review and network meta-analysis

Bassel Al Wattar holds a personal Academic Clinical Lectureship from the UK National Health Institute of Research. Khalid Khan is a Distinguished Investigator funded by the Beatriz Galindo (senior modality) Program Grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.BACKGROUND: Cesarean delivery is the most common surgical procedure worldwide. Intrapartum fetal surveillance is routinely offered to improve neonatal outcomes, but the effects of different methods on the risk of emergency cesarean deliveries remains uncertain. We conducted a systematic review and network meta-analysis to evaluate the effectiveness of different types of fetal surveillance. METHODS: We searched MEDLINE, Embase and CENTRAL until June 1, 2020, for randomized trials evaluating any intrapartum fetal surveillance method. We performed a network meta-analysis within a frequentist framework. We assessed the quality and network inconsistency of trials. We reported primarily on intrapartum emergency cesarean deliveries and other secondary maternal and neonatal outcomes using risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: We included 33 trials (118 863 patients) evaluating intermittent auscultation with Pinard stethoscope/handheld Doppler (IA), cardiotocography (CTG), computerized cardiotocography (cCTG), CTG with fetal scalp lactate (CTG-lactate), CTG with fetal scalp pH analysis (CTG-FBS), CTG with fetal pulse oximetry (FPO-CTG), CTG with fetal heart electrocardiogram (CTG-STAN) and their combinations. Intermittent auscultation reduced the risk of emergency cesarean deliveries compared with other types of surveillance (IA v. CTG: RR 0.83, 95% CI 0.72-0.97; IA v. CTG-FBS: RR 0.71, 95% CI 0.63-0.80; IA v.CTG-lactate: RR 0.77, 95% CI 0.64-0.92; IA v. FPO-CTG: RR 0.75, 95% CI 0.65-0.87; IA v.FPO-CTG-FBS: RR 0.81, 95% CI 0.67-0.99; cCTG-FBS v. IA: RR 1.21, 95% CI 1.04-1.42), except STAN-CTG-FBS (RR 1.17, 95% CI 0.98-1.40). There was a similar reduction observed for emergency cesarean deliveries for fetal distress. None of the evaluated methods was associated with a reduced risk of neonatal acidemia, neonatal unit admissions, Apgar scores or perinatal death. INTERPRETATION: Compared with other types of fetal surveillance, intermittent auscultation seems to reduce emergency cesarean deliveries in labour without increasing adverse neonatal and maternal outcomes.Beatriz Galindo (senior modality) Program Grant by Ministry of Science, Innovation, and Universities of the Spanish Governmen

Ciliotherapy: A Novel Intervention in Polycystic Kidney Disease

Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as ‘cilio-therapy’. Methods and Results In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopa- minergic agonist to regulate cilia length and function

Metabolic inflexibility in women with polycystic ovary syndrome : a systematic review

Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic inflexibility, is a marker of blunted metabolism. We conducted a systematic review on metabolic inflexibility in women with PCOS. We searched MEDLINE, EMBASE and Cochrane central (inception-October 2018) for studies evaluating metabolic inflexibility and reporting on changes in Respiratory Quotient (ΔRQ). We extracted data and assessed quality using The Newcastle–Ottawa Scale. We included five prospective cohort studies (461 women). Three compared PCOS women to unaffected subjects, one to women with obesity or T2DM, and one to adolescent girls; all had medium quality. Three studies showed higher metabolic inflexibility in women with PCOS (ΔRQ range 0.05–0.098) compared to unaffected subjects. Women with PCOS had similar metabolic inflexibility compared to those with T2DM (ΔRQ 0.05 ± 0.03 vs 0.06 ± 0.04, p = .98) and obesity (p = .06). Inflexibility was higher in hyperandrogenemic women with PCOS (ΔRQ 0.091 ± 0.060 vs 0.120 ± 0.010, p = .014). ΔRQ was lower in PCOS women with insulin resistance vs those with normal insulin sensitivity (0.04 ± 0.02 vs. 0.07 ± 0.04, p = .007). In conclusion, women with polycystic ovary syndrome appear to have higher metabolic inflexibility associated with hyperandrogenemia and insulin resistance

Robustness, Security and Privacy in Location-Based Services for Future IoT : A Survey

Internet of Things (IoT) connects sensing devices to the Internet for the purpose of exchanging information. Location information is one of the most crucial pieces of information required to achieve intelligent and context-aware IoT systems. Recently, positioning and localization functions have been realized in a large amount of IoT systems. However, security and privacy threats related to positioning in IoT have not been sufficiently addressed so far. In this paper, we survey solutions for improving the robustness, security, and privacy of location-based services in IoT systems. First, we provide an in-depth evaluation of the threats and solutions related to both global navigation satellite system (GNSS) and non-GNSS-based solutions. Second, we describe certain cryptographic solutions for security and privacy of positioning and location-based services in IoT. Finally, we discuss the state-of-the-art of policy regulations regarding security of positioning solutions and legal instruments to location data privacy in detail. This survey paper addresses a broad range of security and privacy aspects in IoT-based positioning and localization from both technical and legal points of view and aims to give insight and recommendations for future IoT systems providing more robust, secure, and privacy-preserving location-based services.Peer reviewe

Variations in long-term outcome reporting among offspring followed up after lifestyle interventions in pregnancy : a systematic review

Background Mothers and their offspring may benefit from lifestyle interventions during pregnancy. We systematically reviewed the literature to map and evaluate the quality of long-term offspring outcomes in follow-up cohorts of randomised controlled trials (RCTs). Methods We searched MEDLINE, EMBASE, CINAHL, Database of Abstracts of Reviews of Effects and Cochrane Central (until March 2019) for all RCTs evaluating any lifestyle (diet or exercise) intervention during pregnancy and their follow-up cohorts. Two reviews evaluated the extracted outcomes using two standardised assessment tools, one for quality of reporting (score range 0–6) and another for the variation in outcome selection. We extracted data in duplicate and reported using natural frequencies, medians, ranges, means and standard deviation (SD). Results We captured 30 long-term offspring outcomes reported in six articles (four studies). Offspring anthropometric measurements were the most commonly reported outcomes. There was a large variation in the measurement tools used. The mean overall quality score for outcome reporting was 3.33 (SD 1.24), with poor reporting of secondary outcomes and limited justification for the choice of the reported outcomes. Most studies showed selective reporting for both their primary and secondary outcomes. Conclusion The quality of reporting for long-term offspring outcomes following lifestyle interventions in pregnancy is varied with evidence of selective outcome reporting. Developing a core outcome set will help to reduce the variations in outcome reporting to optimise future research

Analysis of Stability and G × E Interaction of Rice Genotypes across Saline and Alkaline Environments in India

Genotype × environment (G × E) interaction effects are of special interest for identifying the most suitable genotypes with respect to target environments, representative locations and other specific stresses. Twenty-two advanced breeding lines contributed by the national partners of the Salinity Tolerance Breeding Network (STBN) along with four checks were evaluated across 12 different salt affected sites comprising five coastal saline and seven alkaline environments in India. The study was conducted to assess the G × E interaction and stability of advanced breeding lines for yield and yield components using additive main effects and multiplicative interaction (AMMI) model. In the AMMI1 biplot, there were two mega-environments (ME) includes ME-A as CARI, KARAIKAL, TRICHY and NDUAT with winning genotype CSR 2K 262; and ME-B as KARSO, LUCKN, KARSA, GOA, CRRI, DRR, BIHAR and PANVE with winning genotypes CSR 36. Genotypes CSR 2K 262, CSR 27, NDRK 11-4, NDRK 11-3, NDRK 11-2, CSR 2K 255 and PNL 1-1-1-6-7-1 were identified as specifically adapted to favorable locations. The stability and adaptability of AMMI indicated that the best yielding genotypes were CSR 2K 262 for both coastal saline and alkaline environments and CSR 36 for alkaline environment. CARI and PANVEL were found as the most discernible environments for genotypic performance because of the greatest GE interaction. The genotype CSR 36 is specifically adapted to coastal saline environments GOA, KARSO, DRR, CRRI and BIHAR and while genotype CSR 2K 262 adapted to alkaline environments LUCKN, NDUAT, TRICH and KARAI. Use of most adapted lines could be used directly as varieties. Using them as donors for wide or specific adaptability with selection in the target environment offers the best opportunity for widening the genetic base of coastal salinity and alkalinity stress tolerance and development of adapted genotypes. Highly stable genotypes can improve the rice productivity in salt-affected areas and ensure livelihood of the resource poor farming communities