Clinical exome sequencing unravels the diverse spectrum of genetic heterogeneity and genotype-phenotype correlations in hypertrophic cardiomyopathy.

BACKGROUND: Catalogues of pathogenic genetic mutations in hypertrophic cardiomyopathy (HCM) are disproportionately small when compared to that of the size of the population with South Asian ancestry and their collective increased risk of heart disease. METHODS: We conducted clinical exome sequencing of 200 HCM patients to identified cardiomyopathy-associated genetic mutations. The clinical and echocardiographic characteristics of genotype-positive and genotype-negative patients were compared, and the likelihood of detecting a positive genetic test result was evaluated. Allelic burden analysis was done to compare the minor allele frequencies (MAF) of the P/LP variants and VUSs identified in the cohort against various population genomics databases. RESULTS: The genetic yield was 40% for pathogenic or likely pathogenic variants, with MYBPC3 and MYH7 as the predominant sarcomere genes. Younger age-at-diagnosis, family history of HCM, asymmetric hypertrophic (ASH) pattern, the ratio of the interventricular septum to posterior wall thickness (IVS/PW ratio), left atrial (LA) dimensions, severe mitral regurgitation grade (MR grade), late gadolinium enhancement (LGE) detected fibrosis and absence of hypertension were associated with an increased likelihood of HCM-associated variants. Patients who experienced ventricular tachycardia and premature cardiovascular death were significantly likely to carry MYBPC3 or loss-of-function variants. LA and interventricular septal (IVS) dimensions were associated with MYH7 variants. The rare variant burden for P/LP variants and VUSs was significantly enriched in HCM cases compared to population controls. CONCLUSION: Our study provides a comprehensive evaluation of HCM-associated genetic mutations from an Indian population. The identified genotype-phenotype associations could improve the yield of targeted genetic testing in HCM.

Significant enhancement in the cold emission characteristics of chemically synthesized super-hydrophobic zinc oxide rods by nickel doping.

The current article presents a huge enhancement in the field emission characteristics of zinc oxide (ZnO) micro/nanorods by nickel doping. The synthesis of pure and nickel-doped zinc oxide (ZnO) micro/nanorods was done by a simple low-temperature chemical method. Both the as-prepared pure and doped samples were analyzed by X-ray diffraction and electron microscopy to confirm the proper phase formation and the developed microstructure. UV-vis transmittance spectra helped in determining the band gap of the samples. Fourier-Transform Infrared Spectroscopy (FTIR) spectra showed the different bonds present in the sample, whereas X-ray Photoelectron Spectroscopy (XPS) confirmed the presence of nickel in the doped sample. Photoluminescence (PL) spectra showed that after doping, the band-to-band transition was affected, whereas defect-induced transition had increased significantly. After the nickel doping, contact angle measurement revealed a significant decrease in the sample's surface energy, leading to a remarkably high water contact angle (within the superhydrophobic region). Simulation through ANSYS suggested that the doped sample has the potential to function as an efficient cold emitter, which was also verified experimentally. The cold emission characteristics of the doped sample showed a significant improvement, with the turn-on field (corresponding to J = 1 µA cm-2) reduced from 5.34 to 2.84 V µm-1. The enhancement factor for the doped sample reached 3426, approximately 1.5 times higher compared to pure ZnO. Efforts have been made to explain the results, given the favorable band bending as well as the increased number of effective emission sites.

Rooftop water harvesting for managed aquifer recharge and flood mitigation in tropical cities: Towards a strategy of co-benefit evaluations in João Pessoa, northeast Brazil.

Intense urbanisation in many coastal areas has led to intensification of groundwater consumption, while reducing permeable areas and increasing the frequency and magnitude of flooding. Among the potential strategies to compensate for these adverse effects, which are expected to become worse as a result of climate change, rooftop rainwater harvesting (RWH) in combination with managed aquifer recharge (MAR), may be indicated. This work investigated the performance of different configurations of such a system, tested as a twofold sustainable stormwater and domestic water management tool in a tropical metropole (João Pessoa, Brazil). This area located over a sedimentary aquifer system illustrates the water security challenges of densely urbanised areas in southern cities. To that end, several configurations of rooftop catchments and storage volumes were evaluated, by simulating a MAR-RWH system connected to the regional unconfined aquifer (Barreiras Formation) through a 6″ diameter injection well. Rainfall-runoff-recharge processes and water balances were simulated using monitored high-temporal resolution rainfall data. The results showed that catchments ranging from 180 to 810 m2, connected to tanks from 0.5 to 30.0 m³, are the optimal solutions in terms of efficient rainwater retention and peak flow reduction. These solutions provided mean annual estimates of aquifer recharge between 57 and 255 m³/yr from 2004 to 2019. The results of this study highlight the opportunity for MAR schemes to reconcile stormwater management and water supply goals.

Impact of environmental variables on some reproductive metrics of white-lipped peccaries (Tayassu pecari) raised in Atlantic Forest of Brazil.

Knowledge on male reproductive physiology is essential for the development of effective conservation strategies. This study investigated the influence of environmental variables on certain reproductive metrics in white-lipped peccaries (Tayassu pecari) raised in the Atlantic Forest. After anesthetization, testicular and cauda epididymis biometry were evaluated in nine adult male individuals subjected to electroejaculation. Semen was evaluated for volume, pH, concentration, total number of sperm, sperm morphology, membrane integrity, and kinematic parameters. Concurrently, environmental variables were collected from the day before, for the previous 14 days (estimated for sperm maturation in epididymis), and the period of 51-55 days (corresponding to the spermatogenic cycle) before semen collection. Overall, it was observed that rainfall is the most important environmental variable influencing the reproductive parameters of white-lipped peccaries, being positively correlated with the amplitude of lateral sperm head displacement (ρ = 0.62, P < 0.05) and the appearance of proximal cytoplasmic droplets in sperm (ρ = 0.62, P < 0.05). In addition, the testicular biometry of the species is influenced by the set of environmental variables of air temperature, rainfall, and relative humidity (ρ ≥ 0.60, P < 0.05). On the other hand, epididymal biometric data showed numerous correlations between cauda epididymis metrics and sperm parameters (ρ = 0.68, P < 0.05). This information will be useful to improving conservation strategies for these animals, contributing to their management in captivity and to reintroduction programs, especially in the Atlantic Forest where the species is declining.

Knowledge and Awareness about Systemic Effects of Periodontal Disease among Medical, Dental and Alternate Medical Practitioners and Their Referral Practice to Periodontists.

In the past few decades, many medical professionals and dentists have paid close notice to their own fields, specializing in medicine pertaining to body and oral cavity respectively. Currently, this void is rapidly closing between all medical specialties, in presence of significant findings that supports association between periodontal disease and systemic conditions. Till now, some practitioners are not aware about the specialties of dentistry that results in improper referral practices. There are few studies on referral practice pertaining to periodontist, not with standing the fact that clear and effective communication between all health practitioners is essential for good practice. A cross-sectional study was carried out to assess the knowledge and awareness about systemic effects of periodontal disease among medical, dental and alternate medical practitioners and their referral practice to periodontist in Kanpur city. This cross-sectional study was carried out using self-reported questionnaire, distributed to 560 practitioners of various medical fields from January 2020 to August 2021. A total of 206(36.8%) Medical, 194(34.6%) Dentists and 160(28.6%) alternative practitioners participated in study. More than half participants agreed about relationship between periodontal diseases and Diabetes Mellitus, Cardio-VascularDisease and Adverse Pregnancy Outcomes. Among all 31.3% showed good knowledge level while 2.7% showed perfect level of practitioner's referral practice to periodontist. Dentists had statistically higher level of awareness compared to physicians. Referral practice to periodontist was deficit by medical and alternate medical practitioners despite of fact; they have good knowledge of relationship between periodontal disease and systemic health. Hence, interdisciplinary dental and medical training of practitioners is recommended.

A Case Report of an Unusual Cause of Dysphagia from Enlarged Subcarinal Lymph Node.

Cough, hemoptysis, chest pain, and weight loss are classic symptoms of bronchial carcinoma. Small cell lung cancer presents late with obviously abnormal chest radiographs and with bulky, usually mediastinal lymph node involvement. Dysphagia rarely occurs in patients with bronchial carcinoma. There are many causes of dysphagia in bronchial carcinoma such as mediastinal lymphadenopathy, direct tumor invasion of the mediastinum, radiotherapy, secondary achalasia. This report presents a case of progressive dysphagia to solid foods and weight loss of a 28-year-old male, non-smoker due to subcarinal lymph node enlargement from metastatic bronchial adenocarcinoma.

Molecular docking analysis of GC-MS analyzed bioactive compounds from the rhizome of Hedychium rubrum with four protein targets.

Hedychium rubrum, a traditional medicinal plant of Manipur belonging to the family Zingeberaceae was screened for its biological activity. The methanolic extract of its rhizome was prepared by Soxhlet extraction method and was further subjected to GC-MS to know its bioactive compounds. The in vitro antimicrobial activity assay was tested against five bacteria causing UTI. Klebseilla pneumoniae showed most sensitive followed by Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Enterococcus faecalis in the order. Plant extract showed higher inhibition zone than the positive control used. According to the higher quality of compounds from the GCMS results nine compounds were selected for further in silico studies using GOLD software against four protein targets. The phytoconstituents present in the methanolic extract have the ability to bind at the receptor site of all four targeted proteins. ADMET and TOPKAT studies were also carried out.

Automated Deep Transfer Learning-Based Approach for Detection of COVID-19 Infection in Chest X-rays.

The most widely used novel coronavirus (COVID-19) detection technique is a real-time polymerase chain reaction (RT-PCR). However, RT-PCR kits are costly and take 6-9 hours to confirm infection in the patient. Due to less sensitivity of RT-PCR, it provides high false-negative results. To resolve this problem, radiological imaging techniques such as chest X-rays and computed tomography (CT) are used to detect and diagnose COVID-19. In this paper, chest X-rays is preferred over CT scan. The reason behind this is that X-rays machines are available in most of the hospitals. X-rays machines are cheaper than the CT scan machine. Besides this, X-rays has low ionizing radiations than CT scan. COVID-19 reveals some radiological signatures that can be easily detected through chest X-rays. For this, radiologists are required to analyze these signatures. However, it is a time-consuming and error-prone task. Hence, there is a need to automate the analysis of chest X-rays. The automatic analysis of chest X-rays can be done through deep learning-based approaches, which may accelerate the analysis time. These approaches can train the weights of networks on large datasets as well as fine-tuning the weights of pre-trained networks on small datasets. However, these approaches applied to chest X-rays are very limited. Hence, the main objective of this paper is to develop an automated deep transfer learning-based approach for detection of COVID-19 infection in chest X-rays by using the extreme version of the Inception (Xception) model. Extensive comparative analyses show that the proposed model performs significantly better as compared to the existing models.

Blood group discrepancy in Ah para-Bombay phenotype: a rare blood group variant and its clinical significance.

Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with FUT1 and/or FUT2 genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of "Ah para-Bombay" phenotype. The patient's Lewis phenotype was Le(a-b+). This patient's serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with FUT1 and/or FUT2 genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of "Ah para-Bombay" phenotype. The patient's Lewis phenotype was Le(a­b+). This patient's serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.

Spatial multicriteria approach to support water resources management with multiple sources in semi-arid areas in Brazil.

Semi-arid regions often face severe drought events that reduce agricultural and livestock production. In recent years, some international studies have used multicriteria decision analysis (MCDA) approaches combined with geographic information systems (GIS-MCDA) to support decision-makers in assessing the suitability of agricultural land for irrigation in semi-arid regions. Unlike previous studies, which have only considered a single source of water for crop irrigation, this study proposes a GIS-MCDA approach that considers all potentially available local water sources (e.g., groundwater, surface water, and wastewater) as possible alternatives for better multisource water resource management (MWRM) in regions facing water shortages. The geospatial multicriteria evaluation implemented in this study considers a series of technical, environmental, and agricultural productivity criteria using the analytical hierarchy process (AHP) method. Three independent baseline maps were generated, showing the spatial distribution of suitable areas for crop irrigation for each considered water source in the studied area. Surface water, groundwater, and wastewater offered suitable crop irrigation for 83%, 70%, and 26% of the study area, respectively. Overlapping these areas produced a final map showing all the feasible areas for each crop irrigation alternative at the same time. The MWRM approach considering all water sources increased the coverage of suitable areas to be irrigated in the study area by 2.2%, 20.4%, and more than 225% compared to considering surface water, groundwater, and wastewater, respectively, independently. The GIS-MCDA framework proposed in this study provides better support for decision-makers and stakeholders, favouring a reduction in possible conflicts over water scarcity, the diversification of irrigated crops, and an improvement in the quality-quantitative management of water resources in semi-arid regions.

Linear lesions in dermatology: a clinicoaetiopathological study.

BACKGROUND: Linear lesions are fairly common in our daily practice. However, the appearance of these lesions can vary, thus complicating the diagnosis. AIMS: To study the various clinical presentations, the demographic profile of patients and the clinicopathological correlations of dermatoses presenting with a linear distribution. METHODS: We conducted an institution-based, cross-sectional, descriptive study of 281 consecutive patients with linear lesions attending dermatology clinics. MedCalc software (V11.6) was used for statistical analysis. RESULTS: Patients were divided into eight groups: lesions along the lines of Blaschko (n = 136), lesions along blood vessels (n = 3), lesions along lymphatics (n = 3), Koebner phenomenon (n = 24), autoinoculation (n = 24), external factors (n = 45), infestations (n = 2) and 'other' (n = 44). The mean age at presentation was 24.50 ± 18.82 years and the male/female ratio was 1.32 : 1. The commonest symptom was itching/burning (56.94% of patients), while the commonest site was the arm (44.48%); followed by the leg (30.60%), trunk and abdomen (22.42%), head and neck (19.20%), and genitalia (0.35%). Apart from the common cases, there was a wide gamut of rare conditions (e.g. angiokeratoma circumscriptum naeviforme, porokeratotic eccrine ostial and dermal duct naevus, Blaschko-linear syringocystadenoma papilliferum, progressive cribriform and zosteriform hyperpigmentation, unilateral naevoid acanthosis nigricans, fixed drug eruption, discoid lupus erythematosus). CONCLUSION: Linear lesions act as diagnostic clues to many dermatological conditions, therefore, the importance of meticulous examination in clinical dermatology cannot be overemphasized.

A Preliminary Study on the Evaluation of In-vitro Inhibition Potential of Antimicrobial Efficacy of Raw and Commercial Honey on Escherichia coli: An Emerging Periodontal Pathogen.

Periodontitis, a multiple pathogen disease has the latest addition to the family i.e. Escherichia coli as a potential and emerging periodontal pathogen owing to its lipopolysaccharide more potent than Porphyromonas gingivalis, which makes it an emerging threat in periodontal disease. The role of antimicrobial agents in the management of periodontal diseases is of utmost importance. However, in the present scenario, antibiotic resistance is a public health concern now and there are very few options left for treatment. So, honey, a pioneer in traditional medicine was tried in the treatment against Escherichia coli to evaluate and compare the "in-vitro" antibacterial activity and efficacy of raw and commercial honey at different concentrations in comparison to tetracycline as a control on patient-isolated Escherichia coli and the American Type Culture Collection (ATCC) Escherichia coli 25922 strain from 5th Aug 2018 to 15th Feb 2019 at the Department of Microbiology, Rama Medical College, Kanpur (UP), India. In the in-vitro study different concentrations (100%, 75%, 50% and 25% v/v) of raw and commercial honey were studied and sensitivity tests were used to evaluate their antibacterial effect on patient-isolated Escherichia coli and the ATCC Escherichia coli 25922 strain. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were also determined for raw honey, and commercial honey in comparison to tetracycline. In case of raw honey, zone of inhibition was seen at 100%, 75% and 50% concentration, with maximum inhibition being 27±1.154mm and 23±0.666mm for patient-isolated Escherichia coli and ATCC Escherichia coli 25922 strain respectively at 100% concentration, whereas, the commercial honey was effective only at 100% and 75% concentration, with maximum inhibition zone of 13±1.054mm and 17±0.942mm at 100% concentration on patient-isolated Escherichia coli and ATCC Escherichia coli 25922 strain respectively. However, no effect was observed at 25% concentration for both raw and commercial honey. The MIC and MBC of raw and commercial honey were determined by the broth dilution method, where raw honey exhibited both MIC and MBC at 512 mg/ml whereas, and commercial honey exhibited MIC at 512mg/ml and MBC at 1024 mg/ml respectively. While comparing the zone of inhibition of raw and commercial honey, it was observed that the raw honey showed almost equivalent potency and efficacy as compared to a positive control tetracycline (2.5%). There was statistically significant difference (p≤0.01) in zone of inhibition of raw and commercial honey at 100% concentration on patient-isolated Escherichia coli and ATCC Escherichia coli 25922 strain. Antimicrobial activity of raw honey at 100% concentration was equivalent to that of tetracycline and was significantly better than commercial honey.

Experiment and FEM Analysis of Silica Nanoparticle-Based Impedance Immunosensor for Sensitivity Enhancement.

This article investigates the impact of incorporating silica nanoparticles of varying diameters in label free impedance immunosensor. It has been observed that even if the surface area improvement has been adjusted to be similar for all the diameters, the sensitivity is enhanced by five times at a particular diameter of 100 nm due to the optimum combination of intersection with electric field lines and surface convexity. This study has enabled the detection of 0.1 fM Hep-B surface antigen with a reliable sensitivity of around 75%. Further, it has been observed that the SNR corresponding to 0.1 fM is 20 dB only for 100 nm particle. This SNR is comparable to a recent report on Hep-B virus detection but the limit of detection in the proposed sensor is lowered by more than three orders of magnitude.

Label free, electric field mediated ultrasensitive electrochemical point-of-care device for CEA detection.

Developing point-of-care (PoC) diagnostic platforms for carcinoembryonic antigen detection is essential. However, thefew implementations of transferring the signal amplification strategies in electrochemical sensing on paper-based platforms are not satisfactory in terms of detection limit (LOD). In the quest for pushing down LOD, majority of the research has been targeted towards development of improved nanostructured substrates for entrapping more analyte molecules and augmenting the electron transfer rate to the working electrode. But, such approaches have reached saturation. This paper focuses on enhancing the mass transport of the analyte towards the sensor surface through the application of an electric field, in graphene-ZnO nanorods heterostructure. These hybrid nanostructures have been deposited on flexible polyethylene terephthalate substrates with screen printed electrodes for PoC application. The ZnO nanorods have been functionalized with aptamers and the working sensor has been integrated with smartphone interfaced indigenously developed low cost potentiostat. The performance of the system, requiring only 50 µl analyte has been evaluated using electrochemical impedance spectroscopy and validated against commercially available ELISA kit. Limit of detection of 1 fg/ml in human serum with 6.5% coefficient of variation has been demonstrated, which is more than three orders of magnitude lower than the existing attempts on PoC device.

Catheter-related blood stream infections: prevalence, risk factors and antimicrobial resistance pattern.

BACKGROUND: Intravascular devices have significant potential for producing iatrogenic diseases resulting in catheter-related blood stream infections (CRBSIs). A study was undertaken to find the prevalence of CRBSI among patients in acute wards and to analyze the associated risk factors, causative pathogens with their antibiotic susceptibility (ABST) patterns. METHODS: Randomly ten days per month were chosen, for a period of two years. All the acute wards patients who were on indwelling blood catheters were identified. Those fulfilling the CRBSI criteria were further worked up for confirmation of diagnosis by differential time to positivity. The catheter tip was cultured by Maki's semiquantitative method. ABST of the isolates obtained was performed by Kirby-Bauer disk diffusion method. RESULTS: The prevalence of CRBSI was found to be 39.25% with the most common organism isolate being Serratia marcescens (23.81%). The immunocompromised status of the patients and catheterisation time were significant risk factors. Methicillin resistance was found to be 33.33% in coagulase-negative staphylococci. The resistance to vancomycin among the Entercoccus faecium isolates was found to be 33.33%. Among the gram negatives, resistance to aminoglycosides, fluoroquinolones and third-generation cephalosporins was high. CONCLUSION: The study highlights the importance of regular surveillance programs, an efficient infection control program, strict adherence to antiseptic measures and use of a rational antibiotic policy for the early diagnosis and better management of CRBSI.

Reverted effect of mesenchymal stem cells in glioblastoma treated with agathisflavone and its selective antitumoral effect on cell viability, migration, and differentiation via STAT3.

Glioblastoma is the most lethal tumor of the central nervous system, presenting a very poor prognostic, with a survival around 16 months. The interaction of mesenchymal stem cells and tumor cells has been studied, showing a bias in their role favoring or going against aggressiveness. Natural products such as flavonoids have showed their anticancer properties and the synergic potential with the activation of microenvironment cells to inhibit tumor progression. Agathisflavone is a flavonoid studied in neurodegenerative diseases and cancer. The present study investigated the effect of flavonoid in the viability of heterogeneous glioblastoma (GBM) cells considering a coculture or conditioned medium of mesenchymal stem cells (MSCs) effect, as well as the dose-dependent effect of this flavonoid in tumor migration and differentiation via STAT3. Agathisflavone (3-10 µM) induced dose-dependent toxicity to GL-15 and U373 human GBM cells, since 24 h after treatments. It was not toxic to human MSC but modified the pattern of interaction with GBM cells. Agathisflavone also inhibited migration and increased differentiation of human GBM cells, associated with the reduction on the expression of STAT3. These results demonstrate that the flavonoid agathisflavone had a direct anti-glioma effect. However, could be observed its effect in MSCs response that may have an impact in controlling GBM growth and aggressiveness, an important factor to consider for new therapies.

Case-fatality From Orally-transmitted Acute Chagas Disease: A Systematic Review and Meta-analysis.

Orally-transmitted acute Chagas disease (CD) is emerging as an important public health problem. The prognosis of acute infection following oral transmission is unknown. The aim of this study was to analyze and summarize data on orally-transmitted acute CD. We searched for publications from 1968 to 31 January 2018. We included studies and unpublished data from government sources that reported patients with acute orally-transmitted CD. We identified 41 papers and we added 932 unpublished cases. In all, our study covered 2470 cases and occurrence of 97 deaths. Our meta-analysis estimated that the case-fatality rate was 1.0% (95% CI 0.0-4.0%). Lethality rates have declined over time (P = .02). In conclusion, orally-transmitted acute CD has considerable lethality in the first year after infection. The lethality in symptomatic cases is similar to that from other routes of infection. The lethality rate of orally-acquired disease has declined over the years.

Risk of Zika virus-associated birth defects in congenital confirmed cases in the Brazilian Amazon.

OBJECTIVE: To establish the risk of microcephaly in neonates born to women infected with ZIKV during pregnancy. METHODS: A cohort of laboratory-confirmed ZIKV cases of congenital infections (109 mothers infected during pregnancy and 101 newborns) among 308 suspect cases was followed in Belem, Pará, Brazil, from October 2015 to December 2017. RESULTS: A microcephaly risk of 1.98% (95% CI 0.54-6.93%) was found, or 2 cases among the 101 neonates infected with ZIKV during pregnancy. 72% of the pregnant women had ZIKV infection confirmed by RT-qPCR during gestation. CONCLUSIONS: Results showed a low incidence of ZIKV-associated birth defects, stillbirth, and miscarriage, which contrasts with previous studies in other Brazilian regions. Previous exposure to yellow fever vaccine and/or multiserotype DENV infection could be implicated in the protection from ZIKV congenital infection.

OBJETIVO: Establecer el riesgo de microcefalia en los recién nacidos de mujeres infectadas con ZIKV durante el embarazo. MÉTODOS: Se siguió a una cohorte de casos con infección congénita por ZIKV confirmada por laboratorio (109 madres infectadas durante el embarazo, 101 recién nacidos) conformada a partir de 308 casos sospechosos en Belem, Pará, Brasil, de octubre de 2015 a diciembre de 2017. RESULTADOS: Se encontró un riesgo de microcefalia de 1,98% (IC95% 0,54-6,93%), o 2 casos entre los 101 neonatos infectados con ZIKV durante el embarazo. En el 72% de las mujeres embarazadas se confirmó mediante RT-qPCR la infección por ZIKV durante la gestación. CONCLUSIONES: Los resultados mostraron una baja incidencia de malformaciones congénitas, mortinatos y abortos asociados al ZIKV, lo que contrasta con estudios anteriores de otras regiones de Brasil. La exposición previa a la vacuna contra la fiebre amarilla o la infección previa por varios serotipos de virus del dengue podrían estar implicados en la protección contra la infección congénita por ZIKV.

Risk of Zika virus-associated birth defects in congenital confirmed cases in the Brazilian Amazon

Objective. To establish the risk of microcephaly in neonates born to women infected with ZIKV during pregnancy. Methods. A cohort of laboratory-confirmed ZIKV cases of congenital infections (109 mothers infected during pregnancy and 101 newborns) among 308 suspect cases was followed in Belem, Pará, Brazil, from October 2015 to December 2017. Results. A microcephaly risk of 1.98% (95% CI 0.54-6.93%) was found, or 2 cases among the 101 neonates infected with ZIKV during pregnancy. 72% of the pregnant women had ZIKV infection confirmed by RT-qPCR during gestation. Conclusions. Results showed a low incidence of ZIKV-associated birth defects, stillbirth, and miscarriage, which contrasts with previous studies in other Brazilian regions. Previous exposure to yellow fever vaccine and/ or multiserotype DENV infection could be implicated in the protection from ZIKV congenital infection.

Objetivo. Establecer el riesgo de microcefalia en los recién nacidos de mujeres infectadas con ZIKV durante el embarazo. Métodos. Se siguió a una cohorte de casos con infección congénita por ZIKV confirmada por laboratorio (109 madres infectadas durante el embarazo, 101 recién nacidos) conformada a partir de 308 casos sospechosos en Belem, Pará, Brasil, de octubre de 2015 a diciembre de 2017. Resultados. Se encontró un riesgo de microcefalia de 1,98% (IC95% 0,54-6,93%), o 2 casos entre los 101 neonatos infectados con ZIKV durante el embarazo. En el 72% de las mujeres embarazadas se confirmó mediante RT-qPCR la infección por ZIKV durante la gestación. Conclusiones. Los resultados mostraron una baja incidencia de malformaciones congénitas, mortinatos y abortos asociados al ZIKV, lo que contrasta con estudios anteriores de otras regiones de Brasil. La exposición previa a la vacuna contra la fiebre amarilla o la infección previa por varios serotipos de virus del dengue podrían estar implicados en la protección contra la infección congénita por ZIKV.

Upfront Xpert MTB/RIF for diagnosis of pediatric TB-Does it work? Experience from India.

BACKGROUND: Diagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings. METHODS: Data were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort. RESULTS: Of the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18). CONCLUSION: This project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.