Feto-placental and coronary endothelial genes implicated in miscarriage, congenital heart disease and stillbirth, a systematic review and meta-analysis.

The first trimester placenta is very rarely investigated for placental vascular formation in developmental or diseased contexts. Defects in placental formation can cause heart defects in the fetus, and vice versa. Determining the causality is therefore difficult as both organs develop concurrently and express many of the same genes. Here, we performed a systematic review to determine feto-placental and coronary endothelial genes implicated in miscarriages, stillbirth and congenital heart defects (CHD) from human genome wide screening studies. 4 single cell RNAseq datasets from human first/early second trimester cardiac and placental samples were queried to generate a list of 1187 endothelial genes. This broad list was cross-referenced with genes implicated in the pregnancy disorders above. 39 papers reported feto-placental and cardiac coronary endothelial genes, totalling 612 variants. Vascular gene variants were attributed to the incidence of miscarriage (8 %), CHD (4 %) and stillbirth (3 %). The most common genes for CHD (NOTCH, DST, FBN1, JAG1, CHD4), miscarriage (COL1A1, HERC1), and stillbirth (AKAP9, MYLK), were involved in blood vessel and cardiac valve formation, with roles in endothelial differentiation, angiogenesis, extracellular matrix signaling, growth factor binding and cell adhesion. NOTCH1, AKAP12, CHD4, LAMC1 and SOS1 showed greater relative risk ratios with CHD. Many of the vascular genes identified were expressed highly in both placental and heart EC populations. Both feto-placental and cardiac vascular genes are likely to result in poor endothelial cell development and function during human pregnancy that leads to higher risk of miscarriage, congenital heart disease and stillbirth.

Pre-Surgery Cortisol Levels as Biomarker of Evolution after Bariatric Surgery: Weight Loss and Weight Regain.

Background: Bariatric surgery (BS) is effective for achieving significant weight loss. However, weight regain (WR) is an emerging problem. Objective: To assess the prognostic value of morning serum cortisol, a 1 mg dexamethasone suppression test (DST), 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) in a cohort of patients with severe obesity (pwSO) undergoing BS in terms of weight loss and WR. Methods: Patients scheduled for BS underwent the following procedures at baseline, 12 months and 24 months after BS: medical history, anthropometric data, blood analysis and cortisol tests. We evaluated total weight loss (TWL) ≥ 30% at 1 year and WR after 2 years as an increase of ≥10% of the maximum weight lost. Results: In total, 142 subjects were included; 101 (71.1%) were females and the mean age was 45.9 ± 9.2 years. Up to 76.8% of subjects achieved ≥30% TWL, without statistically significant differences in DST results or morning serum cortisol, UFC or LNSC levels. However, a higher pre-surgery morning serum cortisol level was a significant predictor of a WR ≥ 10% (cortisol 17.8 [IQR 13.1-18.5] vs. 12.0 [IQR 8.8-15.8] µg/dL; p < 0.01); OR of 1.216 (95% CI 1.069-1.384); AUC [0.761, CI: (0.616-0.906); p < 0.01]. A cut-off value of cortisol > 13.0 µg/dL was predictive of a WR ≥ 10% (sensitivity 0.71; specificity 0.63). Conclusions: No cortisol test was useful in predicting weight loss; however, the pre-surgery morning serum cortisol level was able to predict a WR ≥ 10% in a cohort of pwSO 2 years after BS. A cut-off value of cortisol > 13 µg/dL might be an easy tool to identify patients at higher risk of WR, enabling healthcare providers to implement tailored, long-term strategies to minimize this outcome.

Using AI to Differentiate Mpox From Common Skin Lesions in a Sexual Health Clinic: Algorithm Development and Validation Study.

BACKGROUND: The 2022 global outbreak of mpox has significantly impacted health facilities, and necessitated additional infection prevention and control measures and alterations to clinic processes. Early identification of suspected mpox cases will assist in mitigating these impacts. OBJECTIVE: We aimed to develop and evaluate an artificial intelligence (AI)-based tool to differentiate mpox lesion images from other skin lesions seen in a sexual health clinic. METHODS: We used a data set with 2200 images, that included mpox and non-mpox lesions images, collected from Melbourne Sexual Health Centre and web resources. We adopted deep learning approaches which involved 6 different deep learning architectures to train our AI models. We subsequently evaluated the performance of each model using a hold-out data set and an external validation data set to determine the optimal model for differentiating between mpox and non-mpox lesions. RESULTS: The DenseNet-121 model outperformed other models with an overall area under the receiver operating characteristic curve (AUC) of 0.928, an accuracy of 0.848, a precision of 0.942, a recall of 0.742, and an F1-score of 0.834. Implementation of a region of interest approach significantly improved the performance of all models, with the AUC for the DenseNet-121 model increasing to 0.982. This approach resulted in an increase in the correct classification of mpox images from 79% (55/70) to 94% (66/70). The effectiveness of this approach was further validated by a visual analysis with gradient-weighted class activation mapping, demonstrating a reduction in false detection within the background of lesion images. On the external validation data set, ResNet-18 and DenseNet-121 achieved the highest performance. ResNet-18 achieved an AUC of 0.990 and an accuracy of 0.947, and DenseNet-121 achieved an AUC of 0.982 and an accuracy of 0.926. CONCLUSIONS: Our study demonstrated it was possible to use an AI-based image recognition algorithm to accurately differentiate between mpox and common skin lesions. Our findings provide a foundation for future investigations aimed at refining the algorithm and establishing the place of such technology in a sexual health clinic.

IST Nurse®: development and validity evidence of a mobile application as a support for the clinical management of Sexually Transmitted Infections.

OBJECTIVE: to develop and evaluate the validity evidence of a mobile application to support nurses in the clinical management of sexually transmitted infections. METHOD: methodological study conducted in four steps: analysis and definition of requirements; content definition; computational representation with system design; and coding with testing and refinement. In the first steps, nurses with expertise in the subject participated, and in the last, professionals with education in information and communication technology. Data analysis was performed by calculating the Content Validity Index (CVI), considering the minimum agreement value of 0.78. To confirm the viability of the CVI, the binomial test was used through the R software. Variables with p > 0.05 indicated agreement between the judges. RESULTS: the CVI was 0.98 for content, 1.0 for usability and 0.85 for functional performance, showing that the developed application has high validity. CONCLUSION: it is believed that the IST Nurse® application represents an important technological tool in strengthening evidence-based nursing care. Intervention studies are therefore suggested.

Peer-Delivered HIV Self-Testing, Sexually Transmitted Infection Self-Sampling, and Pre-exposure Prophylaxis for Transgender Women in Uganda: A Randomized Trial.

BACKGROUND: Peer-delivered HIV self-testing (HIVST) and sexually transmitted infection self-sampling (STISS) may promote adherence to oral pre-exposure prophylaxis (PrEP), but no studies have analyzed this approach among transgender women (TGW) in sub-Saharan Africa. SETTING: The Peer study was a cluster randomized trial in Uganda (October 2020-July 2022; NCT04328025). METHODS: Ten TGW peer groups, each with 1 TGW peer and 8 TGW, were randomized 1:1 to receive quarterly in-clinic HIV testing with PrEP refills as standard-of-care (SOC) or SOC plus monthly peer delivery of oral-fluid HIVST, STISS, and PrEP refills (intervention). Participants were followed for 12 months. The primary outcome was PrEP adherence. RESULTS: We screened 85 TGW and enrolled 82 (41 per arm). The median age was 22 years (interquartile range [IQR] 20-24). Twelve-month retention was 88% (72/82). At the 3, 6, 9, and 12-month clinic visits, 10%, 5%, 5%, and 0% of TGW in the intervention arm had TFV-DP levels ≥700 fmol/punch, versus 7%, 15%, 7%, and 2% in the SOC arm, respectively (P = 0.18). At all visits, any detectable TFV-DP levels were significantly higher in SOC than the peer delivery group (P < 0.04). PrEP adherence was associated with sex work (incidence rate ratio 6.93; 95% CI: 2.33 to 20.60) and >10 years of schooling (incidence rate ratio 2.35; 95% CI: 1.14 to 4.84). There was a strong correlation between tenofovir detection in dried blood spots and urine (P < 0.001). No HIV seroconversions occurred. CONCLUSIONS: Peer-delivered HIVST and STISS did not increase low levels of oral PrEP adherence among TGW in Uganda. Long-acting PrEP formulations should be considered for this population.

The dexamethasone suppression test as a biomarker for suicidal behavior: A systematic review and meta-analysis.

BACKGROUND: The dexamethasone suppression test (DST), which measures HPA-axis functioning, is a potential biomarker for suicidal behavior. The current study aimed (a) to synthesize available knowledge on the association between DST non-suppression and suicidal behavior, and (b) to study potential moderators. METHODS: A total of 4236 studies were screened, 43 were included. Suicide attempts and suicide completion were studied separately. The meta-analysis included 37 effect sizes for suicide attempts (n = 3733) and 11 effect sizes for suicide completion (n = 1626). RESULTS: DST non-suppression was associated with completed suicide (odds ratio (OR) = 2.10, (95 % CI [1.37, 3.23]). For suicide attempts, we found no evidence that DST status was associated in the overall meta-analysis including all patient samples. However, moderator analysis indicated that the DST status was associated with suicide attempts in patient samples that included psychopathology other than just mood disorders, such as psychotic, substance use and personality disorders (OR = 2.34, 95 % CI [1.39-3.93], k = 11). LIMITATIONS: The potential influence of publication bias and exclusion of some relevant published studies (since effect sizes could not be calculated, authors could not supply data or authors could not be reached) are limitations. Furthermore, missing moderator data decreased our ability to explain heterogeneity between studies. CONCLUSIONS: The results of this meta-analysis support the hypothesis that DST non-suppression is predictive of suicidal behavior. More research is needed to investigate optimal cut-off values, confounding factors and the potential usefulness of the DST in clinical practice in terms of personalized medicine.

Trends of Toxoplasma gondii and common transfusable venereal infections among blood donors in Menoufia Province, Egypt.

Blood transfusion has a hazard of transmission of many pathogens, including Toxoplasma gondii (T. gondii) and other venereal infections. It is crucial to conduct epidemiological surveillance to detect the prevalence of these pathogens. The study aimed to assess the seroprevalence of T. gondii and common transfusable venereal infections among healthy blood donors in Menoufia Province, Egypt, and identify associated risk factors. Four hundred twenty individuals were recruited between January and April 2023 for cross-sectional descriptive research from the blood banks of Menoufia University medical hospitals. Collected blood samples were screened for anti-T. gondii IgM and IgG, HBsAg, anti-HCV antibodies, HIV p24 antigen and anti-HIV antibodies, and anti-Treponema pallidum antibodies. 46 (11.0%) and 22 donors (5.2%) individuals tested positive for anti-T. gondii IgG with a 95% CI (8.3-14.6) and IgM with a 95% CI (3.5-8.1), respectively, while one patient (0.2%) was positive for both antibodies. Regarding venereal infections, 12 (2.9%) were positive for HBV, 6 (1.4%) were positive for HCV, 7 (1.7%) were positive for HIV, and none of the tested population showed positivity for syphilis. Female gender, consumption of raw meat, agricultural environment, poor awareness about T. gondii, and blood group type (especially AB and O groups) were identified as independent risk factors for T. gondii infection. The study highlights the importance of testing blood donors for T. gondii and common transfusable venereal illnesses. Starting health education programs and preventative measures, such as suitable meat handling and cleanliness practices, is critical for minimizing the occurrence of these illnesses. Larger-scale additional study is advised to confirm these results and provide guidance for public health initiatives.

Genetic diversity, population structure and ecological niche modeling of Thyrinteina arnobia (Lepidoptera: Geometridae), a native Eucalyptus pest in Brazil.

Thyrinteina arnobia (Lepidoptera: Geometridae) is a native American species. Despite its historical importance as an insect pest in Eucalyptus plantations, more information is needed regarding the population diversity, demography, and climatic variables associated with its distribution in different regions of Brazil. We used a phylogeographic approach to infer the genetic diversity, genetic structure, and demographic parameters of T. arnobia. We also conducted an ecological niche modeling (ENM) to predict suitable areas for T. arnobia occurrence in Brazil and other countries worldwide. Although T. arnobia populations have low genetic diversity in Brazil, we identified mitochondrial haplogroups predominating in different Brazilian regions and high ФST and ФCT values in AMOVA, suggesting a low frequency of insect movement among these regions. These results indicate that outbreaks of T. arnobia in Eucalyptus areas in different regions of Brazil are associated with local or regional populations, with no significant contribution from long-distance dispersal from different regions or biomes, suggesting that pest management strategies would be implemented on a regional scale. In Brazil, the demographic and spatial expansion signals of T. arnobia seem to be associated with the history of geographical expansion of Eucalyptus plantations, a new sustainable host for this species. ENM indicated that isothermality and annual rainfall are critical climatic factors for the occurrence of T. arnobia in tropical and subtropical areas in the Americas. ENM also suggested that T. arnobia is a potential pest in Eucalyptus areas in all Brazilian territory and in regions from Africa, Asia, and Oceania.

Evaluating the Impact of a Dutch Sexual Health Intervention for Adolescents: Think-Aloud and Semistructured Interview Study.

BACKGROUND: Engagement with and the potential impact of web-based interventions is often studied by tracking user behavior with web analytics. These metrics do provide insights into how users behave, but not why they behave as such. OBJECTIVE: This paper demonstrates how a mixed methods approach consisting of (1) a theoretical analysis of intended use, (2) a subsequent analysis of actual use, and (3) an exploration of user perceptions can provide insights into engagement with and potential impact of web-based interventions. This paper focuses on the exploration of user perceptions, using the chlamydia page of the Dutch sexual health intervention, Sense.info, as a demonstration case. This prevention-focused platform serves as the main source of sexual and reproductive health information (and care if needed) for young people aged 12-25 years in the Netherlands. METHODS: First, acyclic behavior change diagrams were used to theoretically analyze the intended use of the chlamydia page. Acyclic behavior change diagrams display how behavior change principles are applied in an intervention and which subbehaviors and target behaviors are (aimed to be) influenced. This analysis indicated that one of the main aims of the page is to motivate sexually transmitted infection (STI) testing. Second, the actual use of the chlamydia page was analyzed with the web analytics tool Matomo. Despite the page's aim of promoting STI testing, a relatively small percentage (n=4948, 14%) of the 35,347 transfers from this page were to the STI testing page. Based on these two phases, preliminary assumptions about use and impact were formulated. Third, to further explore these assumptions, a study combining the think-aloud method and semistructured interviews was executed with 15 young individuals aged 16-25 (mean 20, SD 2.5) years. Template analysis was used to analyze interview transcripts. RESULTS: Participants found the information on the Sense.info chlamydia page reliable and would visit it mostly for self-diagnosis purposes if they experienced potential STI symptoms. A perceived facilitator for STI testing was the possibility to learn about the symptoms and consequences of chlamydia through the page. Barriers included an easily overlooked link to the STI testing page and the use of language not meeting the needs of participants. Participants offered suggestions for lowering the threshold for STI testing. CONCLUSIONS: The mixed methods approach used provided detailed insights into the engagement with and potential impact of the Sense.info chlamydia page, as well as strategies to further engage end users and increase the potential impact of the page. We conclude that this approach, which triangulates findings from theoretical analysis with web analytics and a think-aloud study combined with semistructured interviews, may also have potential for the evaluation of web-based interventions in general.

Updating Reaction Mechanistic Domains for Skin Sensitization: 1. Nucleophilic Skin Sensitizers.

It has long been recognized that skin sensitizers either are electrophilic or can be activated to electrophilic species. Several nonanimal assays for skin sensitization are based on this premise. In the course of a project to update dermal sensitization thresholds (DST), we found a substantial number of sensitizers, with no electrophilic or pro-electrophilic alerts, that could be simply explained in terms of the sensitizer acting as a nucleophile. In some cases, the nucleophilic center is a sulfur or phosphorus atom, while in others, it is an aromatic carbon atom. For carbon-centered nucleophiles, a quantitative mechanistic model based on a combination of Hammett σ+ and logP values has been derived. This has been applied to rationalize several groups of known sensitizers with no electrophilic or pro-electrophilic alerts, including anacardic acids and cardols, which are known human sensitizers associated with, inter alia, cashew nut oil, mango, and Ginkgo biloba. The possibility of nucleophilic sensitization needs to be considered when evaluating new chemicals for skin sensitization potential and potency by nonanimal assays, particularly those based on the premise that skin sensitization is dependent upon reactions of electrophiles with skin protein-based nucleophiles.

A Novel Topology Adaptation Strategy for Dynamic Sparse Training in Deep Reinforcement Learning.

Deep reinforcement learning (DRL) has been widely adopted in various applications, yet it faces practical limitations due to high storage and computational demands. Dynamic sparse training (DST) has recently emerged as a prominent approach to reduce these demands during training and inference phases, but existing DST methods achieve high sparsity levels by sacrificing policy performance as they rely on the absolute magnitude of connections for pruning and randomly generating connections. Addressing this, our study presents a generic method that can be seamlessly integrated into existing DST methods in DRL to enhance their policy performance while preserving their sparsity levels. Specifically, we develop a novel method for calculating the importance of connections within the model. Subsequently, we dynamically adjust the sparse network topology by dropping existing connections and introducing new connections based on their respective importance values. Through validation on eight widely used simulation tasks, our method improves two state-of-the-art (SOTA) DST approaches by up to 70% in episode return and average return across all episodes under various sparsity levels.

Fatal disseminated Mycobacterium avium infection with bone marrow infiltration and hemophagocytic syndrome.

Disseminated non-tuberculous mycobacterial (NTM) infection can affect patients with underlying immunosuppressive conditions. Despite being rare, delay in diagnosis can lead to life-threatening uncontrolled immune response and hemophagocytic syndrome (HPS). We report a case of a 63-year-old female with suspected autoimmune disease, in whom HPS was diagnosed according to HLH-2004 criteria and H-score. Mycobacterium avium (M. avium) was isolated from blood culture, bronchoalveolar lavage (BAL) and bone marrow biopsy. In immunosuppressed patients, early clinical suspicion and prompt microbiological diagnosis of mycobacterial infection together with drug susceptibility tests (DST)-based treatment, as well as HPS, are pivotal to increase the likelihood of treatment success.

Developmental screening of neurodevelopmental disorders before age 6: a nationwide health screening program.

BACKGROUND: We aimed to investigate the association between developmental screening before 24 months of age and neurodevelopmental disorders (NDDs) at 4-6 years of age. METHODS: We included 922,899 newborn born between 2014 and 2016 registered in National Health Insurance Service (NHIS). Developmental screening was administered at 9-12 and 18-24 months old with the Korean Developmental Screening Test for Infants & Children (K-DST). Diagnoses of NDDs was based on the World Health Organization's International Classification of Diseases, Tenth Revision (ICD-10), provided by the NHIS database. RESULTS: Among 637,277 individuals who underwent screening at 9-12 and 18-24 months, Screen-positivity (defined as summed score < -2 standard deviation) for gross motor domain at 9-12 months was significantly associated with the incidence of autism spectrum disorder (aHR, 2.24; 95% CI, 1.80-2.80) and cerebral palsy (aHR, 4.81; 95% CI, 3.62-6.38). Screening positive at language domain at 18-24 months old was associated with autism spectrum disorder (aHR 5.50; 95% CI, 4.31- 7.02) and developmental language disorder (aHR 8.67; 95% CI, 7.27-10.33) at 4-6 years of age. CONCLUSION: Widespread nationwide implementation of screening programs before 24 months was effective in identifying NDDs at 4-6 years of age. Further strategies integrating with referral and intervention systems should be established. IMPACT: We investigated the screening effect of nationwide developmental screening program on neurodevelopmental disorders using nationwide data. Gross motor delay during infancy was significant predictor of later neurodevelopmental disorders. Language, cognitive, and social delay before 24 months of age was associated with later autism spectrum disorders and developmental language disorders. Widespread nationwide implementation of screening programs before 24 months was effective in identifying NDDs at 4-6 years of age and should be encouraged.

New evidence on adolescent sexual and reproductive health and rights from the West and Central African region.

The African Journal of Reproductive Health is pleased to publish these compendiums of original research in this special edition that document new findings in adolescent sexual and reproductive health and rights from the West and Central African region (WCA). While sub-Saharan Africa has some of the worst indicators of sexual and reproductive health and rights (SRHR) in the world, the indicators are more daunting in the WCA region. To date, the WCA is recognized to have the highest rates of unwanted pregnancy, unsafe abortion, and human immunodeficiency virus (HIV) and other sexually transmissible infections, as well as the lowest contraceptive prevalence rates among adolescents worldwide.1 Despite the high rate of adverse adolescent reproductive health outcomes in WCA, there has been limited documentations of the socio-cultural and economic circumstances that perpetuate these adverse consequences. There have also been no purposefully designed interventions that provide strong scientific evidence for developing strategies to reverse the trend.

Le Journal africain de la santé reproductive est heureux de publier ces recueils de recherches originales dans cette édition spéciale qui documentent les nouvelles découvertes sur la santé et les droits sexuels et reproductifs des adolescents de la région de l'Afrique de l'Ouest et du Centre (WCA). Alors que l'Afrique subsaharienne possède certains des pires indicateurs au monde en matière de santé et de droits sexuels et reproductifs (SDSR), les indicateurs sont plus intimidants dans la région AOC. À ce jour, l'AOC est reconnue pour avoir les taux les plus élevés de grossesses non désirées, d'avortements à risque, de virus de l'immunodéficience humaine (VIH) et d'autres infections sexuellement transmissibles, ainsi que les taux de prévalence contraceptive les plus faibles parmi les adolescents dans le monde.1 Malgré le taux élevé de En dépit des résultats négatifs en matière de santé reproductive des adolescents en AOC, il existe peu de documentation sur les circonstances socioculturelles et économiques qui perpétuent ces conséquences néfastes. Il n'y a pas non plus d'interventions spécialement conçues qui fournissent des preuves scientifiques solides pour élaborer des stratégies visant à inverser la tendance.

Positive masculinity programmes and sexual and reproductive health behaviours among boys and men in poor urban settlements in Democratic Republic of Congo, Nigeria, and Rwanda.

As Positive Masculinity (PM) Programmes continue to develop globally, it is important to examine their role in Sexual and Reproductive Health and Rights (SRHR) outcomes. This multi-country qualitative study was conducted using in-depth interviews (IDI) and focus group discussions (FGDs) with community members, beneficiaries and implementers of PM programmes. The findings show that PM programmes are designed using a gender lens to make boys and men more aware and conscious of harmful masculinity traits and their effect on SRHR. The beneficiaries of the interventions report imbibing positive SRHR behaviours by being sexually responsible - upholding sexual rights, taking precautions against sexually transmitted Infections (STIs) and learning proper communication with their partners. They also report acting as vanguards of positive gender norms to their families and peers. Although there are challenges in implementing PM programmes, the results of the study suggest that interventions targeting boys and men hold promise for improving boys' and men's health behaviours and promoting gender equality in poor urban settings.

Alors que les programmes de masculinité positive (PM) continuent de se développer à l'échelle mondiale, il est important d'examiner leur rôle dans les résultats en matière de santé et de droits sexuels et reproductifs (SDSR). Cette étude qualitative multi pays a été menée à l'aide d'entretiens approfondis (IDI) et de discussions de groupe (FGD) avec des membres de la communauté, des bénéficiaires et des responsables de la mise en œuvre des programmes PM. Les résultats montrent que les programmes PM sont conçus en utilisant une optique de genre pour rendre les garçons et les hommes plus conscients des traits de masculinité néfastes et de leurs effets sur la SDSR. Les bénéficiaires des interventions déclarent avoir adopté des comportements positifs en matière de SDSR en étant sexuellement responsables ­ en respectant leurs droits sexuels, en prenant des précautions contre les infections sexuellement transmissibles (IST) et en apprenant une bonne communication avec leurs partenaires. Ils déclarent également agir en tant qu'avant-gardes des normes de genre positives auprès de leurs familles et de leurs pairs. Bien que la mise en œuvre des programmes PM présente des difficultés, les résultats de l'étude suggèrent que les interventions ciblant les garçons et les hommes sont prometteuses pour améliorer les comportements de santé des garçons et des hommes et promouvoir l'égalité des sexes dans les milieux urbains pauvres.

Adaptation of sleep to daylight saving time is slower in people consuming a high-fat diet.

Adaptation of the circadian clock to the environment is essential for optimal health, well-being, and performance. Animal models demonstrate that a high-fat diet impairs circadian adaptation to advances of the light-dark cycle; it is unknown whether this occurs in humans. Utilizing a natural experiment that occurs when humans must advance their behaviors to an earlier hour for daylight saving time (DST), we measured the influence of diet on sleep/wake timing relative to dim-light melatonin onset time. Students with a lower-fat diet rapidly altered their sleep-wake timing to match the imposed time change, whereas those with a high-fat diet were slower to adapt to the time change. Moreover, a faster shift in timing after DST was associated with higher general health, lower body mass index, and higher grade point average. These data suggest that diet may influence the speed of sleep and circadian adaptation, which could have implications for health and performance.

Diagnostics Evaluation of Smart Sure™ Mycobacterium tuberculosis Screening Kit and Smart Sure™ Multidrug-resistant Tuberculosis Detection Kit on Nonsputum Specimens at a Tertiary Care Center of North India.

BACKGROUND: Tuberculosis (TB) is caused due to the infection of Mycobacterium tuberculosis (MTB) and it can infect the various parts of the human body. The disease is highly prevalent and is the second most common cause of death worldwide after COVID-19. Apart from sputum specimen, it is exceedingly difficult to diagnose due to its paucibacillary nature. The current study was intended to evaluate the accuracy of Smart Sure™ MTB and multidrug-resistant-TB (MDR-TB) kits (Genetix Biotech Asia Pvt. Ltd., India) with Xpert ultra and Mycobacterium growth indicator tube (MGIT) culture on nonsputum specimens from TB suspects. METHODS: A total of 205 nonsputum specimens were received between October 2023 and May 2024 at Intermediate Reference Laboratory, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India. Xpert ultra and Smart Sure™ MTB and MDR-TB tests were done directly on samples. However, processed specimens were used for MGIT culture and drug-susceptibility testing (DST). Invalid and MGIT contaminated specimens were excluded from the final calculation. RESULTS: Overall, sensitivity and specificity of Smart Sure™ MTB screening kit was 71.59% and 98.28%, respectively, with Xpert ultra and 68.35% and 90.83%, respectively, with MGIT culture. While comparing with both Xpert ultra and MGIT-DST to detect rifampicin (RIF) resistant, Smart Sure™ MDR-TB kits showed sensitivity of 75.0% and 100% of specificity. However, for isoniazid (INH) resistance, Smart Sure™ MDR-TB kits showed 100% of sensitivity and specificity with MGIT-DST. CONCLUSION: For the detection of MTB and its drug-resistance patterns (RIF and INH) in the specimens other than sputum, Smart Sure™ MTB and MDR-TB kits could play a vital role in TB endemic countries. While comparing the set-ups and skilled staffs, it required almost same as compared with previously approved WHO diagnostics used in resource-limited countries.

Agreement between Phenotypically Detected Linezolid Resistance and Mutations in rrl and rplC Genes of Mycobacterium tuberculosis Isolates Using Nanopore Sequencing.

BACKGROUND: Phenotypic drug susceptibility testing (DST) is considered the gold standard for detecting linezolid (LZD) resistance in Mycobacterium tuberculosis (MTB), but it is time-consuming. Nanopore sequencing offers a potentially faster alternative approach. This study evaluated the agreement between phenotypically detected LZD resistance and mutations in the rrl and rplC genes of MTB isolates using nanopore sequencing. METHODS: Consecutive drug-resistant MTB isolates from pulmonary samples collected in 2021 underwent liquid culture (LC) DST for LZD. All resistant isolates and an equal number of susceptible isolates were subjected to targeted sequencing of the rrl and rplC genes using nanopore technology. RESULTS: Sequencing identified a C154R mutation in the rplC gene in only one LZD-resistant isolate. No mutations were detected in the rrl gene. The agreement between sequencing and LC-DST for detecting LZD resistance was poor (Cohen's kappa: 0.03571, 95% confidence interval [CI]: -0.034-0.105). Additionally, no significant association was found between LZD resistance and clinical or microbiological outcomes at 6-month follow-up. CONCLUSION: This study revealed a considerable discrepancy between phenotypic and genotypic detection of LZD resistance in MTB. Further research is needed to better understand the genetic mechanisms underlying LZD resistance and to develop reliable molecular diagnostics for rapid resistance detection.

Multi-drug resistant gene mutation analysis in Mycobacterium tuberculosis by molecular techniques.

Background and Objectives: Rifampicin (RIF) and isoniazid (INH), two most potent antibiotics, are prescribed to cure tuberculosis. Mycobacterium tuberculosis, the causative agent of multidrug-resistant tuberculosis (MDR-TB), is resistant to these first-line drugs. Here, two molecular techniques were demonstrated such as PCR sequencing-based and GeneXpert assay for rapidly identifying MDR-TB. Materials and Methods: Pulmonary samples (sputum) were collected from 55 MDR-TB suspected patients from the National Tuberculosis Reference Laboratory (NTRL), Dhaka where the research work was partially accomplished and continued in the department of Microbiology, University of Dhaka, Bangladesh. We strived for sequencing technique as well as GeneXpert assay to identify mutations in rpoB and katG genes in MTB strains and sputum directly. Culture-based drug susceptibility testing (DST) was performed to measure the efficacy of the molecular methods employed. Results: When analyzed, rpoB gene mutations at codons 531 (54.54%), 526 (14.54%), and 516 (10.91%) were found by sequencing in 80% of the samples. Nucleotide substitution at katG315 (AGC→ACC) was spotted in 16 (76.19%) out of 21 samples. When comparing the sequencing results with DST, sensitivity and specificity were investigated to determine drug-resistance (rifampicin-resistance were 98 and 100% whereas isoniazid-resistance were 94 and 100% respectively). Additionally, as a point of comparison with DST, only 85.45% of RIF mono-resistant TB cases were accurately evaluated by the GeneXpert assay. Conclusion: This research supports the adoption of PCR sequencing approach as an efficient tool in detecting MDR-TB, counting the higher sensitivity and specificity as well as the short period to produce the results.