The impact of gold mining activities: understanding the dynamics of cyanide in river ecosystems in Ecuador.

Understanding the behavior of cyanide in rivers is of utmost importance as it has a direct impact on the health of people who depend on these water sources. Cyanide contamination from gold mining activities poses a significant environmental threat to river ecosystems, particularly in southern Ecuador. This study aimed to investigate the behavior of cyanide when it enters contact with other metals in these rivers. Simulations were conducted to determine the speciation of cyanide, mercury, arsenic, lead, and manganese in a study area, taking into account the water temperature and pH at four locations. The findings revealed that CN-and HCN(aq) species were present in the research area. Additionally, mercury-cyanide (Hg(CN)2(aq), Hg(CN)3-), and manganese-cyanide (MnCN+) complexes were identified 3 km downriver from the site where the mining activity is higher. These metal-cyanide complexes tend to dissociate quickly under weak acidic conditions, making them hazardous to the environment. This research is crucial, not only for the environment but also for human health, as it allows to predict toxicity risks for people supplied with this water source, emphasizing the potential harm to human health. This study highlights the importance of stringent regulations and effective monitoring practices to mitigate cyanide contamination and safeguard environmental and occupational health.

AutoPeptideML: A study on how to build more trustworthy peptide bioactivity predictors.

MOTIVATION: Automated machine learning (AutoML) solutions can bridge the gap between new computational advances and their real-world applications by enabling experimental scientists to build their own custom models. We examine different steps in the development life-cycle of peptide bioactivity binary predictors and identify key steps where automation can not only result in a more accessible method, but also more robust and interpretable evaluation leading to more trustworthy models. RESULTS: We present a new automated method for drawing negative peptides that achieves better balance between specificity and generalisation than current alternatives. We study the effect of homology-based partitioning for generating the training and testing data subsets and demonstrate that model performance is overestimated when no such homology correction is used, which indicates that prior studies may have overestimated their performance when applied to new peptide sequences. We also conduct a systematic analysis of different protein language models as peptide representation methods and find that they can serve as better descriptors than a naive alternative, but that there is no significant difference across models with different sizes or algorithms. Finally, we demonstrate that an ensemble of optimised traditional machine learning algorithms can compete with more complex neural network models, while being more computationally efficient. We integrate these findings into AutoPeptideML, an easy-to-use AutoML tool to allow researchers without a computational background to build new predictive models for peptide bioactivity in a matter of minutes. AVAILABILITY AND IMPLEMENTATION: Source code, documentation, and data are available at https://github.com/IBM/AutoPeptideML and a dedicated web-server at http://peptide.ucd.ie/AutoPeptideML. CONTACT AND SUPPLEMENTARY INFORMATION: Raul.fernandezdiaz@ucdconnect.ie or denis.shields@ucd.ie. Supplementary Information can be accessed from Zenodo: Https://zenodo.org/records/13363975.

A pre-post evaluation of a digital intervention to improve psychosocial outcomes of caregivers of people living with cancer in Vietnam.

OBJECTIVES: To evaluate a co-designed intervention using digital resources "Vietnam Cancer Caring Coping" (V-CCC) on the health literacy, depression, and quality of life of caregivers supporting a cancer patient in oncology hospitals in Vietnam. METHODS: A pre-post quantitative evaluation with adult cancer caregivers across regional Oncology hospitals in Vietnam (Ho Chi Minh City, Da Nang, Can Tho, and Hue). Participants completed baseline and follow-up measures of health literacy (HLS-SF12) depression (PHQ-9) and Health-related Quality of Life (5Q-5D-5L). Participants accessed and reviewed V-CCC for a 2-week period. RESULTS: Two hundred and thirty-four caregivers completed pre and post-tests. Most participants were female (n = 143, 61%), married (n = 165, 70%), aged 18-44 (n = 155, 66%), lived rurally (n = 157, 67%). All health literacy scores of participants in post-intervention were significantly higher than that in pre-intervention across all domain's healthcare, disease prevention, and health promotion as well as the total score (p < 0.001). A significant reduction in the proportion of caregivers reporting PHQ-9 moderately severe/severe depression post-intervention was demonstrated (10.2 vs. 6.1%, respectively (p ≤ 0.001). No significant differences were observed pre and post-intervention across four 5Q-5D-5L health dimensions: mobility, self-care, usual activities, and pain/discomfort. Regarding anxiety/depression as measured by 5Q-5D-5L the proportion of participants who reported having moderate, severe, and extreme problems in pre- and post-intervention was statistically significant (32 vs. 24%), respectively (p = 0.0028). CONCLUSION: Co-designed digital resources can reduce health literacy inequities and improve psychological outcomes for cancer caregivers.

Effects of Teprotumumab and Role of Human Leukocyte Antigens Markers in Patients With Thyroid Eye Disease.

OBJECTIVE: To evaluate the effects of teprotumumab on ophthalmologic and biochemical findings and assess potential genetic markers for response to treatment. METHODS: This is a retrospective study. Participants were 18-76 year old. All subjects were treated with teprotumumab. The primary outcome was the change in proptosis before and after teprotumumab treatment. Secondary outcomes include change in other ophthalmic measures and thyroid laboratory tests. Human leukocyte antigens (HLA) markers were analyzed for response to teprotumumab. RESULTS: Twenty-six patients were included in the final analysis. There was a significant decrease in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and significant increases in glycated hemoglobin A1c, fasting glucose, and total T3 levels. There was also significant reduction in proptosis, clinical activity score, retinal nerve fiber layer thickness, ganglion cell analysis, and intraocular pressure. HLA haplotypes were distinct between responders and nonresponders, with HLA-DRB3 02:02:01G, HLA-DRB4 neg, and HLA-DQB1 02:01:01G demonstrating better response to teprotumumab and HLA-A 23:01:01G strongly correlating to nonresponse. CONCLUSIONS: Patients with both acute and chronic thyroid eye disease treated with teprotumumab had a significant reduction in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and improvement in proptosis, clinical activity score, retinal nerve fiber layer and ganglion cell analysis thickness, and intraocular pressure. HLA may predict responders vs nonresponders. Further studies with longer duration and larger population comparing teprotumumab with steroids or other immunomodulatory agents (tocilizumab, rituximab, etc) may be helpful.

Expanded Polytetrafluoroethylene Combined with Human Acellular Dermis Matrix for the Nasal Reconstruction in Patients with Postoperative Deformities.

INTRODUCTION: Augmentation rhinoplasty is one of five aesthetic surgeries in the world. Expanded polytetrafluoroethylene (ePTFE) has been reported as a rational choice to augment the nasal dorsum and tip. However, its application for nasal tip augmentation has some debates. This study presented a technique using ePTFE grafts combined with human acellular dermis matrix (HADM) to reconstruct a deformed nose caused by previous rhinoplasties. METHODS: 50 female patients who came to the hospital from 08/2022 to 09/2022 for surgical revision of their nasal deformity. ePTFE was applied to reconstruct the nasal dorsum, tip, and columella strut. HADM grafts were utilized to reinforce the reconstructed framework. Patients were evaluated for at least 12 months for both aesthetic and functional results. RESULTS: Postoperatively, the nasal dorsal length increased from 38.9 ± 1.32 to 43.4 ± 1.22 mm; while, the projection of the nasal tip also raised from 19.8 ± 1.16 to 23.9 ± 1.05 mm. 38 patients (76%) reported that their breathing and smelling were improved compared to preoperatively. No cases had implant reactions, extrusion, or warping columella strut. Most of the patients (84%) were satisfied with the surgical outcomes. Three patients (6%) had redness at the nasal tip. The nasal tip of ten patients (20%) was hardened for 3 months postoperatively. There were 6% of patients who developed an infection and 2% of patients had asymmetric soft tissues of the tip 3 postoperative months. CONCLUSION: This technique brought satisfactory aesthetic and functional results to patients, with no extrusion or rejection observed 12 months postoperatively. Infection was a prominent complication that should be considered and strictly monitored. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration.

Many genes are known to regulate retinal regeneration after widespread tissue damage. Conversely, genes controlling regeneration after limited cell loss, as per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 100 genes identified seven knockouts that inhibited and 11 that promoted RGC regeneration. Surprisingly, 35 out of 36 genes known and/or implicated as being required for regeneration after widespread retinal damage were not required for RGC regeneration. The loss of seven even enhanced regeneration kinetics, including the proneural factors neurog1, olig2 and ascl1a. Mechanistic analyses revealed that ascl1a disruption increased the propensity of progenitor cells to produce RGCs, i.e. increased 'fate bias'. These data demonstrate plasticity in the mechanism through which Müller glia convert to a stem-like state and context specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.

Robust reprogramming of glia into neurons by inhibition of Notch signaling and nuclear factor I (NFI) factors in adult mammalian retina.

Generation of neurons through direct reprogramming has emerged as a promising therapeutic approach for treating neurodegenerative diseases. In this study, we present an efficient method for reprogramming retinal glial cells into neurons. By suppressing Notch signaling by disrupting either Rbpj or Notch1/2, we induced mature Müller glial cells to reprogram into bipolar- and amacrine-like neurons. We demonstrate that Rbpj directly activates both Notch effector genes and genes specific to mature Müller glia while indirectly repressing expression of neurogenic basic helix-loop-helix (bHLH) factors. Combined loss of function of Rbpj and Nfia/b/x resulted in conversion of nearly all Müller glia to neurons. Last, inducing Müller glial proliferation by overexpression of dominant-active Yap promotes neurogenesis in both Rbpj- and Nfia/b/x/Rbpj-deficient Müller glia. These findings demonstrate that Notch signaling and NFI factors act in parallel to inhibit neurogenic competence in mammalian Müller glia and help clarify potential strategies for regenerative therapies aimed at treating retinal dystrophies.

Use of corticosteroids for adult chronic pain interventions: sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the International Pain and Spine Intervention Society, and the North American Spine Society.

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models.

Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6ßrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.

The Effects of Medium-Chain Triglyceride Oil and Butter on Lipid Profiles.

Background and objective Butter coffee drinks, mainly a form of a saturated fat diet, are widely accepted as a "healthy energy-boosting drink", especially in the young and healthy military population. The objective of our study was to determine the effects of medium-chain triglyceride (MCT) oil and butter on lipid profile, especially apolipoprotein B (ApoB), low-density lipoprotein (LDL)-cholesterol (LDL-C), high-density lipoprotein (HDL)-cholesterol (HDL-C), and other risk factors for coronary heart disease, such as BMI, BP, fasting blood glucose, HbA1c, and high-sensitivity C-reactive protein (hs-CRP) levels in healthy adults. Materials and methods We conducted a prospective study of 60 subjects who were randomized to one of the two following regimens: (1) coffee or (2) coffee with butter plus MCT oil combination. The primary outcome was the effect on ApoB. Secondary outcomes were as follows: non-HDL-C, LDL-C, triglycerides, BP, waist circumference, fasting blood glucose, and HbA1c. These parameters were evaluated at the baseline and after 12 weeks. The Mann-Whitney U test was utilized for analysis of the results. Results While 60 subjects were recruited for the study, only 41 completed it, meeting the minimum required sample size (17 per group) necessary to achieve the desired effect size: 21 males (nine in the control group and 12 in the experimental group) and 20 females (10 in each group). Anthropometric measures were similar between the two groups at baseline, and so were age and BMI (average age: 33.00 ± 5.84 years among controls and 30.86 ± 6.14 years in the experimental group; BMI: 27.35 ± 4.63 kg/m2 vs. 25.74 ± 2.70 kg/m2). The pulse rate was 69.35 ± 10.98 in the control vs. 70.68 ± 10.32 bpm in the experimental group. The waist size was also similar in both groups. Baseline lab findings were as follows: ApoB: 89.85 ± 17.52 (control), 81.60 ± 12.84 mg/dL (experimental); hs-CRP: 0.18 ± 0.27 (control), 0.17 ± 0.27 mg/L (experimental); LDL-C 113.65 ±23.71 (control), 106.50 ± 18.99 mg/dL (experimental); HDL-C 57.35 ± 14.63 (control), 62.41 ± 16.15 mg/dL (experimental); and triglycerides: 76.00 ± 31.30 (control), 56.77 ± 14.77 mg/dL (experimental), and these values were similar. The values after 12 weeks of intervention were as follows: BMI: 27.37 ± 5.24 (control), 26.36 ± 3.55 (experimental); pulse rate: 78.88 ± 14.00 (control), 74.20 ± 11.90 bpm (experimental); ApoB 87.1 ± 17.38 (control), 85.7 ±20.59 mg/dL (experimental); hs-CRP 0.26 ± 0.22 (control), 0.15 ± 0.14 mg/L (experimental); LDL-C 111.59 ± 20.35 (control), 114.10 ± 26.99 mg/dL (experimental); HDL-C 57.71 ± 12.93 (control), 64.85 ± 13.32 mg/dL (experimental); and triglycerides: 74.71 ± 25.39 (control), 60.80 ± 15.77 mg/dL (experimental). Conclusion At a significance level of 5%, there was no difference between the two groups, either at the baseline or at 12 weeks of intervention. Based on our findings, adding MCT oil and butter to coffee may be safe. However, further studies with larger sample sizes and longer duration are needed to validate our findings.

Monitoring Outcomes of Indeterminate Thyroid Nodules and Predictive Capabilities of Molecular Testing.

OBJECTIVE: This study aimed to compare the effectiveness of reflex molecular testing at identifying thyroid malignancy in indeterminate thyroid nodules (ITNs) since its implementation at our institution. METHOD: Identified all ITNs at our institution from January 2010 to October 2020. Calculated the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ThyroSeq since the initiation of universal reflex testing of all first-time ITNs beginning in March 2016. Analyze effect on frequency of diagnostic surgeries. RESULTS: Study group: March 2016 to October 2020, 378 ITNs underwent ThyroSeq (318 Bethesda III and 60 Bethesda IV). Mean age 52 years, 35.9% male, 61.1% female. 145 surgically excised with overall resection rate of 38.4% (III: 32.7%; IV 68%). Final histology: 49 malignant with overall rate of malignancy (ROM) of ITNs at 33.8% (III: 31.7%; IV: 39%). ThyroSeq sensitivity for ITNs at 84% (III 78.8%, IV 93.8%). ThyroSeq NPV for ITNs at 86% (III 84%, IV 93.3%). ThyroSeq specificity for ITNs at 52% (III 50.7%, IV 56%). ThyroSeq PPV for ITNs at 47% (III 42.6%, IV 57.7%). Control group: From January 2010 to February 2016 there were 242 ITNs (152 Bethesda III, 90 Bethesda IV). Mean age 52.6 years, 25.8% male, 74.2% female. 157 cases were surgically excised, with an overall resection rate of 64.9% (III: 57.2%; IV: 77.8%). Final histology: 32 malignant, with overall ROM of ITNs at 20.4% (III: 27.6%; IV: 11.4%). CONCLUSION: The initiation of universal Thyroseq (sensitivity 84% and NPV 86%) of ITNs at our institution has significantly decreased our percentage of diagnostic lobectomies, with a decreased resection rate of 26.5%.

Residential proximity to oil and gas developments and childhood cancer survival.

BACKGROUND: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers. METHODS: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or gas development. Survival analyses were conducted using Cox regression, adjusting for potential confounders. RESULTS: A total of 14.2% of cases lived within 1000 m of an oil or gas well or horizontal well. Living within 1000 m of an oil or gas well was associated with risk of mortality in cases with acute myeloid leukemia (AML) (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.01-1.84) and hepatoblastoma (aHR, 2.13; 95% CI, 1.03-4.39). An inverse association was observed with Ewing sarcoma (aHR, 0.35; 95% CI, 0.13-0.95). No associations were observed with horizontal well. There was evidence of a dose-response effect in children with AML or hepatoblastoma and residential proximity to oil or gas wells. In general, the magnitude of association increased with decreasing distance and with higher number of wells across the three distances. CONCLUSIONS: Residential proximity to oil or gas wells at diagnosis is associated with the risk of mortality in children with AML or hepatoblastoma.

Genome Characteristics of the Endophytic Fungus Talaromyces sp. DC2 Isolated from Catharanthus roseus (L.) G. Don.

Talaromyces sp. DC2 is an endophytic fungus that was isolated from the stem of Catharanthus roseus (L.) G. Don in Hanoi, Vietnam and is capable of producing vinca alkaloids. This study utilizes the PacBio Sequel technology to completely sequence the whole genome of Talaromyces sp. DC2The genome study revealed that DC2 contains a total of 34.58 Mb spanned by 156 contigs, with a GC content of 46.5%. The identification and prediction of functional protein-coding genes, tRNA, and rRNA were comprehensively predicted and highly annotated using various BLAST databases, including non-redundant (Nr) protein sequence, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Carbohydrate-Active Enzymes (CAZy) databases. The genome of DC2 has a total of 149, 227, 65, 153, 53, and 6 genes responsible for cellulose, hemicellulose, lignin, pectin, chitin, starch, and inulin degradation, respectively. The Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) analyses revealed that strain DC2 possesses 20 biosynthetic gene clusters responsible for producing secondary metabolites. The strain DC2 has also been found to harbor the DDC gene encoding aromatic L-amino acid decarboxylase enzyme. Conclusively, this study has provided a comprehensive understanding of the processes involved in secondary metabolites and the ability of the Talaromyces sp. DC2 strain to degrade plant cell walls.

Collaborative artificial intelligence system for investigation of healthcare claims compliance.

Healthcare fraud, waste and abuse are costly problems that have huge impact on society. Traditional approaches to identify non-compliant claims rely on auditing strategies requiring trained professionals, or on machine learning methods requiring labelled data and possibly lacking interpretability. We present Clais, a collaborative artificial intelligence system for claims analysis. Clais automatically extracts human-interpretable rules from healthcare policy documents (0.72 F1-score), and it enables professionals to edit and validate the extracted rules through an intuitive user interface. Clais executes the rules on claim records to identify non-compliance: on this task Clais significantly outperforms two baseline machine learning models, and its median F1-score is 1.0 (IQR = 0.83 to 1.0) when executing the extracted rules, and 1.0 (IQR = 1.0 to 1.0) when executing the same rules after human curation. Professionals confirm through a user study the usefulness of Clais in making their workflow simpler and more effective.

Protein adsorption on blood-contacting surfaces: A thermodynamic perspective to guide the design of antithrombogenic polymer coatings.

Blood-contacting medical devices often succumb to thrombosis, limiting their durability and safety in clinical applications. Thrombosis is fundamentally initiated by the nonspecific adsorption of proteins to the material surface, which is strongly governed by thermodynamic factors established by the nature of the interaction between the material surface, surrounding water molecules, and the protein itself. Along these lines, different surface materials (such as polymeric, metallic, ceramic, or composite) induce different entropic and enthalpic changes at the surface-protein interface, with material wettability significantly impacting this behavior. Consequently, protein adsorption on medical devices can be modulated by altering their wettability and surface energy. A plethora of polymeric coating modifications have been utilized for this purpose; hydrophobic modifications may promote or inhibit protein adsorption determined by van der Waals forces, while hydrophilic materials achieve this by mainly relying on hydrogen bonding, or unbalanced/balanced electrostatic interactions. This review offers a cohesive understanding of the thermodynamics governing these phenomena, to specifically aid in the design and selection of hemocompatible polymeric coatings for biomedical applications. STATEMENT OF SIGNIFICANCE: Blood-contacting medical devices often succumb to thrombosis, limiting their durability and safety in clinical applications. A plethora of polymeric coating modifications have been utilized for addressing this issue. This review offers a cohesive understanding of the thermodynamics governing these phenomena, to specifically aid in the design and selection of hemocompatible polymeric coatings for biomedical applications.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Interrelationships between physical multimorbidity, depressive symptoms and cognitive function among older adults in China, India and Indonesia: A four-way decomposition analysis.

OBJECTIVE: This paper explores the role of depressive symptoms (mediator/moderator) in the association between physical multimorbidity (exposure) and cognitive function (outcome) among older adults in the three most populous middle-income countries. METHODS: This study used cross-sectional data from China (2015 China Health and Retirement Longitudinal Study), India (2017/2018 Longitudinal Ageing Study in India), and Indonesia (2014/2015 Indonesian Family Life Survey), with a total sample of 73,199 respondents aged ≥ 45 years. Three domains of cognitive tests were harmonised across surveys, including time orientation, word recall, and numeracy. The four-way decomposition analysis assessed the mediation and interaction effects between exposure, mediator/moderator, and outcome, adjusted for covariates. RESULTS: The mean age of the respondents (in years) was slightly younger in Indonesia (56.0, SD = 8.8) than in China (59.5, SD = 9.3) and India (60.0, SD = 10.5). The proportion of male respondents was 49.3 % in China, 47.3 % in India, and 47.5 % in Indonesia. Respondents in China had the highest mean cognitive function z scores (54.7, SD = 19.9), followed by India (51.1, SD = 20.0) and Indonesia (51.0, SD = 18.4). Physical multimorbidity was associated with lower cognitive function in China and India (p < 0.0001), with 48.4 % and 40.0 % of the association explained by the mediating effect of depressive symptoms ('overall proportion due to mediation'). The association was not found in Indonesia. CONCLUSION: Cognitive functions were lower among individuals with physical multimorbidity, and depressive symptoms mainly explained the association. Addressing depressive symptoms among persons with physical multimorbidity is likely to have not only an impact on their mental health but could prevent cognitive decline.

miR-26 Deficiency Causes Alterations in Lens Transcriptome and Results in Adult-Onset Cataract.

Purpose: Despite strong evidence demonstrating that normal lens development requires regulation governed by microRNAs (miRNAs), the functional role of specific miRNAs in mammalian lens development remains largely unexplored. Methods: A comprehensive analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance, was conducted by miRNA sequencing. Mouse lenses lacking each of three abundantly expressed lens miRNAs (miR-184, miR-26, and miR-1) were analyzed to explore the role of these miRNAs in lens development. Results: Mice lacking all three copies of miR-26 (miR-26TKO) developed postnatal cataracts as early as 4 to 6 weeks of age. RNA sequencing analysis of neonatal lenses from miR-26TKO mice exhibited abnormal reduced expression of a cohort of genes found to be lens enriched and linked to cataract (e.g., Foxe3, Hsf4, Mip, Tdrd7, and numerous crystallin genes) and abnormal elevated expression of genes related to neural development (Lhx3, Neurod4, Shisa7, Elavl3), inflammation (Ccr1, Tnfrsf12a, Csf2ra), the complement pathway, and epithelial to mesenchymal transition (Tnfrsf1a, Ccl7, Stat3, Cntfr). Conclusions: miR-1, miR-184, and miR-26 are each dispensable for normal embryonic lens development. However, loss of miR-26 causes lens transcriptome changes and drives cataract formation.

Factors Influencing Tobacco Smoking and Cessation Among People Living with HIV: A Systematic Review and Meta-analysis.

Tobacco smoking is highly prevalent among people living with HIV (PLWH), yet there is a lack of data on smoking behaviours and effective treatments in this population. Understanding factors influencing tobacco smoking and cessation is crucial to guide the design of effective interventions. This systematic review and meta-analysis of studies conducted in both high-income (HICs) and low- and middle-income countries (LMICs) synthesised existing evidence on associated factors of smoking and cessation behaviour among PLWH. Male gender, substance use, and loneliness were positively associated with current smoking and negatively associated with smoking abstinence. The association of depression with current smoking and lower abstinence rates were observed only in HICs. The review did not identify randomised controlled trials conducted in LMICs. Findings indicate the need to integrate smoking cessation interventions with mental health and substance use services, provide greater social support, and address other comorbid conditions as part of a comprehensive approach to treating tobacco use in this population. Consistent support from health providers trained to provide advice and treatment options is also an important component of treatment for PLWH engaged in care, especially in LMICs.