Efficacy of AI-Guided (GenAISTM) Dietary Supplement Prescriptions versus Traditional Methods for Lowering LDL Cholesterol: A Randomized Parallel-Group Pilot Study.

Emerging evidence suggests that personalized dietary supplement regimens can significantly influence lipid metabolism and cardiovascular risk. The efficacy of AI-guided dietary supplement prescriptions, compared with standard physician-guided prescriptions, remains underexplored. In a randomized, parallel-group pilot study, 70 patients aged 40-75 years with LDL-C levels between 70 and 190 mg/dL were enrolled. Participants were randomized to receive either AI-guided dietary supplement prescriptions or standard physician-guided prescriptions for 90 days. The primary endpoint was the percent change in LDL-C levels. Secondary endpoints included changes in total cholesterol, HDL-C, triglycerides, and hsCRP. Supplement adherence and side effects were monitored. Sixty-seven participants completed the study. The AI-guided group experienced a 25.3% reduction in LDL-C levels (95% CI: -28.7% to -21.9%), significantly greater than the 15.2% reduction in the physician-guided group (95% CI: -18.5% to -11.9%; p < 0.01). Total cholesterol decreased by 15.4% (95% CI: -19.1% to -11.7%) in the AI-guided group compared with 8.1% (95% CI: -11.5% to -4.7%) in the physician-guided group (p < 0.05). Triglycerides were reduced by 22.1% (95% CI: -27.2% to -17.0%) in the AI-guided group versus 12.3% (95% CI: -16.7% to -7.9%) in the physician-guided group (p < 0.01). HDL-C and hsCRP changes were not significantly different between groups. The AI-guided group received a broader variety of supplements, including plant sterols, omega-3 fatty acids, red yeast rice, coenzyme Q10, niacin, and fiber supplements. Side effects were minimal and comparable between groups. AI-guided dietary supplement prescriptions significantly reduce LDL-C and triglycerides more effectively than standard physician-guided prescriptions, highlighting the potential for AI-driven personalization in managing hypercholesterolemia.

Collecting Sociodemographic Data in Pediatric Emergency Research: A Working Group Consensus.

Understanding and addressing health care disparities relies on collecting and reporting accurate data in clinical care and research. Data regarding a child's race, ethnicity, and language; sexual orientation and gender identity; and socioeconomic and geographic characteristics are important to ensure equity in research practices and reported outcomes. Disparities are known to exist across these sociodemographic categories. More consistent, accurate data collection could improve understanding of study results and inform approaches to resolve disparities in child health. However, published guidance on standardized collection of these data in children is limited, and given the evolving nature of sociocultural identities, requires frequent updates. The Pediatric Emergency Care Applied Research Network, a multi-institutional network dedicated to pediatric emergency research, developed a Health Disparities Working Group in 2021 to support and advance equitable pediatric emergency research. The working group, which includes clinicians involved in pediatric emergency medical care and researchers with expertise in pediatric disparities and the conduct of pediatric research, prioritized creating a guide for approaches to collecting race, ethnicity, and language; sexual orientation and gender identity; and socioeconomic and geographic data during the conduct of research in pediatric emergency care settings. Our aims with this guide are to summarize existing barriers to sociodemographic data collection in pediatric emergency research, highlight approaches to support the consistent and reproducible collection of these data, and provide rationale for suggested approaches. These approaches may help investigators collect data through a process that is inclusive, consistent across studies, and better informs efforts to reduce disparities in child health.

Trained Immunity Generated by the Recombinant Zoster Vaccine.

Trained immunity may play a role in vaccine-induced protection against infections. We showed that the highly efficacious recombinant VZV-gE zoster vaccine (RZV) generated trained immunity in monocytes, natural killer (NK) cells, and dendritic cells (DCs) and that the less efficacious live zoster vaccine did not. RZV stimulated ex vivo gE-specific monocyte, DC and NK cell responses that did not correlate with CD4 + T-cell responses. These responses were also elicited in purified monocyte and NK cell cocultures stimulated with VZV-gE and persisted above prevaccination levels for ≥ 4 years post-RZV administration. RZV administration also increased ex vivo heterologous monocyte and NK cell responses to herpes simplex and cytomegalovirus antigens. ATAC-seq analysis and ex vivo TGFß1 supplementation and inhibition experiments demonstrated that decreased tgfß1 transcription resulting from RZV-induced chromatin modifications may explain the development of monocyte trained immunity. The role of RZV-trained immunity in protection against herpes zoster and other infections should be further studied.

Effects of oxytocin receptor agonism on acquisition and expression of pair bonding in male prairie voles.

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.

Social Determinants of Health and Other Predictors in Initiation of Treatment with CDK4/6 Inhibitors for HR+/HER2- Metastatic Breast Cancer.

In hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) have replaced endocrine therapy alone as the standard of care; however, several barriers to treatment initiation still exist. We assessed social determinants of health (SDOH) and other factors associated with the initiation of CDK4/6i for HR+/HER2- MBC in the Medicare population. Using a retrospective cohort design, patients aged ≥65 years and diagnosed during 2015-2017 were selected from the SEER-Medicare database. Time from MBC diagnosis to first CDK4/6i initiation was the study outcome. The effect of SDOH measures and other predictors on the outcome was assessed using the multivariable Fine and Gray hazard modeling. Of 752 eligible women, 352 (46.8%) initiated CDK4/6i after MBC diagnosis (median time to initiation: 27.9 months). In adjusted analysis, SDOH factors significantly associated with CDK4/6i initiation included high versus low median household income (HHI) (hazard ratio [HR] = 1.70; 95% CI = 1.03-2.81) and the percentage of population with high versus low Medicare-only coverage (HR = 1.54; 95% CI = 1.04-2.27). In summary, older Medicare patients with HR+/HER2- MBC residing in areas with high median HHI and a high proportion of Medicare-only coverage had higher rates of initiating CDK4/6i, suggesting inequitable access to these novel, effective treatments and a need for policy intervention.

C-terminally phosphorylated p27 activates self-renewal driver genes to program cancer stem cell expansion, mammary hyperplasia and cancer.

In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4. p27pTpT/STAT3 also recruits a SIN3A/HDAC1 complex to co-repress the Pyk2 inhibitor, PTPN12. Pyk2, in turn, activates STAT3, creating a feed-forward loop increasing stem-like properties in vitro and tumor-initiating stem cells in vivo. The p27-activated gene profile is over-represented in STAT3 activated human breast cancers. Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues.

Drug-induced musical hallucination.

Musical hallucination is a rare perceptual phenomenon wherein individuals hear music in the absence of external auditory stimuli. This phenomenon occurs across diverse medical conditions and can be triggered by some drugs. The underlying mechanism of drug-induced hallucination is unknown. This study explores drug-induced musical hallucination through a literature review, aiming to investigate its pathophysiology and potential treatment modalities. A literature search was conducted until January 2024 using databases PubMed, WorldCat, Google Scholar, and DOAJ, with keywords "drugs induced musical hallucination" or "drugs" combined with "musical hallucination." The search yielded 24 articles which met inclusion criteria, encompassing 27 cases. The average patient age was 58.3 years, with 67.9% females. Prevalent conditions among cases included hearing impairments, psychiatric disorders, cancers, and neurodegenerative conditions. Common trigger drugs comprised antidepressants, opioids, anti-Parkinson drugs, ketamine, and voriconazole. Musical hallucination descriptions varied widely, and 6 patients reported concurrent visual hallucinations. The onset of symptoms ranged from 75 min to 240 days. Treatment strategies included termination of trigger drugs, dosage reduction, alteration of administration routes or formula, switching to similar drugs, or addition of antidepressants, sedatives, or atypical antipsychotic medications. Musical hallucinations completely disappeared in 24/27 (88.9%) patients but continued in 3/27 (11.1%) patients. The current study concludes that drug-induced musical hallucination may arise from altering neurotransmitter/receptor balance and intricate interactions between trigger drugs and underlying conditions.

A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION.

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.

Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial.

Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo (p < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, p < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, p < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, p < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.

Effects of social housing on alcohol intake in mice depend on the non-social environment.

Background: Excessive alcohol consumption leads to serious health problems. Mechanisms regulating the consumption of alcohol are insufficiently understood. Previous preclinical studies suggested that non-social environmental and social environmental complexities can regulate alcohol consumption in opposite directions. However, previous studies did not include all conditions and/or did not include female rodents. Therefore, in this study, we examined the effects of social versus single housing in standard versus non-standard housing conditions in male and female mice. Methods: Adult C57BL/6 J mice were housed in either standard shoebox cages or in automated Herdsman 2 (HM2) cages and exposed to a two-bottle choice procedure with 3% or 6% ethanol versus water for 5 days. The HM2 cages use radiotracking devices to measure the fluid consumption of individual mice in an undisturbed and automated manner. In both housing conditions, mice were housed either at one or at four per cage. Results: In standard cages, group housing of animals decreased alcohol consumption and water consumption. In HM2 cages, group housing significantly increased ethanol preference and decreased water intake. There were no significant differences in these effects between male and female animals. These observations were similar for 3 and 6% ethanol solutions but were more pronounced for the latter. The effects of social environment on ethanol preference in HM2 cages were accompanied by an increase in the number of approaches to the ethanol solution and a decrease in the number of approaches to water. The differences in ethanol intake could not be explained by differences in locomotor or exploratory activity as socially housed mice showed fewer non-consummatory visits to the ethanol solutions than single-housed animals. In addition, we observed that significant changes in behaviors measuring the approach to the fluid were not always accompanied by significant changes in fluid consumption, and vice versa, suggesting that it is important to assess both measures of motivation to consume alcohol. Conclusion: Our results indicate that the direction of the effects of social environment on alcohol intake in mice depends on the non-social housing environment. Understanding mechanisms by which social and non-social housing conditions modulate alcohol intake could suggest approaches to counteract environmental factors enhancing hazardous alcohol consumption.

Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.

Factors Determining Black Carbon Exposures among Pregnant Women Enrolled in the HAPIN Trial.

Residential biomass burning is an important source of black carbon (BC) exposure among rural communities in low- and middle-income countries. We collected 7165 personal BC samples and individual/household level information from 3103 pregnant women enrolled in the Household Air Pollution Intervention Network trial. Women in the intervention arm received free liquefied petroleum gas stoves and fuel throughout pregnancy; women in the control arm continued the use of biomass stoves. Median (IQR) postintervention BC exposures were 9.6 µg/m3 (5.2-14.0) for controls and 2.8 µg/m3 (1.6-4.8) for the intervention group. Using mixed models, we characterized predictors of BC exposure and assessed how exposure contrasts differed between arms by select predictors. Primary stove type was the strongest predictor (R2 = 0.42); the models including kerosene use, kitchen location, education, occupation, or stove use hours also provided additional explanatory power from the base model adjusted only for the study site. Our full, trial-wide, model explained 48% of the variation in BC exposures. We found evidence that the BC exposure contrast between arms differed by study site, adherence to the assigned study stove, and whether the participant cooked. Our findings highlight factors that may be addressed before and during studies to implement more impactful cookstove intervention trials.

Effects of Oxytocin Receptor Agonism on Acquisition and Expression of Pair Bonding in Male Prairie Voles.

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4-hour cohabitation. In contrast, while animals injected with vehicle after the 4-hour cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2 hour-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.

WITHDRAWN: Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

The role of implementing instructional design principles on learner experience with training in current good manufacturing practices (cGMP).

INTRODUCTION: The objective of the study was to assess if improvement of the learner experience could be achieved through the use of instructional design strategies in current Good Manufacturing Practices (cGMP) training. This is a novel application in a topic that is known to be boring but is critical to ensuring patient safety. METHODS: An experimental randomized controlled repeated measures cross-over design was utilized in a sample of pharmacy students to determine the effect of an intervention training strategy (which utilized a mix of strategies including weeding, signaling, use of multimedia, and optimized space and type) on the learner experience (Evaluation, Overall Satisfaction, Perceived Knowledge, and Future Recommendation) compared with a control. RESULTS: The sample of 52 pharmacy students that participated evaluated the intervention training strategy with higher scores than the control, with better overall satisfaction, perceived knowledge, and future recommendation scores than the control training strategy. Thus, an apparent effect which resulted from the use of instructional design strategies was seen for all learner experience variables (p < .01). CONCLUSION: Improvement in the learner experience can be achieved by using instructional design strategies in cGMP training. This indicates that similar results could be obtained in other topics where such techniques have not yet been applied.

Identification and management of pediatric venous thromboembolism in the emergency department.

Although the incidence of pediatric venous thromboembolism is increasing, it is often overlooked in children due to the overall low incidence. This issue reviews the epidemiology of pediatric venous thromboembolism, including the factors that have led to its increasing prevalence, and discusses the physiology of hemostasis and coagulation. Key features of the history and physical examination, as well as identification of risk factors, are reviewed, as these have the most diagnostic value for venous thromboembolism in pediatric patients. Recommendations are also provided for diagnostic testing and management in the emergency department.

Peri-Operative Impact of Cannabis Use in Conjunction With Elective Primary Breast Augmentation in a Private Practice.

Background The consumption of recreational and medicinal cannabis in the United States continues to increase. Understanding the effects of cannabis in patients undergoing elective primary breast augmentation (EPBA) is of paramount importance with the expanding rates of reported cannabis consumption. Objectives This study aims to analyze the peri-operative impact of cannabis use in conjunction with EPBA in a single-surgeon practice in San Francisco, California. Methods A retrospective chart review was performed of 134 adult female patients undergoing EPBA from August 2018 to January 2022 within a single-surgeon practice plastic surgery office. Cannabis use was self-reported as current use or former use. Cohorts were grouped as cannabis users and cannabis non-users. Results Of the 134 patient charts identified for analysis, 58 (43.3%) reported cannabis use. Cannabis users were significantly younger than cannabis non-users (26.8 years versus 31.5 years, P<0.001). No significant differences were found between groups among intra-operative blood loss, post-operative complication rates, post-operative narcotic use, or intra-operative anesthetic requirements. The incidence of adverse events, including wound breakdown, skin necrosis, and capsular contracture requiring reoperation, did not differ significantly between cannabis users and cannabis non-user groups. Ninety-six percent of patients had their implants placed subpectorally, and all procedures were done using a Keller funnel. Eighty-three percent of patients had Sientra implants, and 96% of all implants were silicone gel implants. All procedures were done under general anesthesia. Patients were followed for up to two years. Discussion This review found no significant differences in peri-operative and post-operative outcomes between cannabis users and cannabis non-users.

Illuminating Polysulfide Distribution in Lithium Sulfur Batteries; Tracking Polysulfide Shuttle Using Operando Optical Fluorescence Microscopy.

High-energy-density lithium sulfur (Li-S) batteries suffer heavily from the polysulfide shuttle effect, a result of the dissolution and transport of intermediate polysulfides from the cathode, into the electrolyte, and onto the anode, leading to rapid cell degradation. If this primary mechanism of cell failure is to be overcome, the distribution, dynamics, and degree of polysulfide transport must first be understood in depth. In this work, operando optical fluorescence microscope imaging of optically accessible Li-S cells is shown to enable real-time qualitative visualization of the spatial distribution of lithium polysulfides, both within the electrolyte and porous cathode. Quantitative determinations of spatial concentration are also possible at a low enough concentration. The distribution throughout cycling is monitored, including direct observation of polysulfide shuttling to the anode and consequent dendrite formation. This was enabled through the optimization of a selective fluorescent dye, verified to fluoresce proportionally with concentration of polysulfides within Li-S cells. This ability to directly and conveniently track the spatial distribution of soluble polysulfide intermediates in Li-S battery electrolytes, while the cell operates, has the potential to have a widespread impact across the field, for example, by enabling the influence of a variety of polysulfide mitigation strategies to be assessed and optimized, including in this work the LiNO3 additive.

Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

Insights into the enigma of oral streptococci in carcinogenesis.

SUMMARYThe genus Streptococcus consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus Streptococcus, viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes. Perturbations in oral streptococci composition drive oral dysbiosis and therefore impact host-pathogen interactions, resulting in oral inflammation and representing VGS as an opportunistic pathogen. The association of oral streptococci in tumors across distant organs, spanning the esophagus, stomach, pancreas, and colon, illuminates a potential association between oral streptococci, inflammation, and tumorigenesis. This finding emphasizes the need for further investigations into the role of oral streptococci in mucosal homeostasis and their involvement in carcinogenesis. Hence, here, we review the significance of oral streptococci in biofilm dynamics and how the perturbation may impact mucosal immunopathogenesis in the context of cancer, with a vision of exploiting oral streptococci for cancer intervention and for the development of non-invasive cancer diagnosis.