ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation.

High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8-10% of primary NB patients are ALK-positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the "2p-gain" region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v-sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI-sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p-gain, may benefit from ALK TKI-based therapeutic intervention.

HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serologic tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests are needed that are agnostic to the vaccination status of tested individuals (ie, positive only for true HIV-1 infection). Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serologic HIV tests for concurrent deployment with HIV vaccines.

miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Syphilis.

Syphilis is a sexually and vertically transmitted bacterial infection caused by the bacterium Treponema pallidum. Its prevalence is high in low-income and middle-income countries, and its incidence has increased in high-income countries in the last few decades among men who have sex with men. Syphilis is a major cause of adverse pregnancy outcomes in low-income and middle-income countries. Clinical features include a primary chancre at the point of inoculation, followed weeks later by the rash of secondary syphilis, a latent period, and in some cases, involvement of the eyes, CNS, and cardiovascular systems. It is diagnosed serologically. A single intramuscular dose of long-acting benzathine penicillin is recommended for people who have had syphilis for less than 1 year and longer courses for people with late latent syphilis. Control strategies include screening and treatment of all pregnant women, and targeted interventions for groups at high risk. Vaccine development, research on antibiotic prophylaxis, and digital messaging as prevention strategies are ongoing.

Rethinking how development assistance for health can catalyse progress on primary health care.

Global campaigns to control HIV, tuberculosis, malaria, and vaccine-preventable illnesses showed that large-scale impact can be achieved by using additional international financing to support selected, evidence-based, high-impact investment areas and to catalyse domestic resource mobilisation. Building on this paradigm, we make the case for targeting additional international funding for selected high-impact investments in primary health care. We have identified and costed a set of concrete, evidence-based investments that donors could support, which would be expected to have major impacts at an affordable cost. These investments are in: (1) individuals and communities empowered to engage in health decision making, (2) a new model of people-centred primary care, and (3) next generation community health workers. These three areas would be supported by strengthening two cross-cutting elements of national systems. The first is the digital tools and data that support facility, district, and national managers to improve processes, quality of care, and accountability across primary health care. The second is the educational, training, and supervisory systems needed to improve the quality of care. We estimate that with an additional international investment of between US$1·87 billion in a low-investment scenario and $3·85 billion in a high-investment scenario annually over the next 3 years, the international community could support the scale-up of this evidence-based package of investments in the 59 low-income and middle-income countries that are eligible for external financing from the World Bank Group's International Development Association.

Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

DamID transcriptional profiling identifies the Snail/Scratch transcription factor Kahuli as an Alk target in the Drosophila visceral mesoderm.

Development of the Drosophila visceral muscle depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signaling, which specifies founder cells (FCs) in the circular visceral mesoderm (VM). Although Alk activation by its ligand Jelly Belly (Jeb) is well characterized, few target molecules have been identified. Here, we used targeted DamID (TaDa) to identify Alk targets in embryos overexpressing Jeb versus embryos with abrogated Alk activity, revealing differentially expressed genes, including the Snail/Scratch family transcription factor Kahuli (Kah). We confirmed Kah mRNA and protein expression in the VM, and identified midgut constriction defects in Kah mutants similar to those of pointed (pnt). ChIP and RNA-Seq data analysis defined a Kah target-binding site similar to that of Snail, and identified a set of common target genes putatively regulated by Kah and Pnt during midgut constriction. Taken together, we report a rich dataset of Alk-responsive loci in the embryonic VM and functionally characterize the role of Kah in the regulation of embryonic midgut morphogenesis.

Musculoskeletal involvement in systemic lupus erythematosus: a contrast-enhanced magnetic resonance imaging study in 107 subjects.

OBJECTIVE: Joint involvement in SLE is the most frequent manifestation and shows a wide heterogeneity. It has not a valid classification and it is often underestimated. Subclinical inflammatory musculoskeletal involvement is not well known. We aim to describe the prevalence of joint and tendon involvement in hand and wrist of SLE patients, either with clinical arthritis, arthralgia or asymptomatic and compare it with healthy subjects using contrasted MRI. METHODS: SLE patients fulfilling SLICC criteria were recruited and classified as follows: group (G) 1: hand/wrist arthritis, G2: hand/wrist arthralgia, G3: no hand/wrist symptoms. Jaccoud arthropathy, CCPa and RF positivity, hand OA or surgery were excluded. Healthy subjects (HS) were recruited as controls: G4. Contrasted MRI of non-dominant hand/wrist was performed. Images were evaluated following RAMRIS criteria extended to PIP, Tenosynovitis score for RA and peritendonitis from PsAMRIS. Groups were statistically compared. RESULTS: A total of 107 subjects were recruited (G1: 31, G2:31, G3:21, G4:24). Any lesion: SLE patients 74.7%, HS 41.67%; P 0.002. Synovitis: G1: 64.52%, G2: 51.61%, G3: 45%, G4: 20.83%; P 0.013. Erosions: G1: 29.03%; G2: 54.84%, G3: 47.62%; G4: 25%; P 0.066. Bone marrow oedema: G1: 29.03%, G2: 22.58%, G3: 19.05%, G4: 0.0%; P 0.046. Tenosynovitis: G1: 38.71%; G2: 25.81%, G3: 14.29%, G4: 0.0%; P 0.005. Peritendonitis: G1: 12.90%; G2: 3.23%, G3: 0.0%, G4: 0.0%; P 0.07. CONCLUSION: SLE patients have a high prevalence of inflammatory musculoskeletal alterations confirmed by contrasted MRI, even if asymptomatic. Not only tenosynovitis but peritendonitis is also present.

Population assessment of health system performance in 16 countries.

Objective: To demonstrate how the new internationally comparable instrument, the People's Voice Survey, can be used to contribute the perspective of the population in assessing health system performance in countries of all levels of income. Methods: We surveyed representative samples of populations in 16 low-, middle- and high-income countries on health-care utilization, experience and confidence during 2022-2023. We summarized and visualized data corresponding to the key domains of the World Health Organization universal health coverage framework for health system performance assessment. We examined correlation with per capita health spending by calculating Pearson coefficients, and within-country income-based inequities using the slope index of inequality. Findings: In the domain of care effectiveness, we found major gaps in health screenings and endorsement of public primary care. Only one in three respondents reported very good user experience during health visits, with lower proportions in low-income countries. Access to health care was rated highest of all domains; however, only half of the populations felt secure that they could access and afford high-quality care if they became ill. Populations rated the quality of private health systems higher than that of public health systems in most countries. Only half of respondents felt involved in decision-making (less in high-income countries). Within countries, we found statistically significant pro-rich inequalities across many indicators. Conclusion: Populations can provide vital information about the real-world function of health systems, complementing other system performance metrics. Population-wide surveys such as the People's Voice Survey should become part of regular health system performance assessments.

Bezlotoxumab during the first episode of Clostridioides difficile infection in patients at high risk of recurrence.

PURPOSE: To describe a cohort with a high risk of recurrence who received bezlotoxumab during the first episode of Clostridioides difficile infection (CDI) and to compare this cohort with patients with similar characteristics who did not receive the monoclonal antibody. METHODS: A prospective and multicentre study of patients with a high risk of recurrence (expected recurrence rate>35%) who were treated with bezlotoxumab during their first episode of CDI was conducted. A propensity score-matched model 1:2 was used to compare both cohorts that were weighed according to basal characteristics (hospital-acquisition, creatinine value, and fidaxomicin as a CDI treatment). RESULTS: Sixty patients (mean age:72 years) were prospectively treated with bezlotoxumab plus anti-Clostridioides antibiotic therapy. Vancomycin (48 patients) and fidaxomicin (12 patients) were prescribed for CDI treatment, and bezlotoxumab was administered at a mean of 4.2 (SD:2.1) days from the beginning of therapy. Recurrence occurred in nine out of 54 (16.7%) evaluable patients at 8 weeks. Forty bezlotoxumab-treated patients were matched with 69 non-bezlotoxumab-treated patients. Recurrence rates at 12 weeks were 15.0% (6/40) in bezlotoxumab-treated patients vs. 23.2% (16/69) in non-bezlotoxumab-treated patients (OR:0.58 [0.20-1.65]). No adverse effects were observed related to bezlotoxumab infusion. Only one of 9 patients with previous heart failure developed heart failure. CONCLUSION: We observed that patients treated with bezlotoxumab in a real-world setting during a first episode of CDI having high risk of recurrence, presented low rate of recurrence. However, a significant difference in recurrence could not be proved in comparison to the controls. We did not detect any other safety concerns.

Sex significantly predicts medial temporal volume when controlling for the influence of ApoE4 biomarker and demographic variables: A cross-ethnic comparison.

OBJECTIVE: To explore the relationship between age, education, sex, and ApoE4 (+) status to brain volume among a cohort with amnestic mild cognitive impairment (aMCI). METHOD: One hundred and twenty-three participants were stratified into Hispanic (n = 75) and White non-Hispanic (WNH, N = 48). Multiple linear regression analyses were conducted with age, education, sex, and ApoE4 status as predictor variables and left and right combined MRI volumes of the hippocampus, parahippocampus, and entorhinal cortex as dependent variables. Variations in head sizes were corrected by normalization with a total intracranial volume measurement. RESULTS: Bonferroni-corrected results indicated that when controlling for ApoE4 status, education, and age, sex was a significant predictor of hippocampal volume among the Hispanic group (ß = .000464, R2 = .196, p < .01) and the WNH group (ß = .000455, R2 = .195, p < .05). Education (ß = .000028, R2 = .168, p < .01) and sex (ß = .000261, R2 = .168, p < .01) were significant predictors of parahippocampal volume among the Hispanic MCI group when controlling for the effects of ApoE4 status and age. One-way ANCOVAs comparing hippocampal and parahippocampal volume between males and females within groups revealed that females had significantly larger hippocampal volumes (p < .05). Hispanic females had significantly larger hippocampal (p < .001) and parahippocampal (p < .05) volume compared to males. No sex differences in parahippocampal volume were noted among WNHs. CONCLUSIONS: Biological sex, rather than ApoE4 status, was a greater predictor of hippocampal volume among Hispanic and WNH females. These findings add to the mixed literature on sex differences in dementia research and highlight continued emphasis on ethnic populations to elucidate on neurodegenerative disparities.

Corrigendum: mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.

This corrects the article DOI: 10.1038/nature22964.

Lessons from Peru to reduce under-5 mortality: understanding program implementation and context.

BACKGROUND: Health policymakers aiming to reduce under-5 mortality (U5M) often lack data regarding how successful interventions in other countries were implemented. The Exemplars in U5M Study identified countries that achieved significant reductions in amenable U5M. This case study in Peru used implementation research to explore the contextual factors and strategies that contributed to the successful implementation of key evidence-based interventions (EBIs). METHODS: This research utilized a hybrid implementation research framework and a mixed-methods approach to understand the factors associated with EBI implementation and the successful reduction of U5M between 2000-2015. A desk review of existing literature on EBIs and U5M in Peru was completed, and in-depth interviews were performed with key Peruvian informants to understand the implementation strategies employed and the contextual factors that facilitated or were barriers to success. For the purposes of this analysis, three EBIs were selected and evaluated: antenatal care visits (ANC), facility-based deliveries, and infant vaccination. RESULTS: Between 2000-2015, the percent of mothers attending at least four antenatal care visits rose from 69% to 96.9%, and the percent of facility-based deliveries increased from 56 to 91%. Three doses of the tetanus/diphtheria/pertussis vaccine, widely acknowledged as a key global health indicator, reached 90% by 2015. Key informants noted that economic growth, financial reforms, strong national commitment to reduce poverty in Peru, and national prioritization of maternal and child health, were important contextual factors that contributed to the successful reduction of U5M. They noted key strategies that helped achieve success during the implementation of EBIs, including utilization of data for decision-making, adaptation driven by cultural sensitivity to address gaps in coverage, and a focus on equity and anti-poverty initiatives with the participation of government, civil society, and political parties to assure continuity of policies. CONCLUSION: Several EBIs contributed to the successful reduction of U5M in Peru between 2000-2015. Strategies such as the focus on equity throughout the study period contributed to an increase in coverage of EBIs like ANC visits, facility-based deliveries and infant vaccination which worked to reduce U5M. Understanding how Peru successfully implemented programs that reduced preventable infant and child deaths could be useful to replicating this substantial public health success in other low- and middle-income countries.

Cross-country analysis of contextual factors and implementation strategies in under-5 mortality reduction in six low- and middle-income countries 2000-2015.

BACKGROUND: The Exemplars in Under-5 Mortality (U5M) was a multiple cases study of how six low- and middle-income countries (LMICs), Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal, implemented health system-delivered evidence-based interventions (EBIs) to reduce U5M between 2000 and 2015 more effectively than others in their regions or with similar economic growth. Using implementation research, we conducted a cross-country analysis to compare decision-making pathways for how these countries chose, implemented, and adapted strategies for health system-delivered EBIs that mitigated or leveraged contextual factors to improve implementation outcomes in reducing amenable U5M. METHODS: The cross-country analysis was based on the hybrid mixed methods implementation research framework used to inform the country case studies. The framework included a common pathway of Exploration, Preparation, Implementation, Adaptation, and Sustainment (EPIAS). From the existing case studies, we extracted contextual factors which were barriers, facilitators, or determinants of strategic decisions; strategies to implement EBIs; and implementation outcomes including acceptability and coverage. We identified common factors and strategies shared by countries, and individual approaches used by countries reflecting differences in contextual factors and goals. RESULTS: We found the six countries implemented many of the same EBIs, often using similar strategies with adaptations to local context and disease burden. Common implementation strategies included use of data by decision-makers to identify problems and prioritize EBIs, determine implementation strategies and their adaptation, and measure outcomes; leveraging existing primary healthcare systems; and community and stakeholder engagement. We also found common facilitators included culture of donor and partner coordination and culture and capacity of data use, while common barriers included geography and culture and beliefs. We found evidence for achieving implementation outcomes in many countries and EBIs including acceptability, coverage, equity, and sustainability. DISCUSSION: We found all six countries used a common pathway to implementation with a number of strategies common across EBIs and countries which contributed to progress, either despite contextual barriers or by leveraging facilitators. The transferable knowledge from this cross-country study can be used by other countries to more effectively implement EBIs known to reduce amenable U5M and contribute to strengthening health system delivery now and in the future.

Inequity in the face of success: understanding geographic and wealth-based equity in success of facility-based delivery for under-5 mortality reduction in six countries.

BACKGROUND: Between 2000-2015, many low- and middle-income countries (LMICs) implemented evidence-based interventions (EBIs) known to reduce under-5 mortality (U5M). Even among LMICs successful in reducing U5M, this drop was unequal subnationally, with varying success in EBI implementation. Building on mixed methods multi-case studies of six LMICs (Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal) leading in U5M reduction, we describe geographic and wealth-based equity in facility-based delivery (FBD), a critical EBI to reduce neonatal mortality which requires a trusted and functional health system, and compare the implementation strategies and contextual factors which influenced success or challenges within and across the countries. METHODS: To obtain equity gaps in FBD coverage and changes in absolute geographic and wealth-based equity between 2000-2015, we calculated the difference between the highest and lowest FBD coverage across subnational regions and in the FBD coverage between the richest and poorest wealth quintiles. We extracted and compared contextual factors and implementation strategies associated with reduced or remaining inequities from the country case studies. RESULTS: The absolute geographic and wealth-based equity gaps decreased in three countries, with greatest drops in Rwanda - decreasing from 50 to 5% across subnational regions and from 43 to 13% across wealth quintiles. The largest increases were seen in Bangladesh - from 10 to 32% across geography - and in Ethiopia - from 22 to 58% across wealth quintiles. Facilitators to reducing equity gaps across the six countries included leadership commitment and culture of data use; in some countries, community or maternal and child health insurance was also an important factor (Rwanda and Peru). Barriers across all the countries included geography, while country-specific barriers included low female empowerment subnationally (Bangladesh) and cultural beliefs (Ethiopia). Successful strategies included building on community health worker (CHW) programs, with country-specific adaptation of pre-existing CHW programs (Rwanda, Ethiopia, and Senegal) and cultural adaptation of delivery protocols (Peru). Reducing delivery costs was successful in Senegal, and partially successful in Nepal and Ethiopia. CONCLUSION: Variable success in reducing inequity in FBD coverage among countries successful in reducing U5M underscores the importance of measuring not just coverage but also equity. Learning from FBD interventions shows the need to prioritize equity in access and uptake of EBIs for the poor and in remote areas by adapting the strategies to local context.

Clinical Trials That Have Changed Clinical Practice and Care of Pregnant People With HIV.

Over the last 4 decades, significant advances in the care of HIV during pregnancy have successfully reduced, and nearly eliminated, the risk of perinatal HIV transmission. The baseline risk of transmission without intervention (25% to 30%) is now <1% to 2% in the United States with contemporary antepartum, intrapartum, and postnatal interventions. In this review, we discuss 3 landmark clinical trials that substantially altered obstetric practice for pregnant individuals with HIV and contributed to this extraordinary achievement: 1) the Pediatric AIDS Clinical Trials Group 076 Trial determined that antepartum and intrapartum administration of antiretroviral drug zidovudine to the pregnant individual, and postnatally to the newborn, could reduce the risk of perinatal transmission by approximately two-thirds; 2) the European Mode of Delivery Collaboration Trial demonstrated performance of a prelabor cesarean birth before rupture of membranes among pregnant people with viremia reduced the risk of perinatal transmission compared with vaginal birth; and 3) the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 Trial identified that dolutegravir-containing, compared with efavirenz-containing, antiretroviral regimens during pregnancy achieved a significantly higher rate of viral suppression at delivery with shorter time to viral suppression, with fewer adverse pregnancy outcomes. Collectively, these trials not only advanced obstetric practice but also advanced scientific understanding of the timing, mechanisms, and determinants of perinatal HIV transmission. For each trial, we will describe key aspects of the study protocol and outcomes, insights gleaned about the dynamics of perinatal transmission, how each study changed clinical practice, and relevant updates to current practice since the trial's publication.

Statewide Implementation of Universal Third-Trimester Repeat HIV Testing in Illinois.

OBJECTIVE: This article aims to assess statewide uptake of HIV repeat testing in the first 2 years after the implementation of an amendment to the Illinois Perinatal HIV Prevention Act (IPHPA) mandating universal repeat HIV testing in the third trimester. STUDY DESIGN: This is a retrospective, population-based study of all birthing individuals in Illinois (2018-2019). Data were collected using the state-mandated closed system of perinatal HIV test reporting. We evaluated the incidence of mother-infant pairs with negative early tests and repeat third-trimester tests (RTTTs) performed in adherence with the law, as well as the timing of the performance of the RTTTs (outpatient vs. inpatient). Chi-square tests of trend by quarter were performed to ascertain sustainability. RESULTS: Of 138,805 individuals delivered in 2018, 80.6% presented with early test and RTTTs. In 2018, outpatient RTTTs improved from 71.8% (quarter 1) to 85.1% (quarter 4; p < 0.001). In 2018, the proportion of mother-infant dyads who received testing that was adherent to the IPHPA Amendment was 92.1, 95.5, 96.7, and 96.4% in quarters 1 through 4, respectively (p < 0.001). In 2019, outpatient RTTTs performance remained high (87.4%) and stable (p = 0.06). In 2019, 99.9% of mother-infant dyads had testing adherent to the mandate in quarters 1 through 4 (p = 0.39). Of individuals who presented without RTTTs, 93.5% (2018) and 98.8% (2019) underwent inpatient testing before delivery. CONCLUSION: Implementation of RTTTs in Illinois was rapid, successful, and sustained in its first 2 years. Public health methodologies from Illinois may benefit other states implementing RTTT programs. KEY POINTS: · In 2018, Illinois enacted statewide RTTT for HIV among all parturients.. · In 2019, over 99% of mother-infant dyads had documentation of both early and repeat HIV testing before hospital discharge.. · Implementation of repeat third-trimester HIV testing in Illinois was rapid, successful, and sustained in its first 2 years.. · Public health methodologies from Illinois may benefit other states implementing similar programs..

A Systematic Review on the Reinforcement Loop in Aesthetic Medicine and Surgery: The Interplay of Social Media, Self-Perception, and Repeat Procedures.

INTRODUCTION: This systematic review delves into the impact of social media on self-perception and the escalating interest in clinical aesthetic procedures, proposing that social media significantly influences beauty standards and increases demand for aesthetic enhancements. METHOD: Following PRISMA guidelines, a mixed-method analysis of 34 articles was conducted, sourced from various databases, focusing on social media's psychological effects on clinical aesthetics decisions. The studies encompassed a broad spectrum, including qualitative, quantitative, and mixed methodologies, reflecting diverse geographical and cultural perspectives. RESULTS: The quantitative analysis demonstrated a strong positive correlation between social media usage and the consideration of aesthetic procedures (r=0.45, p<0.001), indicating a significant impact. Specific findings included a large effect size (Cohen's d=0.8) for the relationship between time spent on social media and the desire for aesthetic enhancements. Individuals spending more than 3 hours per day on social media platforms were twice as likely to consider aesthetic procedures compared to those with less usage, with a 95% confidence interval indicating robustness in these findings. CONCLUSION: Confirming the reinforcing effect of social media on aesthetic decision-making, this study highlights the complex interplay between digital media exposure, altered self-perception, and the increased inclination towards aesthetic procedures. It suggests a critical need for practitioners to carefully navigate the digital influence on patient's desires, reinforcing the significance of understanding psychological motivations and societal pressures in clinical aesthetics. This comprehensive analysis offers pivotal insights for clinical practice and ongoing research into social media's role in contemporary beauty standards. 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Generational Exploration on Aesthetic Medicine Products: Influence of Social Media, Reviews, and Brand Identity-GEMS Bond Survey.

INTRODUCTION: The study investigates the impact of social media reviews and brand identity on consumer preferences in the non-surgical aesthetics products across different generations. It highlights the evolving landscape of aesthetic medicine and surgery, driven by technological advancements and a cultural shift towards individual well-being. The research aims to explore the interplay between generational preferences, the influence of social media, and the role of brand identity in shaping consumer decisions. METHODS: A cross-sectional study design was employed, with a sample size of > 5000 participants stratified across various generational cohorts. The study utilized an online questionnaire to capture both quantitative and qualitative insights into consumer behaviour, with statistical analysis performed to identify patterns and relationships. RESULTS: Analysis of 5850 responses revealed distinct generational preferences and behaviours. Social media engagement varied significantly across generations, with younger cohorts placing a higher emphasis on online reviews. The study also found that brand identity's influence is diminishing in decision-making processes, with consumers increasingly relying on peer reviews and social media content. CONCLUSION: The findings highlight a pivotal shift in the non-surgical aesthetics consumer market, emphasizing the growing importance of social media and peer reviews over traditional brand identities. Importantly, the study underscores the critical need for integrating patient safety and evidence-based practice within marketing strategies. As consumer preferences evolve towards valuing transparency and authenticity, non-surgical aesthetics providers must prioritize these elements, ensuring that their services are not only appealing but also grounded in safety and scientific validity. LEVEL OF EVIDENCE IV: "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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells.

Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.