A chemogenetic approach for dopamine imaging with tunable sensitivity.

Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.

Online retail nudges to help parents with lower-income choose healthy beverages for their children: A randomized clinical trial.

BACKGROUND: Nudges offer a promising tool to reduce sugary drink intake among children who are most at risk for diet-related disease. OBJECTIVE: To examine the impact of online store nudges on purchases of sugary drinks for children in lower-income households. METHODS: Caregivers with lower-income were recruited to an online shopping experiment and instructed to spend $10-$30 on three beverages for their child aged 1-5 years. Participants were randomized to navigate an online supermarket in its standard version (n = 1106) or a version with nudges (n = 1135), including a product placement nudge (i.e. placing healthy beverages in prominent positions) and a swap nudge (i.e. offering a swap of water, plain milk and/or 100% fruit juice upon selection of sugary drinks). RESULTS: On average, participants purchased 1887 (SD = 2113) and 620 (SD = 1528) calories from sugary drinks per basket in the control and experimental conditions, respectively. Model-based results indicate that those in the experimental condition purchased 1267 (95% CI: 1419, 1114) fewer calories from sugary drinks, and fewer grams of total sugar (ß = -253.5 g (95% CI: -286.3, -220.6)) and added sugar (ß = -287.8 g (95% CI: -323.1, -252.5)) purchased from sugary drinks. CONCLUSION: Nudges may be an effective, acceptable, scalable strategy for leading caregivers in lower-income households to purchase fewer sugary drinks for their children.

Natural History of Cavernous Carotid Artery Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Cavernous carotid artery aneurysms (CCAAs) represent a common condition seen in clinical practice with significant practice variability. The aim of this systematic review and meta-analysis was to aggregate current evidence on the natural history of CCAAs. METHODS: MEDLINE/PubMed, EMBASE, and Cochrane Library were queried from inception until December 2023. The primary outcome of this study was CCAA-related mortality. The secondary outcomes of this study were aneurysm growth, intracranial ischemic and hemorrhagic events, improved non-cerebrovascular symptoms, and new or worsened non-cerebrovascular symptoms during follow-up. RESULTS: Ten studies met our inclusion criteria, involving 835 patients and 975 CCAAs. CCAA-related mortality had an incidence rate of 0.28 (95% confidence interval 0.12-0.64) per 100 person-years (PYs) of follow-up. The incidence rate of CCAA growth was 2.91 (1.05-8.07) per 100 PYs of follow-up. The incidence rate of CCAA-related intracranial ischemic events was 0.4 (0.16-1.01) per 100 PYs of follow-up. The incidence rate of CCAA-related intracranial hemorrhagic events was 0.54 (0.33-0.87) per 100 PYs of follow-up. The incidence rate of improved non-cerebrovascular symptoms was 2.51 (1.18-5.33) per 100 PYs of follow-up. The incidence rate of new or worsened non-cerebrovascular symptoms was 3.41 (2.03-5.73) per 100 PYs of follow-up. CONCLUSIONS: CCAAs are typically benign lesions with a low risk of rupture and life-threatening complications. CCAAs tend to follow an indolent course regarding non-cerebrovascular outcomes, and new or worsening symptoms are infrequent during the clinical course. However, spontaneous resolution of non-cerebrovascular symptoms and cranial nerve deficits at presentation is uncommon.

Multimodality assessment of the coronary microvasculature with TIMI frame count versus perfusion PET highlights coronary changes characteristic of coronary microvascular disease.

Background: The diagnosis of coronary microvascular disease (CMVD) remains challenging. Perfusion PET-derived myocardial blood flow (MBF) reserve (MBFR) can quantify CMVD but is not widely available. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based method that has been proposed as a measure of CMVD. Here, we compare TFC and PET-derived MBF measurements to establish the role of TFC in assessing for CMVD. We use coronary modeling to elucidate the relationship between MBFR and TFC and propose TFC thresholds for identifying CMVD. Methods: In a cohort of 123 individuals (age 58 ± 12.1, 63% women, 41% Caucasian) without obstructive coronary artery disease who had undergone perfusion PET and coronary angiography for clinical indications, we compared TFC and perfusion PET parameters using Pearson correlation (PCC) and linear regression modeling. We used mathematical modeling of the coronary circulation to understand the relationship between these parameters and performed Receiver Operating Curve (ROC) analysis. Results: We found a significant negative correlation between TFC and MBFR. Sex, race and ethnicity, and nitroglycerin administration impact this relationship. Coronary modeling showed an uncoupling between TFC and flow in epicardial vessels. In ROC analysis, TFC performed well in women (AUC 0.84-0.89) and a moderately in men (AUC 0.68-0.78). Conclusions: We established an inverse relationship between TFC and PET-derived MBFR, which is affected by patient selection and procedural factors. TFC represents a measure of the volume of the epicardial coronary compartment, which is increased in patients with CMVD, and performs well in identifying women with CMVD.

Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy: results of a randomised trial.

BACKGROUND: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. METHODS: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. RESULTS: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. DISCUSSION: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. CLINICAL TRIAL REGISTRATION: NCT03611517.

Engineering microvascular networks using a KLF2 reporter to probe flow-dependent endothelial cell function.

Shear stress generated by the flow of blood in the vasculature is a potent regulator of endothelial cell function and vascular structure. While vascular responses to flow are complex and context-dependent, endothelial cell signaling in response to shear stress induced by laminar flows is coordinated by the transcription factor KLF2. The flow-dependent expression of KLF2 in endothelial cells is associated with a quiescent, anti-inflammatory phenotype and has been well characterized in two-dimensional systems but has not been studied in three-dimensional in vitro systems. Here we develop engineered microvascular networks (MVNs) that incorporate a KLF2-based endothelial cell flow sensor within a microfluidic chip, apply continuous flow using an attached microfluidic pump, and study the effects of this flow on vascular structure and function. We found that application of flow to MVNs for 48 h resulted in increased expression of the KLF2 reporter, larger vessel diameters, and decreased vascular branching and resistance. Notably, vessel diameters after the application of flow were independent of initial MVN morphologies. Finally, we found that MVNs exposed to flow have improved vascular barrier function and decreased platelet adhesion. MVNs with KLF2-based flow sensors represent a novel, powerful tool for evaluating the structural and functional effects of flow on engineered three-dimensional vascular systems.

Educational Debt and Income Among Pharmacists and Other Health Professionals.

OBJECTIVE: Given substantial increases in student educational loan debt in recent years, the objective was to assess trends in educational debt-to-income ratios for graduates of pharmacy, medicine, dentistry, optometry, and veterinary medicine programs in the United States for the period of 2017 to 2022. METHODS: A retrospective analysis was conducted of 2017 to 2022 data for educational debt and income for select health professions. Annual income data were collected from the American Community Survey, and educational debt data were collected from health professions organizations. Educational debt-to-income ratios for each health profession were calculated, as was mean change per year in debt-to-income ratio. RESULTS: With the exception of medicine, educational debt consistently exceeded income across pharmacy and the other health professions for the period of 2017 to 2022. Debt-to-income ratios of pharmacists and the remaining health professionals decreased on average per year between 2017 and 2022. Physicians had the lowest debt-to-income ratios and dentists had the highest debt-to-income ratios for the study period. CONCLUSION: Debt-to-income ratios fell to below 2017 levels for the health professions of interest, suggesting average growth in income outpaced that of debt for the study period. Regardless, debt remains high and may influence health care professionals' postgraduate training and career decisions, and in turn affect access to health care. Therefore, a call to action is proposed to address educational debt burden. Several strategies are suggested including federal policy changes, implementing tuition reductions or minimal increases, facilitating financial aid options, and reducing underlying costs of health professions programs.

CSF Proteomics in Patients With Progressive Supranuclear Palsy.

BACKGROUND AND OBJECTIVES: Identification of fluid biomarkers for progressive supranuclear palsy (PSP) is critical to enhance therapeutic development. We implemented unbiased DNA aptamer (SOMAmer) proteomics to identify novel CSF PSP biomarkers. METHODS: This is a cross-sectional study in original (18 clinically diagnosed PSP-Richardson syndrome [PSP-RS], 28 cognitively healthy controls]), validation (23 PSP-RS, 26 healthy controls), and neuropathology-confirmed (21 PSP, 52 non-PSP frontotemporal lobar degeneration) cohorts. Participants were recruited through the University of California, San Francisco, and the 4-Repeat Neuroimaging Initiative. The original and neuropathology cohorts were analyzed with the SomaScan platform version 3.0 (5026-plex) and the validation cohort with version 4.1 (7595-plex). Clinical severity was measured with the PSP Rating Scale (PSPRS). CSF proteomic data were analyzed to identify differentially expressed targets, implicated biological pathways using enrichment and weighted consensus gene coexpression analyses, diagnostic value of top targets with receiver-operating characteristic curves, and associations with disease severity with linear regressions. RESULTS: A total of 136 participants were included (median age 70.6 ± 8 years, 68 [50%] women). One hundred fifty-five of 5,026 (3.1%), 959 of 7,595 (12.6%), and 321 of 5,026 (6.3%) SOMAmers were differentially expressed in PSP compared with controls in original, validation, and neuropathology-confirmed cohorts, with most of the SOMAmers showing reduced signal (83.1%, 95.1%, and 73.2%, respectively). Three coexpression modules were associated with PSP across cohorts: (1) synaptic function/JAK-STAT (ß = -0.044, corrected p = 0.002), (2) vesicle cytoskeletal trafficking (ß = 0.039, p = 0.007), and (3) cytokine-cytokine receptor interaction (ß = -0.032, p = 0.035) pathways. Axon guidance was the top dysregulated pathway in PSP in original (strength = 1.71, p < 0.001), validation (strength = 0.84, p < 0.001), and neuropathology-confirmed (strength = 0.78, p < 0.001) cohorts. A panel of axon guidance pathway proteins discriminated between PSP and controls in original (area under the curve [AUC] = 0.924), validation (AUC = 0.815), and neuropathology-confirmed (AUC = 0.932) cohorts. Two inflammatory proteins, galectin-10 and cytotoxic T lymphocyte-associated protein-4, correlated with PSPRS scores across cohorts. DISCUSSION: Axon guidance pathway proteins and several other molecular pathways are downregulated in PSP, compared with controls. Proteins in these pathways may be useful targets for biomarker or therapeutic development.

Cancer misinformation on social media.

Social media is widely used globally by patients, families of patients, health professionals, scientists, and other stakeholders who seek and share information related to cancer. Despite many benefits of social media for cancer care and research, there is also a substantial risk of exposure to misinformation, or inaccurate information about cancer. Types of misinformation vary from inaccurate information about cancer risk factors or unproven treatment options to conspiracy theories and public relations articles or advertisements appearing as reliable medical content. Many characteristics of social media networks-such as their extensive use and the relative ease it allows to share information quickly-facilitate the spread of misinformation. Research shows that inaccurate and misleading health-related posts on social media often get more views and engagement (e.g., likes, shares) from users compared with accurate information. Exposure to misinformation can have downstream implications for health-related attitudes and behaviors. However, combatting misinformation is a complex process that requires engagement from media platforms, scientific and health experts, governmental organizations, and the general public. Cancer experts, for example, should actively combat misinformation in real time and should disseminate evidence-based content on social media. Health professionals should give information prescriptions to patients and families and support health literacy. Patients and families should vet the quality of cancer information before acting upon it (e.g., by using publicly available checklists) and seek recommended resources from health care providers and trusted organizations. Future multidisciplinary research is needed to identify optimal ways of building resilience and combating misinformation across social media.

Missed opportunities for guidance on sexually transmitted infection services: a global review of national HIV PrEP guidance.

OBJECTIVES: People who use or would benefit from pre-exposure prophylaxis (PrEP) for HIV infection are disproportionately affected by sexually transmitted infections (STIs). Integrating STI services when offering PrEP fosters synergies and efficiencies in response to HIV/STI and promotes people-centred care. Including guidance on STI interventions for people on PrEP may facilitate implementation and uptake. We conducted a global review of national PrEP guidance documents and analysed the inclusion of recommendations for the provision of STI services by country level of income. METHODS: We searched national PrEP guidance documents published by WHO Member States through the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS) databases, the PrEPWatch repository and Google. Information on a range of STI-related interventions was extracted from documents available by October 2023. RESULTS: Of the 113 national PrEP guidance documents retrieved, STIs were mentioned in 77% (90/117). Viral hepatitis B testing and vaccination were recommended by most high-income countries (HICs) and low-income and middle-income countries (LMICs). Recommendation for syphilis testing was prominent in HICs (91%) and moderately noted in LMICs (68%). Gonorrhoea and chlamydia testing was recommended frequently in HICs (88%) and 42% in LMICs. However, the review noted that, to a much lesser extent, specific type of testing for these pathogens was mentioned. Recommendation for quarterly STI testing for syphilis, gonorrhoea and chlamydia was ubiquitous, while the need to offer STI partner services was rarely mentioned. CONCLUSIONS: PrEP services offer an opportunity for improved and expanded STI services, increasing person-centred care and addressing STI epidemics alongside HIV. Our review highlights the strengths and gaps in incorporating critical STI interventions into national PrEP normative guidance. Addressing these gaps through a stepwise approach and increasing targeted testing and partner services can help improve quality of care and support an effective response to HIV and other STIs.

Recovery of europium from E-waste using redox active tetrathiotungstate ligands.

Rare-earth elements (REEs) are critical to our modern economy, yet their mining from natural ores bears a profound environmental impact. Traditional separation techniques are chemical and energy-intensive because their chemical similarities make REEs very challenging to purify, requiring multiple extraction steps to achieve high purity products. This emphasizes the need for sustainable and straightforward separation methods. Here we introduce a strategy for the direct separation of europium (Eu) from complex mixtures under ambient conditions, leveraging on the redox non innocence of purely inorganic tungsten tetrathiolate (WS42-) ligands. The recovery of Eu is achieved upon reduction of Eu(III) to a Eu(II) coordination polymer, driven by an induced internal electron transfer from the tetrathiotungstate ligand. Applying this strategy to unconventional feedstock such as spent energy-saving lamps allows selective europium recovery with separation factors over 1000 and recovery efficiency as high as 99% without pre-treatment of the waste.

A novel mouse home cage lickometer system reveals sex- and housing-based influences on alcohol drinking.

Alcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment. We developed LIQ PARTI (Lick Instance Quantifier with Poly-Animal RFID Tracking Integration), an open-source tool to examine home cage continuous access two-bottle choice drinking behavior in a group-housed setting, investigating the influence of sex and social isolation on ethanol consumption and bout microstructure in C57Bl/6J mice. LIQ PARTI, based on our previously developed single-housed LIQ HD system, accurately tracks drinking behavior using capacitive-based sensors and RFID technology. Group-housed female mice exhibited higher ethanol preference than males, while males displayed a unique undulating pattern of ethanol preference linked to cage changes, suggesting a potential stress-related response. Chronic ethanol intake distinctly altered bout microstructure between male and female mice, highlighting sex and social environmental influences on drinking behavior. Social isolation with the LIQ HD system amplified fluid intake and ethanol preference in both sexes, accompanied by sex- and fluid-dependent changes in bout microstructure. However, these effects largely reversed upon resocialization, indicating the plasticity of these behaviors in response to social context. Utilizing a novel group-housed home cage lickometer device, our findings illustrate the critical interplay of sex and housing conditions in voluntary alcohol drinking behaviors in C57Bl/6J mice, facilitating nuanced insights into the potential contributions to AUD etiology.

Distribution of COVID-19 mitigation measures by industry and work arrangement-US blood donors, May 2021-December 2021.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) mitigation measures in workplaces of employed US blood donors by industry and work arrangement. METHODS: During May-December 2021, blood donors responded to a survey; we describe the distribution of reported workplace mitigation measures by industry and work arrangement, organized using the hierarchy of controls. RESULTS: Of 53,433 respondents representing 21 industries, ventilation upgrades were reported by 4%-38% of respondents (overall: 20%); telework access ranged from 14%-80% (53% overall). Requiring masks (overall: 84%; range: 40%-94%), physical distancing (77%; 51%-86%), paid leave for illness (70%; 38%-87%), and encouraging vaccination (61%; 33%-80%) were common. Independent workers reported fewer mitigation measures than those in traditional employment settings. CONCLUSIONS: Mitigation measures varied by industry and work arrangement. Some mitigation measures may be challenging to implement or irrelevant in certain industries, supporting the idea that mitigation is not a one-size-fits-all strategy. POLICY IMPLICATIONS: Tailored strategies to mitigate workplace risks of disease transmission are vital. Strategies should rely on effective methods for identifying workplace controls (e.g., through the hierarchy of controls) and account for industry-specific characteristics and workplace environments.

Cardiovascular Outcomes in Fontan Patients With Right vs Left Univentricular Morphology: A Multicenter Study.

Background: There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle. Objectives: The purpose of this study was to compare the incidence of atrial arrhythmias, thromboembolic events, cardiac transplantation, and death following Fontan palliation in patients with uRV vs uLV. Methods: The Alliance for Adult Research in Congenital Cardiology conducted a multicenter retrospective cohort study on patients with total cavopulmonary connection Fontan palliation across 12 centers in North America. All components of the composite outcome, that is, atrial arrhythmias, thromboembolic events, cardiac transplantation, and death, were reviewed and classified by a blinded adjudicating committee. Time-to-event analyses were performed that accounted for competing risks. Results: A total of 384 patients were followed for 10.5 ± 5.9 years. The composite outcome occurred in 3.7 vs 1.7 cases per 100 person-years for uRV (N = 171) vs uLV (N = 213), respectively (P < 0.001). In multivariable analyses, uRV conferred a >2-fold higher risk of the composite outcome (HR: 2.17, 95% CI: 1.45-3.45, P < 0.001). In secondary analyses of components of the primary outcome, uRV was significantly associated with a greater risk of cardiac transplantation or death (HR: 9.09, 95% CI: 2.17-38.46, P < 0.001) and atrial arrhythmias (HR: 2.17, 95% CI: 1.20-4.00, P = 0.010) but not thromboembolic events (HR: 1.64, 95% CI: 0.86-3.16, P = 0.131). Conclusions: Fontan patients with uRV vs uLV morphology have a higher incidence of adverse cardiovascular events, including atrial arrhythmia, cardiac transplantation, and all-cause mortality.

Adherence with post-hospitalization follow-up after pediatric critical illness due to respiratory failure.

BACKGROUND: Adherence with follow-up appointments after a pediatric intensive care unit (PICU) admission is likely a key component in managing post-PICU sequalae. However, prior work on PICU follow-up adherence is limited. The objective of this study is to identify hospitalization characteristics, discharge child health metrics, and follow-up characteristics associated with full adherence with recommended follow-up at a quaternary care center after a PICU admission due to respiratory failure. METHODS: We conducted a retrospective cohort study of patients ≤ 18 years with respiratory failure admitted between 1/2013-12/2014 to a quaternary care PICU. Post-hospitalization full adherence with recommended follow-up in the two years post discharge (1/2013-3/2017) at the quaternary care center was quantified and compared by demographics, baseline child health metrics, hospitalization characteristics, discharge child health metrics, and follow-up characteristics in bivariate and multivariate analyses. Patients were dichotomized into being non-adherent with follow-up (patients who attended less than 100% of recommended appointments at the quaternary care center) and fully adherent (patients who attended 100% of recommended appointments at the quaternary care center). RESULTS: Of 155 patients alive at hospital discharge, 140 (90.3%) were recommended to follow-up at the quaternary care center. Of the 140 patients with recommended follow-up at the quaternary care center, 32.1% were non-adherent with follow-up and 67.9% were fully adherent. In a multivariable logistic regression model, each additional recommended unique follow-up appointment was associated with lower odds of being fully adherent with follow-up (OR 0.74, 95% CI 0.60-0.91, p = 0.005), and each 10% increase in the proportion of appointments scheduled before discharge was associated with higher odds of being fully adherent with follow-up (OR 1.02, 95% CI 1.01-1.03, p = 0.004). CONCLUSIONS: After admission for acute respiratory failure, only two-thirds of children were fully adherent with recommended follow-up at a quaternary care center. Our findings suggest that limiting the recommended follow-up to only key essential healthcare providers and working to schedule as many appointments as possible before discharge could improve follow-up adherence. However, a better understanding of the factors that lead to non-adherence with follow-up appointments is needed to inform broader system-level approaches could help improve PICU follow-up adherence.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action.

OBJECTIVES: To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae. METHODS: After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent. RESULTS: A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%). CONCLUSIONS: Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.

Accelerated Orthodontic Treatment using Biomodulation: A Randomized Clinical Trial.

Background: Orthodontic treatment often spans several months or even years, which can be burdensome for patients. Biomodulation techniques have emerged as potential strategies to expedite orthodontic tooth movement. Materials and Methods: A randomized clinical trial was conducted with a sample of 60 orthodontic patients, aged 12-30 years, requiring fixed appliance therapy. Patients were randomly assigned to either the biomodulation group (n = 30) or the control group (n = 30). The biomodulation group received low-level laser therapy (LLLT) along with traditional orthodontic treatment, while the control group received conventional orthodontic treatment without LLLT. Treatment duration, pain perception, and orthodontic tooth movement were assessed during the study period. Results: The results demonstrated a significant reduction in treatment duration in the biomodulation group compared to the control group. The biomodulation group exhibited a 30% reduction in overall treatment time, with an average treatment duration of 8.4 months, while the control group required an average of 12 months (P < 0.001). Pain perception during orthodontic adjustments was lower in the biomodulation group. Additionally, biomodulation was associated with a statistically significant increase in the rate of tooth movement, as evidenced by a 20% reduction in the time required to achieve desired tooth alignment (P < 0.01). Conclusion: Biomodulation through low-level laser therapy represents a promising adjunct to traditional orthodontic treatment, significantly accelerating tooth movement and reducing treatment duration.

Racial and Ethnic Differences in Time to Completion of Academic Enrichment Program Applications.

INTRODUCTION: Diversity in healthcare and research is integral to serving our increasingly diverse population. Access to academic enrichment programs, an important pathway to science, technology, engineering, and mathematics (STEM) careers promotes educational attainment through academic preparation and increased interest, useful strategies for improving diverse representation in higher learning. Given this important pathway to STEM fields, attention to equity in enrichment programs admissions is as important as the increasing focus on mitigating racial/ethnic disparities in undergraduate and graduate admissions.  Methods: In a retrospective cohort study at the University of Washington, we used descriptive and Chi-Square statistics to compare a hybrid competitive summer application program with stipend with an asynchronous first-come, first-served enrollment program in injury and violence prevention research. The three main outcomes were: 1) time to application, measured by number of days to apply/enroll after application or enrollment period start date, 2) percentage of application/enrollment period, measured by when application or enrollment occurred in relation to the total application or enrollment period, and 3) differences in Black, Hispanic, and Native American applicants and enrollees.  Results: In a study examining two injury and violence prevention programs, which reached educational institutions including Historically Black Colleges and Universities (HBCU) and Tribal Colleges: 1) Applicants were 9.6% and 6.4% Black (application vs enrollment programs; p<0.0001), 0.4% and 0% Native American to the application and enrollment programs, and 9.1% and 10.3% Hispanic (application vs enrollment programs; p=0.6), 2) Across all racial and ethnic groups, students applied later (last 15% percent of application period) in the competitive application program than to the first-come first-served enrollment program in which students enrolled throughout the enrollment period, and 3) Across both program types, there were racial and ethnic differences in time to application and enrollment start and completion. CONCLUSION: Findings show that free enrollment programs alone do not incentivize educational attainment for all groups and that application rolling admissions processes may not equally promote racial and ethnic diversity for all groups.