Antimicrobial exposure during infancy in a longitudinal California cohort.

BACKGROUND: To describe temporal and sociodemographic patterns of antimicrobial exposure during the first year of life in a large US cohort. METHODS: Singleton infants born 1998-2014 enrolled in Kaiser Permanente Northern California integrated health system (n = 345,550) were followed longitudinally via comprehensive electronic health records, capturing all systemic antimicrobial inpatient administrations and outpatient dispensings. Antimicrobial exposure was summarized by maternal and infant characteristics, birth year, inpatient/outpatient status, age in months, and drug class. RESULTS: Overall, 44% of infants in this cohort received at least one dose of antimicrobials during infancy. Decreases over time were driven by reduced outpatient dispensings specifically in later infancy, primarily for penicillins. Among infants receiving any antimicrobials the median number of exposure-days was 16. Inpatient dispensings peaked in the first 30 days of life and outpatient dispensings peaked at 10-11 months. Birth characteristics (i.e., NICU admission, gestational age) were strong independent predictors of antimicrobial exposure between 0- < 3 months; sociodemographic factors were modest predictors of exposure for 3-12 months. CONCLUSION: Predictors of antimicrobial exposure in early and late infancy are distinct with early infancy exposures highly correlated to birth characteristics. The cumulative proportion of infants exposed has decreased due to fewer late infancy outpatient dispensings. IMPACT: Comprehensive antimicrobial exposure histories and the maternal and infant characteristics predicting exposure have not been well described in US populations. This analysis provides estimates of cumulative antimicrobial exposures by sociodemographic factors, delivery characteristics, month of life, inpatient/outpatient status, and antibiotic class among one of the largest US HMOs. Predictors of early infancy antimicrobial exposures differ from those in late infancy, with early exposures strongly correlated to birth characteristics and late infancy exposures modestly related to sociodemographic factors. Antimicrobial exposure among infants decreased over the time period primarily due to reduced outpatient dispensings in later infancy.

The relationship between playing musical instruments and cognitive trajectories: Analysis from a UK ageing cohort.

BACKGROUND: The accumulation of age-associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. OBJECTIVES: Explore the relationship between musicality and cognitive function in a large cohort of older adults. METHODS: This was a nested study within the PROTECT-UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT-UK. RESULTS: Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. CONCLUSIONS: Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health.

Confounding by Conception Seasonality in Studies of Temperature and Preterm Birth: A Simulation Study.

BACKGROUND: Seasonal patterns of conception may confound acute associations between birth outcomes and seasonally varying exposures. We aim to evaluate four epidemiologic designs (time-stratified case-crossover, time-series, pair-matched case-control, and time-to-event) commonly used to study acute associations between ambient temperature and preterm births. METHODS: We conducted simulations assuming no effect of temperature on preterm birth. We generated pseudo-birth data from the observed seasonal patterns of birth in the United States and analyzed them in relation to observed temperatures using design-specific seasonality adjustments. RESULTS: Using the case-crossover approach (time-stratified by calendar month), we observed a bias (among 1,000 replicates) = 0.016 (Monte-Carlo standard error 95% CI: 0.015-0.018) in the regression coefficient for every 10°C increase in mean temperature in the warm season (May-September). Unbiased estimates obtained using the time-series approach required accounting for both the pregnancies-at-risk and their weighted probability of birth. Notably, adding the daily weighted probability of birth from the time-series models to the case-crossover models corrected the bias in the case-crossover approach. In the pair-matched case-control design, where the exposure period was matched on gestational window, we observed no bias. The time-to-event approach was also unbiased but was more computationally intensive than others. CONCLUSIONS: Most designs can be implemented in a way that yields estimates unbiased by conception seasonality. The time-stratified case-crossover design exhibited a small positive bias, which could contribute to, but not fully explain, previously reported associations.

Prepregnancy body mass index and risk of childhood asthma.

BACKGROUND: Growing evidence suggests that maternal obesity may affect the intrauterine environment and increase a child's risk of developing asthma. We aim to investigate the relationship between prepregnancy obesity and childhood asthma risk. METHODS: Cohorts of children enrolled in Kaiser Permanente Northern California integrated healthcare system were followed from birth (2005-2014) to age 4 (n = 104,467), 6 (n = 63,084), or 8 (n = 31,006) using electronic medical records. Child's asthma was defined using ICD codes and asthma-related prescription medication dispensing. Risk ratios (RR) and 95% confidence intervals (95% CIs) for child's asthma were estimated using Poisson regression with robust error variance for (1) prepregnancy BMI categories (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese 1 [30-34.9], and obese 2/3 [≥35]) and (2) continuous prepregnancy BMI modeled using cubic splines with knots at BMI category boundaries. Models were adjusted for maternal age, education, race, asthma, allergies, smoking, gestational weight gain, child's birth year, parity, infant sex, gestational age, and child's BMI. RESULTS: Relative to normal BMI, RRs (95%CIs) for asthma at ages 4, 6, and 8 were 0.91 (0.75, 1.11), 0.95 (0.78, 1.16), and 0.97 (0.75, 1.27) for underweight, 1.06 (0.99, 1.14), 1.08 (1.01, 1.16), and 1.03 (0.94, 1.14) for overweight, 1.09 (1.00, 1.19), 1.12 (1.03, 1.23), 1.03 (0.91, 1.17) for obese 1, and 1.10 (0.99, 1.21), 1.13 (1.02, 1.25), 1.14 (0.99, 1.31) for obese 2/3. When continuous prepregnancy BMI was modeled with splines, child's asthma risk generally increased linearly with increasing prepregnancy BMI. CONCLUSIONS: Higher prepregnancy BMI is associated with modestly increased childhood asthma risk.

Maternal obesity and childhood asthma risk: Exploring mediating pathways.

BACKGROUND: Growing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways. OBJECTIVE: To investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk. METHODS: We used electronic medical records from mother-child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005-2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD-9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese [≥30] kg/m2 ) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI-for-age percentiles: underweight [<5th], normal [5th-85th], overweight [85th-95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow-up age. GWG (delivery weight-prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma. RESULTS: Overall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed. CONCLUSIONS: Childhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma.

Gestational Weight Gain and Birth Outcome: A Comparison of Methods of Accounting for Gestational Age.

Cross-sectional studies of total gestational weight gain (GWG) and perinatal outcomes have used different approaches to operationalize GWG and adjust for duration of gestation. Using birth records from California (2007-2017), Nevada (2010-2017), and Oregon (2008-2017), we compared 3 commonly used approaches to estimate associations between GWG and cesarean delivery, small-for-gestational-age birth, and low birth weight (LBW): 1) the Institute of Medicine-recommended GWG ranges at a given gestational week, 2) total weight gain categories directly adjusting for gestational age as a covariate, and 3) weight-gain-for-gestational-age z scores derived from an external longitudinal reference population. Among 5,461,130 births, the 3 methods yielded similar conclusions for cesarean delivery and small-for-gestational-age birth. However, for LBW, some associations based on z scores were in the opposite direction of methods 1 and 2, paradoxically suggesting that higher GWG increases risk of LBW. This was due to a greater proportion of preterm births among those with high z scores, and controlling for gestational age in the z score model brought the results in line with the other methods. We conclude that the use of externally derived GWG z scores based on ongoing pregnancies can yield associations confounded by duration of pregnancy when the outcome is strongly associated with gestational age at delivery.

Acute association between heatwaves and stillbirth in six US states.

BACKGROUND: Heatwaves are becoming more frequent and may acutely increase the risk of stillbirth, a rare and severe pregnancy outcome. OBJECTIVES: Examine the association between multiple heatwave metrics and stillbirth in six U.S. states. METHODS: Data were collected from fetal death and birth records in California (1996-2017), Florida (1991-2017), Georgia (1994-2017), Kansas (1991-2017), New Jersey (1991-2015), and Oregon (1991-2017). Cases were matched to controls 1:4 based on maternal race/ethnicity, maternal education, and county, and exposure windows were aligned (gestational week prior to stillbirth). County-level temperature data were obtained from Daymet and linked to cases and controls by residential county and the exposure window. Five heatwave metrics (1 categorical, 3 dichotomous, 1 continuous) were created using different combinations of the duration and intensity of hot days (mean daily temperature exceeding the county-specific 97.5th percentile) during the exposure window, as well as a continuous measure of mean temperature during the exposure window modeled using natural splines to allow for nonlinear associations. State-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. State-specific results were pooled using a fixed-effects meta-analysis. RESULTS: In our data set of 140,428 stillbirths (553,928 live birth controls), three of the five heatwave metrics examined were not associated with stillbirth. However, four consecutive hot days during the previous week was associated with a 3% increase in stillbirth risk (CI: 1.01, 1.06), and a 1 °C average increase over the threshold was associated with a 10% increase in stillbirth risk (CI: 1.04, 1.17). In continuous temperature analyses, there was a slight increased risk of stillbirth associated with extremely hot temperatures (≥ 35 °C). DISCUSSION: Most heat wave definitions examined were not associated with acute changes in stillbirth risk; however, the most extreme heatwave durations and temperatures were associated with a modest increase in stillbirth risk.

Acute associations between heatwaves and preterm and early-term birth in 50 US metropolitan areas: a matched case-control study.

BACKGROUND: The effect of heatwaves on adverse birth outcomes is not well understood and may vary by how heatwaves are defined. The study aims to examine acute associations between various heatwave definitions and preterm and early-term birth. METHODS: Using national vital records from 50 metropolitan statistical areas (MSAs) between 1982 and 1988, singleton preterm (< 37 weeks) and early-term births (37-38 weeks) were matched (1:1) to controls who completed at least 37 weeks or 39 weeks of gestation, respectively. Matching variables were MSA, maternal race, and maternal education. Sixty heatwave definitions including binary indicators for exposure to sustained heat, number of high heat days, and measures of heat intensity (the average degrees over the threshold in the past 7 days) based on the 97.5th percentile of MSA-specific temperature metrics, or the 85th percentile of positive excessive heat factor (EHF) were created. Odds ratios (OR) for heatwave exposures in the week preceding birth (or corresponding gestational week for controls) were estimated using conditional logistic regression adjusting for maternal age, marital status, and seasonality. Effect modification by maternal education, age, race/ethnicity, child sex, and region was assessed. RESULTS: There were 615,329 preterm and 1,005,576 early-term case-control pairs in the analyses. For most definitions, exposure to heatwaves in the week before delivery was consistently associated with increased odds of early-term birth. Exposure to more high heat days and more degrees above the threshold yielded higher magnitude ORs. For exposure to 3 or more days over the 97.5th percentile of mean temperature in the past week compared to zero days, the OR was 1.027 for early-term birth (95%CI: 1.014, 1.039). Although we generally found null associations when assessing various heatwave definitions and preterm birth, ORs for both preterm and early-term birth were greater in magnitude among Hispanic and non-Hispanic black mothers. CONCLUSION: Although associations varied across metrics and heatwave definitions, heatwaves were more consistently associated with early-term birth than with preterm birth. This study's findings may have implications for prevention programs targeting vulnerable subgroups as climate change progresses.

Food insecurity, gestational weight gain and gestational diabetes in the National Children's Study, 2009-2014.

BACKGROUND: Household food insecurity (HFI) and gestational diabetes mellitus (GDM) are both common during pregnancy, yet it is unknown if these two factors are related. We aimed to determine the independent and joint associations between HFI, gestational weight gain (GWG) and GDM among pregnant women in the USA. METHODS: We used data from 592 women in the National Children's Study, Initial Vanguard Study from 2009 to 2014. HFI was assessed using the Household Food Security Survey Module at the first study visit; GDM was assessed through questionnaires and medical chart review. Logistic regression models were used to investigate the exposures of HFI, GWG and their joint effect on GDM. RESULTS: Among participants, 20.1% were marginally food secure or food insecure and 7.4% were diagnosed with GDM. The elevated unadjusted association between HFI and GDM was attenuated after adjustment (aOR: 1.12; 95%CI: 0.47, 2.66). There was an elevated risk of GDM associated with inadequate GWG, (aOR: 2.42; 95%CI: 0.97, 6.00), but results were imprecise. There were no statistically significant associations in the joint exposure analysis. CONCLUSION: The relationship between HFI and GDM is mostly explained by other covariates, but there is some evidence that inadequate GWG is a possible risk factor for GDM.

What Is the Best Evidence to Guide Management of Acute Achilles Tendon Ruptures? A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Uncertainty exists regarding the best treatment for acute Achilles tendon ruptures. Simultaneous comparison of the multiple treatment options using traditional study designs is problematic; multiarm clinical trials often are logistically constrained to small sample sizes, and traditional meta-analyses are limited to comparisons of only two treatments that have been compared in head-to-head trials. Network meta-analyses allow for simultaneous comparison of all existing treatments utilizing both direct (head-to-head comparison) and indirect (not previously compared head-to-head) evidence. QUESTIONS/PURPOSES: We performed a network meta-analysis of randomized controlled trials (RCTs) to answer the following questions: Considering open repair, minimally invasive surgery (MIS) repair, functional rehabilitation, or primary immobilization for acute Achilles tendon ruptures, (1) which intervention is associated with the lowest risk of rerupture? (2) Which intervention is associated with the lowest risk of complications resulting in surgery? METHODS: This study was conducted with methods guided by the Cochrane Handbook for Systematic Reviews of Interventions and is reported in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension statement for incorporating network meta-analysis. Five databases and grey literature sources (such as major orthopaedic meeting presentation lists) were searched from inception to September 30, 2019. Included studies were RCTs comparing treatment of acute Achilles tendon ruptures using two or more of the following interventions: primary immobilization, functional rehabilitation, open surgical repair, or MIS repair. We excluded studies enrolling patients with chronic ruptures, reruptures, and preexisting Achilles tendinopathy as well as studies with more than 20% loss to follow-up or less than 6 months of follow-up. Nineteen RCTs (1316 patients) were included in the final analysis. The mean number of patients per study treatment arm was 35 ± 16, mean age was 41 ± 5 years, mean sex composition was 80% ± 10% males, and mean follow-up was 22 ± 12 months. The four treatment groups were compared for the main outcomes of rerupture and complications resulting in operation. The analysis was conducted using random-effects Bayesian network meta-analysis with vague priors. Evidence quality was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation methodology. We found risk of selection, attrition, and reporting bias to be low across treatments, and we found the risk of performance and detection bias to be high. Overall risk of bias between treatments appeared similar. RESULTS: We found that treatment with primary immobilization had a greater risk of rerupture than open surgery (odds ratio 4.06 [95% credible interval {CrI} 1.47 to 11.88]; p < 0.05). There were no other differences between treatments for risk of rerupture. Minimally invasive surgery was ranked first for fewest complications resulting in surgery and was associated with a lower risk of complications resulting in surgery than functional rehabilitation (OR 0.16 [95% CrI 0.02 to 0.90]; p < 0.05), open surgery (OR 0.22 [95% CrI 0.04 to 0.93]; p < 0.05), and primary immobilization (OR < 0.01 [95% CrI < 0.01 to 0.01]; p < 0.05). Risk of complications resulting in surgery was no different between primary immobilization and open surgery (OR 1.46 [95% CrI 0.35 to 5.36]). Data for patient-reported outcome scores and return to activity were inappropriate for pooling secondary to considerable clinical heterogeneity and imprecision associated with small sample sizes. CONCLUSION: Faced with acute Achilles tendon rupture, patients should be counseled that, based on the best-available evidence, the risk of rerupture likely is no different across contemporary treatments. Considering the possibly lower risk of complications resulting in surgery associated with MIS repair, patients and surgeons must balance any benefit with the potential risks of MIS techniques. As treatments continue to evolve, consistent reporting of validated patient-reported outcome measures is critically important to facilitate analysis with existing RCT evidence. Infrequent but serious complications such as rerupture and deep infection should be further explored to determine whether meaningful differences exist in specific patient populations. LEVEL OF EVIDENCE: Level I, therapeutic study.

Caesarean delivery and the risk of atopic dermatitis in children.

BACKGROUND: Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. OBJECTIVE: Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. METHODS: Maternal and child information was collected through Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n = 173 105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. RESULTS: Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. CONCLUSION: Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.

Cesarean delivery and the risk of allergic rhinitis in children.

BACKGROUND: Cesarean delivery (C-section) may influence the infant microbiome and affect immune system development and subsequent risk for allergic rhinitis (AR). OBJECTIVE: To investigate the association between C-section and AR at ages 6, 8, and 10 years. METHODS: Data were collected prospectively through Kaiser Permanente Northern Californias (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital and remained in the KPNC system for minimum 6 years (n = 117,768 age 6; n = 75,115 age 8; n = 40,332 age 10). Risk ratios (RR) for C-section and AR were estimated at each follow-up age and adjusted for important covariates, including intrapartum antibiotics, pre-pregnancy body mass index, maternal allergic morbidities, and breastfeeding. Subanalyses considered information on C-section indication, labor, and membrane rupture. RESULTS: After adjusting for confounders, we did not observe an association between C-section and AR at follow-up ages 6, 8, or 10 years (RR [CI]: 6 years, 0.98 [0.91, 1.04]; 8 years, 1.00 [0.95, 1.07]; 10 years, 1.03 [0.96, 1.10]). In stratified analyses, there was limited evidence that C-section increases the risk of AR in certain subgroups (eg, children of non-atopic mothers, second or higher birth order children), but most estimated risk ratios were consistent with no association. Estimated associations were unaffected by participant attrition, missing data, or intrapartum antibiotics. CONCLUSION: C-section delivery was not associated with AR at follow-up ages of 6, 8, or 10 years in a large contemporary US cohort.

An Evaluation of the Safety and Effectiveness of Total Hip Arthroplasty as an Outpatient Procedure: A Matched-Cohort Analysis.

BACKGROUND: Outpatient hip arthroplasty is being performed more routinely; however, safety remains a concern. The purpose of this study was to compare the rate of adverse events of outpatient total hip arthroplasty (THA) and assess barriers to discharge. METHODS: We examined 136 patients who underwent unilateral THA by one surgeon and were discharged on the same day of surgery. Using propensity matching, 136 inpatients who received the same procedure, and were discharged on postoperative day one or later, were identified. For each cohort, 90-day occurrence of adverse events, readmissions, and emergency visits were recorded and compared. Adverse events were graded using the OrthoSAVES tool. A secondary objective was to assess potential barriers to same-day discharge. RESULTS: Within 90 days postoperatively, 12 outpatients (8.82%) and 14 inpatients (10.29%) developed an adverse event. There were no significant differences between the rate or severity of adverse events between the 2 groups and no serious adverse events in either group. In the outpatient group, there was a correlation between the dosage of spinal anesthetic (bupivacaine) given and time required to stay in postanesthetic care unit postoperatively. CONCLUSION: When comparing the 2 groups, there were no differences in adverse events at 90 days. At our center, in the appropriate patient population, outpatient THA is a safe and cost-effective option. A potential barrier to mobility postoperatively and successful same-day discharge is the time required to stay in postanesthetic care unit postoperatively, which was significantly correlated with an increased dose of spinal anesthetic given in our outpatient cohort.

Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 µs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 µs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application.

A primer on thermodynamic-based models for deciphering transcriptional regulatory logic.

A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed.

Procedure, Screening, and Cost of Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) is currently considered a potential treatment for various GI-related illnesses, with the goal to replenish natural healthy flora of the GI tract that has been harmed because of antibiotic use or overgrowth of harmful bacteria. Current methods of administering the processed stool include colonoscopy and enema, while an oral capsule is being developed. Each method of administration carries its own set of risks, including adverse reactions to treatment, infection following the invasive administration procedure, and flare-ups of GI-related symptoms. Current oral administration through nasoduodenal tube poses a risk for aspiration which has not been ruled out as the cause of subsequent pneumonia and death in patient trials. The development of an oral capsule could address some of the faults of the current methods, not only making treatment more affordable and accessible but also less of a risk due to its minimally invasive nature. FMT is also a treatment option to attenuate adverse effects associated with antibiotic use, including combatting the emergence of antibiotic resistance, as well as adverse effects related to other medical treatments such as chemotherapy. While FMT is an unexplored treatment option for multiple gastrointestinal disorders and is currently still largely inaccessible for many patients financially, studies have suggested that it could be a more affordable treatment option long-term for patients as aspects of the treatment become more affordable with further research.

Optimal site of care for administration of extended half-life respiratory syncytial virus (RSV) antibodies to infants in the United States (US).

INTRODUCTION: New extended half-life antibodies for the single-dose prevention of medically attended (MA) respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) have been developed for administration to all infants before or during their first RSV season. For infants born during the season, administration as soon as feasible after birth would provide optimal protection and minimize access disparities. The objective of this study was to assess the time from birth hospitalization discharge to the first outpatient visit (FOV) among US infants in order to determine optimal site of administration for the extended half-life antibody. MATERIAL AND METHODS: This retrospective, observational, time-to-event analysis uses the Merative™ MarketScan® Commercial and Multi-State Medicaid Databases. Time to FOV is reported separately for the COVID-19 and recent pre-COVID-19 eras and for commercially insured and Medicaid infants. RESULTS: Overall, 73.8 % of Medicaid infants had an FOV within 5 days as compared to 84.7 % of commercially insured infants. Estimates were higher during the COVID-19 era. Urban commercially insured infants had much higher FOV completion than their counterparts. Among Medicaid infants, urban Black and rural White infants were least likely to complete their FOV within 5 days of birth hospitalization discharge. DISCUSSION AND CONCLUSION: FOV within 5 days after birth hospitalization discharge for Medicaid infants is substantially lower than that of commercially insured infants. Approximately 1 in 4 Medicaid infants and 1 in 8 infants with commercial insurance did not have an outpatient visit within 5 days of birth hospitalization discharge. For US infants born during the RSV season, administration of extended half-life RSV antibodies in the newborn nursery prior to discharge would ensure optimal uptake and minimize access disparities.

Assessing interest in cardiothoracic surgery at an osteopathic medical school: Results of an institutional survey.

Objective: Cardiothoracic surgery is a surgical subspecialty that attracts few medical students. As integrated surgical residency programs continue to grow in number, there is increased interest in what factors influence specialty selection during undergraduate medical education. Previous institutional studies have studied allopathic medical schools affiliated with academic institutions. This study aimed to assess the interest and perception of cardiothoracic surgery at an osteopathic institution. Methods: Active medical students at a US osteopathic institution were invited to complete an original online survey. Means and 95% confidence intervals were calculated and graphed for questions using Likert scale responses. Comparison of mean responses for preclinical versus clinical students was assessed by a Kruskal-Wallis nonparametric analysis of variance. Results: There were 166 surveys (22%) completed, and interest in cardiothoracic surgery was indicated by 7.8% of respondents. Work/life balance, personality of cardiothoracic surgeons, and lack of family time were negative factors associated with cardiothoracic surgery. Clinical exposure, shadowing, mentorship, and significant personal/life events before medical school were strong factors in establishing students' interest in cardiothoracic surgery. Preclinical students noted exposure to cardiothoracic surgery would further increase their interest when compared with clinical students (µ = 3.39 vs µ = 2.69, P = .008). Conclusions: All factors that established interest in cardiothoracic surgery occurred before students entered medical school. Although there are negative perceptions associated with cardiothoracic surgery, these may be ameliorated with more exposure to the field. Further research is needed to explore how early exposure in preclinical years of medical school affects students' perceptions and ultimate interest in cardiothoracic surgery.

Building Interest in Cardiothoracic Surgery at an Osteopathic Medical School: Results of an Institutional Study and a Guide for Medical Schools.

Objective A previous study at this institution revealed a connection between interest group involvement and specialty interest while identifying the negative perceptions of cardiothoracic (CT) surgery. This study aimed to build interest and ameliorate the negative perceptions of CT surgery by exposing pre-clinical students to the field through engaging events. Methods Students at a US osteopathic institution who attended CT surgery committee events were invited to complete an online survey after each event. Associations between the number of events attended and ranked responses to survey questions were assessed by two-tailed Spearman correlations. Statistical comparisons in ranked responses between the events attended and the survey questions were assessed by a two-way analysis of variance (ANOVA). Pre-clinical students actively enrolled at the institution during the 2022-2023 academic year were eligible for inclusion. Results There were 83 surveys completed over seven events. There was a significant association between the number of events a student attended and their perception of CT surgeon's work/life balance with a correlation coefficient of .258 (P=0.019) and whether CT surgeons have time for their families with a correlation coefficient of .235 (P=0.035). Residents and medical student events as well as wet lab events increased interest the most and helped students feel equipped to apply for CT surgery. Conclusions While negative perceptions associated with CT surgery exist, these may be ameliorated with more exposure to the field. Unique events that expose pre-clinical students to multiple facets of CT surgery, including physicians and trainees in the field, as well as offering hands-on activities, may increase interest in the field and further pursuit of the field during clinical years.