Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

BACKGROUND: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear. METHODS: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. RESULTS: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). CONCLUSIONS: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

Internal Medicine Acting Internship Trends in Rotation Structure and Student Responsibilities: Results from a 2023 National Survey.

BACKGROUND: The acting internship (AI) in internal medicine plays a key role in the transition from medical school to residency. While there have been recent changes in medical education including a pass/fail USMLE Step 1 and increasing use of competency-based assessment, there has not been a large survey of the state of the AI in many years. OBJECTIVE: To assess the current landscape of the internal medicine AI and identify areas in need of standardization. DESIGN: This was a voluntary online survey of medical schools in the United States (U.S.). PARTICIPANTS: Course directors of the AI rotation at U.S. medical schools. MAIN MEASURES: Number of AI rotations required for graduation, length of AI rotation, types of services allowed for AI, clinical responsibilities of students, curricular components. KEY RESULTS: Response rate was 50.7% (71/140 LCME accredited schools). All responding institutions require at least one AI for graduation, with nearly all schools integrating students into resident teaching teams, and almost half also allowing AI students to work on hospitalist services. Students carry 3-4 patients per day on average with a maximum of 5-6 in most institutions. Students are responsible for most aspects of patient care including notes, orders, interprofessional communication, and transitions of care. Night call or night float responsibilities are infrequently required. The structured curriculum published by AAIM is used by only 41% of schools. CONCLUSIONS: The internal medicine AI continues to be a staple in the medical school experience, but there is variation in the structure, curriculum, and expectations on the rotation. Opportunities exist to improve standardization of the AI experience and expectations to better prepare medical students for the transition from medical school to residency.

Physician awareness of patients' preferred level of involvement in decision-making at the initial urogynecology visit: a randomized trial.

BACKGROUND: Studies have shown up to a 40% discordance between patients' preferred roles in decision-making before and their perceived roles after their visit. This can negatively affect patients' experiences; interventions to minimize this discordance may significantly improve patient satisfaction. OBJECTIVE: We aimed to determine whether physicians' awareness of patients' preferred involvement in decision-making before their initial urogynecology visit affects patients' perceived level of involvement after their visit. STUDY DESIGN: This randomized controlled trial enrolled adult English-speaking women presenting for their initial visit at an academic urogynecology clinic from June 2022 to September 2022. Before the visit, participants completed the Control Preference Scale to determine the patient's preferred level of decision-making: active, collaborative, or passive. The participants were randomized to either the physician team being aware of their decision-making preference before the visit or usual care. The participants were blinded. After the visit, participants again completed a Control Preference Scale and the Patient Global Impression of Improvement, CollaboRATE, patient satisfaction, and health literacy questionnaires. Fisher exact, logistic regression, and generalized estimating equations were used. Based on a 21% difference in preferred and perceived discordance, we calculated the sample size to be 50 patients in each arm to achieve 80% power. RESULTS: Women (n=100) with a mean age of 52.9 years (standard deviation=15.8) participated in the study. Most participants identified as White (73%) and non-Hispanic (70%). Before the visit, most women preferred an active role (61%) and few preferred a passive role (7%). There was no significant difference between the 2 cohorts in the discordance between their pre- and post-Control Preference Scale responses (27% vs 37%; P=.39) or whether their symptoms were much better or very much better following the visit (18% vs 37%; P=.06). However, when asked whether they were completely satisfied with the visit, those assigned to the physician awareness cohort reported higher satisfaction than those in the treatment as usual cohort (100% vs 90%; P=.03). CONCLUSION: Although there was no significant decrease in discordance between the patient's desired and perceived level of decision-making following physician awareness, it had a significant effect on patient satisfaction. All patients whose physicians were aware of their preferences reported complete satisfaction with their visit. Although patient-centered care does not always entail meeting all of the patients' expectations, the mere understanding of their preferences in decision-making can lead to complete patient satisfaction.

F-SHARP: a Phase I/II trial of focal salvage high-dose-rate brachytherapy for Radiorecurrent prostate cancer.

BACKGROUND: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high-dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F-SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. STUDY DESIGN: The F-SHARP is a multi-institutional two-stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. ENDPOINTS: The primary endpoint is the acute radiation-related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease-specific and overall survival, and health-related quality of life, as measured by the International Prostate Symptom Score and 26-item Expanded Prostate Cancer Index Composite instruments. PATIENTS AND METHODS: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1-3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long-term toxicity profile, quality of life, and compare single- vs multi-fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.

The Longitudinal Reciprocal Relationships of Tooth Brushing Behaviors Between Underserved Children and Their Caregivers.

BACKGROUND: Tooth brushing is effective in preventing early childhood caries. However, it is unclear how children's and caregiver's tooth brushing are reciprocally related. PURPOSE: The current study investigated whether the longitudinal relationships between children and caregiver tooth brushing are moderated by a caregiver-targeted child oral health intervention and caregiver depression. METHODS: Secondary analysis of a randomized clinical trial that tested whether caregiver-targeted oral health text messages (OHT) outperformed child wellness text messages (CWT) on pediatric dental caries and oral health behaviors (n = 754, mean child age = 2.9 years, 56.2% Black, 68.3%

Tooth brushing is effective in preventing dental cavities in children, but we do not know if or how children and caregiver brushing frequencies are related. This is important because interventions targeting children's oral health may also have the potential to benefit their caregiver's behaviors. Our study examined whether caregiver brushing of their own teeth and caregiver brushing of their young child's teeth positively influenced each other over time. We also explored whether this relationship was less likely if caregivers experienced depressive symptoms and more likely if caregivers participated in a text message program focused on improving their child's oral health. Results showed that caregiver and child tooth brushing behaviors positively influenced each other over time, but this relationship was observed only in caregivers who received the child oral health program (as opposed to the control group) and who reported low depressive symptoms (in contrast to caregivers with high depression symptoms). Our findings suggest that while caregivers and children positively influence each other's tooth-brushing behaviors over time, additional support is essential for caregivers experiencing depression to fully realize these reciprocal benefits.

Locoregional Therapies for Hepatocellular Carcinoma prior to Liver Transplant: Comparative Pathologic Necrosis, Radiologic Response, and Recurrence.

PURPOSE: To compare pathologic tumor necrosis rates after locoregional therapies (LRTs) for hepatocellular carcinoma (HCC) prior to liver transplantation and evaluate radiologic-pathologic correlation along with posttransplant HCC recurrence. MATERIALS AND METHODS: Consecutive patients with solitary HCC bridged or downstaged with LRT from 2010 to 2022 were included. LRTs were transarterial chemoembolization (TACE), radioembolization (yttrium-90 [90Y]), ablation, and stereotactic body radiotherapy (SBRT). Upfront combination therapy options were TACE/ablation and TACE/SBRT. Subsequent therapy crossover due to local recurrence was allowed. Posttreatment imaging closest to the time of transplant, explant histopathologic necrosis, and tumor recurrence after transplant were reviewed. RESULTS: Seventy-three patients met inclusion criteria, of whom 5 (7%) required downstaging. 90Y alone (n = 36) and multimodal therapy (pooled upfront combination and crossover therapy, n = 23) resulted in significantly greater pathologic necrosis compared with TACE alone (n = 14; P = .01). High dose 90Y radiation segmentectomy (≥190 Gy; n = 27) and TACE/ablation (n = 7) showed highest rates of complete pathologic necrosis (CPN)-63% (n = 17) and 71% (n = 5), respectively. Patients with CPN had a mean lesion size of 2.5 cm, compared with 3.2 cm without CPN (P = .04), irrespective of LRT modality. HCC recurrence was more common in patients without CPN (16%, 6/37) than in those with CPN (3%, 1/36; P = .11). Using Liver Imaging Reporting and Data System (LI-RADS), a nonviable imaging response was 75% sensitive and 57% specific for CPN. CONCLUSIONS: Radiation segmentectomy and multimodal therapy significantly improved CPN rates compared with TACE alone. A LI-RADS treatment response of nonviable did not confidently predict CPN.

A GPT-based EHR modeling system for unsupervised novel disease detection.

OBJECTIVE: To develop an Artificial Intelligence (AI)-based anomaly detection model as a complement of an "astute physician" in detecting novel disease cases in a hospital and preventing emerging outbreaks. METHODS: Data included hospitalized patients (n = 120,714) at a safety-net hospital in Massachusetts. A novel Generative Pre-trained Transformer (GPT)-based clinical anomaly detection system was designed and further trained using Empirical Risk Minimization (ERM), which can model a hospitalized patient's Electronic Health Records (EHR) and detect atypical patients. Methods and performance metrics, similar to the ones behind the recent Large Language Models (LLMs), were leveraged to capture the dynamic evolution of the patient's clinical variables and compute an Out-Of-Distribution (OOD) anomaly score. RESULTS: In a completely unsupervised setting, hospitalizations for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection could have been predicted by our GPT model at the beginning of the COVID-19 pandemic, with an Area Under the Receiver Operating Characteristic Curve (AUC) of 92.2 %, using 31 extracted clinical variables and a 3-day detection window. Our GPT achieves individual patient-level anomaly detection and mortality prediction AUC of 78.3 % and 94.7 %, outperforming traditional linear models by 6.6 % and 9 %, respectively. Different types of clinical trajectories of a SARS-CoV-2 infection are captured by our model to make interpretable detections, while a trend of over-pessimistic outcome prediction yields a more effective detection pathway. Furthermore, our comprehensive GPT model can potentially assist clinicians with forecasting patient clinical variables and developing personalized treatment plans. CONCLUSION: This study demonstrates that an emerging outbreak can be accurately detected within a hospital, by using a GPT to model patient EHR time sequences and labeling them as anomalous when actual outcomes are not supported by the model. Such a GPT is also a comprehensive model with the functionality of generating future patient clinical variables, which can potentially assist clinicians in developing personalized treatment plans.

Contextual predictors of self-management and independence trajectories in adolescents and young adults with spina bifida.

AIM: To examine socioeconomic, condition-related, and neuropsychological predictors of self-management trajectories in adolescents and young adults with spina bifida. METHOD: In this longitudinal study, participants completed the Adolescent/Young Adult Self-Management and Independence Scale interview. Socioeconomic status (SES), shunt status, lesion level, and executive functioning were assessed. Growth in self-management was estimated using linear mixed-effects models. RESULTS: Participants (n = 99) were aged 18 to 27 years. Approximately half (52.5%) were female and White; 15.2% were Black; and 32.3% Hispanic or Latino. Although none of the predictors were associated with growth in self-management from ages 18 to 27 years (p > 0.05), several factors were associated with the intercept at age 18 years for total self-management. Higher SES at baseline predicted a higher total self-management score at age 18 years (b = 0.03, standard error [SE] = 0.01; p < 0.001). On average, participants at age 18 years with a shunt scored lower than those without a shunt (b = -0.90, SE = 0.32; p = 0.01); those with a thoracic lesion scored lower than those with lower lesion levels (lumbar: b = -1.22, SE = 0.34; sacral: b = -1.20, SE = 0.36; p = 0.001 for both). Better parent-reported and teacher-reported executive functions predicted higher total self-management (metacognitive: b = -0.03, SE = 0.01; behavioral regulation: b = -0.04, SE = 0.01; p < 0.05 for both). INTERPRETATION: On average, all participants improved in self-management over time. Additionally, baseline superiority in self-management for adolescents and young adults without a shunt, less severe lesions, better executive functions, and higher SES persisted over time.

GBasis: A Python library for evaluating functions, functionals, and integrals expressed with Gaussian basis functions.

GBasis is a free and open-source Python library for molecular property computations based on Gaussian basis functions in quantum chemistry. Specifically, GBasis allows one to evaluate functions expanded in Gaussian basis functions (including molecular orbitals, electron density, and reduced density matrices) and to compute functionals of Gaussian basis functions (overlap integrals, one-electron integrals, and two-electron integrals). Unique features of GBasis include supporting evaluation and analytical integration of arbitrary-order derivatives of the density (matrices), computation of a broad range of (screened) Coulomb interactions, and evaluation of overlap integrals of arbitrary numbers of Gaussians in arbitrarily high dimensions. For circumstances where the flexibility of GBasis is less important than high performance, a seamless Python interface to the Libcint C package is provided. GBasis is designed to be easy to use, maintain, and extend following many standards of sustainable software development, including code-quality assurance through continuous integration protocols, extensive testing, comprehensive documentation, up-to-date package management, and continuous delivery. This article marks the official release of the GBasis library, outlining its features, examples, and development.

Centering the female athlete voice in a sports science research agenda: a modified Delphi survey with Team USA athletes.

OBJECTIVES: To co-construct a sports medicine and exercise science research and translational agenda with Team USA elite female athletes serving as the experts on their health, performance and well-being. METHODS: 40 Team USA female athletes across sports disciplines participated in an online, anonymous, modified Delphi survey by ranking topics on a Likert scale (1='strongly disagree' and 5='strongly agree') and providing qualitative justification regarding whether they believed having more information and research on each topic would support their athletic performance, health and well-being. After each Delphi round, quantitative rankings of topics and qualitative justifications were analysed, informing revisions to the list of topics for review in the subsequent round. Researchers provided athletes with a detailed report of findings and revisions following each round. RESULTS: The final list contained 14 ranked topics. The top five were menstrual cycle symptoms (4.58±0.74), recovery (4.58±0.59), birth control (4.55±0.89), mental health (4.50±0.55) and fueling and the menstrual cycle (4.43±0.74). New topics originating from athletes included recovery, menstrual cycle symptoms, fueling and the menstrual cycle, mental health and sports performance, team dynamics, and institutionalised sexism. CONCLUSION: This is the first study to co-construct a research and translational agenda with Team USA elite female athletes. The list of sports science research topics developed by focusing on elite female athletes' voices lays the foundation for future research and provides valuable insight into the specific needs of female athletes.

High rates of respiratory illnesses upon arrival: lessons from Team USA at the Santiago 2023 Pan American and Parapan American Games.

OBJECTIVE: To describe the incidence and characteristics of injuries and illnesses among Team USA athletes competing at the Santiago 2023 Pan American Games (PAG) and Parapan American Games (PPAG), with a particular focus on the incidence of respiratory illnesses and on injuries for sports new to the Olympic and Paralympic programmes. METHODS: Illnesses and injuries occurring among the 870 Team USA athletes competing in the Santiago 2023 PAG or PPAG were documented within Team USA's Injury and Illness Surveillance system. Illness and injury incidence per 1000 athlete-days (ADs) and incidence ratios (IR) were calculated, both with 95% CIs. RESULTS: Illness (IR 2.5, 95% CI 1.6, 3.9) and injury (IR 1.8, 95% CI 1.3, 2.5) rates were greater during PPAG compared with PAG. Illness rates were higher in the pre-opening ceremony period compared with the competition period for both PAG (IR 2.7, 95% CI 1.1, 5.9) and PPAG (IR 1.9, 95% CI 0.9, 3.8). Respiratory illness was the most common illness with 3.2% and 8.9% of all Team USA athletes reporting a respiratory illness during the PAG and PPAG, respectively. Sports that are relatively new to the Olympic/Paralympic programmes exhibited the highest injury rates during the Games: breaking (250.0 (91.7, 544.2) per 1000 ADs), Para taekwondo (93.8 (19.3, 274.0) per 1000 ADs) and surfing (88.9 (24.2, 227.6) per 1000 ADs). CONCLUSION: Respiratory illness rates were the most common type of illness during both PAG and PPAG and were more likely to occur prior to competition starting. Our data have identified high injury risk populations (breaking, surfing, Para taekwondo) and timing (pre-opening ceremony period) for further risk factor analysis.

Trajectories of self-management and independence in youth with spina bifida: Family-related predictors of growth.

The purpose of this study was to assess family-related predictors of self-management trajectories in youth with spina bifida (SB). Participants with SB completed the Adolescent/Young Adult Self-Management and Independence Scale (AMIS II) interview across four time points. Family functioning, family-related stress, and perceived family support were assessed by multiple reporters and multiple methods. Growth in AMIS II total self-management and the AMIS II subscales (Condition and Independent Living) were estimated using linear mixed effect models as a function of family factors, after controlling for socio-demographic, condition-related, and neuropsychological variables that had been found to be significant predictors of self-management in prior studies. Model fit and parsimony were assessed using Akaike's information criterion (AIC). This diverse community sample included 99 respondents aged 18-27 years old. About half were female (52.5%) and White (52.5%); 15.2% were Black, and 32.3% were Hispanic/Latino. Observed family cohesion at baseline was associated with all self-management scales at age 18 (all p < 0.05). Growth in self-management was associated with parent-reported number of family stress events. For growth in total self-management, the best model included age, race/ethnicity, family income, shunt status, lesion level, neuropsychological function, observed family cohesion, and an age-by-number of family stress events interaction effect. The study findings suggested that family factors were important predictors of self-management trajectories, even after controlling for socio-demographic, condition-related, and neuropsychological covariates. Risk and protective factors identified in families of youth with SB can inform family-focused interventions for self-management.

Adolescent/Young Adult Self-Management and Independence Self-Report Scale: Preliminary psychometric findings.

PURPOSE: This study examined preliminary psychometrics of the Adolescent/Young Adult Self-Management and Independence Self-Report Scale (AMIS II SR). METHODS: Adolescents and adults (N = 159; 13-38 years old) with spina bifida from two clinics and one community sample completed the AMIS II SR. The majority (83%) had myelomeningocele, and about half were female (51.6%). The sample included 44.7% White, 11.3% Black and over one-third Hispanic/Latino (38.4%) participants. Descriptive analyses and reliability were assessed; a confirmatory factor analysis (CFA) was conducted. RESULTS: Item-to-total correlations support the AMIS II SR total scale (r = .38-.79) and its two subscales: condition (r = .49-.67) and independent living (r = .49-.85). Internal consistency reliability was high (α = .91-.96) for the AMIS II SR total scale and subscales. A higher order CFA model that included independent living and condition self-management as first-order factors and a second-order overall self-management factor had excellent fit (RMSEA = 0.06; CFI = 0.97; TLI = 0.96). Descriptive analyses findings were reported. CONCLUSIONS: This study provides psychometric evidence for the use of the AMIS II SR total (overall) scale and subscales (condition and independent living) to assess self-management and independence.

Long-term Outcomes of Poly-4-Hydroxybutyrate (P4HB) in Aesthetic Breast Surgery.

BACKGROUND: Over the past decade, the use of poly-4-hydroxybutyrate (P4HB) in aesthetic breast surgery has grown in popularity. Published data on long-term outcomes, however, is scarce. OBJECTIVES: The purpose of this study was to assess long-term outcomes when using P4HB in various aesthetic breast procedures. METHODS: A retrospective review of all patients undergoing breast procedures with P4HB performed by the senior author (WPA) between July 2012 and March 2022. All patients with greater than one year of follow-up were evaluated, including demographics, surgical indications, complications, secondary procedures, and patient satisfaction. A Kruskal-Wallis test was performed to assess the stability of satisfaction over time. RESULTS: A total of 248 patients were evaluated. The mean follow-up length was 2.9 years (range, 1-9.3y). The most common surgical indication was breast ptosis, which comprised 68 percent (n=167) of patients. The overall complication rate was 8.0 percent (n=20), with an unplanned reoperation rate of 2.8 percent (n=7). Across the entire study population, the mean satisfaction score was 3.42 out of 4. When satisfaction scores were compared to follow-up length, Kruskal-Wallis test demonstrated no statistical differences (H = 18.2, p = 0.89, df = 2), suggesting stability of satisfaction over time. CONCLUSIONS: This study presents the senior author's entire experience with P4HB across a wide range of aesthetic breast procedures. With an average follow-up length of almost 3 years, P4HB appears to be both a safe and effective tool to support soft tissue in aesthetic breast surgery. Further, high patient satisfaction appears stable.

Outcomes of In-Office, High Resolution, Ultrasound Silicone Breast Implant Surveillance by Plastic Surgeons.

BACKGROUND: Implant rupture is a known complication in cosmetic breast surgery but access and cost barriers hinder proper implant surveillance. OBJECTIVES: This study aims to validate High Resolution Ultrasound (HRUS) for diagnosing silicone implant rupture, and secondarily, explore the predictors of implant rupture in a single-surgeon cohort. METHODS: A retrospective chart review identified patients who underwent HRUS of silicone breast implants that were placed by the senior author (WPA). HRUS sensitivity/specificity and predictive values were calculated. Multivariable logistic regression assessed predictors of implant rupture. Kaplan-Meier methods estimated 10 and 15-year implant survival. RESULTS: Among 254 patients (508 implants) included, 52 patients (104 implants) underwent operative exploration for various reasons; 20 implants had confirmed ruptures. Examining this operative cohort, HRUS had excellent positive and negative predictive value, respectively, 100% (95% CI 83.1-100%) and 97.6% (95% CI 91.6-99.3%); the sensitivity was 90.9% (95% CI 70.8-98.9%) and specificity was 100% (95% CI 95.6%-100%). The median age of the implant at the time of ultrasound was 119 months (10 years; IQR 79-152 months). After multivariable adjustment, the only the implant age was a significant predictor of implant rupture (p=0.04). Across the entire cohort, Kaplan-Meier methods estimated a 10-year and 15-year implant survival rate of 0.98 (95% CI 0.96-0.99) and 0.80 (95% CI 0.71-0.87), respectively. Subgroup analysis showed 10 and 15-year implant survival rates of 0.99 and 0.92, respectively, for surveillance-only HRUS patients. CONCLUSIONS: Plastic surgeon delivered office-based HRUS surveillance is a highly sensitive and specific method to assess silicone breast implant integrity.

Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort.

BACKGROUND: Maternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations. METHODS: This study included 903 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses. RESULTS: The study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1-18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B). CONCLUSIONS: This prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.

Multidisciplinary approach to the treatment of sexual dysfunction in couples using a biopsychosocial model.

BACKGROUND: Given the complexity of the psychological and biological pathologies associated with sexual dysfunction, which affects at least a third of adult women and men worldwide, a multidisciplinary approach has been advocated. AIM: To assess sexual functioning, relationship satisfaction, and mood stability pre- and post- treatment at the Loyola University Sexual Wellness Program. METHODS: Couples attending the 6-week multidisciplinary Sexual Wellness Program provided consent and completed pre- and post- intervention assessments. Linear mixed effects models were used to estimate the mean change from baseline to first follow-up. A covariance matrix was used to account for dependency. OUTCOMES: All patients completed self-reported surveys: Dyadic Adjustment Scale, PROMIS Sexual Function and Satisfaction Measures Brief Profile (Patient-Reported Outcomes Measurement Information), and International Index of Erectile Function. RESULTS: There were 85 respondents: 42 men and 43 women. The mean age was 49.82 years (range, 25-77). The largest improvement was on the total Dyadic Adjustment Scale score, which increased by approximately 5.18 points (95% CI, 2.55-7.81). PROMIS scores for global satisfaction with sex life, erectile function, and interest in sexual activity significantly increased from baseline, while the vaginal discomfort score significantly declined. Overall the score for global satisfaction with sex life increased from baseline by approximately 5.57 points (95% CI, 3.03-8.10). On average, men reported a 4.33-point increase (95% CI, 0.04-8.62) in their International Index of Erectile Function score from baseline. CLINICAL IMPLICATIONS: A multidisciplinary treatment approach focused on the couple positively affects a couple's relationship, including global satisfaction with sex life, relationship satisfaction, interest in sexual activity, and erectile function. STRENGTHS AND LIMITATIONS: This study is one of the few to document the effects of a multidisciplinary treatment approach for both members of a heterosexual couple-male and female. Limitations include the narrow demographics and lack of a control group in our population. Furthermore, this was completed at 1 academic center. CONCLUSION: These findings emphasize that multidisciplinary sexual therapy programs aimed at the couple can help address multiple aspects of sexual well-being.

Grade of Primary Cutaneous Leiomyosarcoma Dictates Risk for Metastatic Spread and Disease-Specific Mortality.

BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.

Characterizing fluid intake and physical activity in university students within the United States during the COVID-19 pandemic.

PURPOSE: This study determined fluid intake and physical activity behaviors among college students during the COVID-19 pandemic. METHODS: College students (n = 1014; females, 75.6%) completed an online survey during the Spring 2020 academic semester following the initial global response to the COVID-19 pandemic. Academic standing, habitation situation, and University/College responses to COVID-19 were collected. Participants completed the Godin Leisure-Time Exercise Questionnaire and a 15-item Beverage Questionnaire (BEVQ-15) to determine physical activity level and fluid intake behaviors, respectively. RESULTS: Females (1920 ± 960 mL) consumed significantly less fluid than males (2400 ± 1270 mL, p < 0.001). Living off-campus (p < 0.01) and living with a spouse/partner (p < 0.01) was associated with increased consumption of alcoholic beverages. 88.7% of participants reported being at least moderately active; however, Black/African American and Asian participants were more likely to be less active than their Caucasian/White counterparts (p < 0.05). Participants reporting no change in habitation in response to COVID-19 had a higher fluid intake (p = 0.002); however, the plain water consumption remained consistent (p = 0.116). While there was no effect of habitation or suspension of classes on physical activity levels (p > 0.05), greater self-reported physical activity was associated with greater fluid intake (std. ß = 0.091, p = 0.003). CONCLUSIONS: Fluid intake among college students during the initial response to the COVID-19 pandemic approximated current daily fluid intake recommendations. Associations between COVID-19-related disruptions (i.e., suspension of classes and changes in habitation) and increased alcohol intake are concerning and may suggest the need for the development of targeted strategies and programming to attenuate the execution of negative health-related behaviors in college students.