Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease.

Krabbe disease (Kd) is a lysosomal storage disorder (LSD) caused by the deficiency of the lysosomal galactosylceramidase (GALC) which cleaves the myelin enriched lipid galactosylceramide (GalCer). Accumulated GalCer is catabolized into the cytotoxic lipid psychosine that causes myelinating cells death and demyelination which recruits microglia/macrophages that fail to digest myelin debris and become globoid cells. Here, to understand the pathological mechanisms of Kd, we used induced pluripotent stem cells (iPSCs) from Kd patients to produce myelinating organoids and microglia. We show that Kd organoids have no obvious defects in neurogenesis, astrogenesis, and oligodendrogenesis but manifest early myelination defects. Specifically, Kd organoids showed shorter but a similar number of myelin internodes than Controls at the peak of myelination and a reduced number and shorter internodes at a later time point. Interestingly, myelin is affected in the absence of autophagy and mTOR pathway dysregulation, suggesting lack of lysosomal dysfunction which makes this organoid model a very valuable tool to study the early events that drive demyelination in Kd. Kd iPSC-derived microglia show a marginal rate of globoid cell formation under normal culture conditions that is drastically increased upon GalCer feeding. Under normal culture conditions, Kd microglia show a minor LAMP1 content decrease and a slight increase in the autophagy protein LC3B. Upon GalCer feeding, Kd cells show accumulation of autophagy proteins and strong LAMP1 reduction that at a later time point are reverted showing the compensatory capabilities of globoid cells. Altogether, this supports the value of our cultures as tools to study the mechanisms that drive globoid cell formation and the compensatory mechanism in play to overcome GalCer accumulation in Kd.

The impact of pulse repetition frequency on microbubble activity and drug delivery during focused ultrasound-mediated blood-brain barrier opening.

Objective.Pulsed focused ultrasound (FUS) can deliver therapeutics to the brain by using intravenous microbubbles (MBs) to open the blood-brain barrier (BBB). MB emissions indicate treatment outcomes, like BBB opening (harmonics) and damage (broadband). Typically, a pulse repetition frequency (PRF) of 1 Hz is used, but the effect of PRF on MBs is not fully understood. We investigated the effect of PRF on MB activity and tracer delivery.Approach.The effect of PRF (0.125, 0.25, 0.5, 1, and 2 Hz) on MB activity was monitored through harmonic and wideband emissions during FUS sonications of the rat brain at 274.3 kHz. BBB opening was quantified through fluorescence imaging to estimate the concentration of Trypan Blue (TB) dye following a 75-pulse FUS exposure for PRFs of 1 and 0.25 Hz.Main results.At a fixed acoustic pressure, the percentage change in maximum harmonic amplitude compared to the control (PRF = 1 Hz) decreased with increasing PRF, with a median change of 73.8% at 0.125 Hz and -38.3% at 2 Hz. There was no difference in the pressure threshold for broadband emissions between PRFs of 0.25 and 1 Hz. PRF = 0.25 Hz, led to a 68.2% increase in the mean concentration of TB measured after FUS, with a 53.9% increase in the mean harmonic sum, compared with PRF = 1 Hz. Harmonic emissions-based control at PRF = 0.25 Hz yielded similar TB delivery, with less damage at histology, compared with 1 Hz.Significance.For a fixed number of FUS pulses, reducing the PRF was shown to increase the magnitude of harmonic emissions and TB delivery, but not the threshold for broadband emissions. While further research is necessary to understand the mechanisms involved, these results may be useful to improve clinical safety margins and sensitivity to detecting small harmonic signals from cavitating MBs.

Patient medication management, understanding and adherence during the transition from hospital to outpatient care - a qualitative longitudinal study in polymorbid patients with type 2 diabetes.

BACKGROUND: Continuity of care is under great pressure during the transition from hospital to outpatient care. Medication changes during hospitalization may be poorly communicated and understood, compromising patient safety during the transition from hospital to home. The main aims of this study were to investigate the perspectives of patients with type 2 diabetes and multimorbidities on their medications from hospital discharge to outpatient care, and their healthcare journey through the outpatient healthcare system. In this article, we present the results focusing on patients' perspectives of their medications from hospital to two months after discharge. METHODS: Patients with type 2 diabetes, with at least two comorbidities and who returned home after discharge, were recruited during their hospitalization. A descriptive qualitative longitudinal research approach was adopted, with four in-depth semi-structured interviews per participant over a period of two months after discharge. Interviews were based on semi-structured guides, transcribed verbatim, and a thematic analysis was conducted. RESULTS: Twenty-one participants were included from October 2020 to July 2021. Seventy-five interviews were conducted. Three main themes were identified: (A) Medication management, (B) Medication understanding, and (C) Medication adherence, during three periods: (1) Hospitalization, (2) Care transition, and (3) Outpatient care. Participants had varying levels of need for medication information and involvement in medication management during hospitalization and in outpatient care. The transition from hospital to autonomous medication management was difficult for most participants, who quickly returned to their routines with some participants experiencing difficulties in medication adherence. CONCLUSIONS: The transition from hospital to outpatient care is a challenging process during which discharged patients are vulnerable and are willing to take steps to better manage, understand, and adhere to their medications. The resulting tension between patients' difficulties with their medications and lack of standardized healthcare support calls for interprofessional guidelines to better address patients' needs, increase their safety, and standardize physicians', pharmacists', and nurses' roles and responsibilities.

Using a Semiautomated Procedure (CleanADHdata.R Script) to Clean Electronic Adherence Monitoring Data: Tutorial.

BACKGROUND: Patient adherence to medications can be assessed using interactive digital health technologies such as electronic monitors (EMs). Changes in treatment regimens and deviations from EM use over time must be characterized to establish the actual level of medication adherence. OBJECTIVE: We developed the computer script CleanADHdata.R to clean raw EM adherence data, and this tutorial is a guide for users. METHODS: In addition to raw EM data, we collected adherence start and stop monitoring dates and identified the prescribed regimens, the expected number of EM openings per day based on the prescribed regimen, EM use deviations, and patients' demographic data. The script formats the data longitudinally and calculates each day's medication implementation. RESULTS: We provided a simulated data set for 10 patients, for which 15 EMs were used over a median period of 187 (IQR 135-342) days. The median patient implementation before and after EM raw data cleaning was 83.3% (IQR 71.5%-93.9%) and 97.3% (IQR 95.8%-97.6%), respectively (Δ+14%). This difference is substantial enough to consider EM data cleaning to be capable of avoiding data misinterpretation and providing a cleaned data set for the adherence analysis in terms of implementation and persistence. CONCLUSIONS: The CleanADHdata.R script is a semiautomated procedure that increases standardization and reproducibility. This script has broader applicability within the realm of digital health, as it can be used to clean adherence data collected with diverse digital technologies.

Navigating outpatient care of patients with type 2 diabetes after hospital discharge - a qualitative longitudinal study.

BACKGROUND: The transition from hospital to outpatient care is a particularly vulnerable period for patients as they move from regular health monitoring to self-management. This study aimed to map and investigate the journey of patients with polymorbidities, including type 2 diabetes (T2D), in the 2 months following hospital discharge and examine patients' encounters with healthcare professionals (HCPs). METHODS: Patients discharged with T2D and at least two other comorbidities were recruited during hospitalization. This qualitative longitudinal study consisted of four semi-structured interviews per participant conducted from discharge up to 2 months after discharge. The interviews were based on a guide, transcribed verbatim, and thematically analyzed. Patient journeys through the healthcare system were represented using the patient journey mapping methodology. RESULTS: Seventy-five interviews with 21 participants were conducted from October 2020 to July 2021. The participants had a median of 11 encounters (min-max: 6-28) with HCPs. The patient journey was categorized into six key steps: hospitalization, discharge, dispensing prescribed medications by the community pharmacist, follow-up calls, the first medical appointment, and outpatient care. CONCLUSIONS: The outpatient journey in the 2 months following discharge is a complex and adaptive process. Despite the active role of numerous HCPs, navigation in outpatient care after discharge relies heavily on the involvement and responsibilities of patients. Preparation for discharge, post-hospitalization follow-up, and the first visit to the pharmacy and general practitioner are key moments for carefully considering patient care. Our findings underline the need for clarified roles and a standardized approach to discharge planning and post-discharge care in partnership with patients, family caregivers, and all stakeholders involved.

Large-scale, mobile and technology-enhanced serious game for interprofessional education: pilot study and lessons learnt.

Recent research suggests that serious gaming is a promising strategy for interprofessional education (IPE). This report describes the design and pilot testing of a large-scale, mobile, technology-enhanced serious game embedded in the IPE curriculum in Geneva, Switzerland. Organized into teams of eight, the students were tasked with finding a young patient who had just escaped from the intensive care unit. Through a series of 10 stations, they explored hospital- and community-based locations of the healthcare system and were engaged in various learning and game activities; they were rewarded with cues to unveil the mystery. A total of 582 undergraduate students from seven disciplines (medicine, midwifery, nursing, nutrition-dietetics, pharmacy, physiotherapy, and technology in medical radiology) took part. Survey results (response rate: 62.8%) suggest that an overall majority of students valued the game, particularly the collaborative experience of actively learning from others in autonomous teams. Qualitative feedback allowed us to identify future areas for improvement: simplifying the adventure storyline and optimizing student flow. Educational institutions across the world facing challenges when creating IPE activities will find in this report ideas and lessons learnt to use mobile technology and serious gaming for large cohorts of students.

Higher prenatal anxiety predicts lower neonatal hair cortisol.

BACKGROUND: Prenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. METHOD: Pregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75-2.00). RESULTS: Both higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: ß = -0.614, p =.012; slope: ß = -0.681, p =.006), but not general anxiety (intercept: ß = -0.389, p =.114; slope: ß = -0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. CONCLUSION: Cortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.

Determining Factors Influencing Collegiate Players' Intention to Pursue a Professional Career.

The rise of professional careers in playing sports has been seen in the recent generation. Ranging from traditional sports to recent e-games, it can be seen that student athletes are not only considering these as motivational factors for education, but also as future career paths. This study aims to fill the knowledge gap about the factors influencing college athletes' aspirations to play professionally. The study examines the complex web of athlete decision-making by utilizing the extended Theory of Planned Behavior (TPB) and analyzing the roles of motivational factors, self-efficacy, affective behavior, and behavioral domains. With the use of structural equation modeling, the study deciphers the intricate links, emphasizing the critical role that attitude plays in affective behavior. It emphasizes how much optimism and self-efficacy shape an athlete's behavior and subsequent pursuit of professional careers. The current research provides a benchmark for future studies exploring student athletes' career goals. This research adds understanding to the knowledge gap regarding the complex decision-making procedures of aspiring professional athletes. Both theoretical and practical implications are provided based on the results of the study, which stakeholders and institutions may consider for student athletes wanting to pursue a professional sports career.

Physical integrity and bioefficacy of used long-lasting insecticidal nets in Makenene, Centre Region of Cameroon.

Long-lasting insecticide nets (LLINs) are the recommended tools against mosquito-borne diseases. However, their physical integrity and bioefficacy in the field could be affected by several factors. This study evaluated the physical integrity and bioefficacy of nets used in Makenene since 2016. Cross-sectional field surveys were carried out after 6 y. A questionnaire was first administered to the heads of households, and then the physical integrity of the LLINs was determined by calculating the proportional hole index (pHI). WHO cone bioassays were conducted to determine the bioefficacy of LLINs currently being used against wild strains of Anopheles gambiae s.l., Culex pipiens s.l., and laboratory-reared pyrethroid-susceptible strain of Anopheles coluzzii (Ngousso). Of the 167 LLINs examined in households, 39.5% were fairly good, 26.4% were acceptable, and 34.1% were damaged. The most torn faces of the nets were the sides used for entering and exiting. None of the 30 LLINs used for WHO cone bioassays was still effective against An. gambiae s.l. and Cx. pipiens s.l. while up to 85.7% of these LLINs were at least effective against the susceptible strain after 24 h, with a significant difference observed when comparing the mortality rates between wild and laboratory-susceptible strain of Anopheles (P-value < 0.01). Anopheles gambiae s.l. were all (100%) identified as An. gambiae s.s. by PCR. The LLINs distributed in Makenene since the 2016 campaign are only effective on susceptible strain and should be replaced for a better control of residual malaria transmission and the nuisance by Culex mosquitoes in the locality.

A study combining microbubble-mediated focused ultrasound and radiation therapy in the healthy rat brain and a F98 glioma model.

Focused Ultrasound (FUS) has been shown to sensitize tumors outside the brain to Radiotherapy (RT) through increased ceramide-mediated apoptosis. This study investigated the effects of FUS + RT in healthy rodent brains and F98 gliomas. Tumors, or striata in healthy rats, were targeted with microbubble-mediated, pulsed FUS (220 kHz, 102-444 kPa), followed by RT (4, 8, 15 Gy). FUS + RT (8, 15 Gy) resulted in ablative lesions, not observed with FUS or RT only, in healthy tissue. Lesions were visible using Magnetic Resonance Imaging (MRI) within 72 h and persisted until 21 days post-treatment, indicating potential applications in ablative neurosurgery. In F98 tumors, at 8 and 15 Gy, where RT only had significant effects, FUS + RT offered limited improvements. At 4 Gy, where RT had limited effects compared with untreated controls, FUS + RT reduced tumor volumes observed on MRI by 45-57%. However, survival benefits were minimal (controls: 27 days, RT: 27 days, FUS + RT: 28 days). Histological analyses of tumors 72 h after FUS + RT (4 Gy) showed 93% and 396% increases in apoptosis, and 320% and 336% increases in vessel-associated ceramide, compared to FUS and RT only. Preliminary evidence shows that FUS + RT may improve treatment of glioma, but additional studies are required to optimize effect size.

Assisted teleconsultation in an outpatient pharmacy: Results of a pilot study in Geneva, Switzerland.

INTRODUCTION: Assisted teleconsultation (ATC) is the act of telemedicine involving on one side a patient in the presence of a healthcare professional, and an expert on the other side. ATC in outpatient pharmacies may be an alternative to the emergency room for patients with a semi-urgent medical problem. This project aimed at pilot testing the ATC in an outpatient pharmacy to assess its feasibility and to collect initial real-world data. METHODS: After initial evaluation and triage by the pharmacist, ATC was proposed to patients consulting at one outpatient pharmacy for semi-urgent medical problems. Prospective data on patients, consultation reasons, teleconsultation duration, patient's orientation and pharmacist' satisfaction were prospectively collected. RESULTS: Between December 2020 and June 2021, 39 consultations took place, 12 with video and 27 with telephone. Patients' median age was 37 years (IQR 26-50), 59% were women. Near half of the consultations (19) happened during the weekend. Mean ATC duration was 22 min (IC95% 18.6-26.1). Twenty-nine (74%) consultations ended with a prescription, 8 (21%) with medical recommendations and 2 (5%) with an emergency care referral. Without teleconsultation, 34 (87%) patients would have consulted a physician for their problem, and 24 (62%) would have been to the emergency room (self-reported). Fourteen (36%) consultations involved ENT, ophthalmologic and dermatologic complaints. CONCLUSION: A young population with semi-urgent medical problems can be managed in the pharmacy using ATC with a primary care physician. Financial, technical and training aspects should be developed and optimized in the future.

Do school-based smoking preventive interventions have unintended effects? Post hoc analysis of the Focus cluster randomised controlled trial.

OBJECTIVES: Public health interventions are designed to improve specific health-related outcomes; however, they may also produce negative side effects, such as substitution use, psychological or social harms. Knowledge about the unintended effects of school-based smoking preventive interventions is sparse. Hence, this study examined these potential unintended effects of the smoking-reducing intervention, Focus, among students in the vocational education and training setting. DESIGN: Cluster randomised controlled trial stratified by school type with 5 months follow-up. SETTING AND PARTICIPANTS: Across Denmark, eight schools were randomised to the intervention group (n=844 students, response proportion 76%) and six schools to the control group (n=815 students, response proportion 75%). This study focused solely on students who smoked at baseline (N=491). INTERVENTIONS: The intervention was developed systematically based on theory and a thoroughly mixed-methods needs assessment. Intervention components included a comprehensive school tobacco policy (smoke-free school hours) supported by a 3-day course for school staff and launched by an edutainment session for students; class-based lessons and a quit-and-win competition; and individual telephone smoking cessation support. OUTCOMES: Alternative tobacco and nicotine products (regular use of smokeless tobacco, hookah and e-cigarettes), regular cannabis use, boredom and loneliness at school, stress and perceived stigmatisation among smokers. RESULTS: We found no statistically significant unintended effects of the intervention. Nonetheless, insignificant findings indicated that students in the intervention group were less likely to be bored during school hours (OR 0.59, 95% CI 0.32 to 1.10) and experience stress (OR 0.62, 95% CI 0.35 to 1.10), but more likely to report feeling stigmatised compared with the control group (OR 1.55, 95% CI 0.71 to 3.40). CONCLUSIONS: Overall, findings suggested no unintended effects of the Focus trial with respect to substitution use, psychological, nor group or social harms. Future research is encouraged to report potential harmful outcomes of smoking preventive interventions, and interventions should be aware of the possible stigmatisation of smokers. TRIAL REGISTRATION NUMBER: ISRCTN16455577.

Prevalence of depression and its factors among elderly population in Barangay Cabangahan, Consolacion, Cebu

@#<strong>BACKGROUND</strong><p style="text-align: justify;" data-mce-style="text-align: justify;">Depression is a widespread mental disorder that affects 3.8% of the global population, with a total prevalence rate of 5.7% in the age group of 60 and older. Symptoms include feelings of guilt, hopelessness, and thoughts of dying or suicide. The Philippines has a high mental health issue among its older adults, with 7.5 million accounting for 7.5% of the population. The country ranks third in the Western Pacific Region, with 6 million Filipinos suffering from depression and anxiety.</p><strong>OBJECTIVE</strong><p style="text-align: justify;" data-mce-style="text-align: justify;">This study aimed to determine the prevalence of depression and its associated factors among the elderly group ages 60 and older in Barangay Cabangahan, Consolacion, Cebu.</p><strong>METHOD</strong><p style="text-align: justify;" data-mce-style="text-align: justify;">This study used a cross-sectional research design. Respondents were randomly selected through convenient sampling through house-to-house visitation and face-to-face interviews. Assessment tools were distributed assessing the demographic profile, Family APGAR, and Patient Health Questionnaire 9 (PHQ-9). The depression scale was adapted to determine the prevalence of depression among the elderly. Descriptive statistics were used to analyze the data, which displayed the frequency distribution and percentage of the respondents’ demographic profile, family function, and prevalence of depression. The Pearson correlation coefficient was used to determine the association of the demographic profile and family function with the prevalence of depression.</p><strong>RESULTS</strong><p style="text-align: justify;" data-mce-style="text-align: justify;">The demographic profile of the elderly group is mostly women, comprising 93 (80.87%) of the population; 53 (46.09%) belong to the young-old age group (aged 60–65), and 65 (56.53%) are married. The majority are elementary school graduates, 72 (62.61%); their source of financial support is their children, 42 (35.5%), and employment is 35 (30.43%). Most live together with their immediate family, 106 (92.17%). This study identified 60 (52.17%) of the 115 respondents as having a highly functional family. Only 35.65% (41) of the respondents had mild depression, while 54 (46.09%) reported no or minimal depression. Among the demographic profiles, living alone, having more than one comorbidity, and taking more than one medication may lead to depression among the elderly, with r-values of .191,213 and.222, respectively. The study indicates a significant relationship between family function and the prevalence of depression in the elderly, with a p-value of 0.022 and a weak negative correlation with an r-value of -.214.</p><strong>SUMMARY/CONCLUSION</strong><p style="text-align: justify;" data-mce-style="text-align: justify;">The elderly population is predominantly women, with most being married and living with their immediate family. Highly functional families are evident, while the prevalence of depression is low, with only 35.65% experiencing mild symptoms. The study suggests improving the quality of life for the elderly through intervention programs, health education, and strong, cohesive community networks. Additional assessment instruments, such as the Geriatric Depression Scale, are recommended, as well as increasing the study’s sample size and geographic setting.</p>

Maternal anxiety during pregnancy predicts infant attention to affective faces.

BACKGROUND: Prenatal maternal anxiety is a known influence on offspring development. General anxiety and pregnancy-related anxiety (a distinct type of anxiety encompassing fears associated with pregnancy) are associated with offspring socioemotional development, with potential consequences for later emotional and behavioral problems. This study examines whether maternal pregnancy-related and general anxiety relate to infant attention to affective faces, a process which plays an integral role in early socioemotional development. METHODS: Participants included 86 mothers and their 6-month-old infants (56.3 % female). Mothers completed measures of pregnancy-related and general anxiety three times through gestation. Infants' attention to affective faces was assessed with an eye-tracking task during which a series of face pairs were presented (happy, angry, or sad face paired with a neutral face). Overall attention measures included attention-holding (total looking time) and attention-orienting (latency to faces); affect-biased attention measures included proportion of total looking time to emotional faces and latency difference score. RESULTS: Higher maternal pregnancy-related anxiety across gestation predicted decreased infant attention-holding to affective faces [F(1,80) = 7.232, p = .009, partial η2 = 0.083]. No differences were found in infant attention-orienting or affect-biased attention. LIMITATIONS: Reliance on a correlational study design precludes the ability to make causal inferences. CONCLUSIONS: Maternal pregnancy-related anxiety is an important predictor of child outcomes. We provide novel evidence that pregnancy-related anxiety predicts infant attention to emotional faces, behaviors which have important implications for socioemotional development. Providers may consider pregnancy-related anxiety as a target for screening and treatment that may benefit both pregnant individual and offspring.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Nucleation of α-Synuclein Amyloid Fibrils Induced by Cross-Interaction with ß-Hairpin Peptides Derived from Immunoglobulin Light Chains.

Heterologous interactions between different amyloid-forming proteins, also called cross-interactions, may have a critical impact on disease-related amyloid formation. ß-hairpin conformers of amyloid-forming proteins have been shown to affect homologous interactions in the amyloid self-assembly process. Here, we applied two ß-hairpin-forming peptides derived from immunoglobulin light chains as models to test how heterologous ß-hairpins modulate the fibril formation of Parkinson's disease-associated protein α-synuclein (αSyn). The peptides SMAhp and LENhp comprise ß-strands C and C' of the κ4 antibodies SMA and LEN, which are associated with light chain amyloidosis and multiple myeloma, respectively. SMAhp and LENhp bind with high affinity to the ß-hairpin-binding protein ß-wrapin AS10 according to isothermal titration calorimetry and NMR spectroscopy. The addition of SMAhp and LENhp affects the kinetics of αSyn aggregation monitored by Thioflavin T (ThT) fluorescence, with the effect depending on assay conditions, salt concentration, and the applied ß-hairpin peptide. In the absence of agitation, substoichiometric concentrations of the hairpin peptides strongly reduce the lag time of αSyn aggregation, suggesting that they support the nucleation of αSyn amyloid fibrils. The effect is also observed for the aggregation of αSyn fragments lacking the N-terminus or the C-terminus, indicating that the promotion of nucleation involves the interaction of hairpin peptides with the hydrophobic non-amyloid-ß component (NAC) region.

Perceptions of conflicting information about long-term medications: a qualitative in-depth interview study of patients with chronic diseases in the Swiss ambulatory care system.

OBJECTIVE: Patients with multiple long-term conditions visit various healthcare professionals and are exposed to medication information from various sources causing an increased risk of patients perceiving contradictory medication information. The aims of this study are to: (1) characterise conflicting medication information perceived by patients with long-term conditions, (2) better understand the related impact on patients' medication self-management and healthcare system navigation and (3) explore ways in which such events could be prevented. DESIGN: This study was conducted through qualitative semistructured interviews. Data were analysed using thematic analysis. SETTING: Community pharmacies and medical centres in Geneva, Switzerland. PARTICIPANTS: This study included outpatients from April 2019 to February 2020. Patients were included after participating in a quantitative survey of perceived conflicting information about medications for long-term diseases. METHODS: Semistructured audiotaped interviews of 20 to 60 min following a pre-established interview guide to explore participants' perceptions of conflicting information. Interviews were transcribed verbatim, and a thematic analysis was conducted with inductive and deductive coding using MAXQDA (2018, Release 18.2.3). RESULTS: Twenty-two patients were interviewed, until data saturation, mentioning indication or need for a medication as the main topic of conflicting information between two healthcare professionals. Perceived conflicting information often resulted from insufficient information provided and poor communication leading to confusion, doubts and medication non-adherence. Patients expected more information and more interprofessional communication on their medications. As a result of conflicting information, most participants learnt or were learning to take an active role and become partners of the healthcare providers. CONCLUSION: The need to strengthen and improve communication and interprofessional collaborative practice among healthcare professionals and with the patient is emerging to increase the quality and consistency of information about medications, and consequently, to ensure better use and experience of medications.

Predictors of Preexposure Prophylaxis Eligibility among Pregnant People with Opioid Use Disorder.

OBJECTIVE: We seek to evaluate risk factors for eligibility for preexposure prophylaxis (PrEP) among pregnant people with opioid use disorder (OUD). STUDY DESIGN: This is a single-site retrospective cohort study of pregnant people admitted for management of OUD at an urban, tertiary care center from 2013 to 2022. PrEP eligibility was defined based on (1) modified American College of Obstetricians and Gynecologists' (ACOG) 2014 criteria: diagnosis of a sexually transmitted infection (STI), engagement in transactional sex work, intravenous drug use (IVDU), or incarceration and (2) modified 2021 Centers for Disease Control (CDC) criteria: diagnosis of bacterial STI (e.g., gonorrhea or syphilis) or transactional sex work. Risk factors associated with PrEP eligibility were evaluated using chi- square or Fischer's exact tests for categorical variables and t-tests or Wilcoxon rank-sum tests for continuous variables. Multivariable regression was used to control for confounding covariates, defined as p < 0.10 on bivariate analysis. p < 0.05 was used to indicate statistical significance. RESULTS: A total of 132 individuals met inclusion criteria, of whom 101 (76.5%) were deemed eligible for PrEP by meeting one or more modified 2014 ACOG criteria: 42 (31.8%) were incarcerated or had one or more STIs, while 30 (22.7%) endorsed engaging in transactional sex work and 68 (58.6%) endorsed IVDU. Using modified 2021 CDC criteria, 37 (28%) met PrEP eligibility, with 12 (9.1%) diagnosed specifically with a bacterial STI and 30 (22.7%) engaging in transactional sex work. Only comorbid psychiatric illness was associated with an increased risk for PrEP eligibility based on 2014 criteria, which persisted after controlling for maternal race/ethnicity (aRR 1.52, 95% confidence interval [CI] 1.24-1.86), and 2021 criteria, which persisted after controlling for nulliparity (aRR 2.12, 95% CI 1.30-3.57). CONCLUSION: A significant number of pregnant people with OUD meet one or more criteria for PrEP, with comorbid psychiatric conditions increasing the risk of meeting criteria. KEY POINTS: · Comorbid psychiatric illness is significantly associated with high risk of PrEP eligibility.. · A large proportion of pregnant individuals with active OUD meet criteria for PrEP prescribing.. · Risk-based screening algorithms for PrEP eligibility have limitations..

A Critique of Automated Approaches to Code Facial Expressions: What Do Researchers Need to Know?

Facial expression recognition software is becoming more commonly used by affective scientists to measure facial expressions. Although the use of this software has exciting implications, there are persistent and concerning issues regarding the validity and reliability of these programs. In this paper, we highlight three of these issues: biases of the programs against certain skin colors and genders; the common inability of these programs to capture facial expressions made in non-idealized conditions (e.g., "in the wild"); and programs being forced to adopt the underlying assumptions of the specific theory of emotion on which each software is based. We then discuss three directions for the future of affective science in the area of automated facial coding. First, researchers need to be cognizant of exactly how and on which data sets the machine learning algorithms underlying these programs are being trained. In addition, there are several ethical considerations, such as privacy and data storage, surrounding the use of facial expression recognition programs. Finally, researchers should consider collecting additional emotion data, such as body language, and combine these data with facial expression data in order to achieve a more comprehensive picture of complex human emotions. Facial expression recognition programs are an excellent method of collecting facial expression data, but affective scientists should ensure that they recognize the limitations and ethical implications of these programs.

Unlocking foraminiferal genetic diversity on estuarine mudflats with eDNA metabarcoding.

Environmental biomonitoring is a prerequisite for efficient evaluation and remediation of ecosystem degradation due to anthropogenic pressure or climate change. Estuaries are key habitats subject to multiple anthropogenic and natural stressors. Due to these multiple stressors, the detection of anthropogenic pressure is challenging. The fact that abundant natural stressors often lead to negative quality assessments has been coined the "estuarine quality paradox". To solve this issue, the application of molecular approaches with successful bioindicators like foraminifera is promising. However, sampling protocols, molecular procedures and data analyses need to be validated before such tools can be routinely applied. We conducted an environmental DNA survey of estuarine mudflats along the French Atlantic coast, using a metabarcoding approach targeting foraminifera. Our results demonstrate that estuarine environments have only a few active OTUs dominating the community composition and a large stock of dormant or propagule stages. This last genetic diversity components constitute an important reservoir, with different species which can potentially develop in response to the temporal variability of the multiple stressors. In fact, different OTUs were dominant in the studied estuaries. Our statistical model shows that the physical and chemical characteristics of the sediment and the climatic conditions explain only 43 % of the community composition variance. This suggests that other, less easily quantifiable factors, such as the history and use of the estuaries or the ecological drift could play an important role as well. Environmental DNA biomonitoring opens new perspectives to better characterize the genetic diversity in estuaries.