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1.
Clin Exp Emerg Med ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39026449

ABSTRACT

Objective: Family presence during resuscitation (FPDR) is known as part of family-centered care. However, it is unknown or how physicians are educated for FPDR. We aim to review the current status of simulation related FPDR for physicians and medical students. Methods: A scoping review of literature published from 1999 to May 5 2023 and written in English was undertaken. The articles were searched for using keyword combinations of the following words; family, resuscitation, and simulation-related words. Results: Eight articles were included in the final review. This review of FPDR simulation for physicians and medical students revealed findings in three categories; measuring CPR quality, investigating participant responses after FPDR simulation, and extracting exemplar good communication elements. First, in four studies measuring resuscitation quality, physicians participated in adult resuscitation, and resuscitation quality was reduced with overt reaction family presence. Second, in three studies investigating the response to simulation training, interprofessional teams participating in pediatric resuscitation had negative responses to FPDR simulation. Third, in one study, good communication elements during FPDR were found in infant simulation, in which interprofessional teams participated. FPDR simulation training for medical students has not been reported. Conclusion: It highlighted a gap in FPDR simulations involving physicians and/or medical students. Physicians were more concerned with resuscitation quality than supporting families during resuscitation simulations. Medical students should be considered as the main participants for FPDR simulation. More high-evidence studies with interprofessional teams including physicians and/or medical students are needed to evaluate curriculum design and participant response changes following FPDR simulation.

3.
J Biol Chem ; : 107580, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025452

ABSTRACT

Protein-protein interactions with high specificity and low affinity are functionally important but are not comprehensively understood because they are difficult to identify. Particularly intriguing are the dynamic and specific interactions between folded protein domains and short unstructured peptides known as short linear motifs (SLiMs). Such domain-motif interactions (DMIs) are often difficult to identify and study because affinities are modest to weak. Here we describe "electrophoretic crosslinking shift assay" (ECSA), a simple in vitro approach that detects transient, low affinity interactions by covalently crosslinking a prey protein and a fluorescently labeled bait. We demonstrate this technique on the well characterized DMI between MAP kinases and unstructured D-motif peptide ligands. We show that ECSA detects sequence-specific micromolar interactions using less than a microgram of input prey protein per reaction, making it ideal for verifying candidate low-affinity DMIs of components that purify with low yield. We propose ECSA as an intermediate step in SLiM characterization that bridges the gap between high throughput techniques such as phage display and more resource-intensive biophysical and structural analysis.

4.
JAMA Netw Open ; 7(7): e2419976, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38958977

ABSTRACT

Importance: Little is known about whether concurrent use of tobacco and cannabis is associated with higher or lower levels of mental health problems than use of either substance alone among youths. Objective: To examine the association between concurrent use of tobacco and cannabis and mental health problems in a national sample of US youths. Design, Setting, and Participants: This cross-sectional study analyzed publicly available wave 6 data within the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative cohort study of US youths aged 14 to 17 years, collected from March to November 2021. This analysis used wave 6 single-wave weights to obtain statistically valid estimates for cross-sectional analyses generalizable to the wave 4 cohort sample. Data were analyzed from November 15, 2023, to April 20, 2024. Exposure: Past 30-day use of any tobacco and cannabis products was self-reported and categorized into 4 exclusive patterns: concurrent, tobacco only, cannabis only, and nonuse. Main Outcomes and Measures: Self-reported past-year internalizing and externalizing mental health problems were measured using the modified version of the Global Appraisal of Individual Needs-Short Screener and separately categorized into 3 levels: low (0-1 symptoms), moderate (2-3 symptoms), and high (≥4 symptoms). Results: A total of 5585 youths were included in the study, with a weighted proportion of 51.3% being male and 72.5% aged 15 to 17 years. In terms of race and ethnicity, 1606 youths (25.7%) were Hispanic, 626 (12.7%) were non-Hispanic Black, 2481 (50.5%) were non-Hispanic White, and 555 (11.0%) were non-Hispanic other. The prevalence of concurrent use (3.4% [95% CI, 2.9%-4.0%]) was comparable to tobacco-only use (3.9% [95% CI, 3.2%-4.6%]), but greater than cannabis-only use (2.5% [95% CI, 2.1%-2.9%]). High levels of internalizing and externalizing problems were most common for the concurrent use group (internalizing: 47.4% [95% CI, 39.2%-55.9%]; externalizing: 61.6% [95% CI, 54.1%-68.7%]), followed by the cannabis-only use group (internalizing: 44.8% [95% CI, 35.7%-54.1%]; externalizing: 48.5% [95% CI, 39.1%-57.9%]), the tobacco-only use group (internalizing: 41.4% [95% CI, 33.7%-49.5%]; externalizing: 46.3% [95% CI, 38.3%-54.5%]), and the nonuse group (internalizing: 22.4% [95% CI, 21.1%-23.8%]; externalizing: 30.4% [95% CI, 28.9%-31.9%]). After controlling for covariates in ordinal logistic regression models, concurrent use of tobacco and cannabis was associated with greater odds of reporting higher levels of externalizing problems compared with tobacco-only use (adjusted odds ratio [AOR], 1.83 [95% CI, 1.15-2.91]) and cannabis-only use (AOR, 1.85 [95% CI, 1.11-3.06]). However, there were no statistically significant differences in the odds of internalizing problems between concurrent use and use of tobacco or cannabis alone. Conclusions and Relevance: In this cross-sectional study of the PATH Study wave 6 youth data, concurrent use of tobacco and cannabis was linked to higher levels of externalizing mental health problems than use of single substances, indicating a potential need to combine mental health support with tobacco and cannabis cessation interventions for youths.


Subject(s)
Mental Disorders , Humans , Adolescent , Male , Female , Cross-Sectional Studies , United States/epidemiology , Mental Disorders/epidemiology , Cohort Studies
5.
Childs Nerv Syst ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39030337

ABSTRACT

INTRODUCTION: Myelomeningocele (MMC) is the most common neural tube defect, but rarely seen in premature infants. Most centers advocate for closure of MMC within 24 h of birth. However, this is not always possible in severely premature infants. Given the rarity of this patient population, we aimed to share our institutional experience and outcomes of severely premature infants with MMC. METHODS: We performed a retrospective, observational review of premature infants (≤ 32 weeks gestational age) identified through our multidisciplinary spina bifida clinic (1995-2021) and surgical logs. Descriptive statistics were compiled about this sample including timing of MMC closure and incidence of adverse events such as sepsis, CSF diversion, meningitis, and death. RESULTS: Eight patients were identified (50% male) with MMC who were born ≤ 32 weeks gestational age. Mean gestational age of the population was 27.3 weeks (SD 3.5). Median time to MMC closure was 1.5 days (IQR = 1-80.8). Five patients were taken for surgery within the recommended 48 h of birth; 2 patients underwent significantly delayed closure (107 and 139 days); and one patient's defect epithelized without surgical intervention. Six of eight patients required permanent cerebrospinal fluid (CSF) diversion (2 patients were treated with ventriculoperitoneal shunting (VPS), three were treated with endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and 1 patient treated with ETV; mean of 3 years after birth, ranging from 1 day to 16 years). Two patients required more than one permanent CSF diversion procedure. Two patients developed sepsis (defined as meeting at least 2/4 SIRS criteria). In both cases of sepsis, patients developed signs and symptoms more than 72 h after birth. Notably, both instances of sepsis occurred unrelated to operative intervention as they occurred before permanent MMC closure. Two patients had intraventricular hemorrhage (both grade III). No patients developed meningitis (defined as positive CSF cultures) prior to MMC closure. Median follow up duration was 9.7 years. During this time epoch, 3 patients died: Two before 2 years of age of causes unrelated to surgical intervention. One of the two patients with grade III IVH died within 24 h of MMC closure. CONCLUSIONS: In our institutional experience with premature infants with MMC, some patients underwent delayed MMC closure. The overall rate of meningitis, sepsis, and mortality for preterm children with MMC was similar to MMC patients born at term.

6.
JSES Int ; 8(4): 756-762, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39035644

ABSTRACT

Background: Intramedullary nail fixation for proximal humerus fractures has been shown to provide satisfactory results. The quality of reduction correlates with clinical outcomes, the rate of complications, avascular necrosis, and postoperative loss of fixation. The purpose of this study was to evaluate the clinical outcomes and complications of 2-part proximal humerus fractures compared to 3- or 4-part proximal humerus fractures. Methods: A single-center retrospective review was carried out of patients who underwent an intramedullary nail for a proximal humerus fracture by one of three surgeons between the years of 2009 and 2022, and who had a minimum of 12-months follow-up. Fracture pattern, American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation score, satisfaction, pain score, range of motion, and complications were recorded. The mechanism of injury (high energy vs. low energy), method of reduction (open vs. percutaneous), and evidence of radiographic healing were assessed. A P value of <.05 was considered to be statistically significant. Results: The study included 78 patients (62 female, 16 male). The number of patients in each group (2-part, N = 32 vs. 3- or 4-part, N = 46), mean age (2-part, 64 vs. 3- or 4-part,61), follow-up (2-part, 42.5 months vs. 3- or 4-part, 34.5 months), injury type (2-part, 88% low energy vs. 3- or 4-part, 78% low energy), and method of reduction (2-part, 81% percutaneous vs. 3- or 4-part 72% percutaneous) were similar among the two groups. There was fracture union in all patients. All patients demonstrated satisfactory patient-reported outcome measures. However, 2-part fractures did have a significantly lower pain score, higher Single Assessment Numeric Evaluation score, and higher percentage of patients being satisfied or very satisfied when compared to 3- or 4-part fractures. The rate of subsequent procedures was 13% (n = 4) in 2-part fractures compared to 19% (n = 9) in 3- or 4-part fractures but was not statistically significant (P = .414). The overall rate of conversion to arthroplasty was 3.2% in 2-part fractures and 10.4% in 3- or 4-part fractures. Conclusion: Multipart proximal humerus fractures remain difficult to treat. However, this study demonstrates an overall acceptable outcome with improvement in range of motion, patient-reported outcomes, and similar complication rates between 2-part and 3- or 4-part proximal humerus fractures treated with an intramedullary nail. However, the improvement in certain parameters is not as marked in 3- or 4-part fractures as 2-part fractures.

7.
Arch Sex Behav ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039340

ABSTRACT

Substance-involved rape is increasing among college students, particularly women (Koss et al., 2022). Addressing rape requires first measuring it accurately in surveys to understand its true scope and nature. We used cognitive interviews with 40 young adults to qualitatively test the construct validity of an alcohol- and other drugs (AOD)-involved rape item in the Sexual Experiences Survey by asking participants to comment on different operationalizations of this construct. Our findings revealed that different phrasings elicited different interpretations of the items by participants. Specifically, the results indicated that (1) respondents viewed the different operationalizations as a sequence of events with varying severity; (2) some participants focused on the intentionality and responsibility of the perpetrator as opposed to opportunistic perpetration; and (3) study participants consistently chose one of the operationalizations as describing "being roofied" (being drugged without consent). Participants also contributed additional scenarios not described in the questionnaire and shared their interpretations of the items. The results underscore the importance of refining survey language to properly measure AOD-involved rape and allow us to understand how to tailor appropriate questions for best comprehension. The findings indicate the benefit in including several items about AOD-involved rape in questionnaires such as the Sexual Experiences Survey, with each item addressing different scenarios of victim intoxication. The results could also have important implications for sexual violence prevention programs, which should discuss consent, intentions, and responsibility specifically in the context of AOD consumption.

8.
Equine Vet J ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994580

ABSTRACT

BACKGROUND: Prioritising equine welfare, making evidenced-based policy, and consistent decision-making across sports are crucial to maintaining the social licence for equestrian sport. Regulations on the use of omeprazole during competition differ; all regulators argue that their rules prioritise welfare. This discrepancy is a matter of concern to the public and equestrian stakeholders. OBJECTIVES: To apply Campbell's Ethical Framework for the use of Horses in Sport to the question: 'Should the use of omeprazole be allowed during equestrian competition?' STUDY DESIGN: A desk-based ethico-legal study. METHODS: Campbell's Ethical Framework for the Use of Horses in Sport was applied in a stepwise fashion: definition of the ethical question; analysis of the evidence base; consideration of stakeholders' interests; harm:benefit analysis; application of the three central tenets of the framework, and formulation of conclusions and recommendations. RESULTS: Stakeholders in equine sports have a variety of (frequently conflicting) interests; all of them share an interest in optimising equine welfare. The incidence of EGUS in competition horses is high. Omeprazole is a cornerstone treatment. There are currently discrepancies in regulation about the use of omeprazole during competitions. Recent evidence suggests that withholding omeprazole treatment for two clear days before competition allows the recurrence of squamous EGUS, whereas withholding treatment on the day of competition only does not have that effect. MAIN LIMITATIONS: The current state of scientific knowledge about the use of omeprazole in horses. The analysis did not consider possible health and thus welfare effects of the out-of-competition treatment with omeprazole. CONCLUSIONS: Based on recent scientific evidence, if horses are being treated with omeprazole outside of competition then treatment on the day of competition should be permitted on welfare grounds. Revision of regulations around the use of omeprazole during competition by governing bodies is necessary to safeguard the ethical use of horses in sport.


CONTEXTO: Priorizar o bem­estar equino, elaborar políticas baseadas em evidências e tomar decisões consistentes em todos os esportes são cruciais para manter a licença social para o esporte equestre. As regulamentações sobre o uso de omeprazol durante a competição diferem; todos os reguladores argumentam que suas regras priorizam o bem­estar. Essa discrepância é motivo de preocupação para o público. OBJETIVOS: Aplicar o Modelo Ético de Campbell para o Uso de Cavalos em Esportes1 à pergunta: 'Deve o uso de omeprazol ser permitido durante a competição equestre?' DESENHO DO ESTUDO: Um estudo ético­legal baseado em pesquisa documental. METODOLOGIA: O Modelo Ético de Campbell para o Uso de Cavalos em Esportes1 foi aplicado de forma gradual: definição da questão ética; análise da base de evidências; consideração dos interesses do público alvo; uma análise de dano:benefício; aplicação dos três princípios centrais do modelo; e formulação de conclusões e recomendações. RESULTADOS: O público de esporte equino têm uma variedade de interesses (frequentemente conflitantes), enquanto todos compartilham o interesse em otimizar o bem­estar equino. A incidência de EGUS (Síndrome da Úlcera Gástrica Equina) em cavalos de competição é alta, a qual o omeprazol é um tratamento fundamental. Atualmente, há discrepâncias na regulamentação sobre o uso de omeprazol durante competições. Evidências recentes sugerem que a suspensão do tratamento com omeprazol por 2 dias antes da competição permite a recorrência da EGUS da porção escamosa, enquanto a suspensão do tratamento apenas no dia da competição não tem esse efeito. PRINCIPAIS LIMITAÇÕES: O estado atual do conhecimento científico sobre o uso de omeprazol em cavalos. A análise não considerou possíveis efeitos sobre a saúde e, portanto, sobre o bem­estar do tratamento com omeprazol fora da competição. CONCLUSÕES: Com base em evidências científicas recentes, se os cavalos estão sendo tratados com omeprazol fora da competição, o tratamento no dia da competição deve ser permitido por razões de bem­estar. A revisão das regulamentações sobre o uso de omeprazol durante a competição pelos órgãos reguladores é necessária para salvaguardar o uso ético dos cavalos no esporte.

9.
Fam Syst Health ; 42(2): 290-291, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38990672

ABSTRACT

The author presents a short story about doctors listening to patients and remaining committed to to their patients health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

10.
Front Neurosci ; 18: 1415575, 2024.
Article in English | MEDLINE | ID: mdl-39010943

ABSTRACT

Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch's membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting light-sensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors.

11.
Elife ; 132024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990208

ABSTRACT

Rare early-onset lower urinary tract disorders include defects of functional maturation of the bladder. Current treatments do not target the primary pathobiology of these diseases. Some have a monogenic basis, such as urofacial, or Ochoa, syndrome (UFS). Here, the bladder does not empty fully because of incomplete relaxation of its outflow tract, and subsequent urosepsis can cause kidney failure. UFS is associated with biallelic variants of HPSE2, encoding heparanase-2. This protein is detected in pelvic ganglia, autonomic relay stations that innervate the bladder and control voiding. Bladder outflow tracts of Hpse2 mutant mice display impaired neurogenic relaxation. We hypothesized that HPSE2 gene transfer soon after birth would ameliorate this defect and explored an adeno-associated viral (AAV) vector-based approach. AAV9/HPSE2, carrying human HPSE2 driven by CAG, was administered intravenously into neonatal mice. In the third postnatal week, transgene transduction and expression were sought, and ex vivo myography was undertaken to measure bladder function. In mice administered AAV9/HPSE2, the viral genome was detected in pelvic ganglia. Human HPSE2 was expressed and heparanase-2 became detectable in pelvic ganglia of treated mutant mice. On autopsy, wild-type mice had empty bladders, whereas bladders were uniformly distended in mutant mice, a defect ameliorated by AAV9/HPSE2 treatment. Therapeutically, AAV9/HPSE2 significantly ameliorated impaired neurogenic relaxation of Hpse2 mutant bladder outflow tracts. Impaired neurogenic contractility of mutant detrusor smooth muscle was also significantly improved. These results constitute first steps towards curing UFS, a clinically devastating genetic disease featuring a bladder autonomic neuropathy.


Subject(s)
Dependovirus , Disease Models, Animal , Gene Transfer Techniques , Glucuronidase , Urinary Bladder , Animals , Mice , Humans , Urinary Bladder/physiopathology , Glucuronidase/genetics , Glucuronidase/metabolism , Dependovirus/genetics , Genetic Therapy/methods , Genetic Vectors , Intestinal Pseudo-Obstruction/genetics , Intestinal Pseudo-Obstruction/therapy , Intestinal Pseudo-Obstruction/physiopathology , Urologic Diseases , Facies
12.
Sci Transl Med ; 16(756): eadm8842, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018366

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.


Subject(s)
Disease Models, Animal , Heart Failure , Myocytes, Cardiac , Stroke Volume , Animals , Heart Failure/drug therapy , Heart Failure/physiopathology , Heart Failure/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Stroke Volume/drug effects , Rats, Inbred WKY , Rats , Male , Humans , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/antagonists & inhibitors , Diastole/drug effects , Tubulin/metabolism , Myocardium/pathology , Myocardium/metabolism , Obesity/drug therapy , Obesity/physiopathology
13.
Osteoporos Int ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39020092

ABSTRACT

A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.

14.
Psychon Bull Rev ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020241

ABSTRACT

Temporal Binding (TB) is the subjective compression of action-effect intervals. While the effects of nonsocial actions are highly predictable, it is not the case when interacting with conspecifics, who often act under their own volition, at a time of their choosing. Given the relative differences in action-effect predictability in non-social and social interactions, it is plausible that TB and its properties differ across these situations. To examine this, in two experiments, we compared the time course of TB in social and nonsocial interactions, systematically varying action-effect intervals (200-2,100 ms). Participants were told they were (a) interacting with another person via a live webcam, who was in fact a confederate (social condition), (b) interacting with pre-recorded videos (nonsocial condition), or (c) observing two pre-recorded videos (control condition; Experiment 2). Results across experiments showed greater TB for social compared to nonsocial conditions, and the difference was proportional to the action-effect intervals. Further, in Experiment 1, TB was consistently observed throughout the experiment for social interactions, whereas nonsocial TB decreased from the first to the second half of the experiment. In Experiment 2, the nonsocial condition did not differ from control, whereas the social condition did, exhibiting enhanced binding. We argue these results suggest that the sociality of an interaction modulates the 'internal clock' of time perception.

15.
Sci Rep ; 14(1): 16086, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38992064

ABSTRACT

The classical amyloid cascade hypothesis postulates that the aggregation of amyloid plaques and the accumulation of intracellular hyperphosphorylated Tau tangles, together, lead to profound neuronal death. However, emerging research has demonstrated that soluble amyloid-ß oligomers (SAßOs) accumulate early, prior to amyloid plaque formation. SAßOs induce memory impairment and disrupt cognitive function independent of amyloid-ß plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SAßO (E3) nanobody generated from an alpaca immunized with SAßO. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SAßOs and amyloid-ß plaques. The E3 nanobody traverses across the blood-brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SAßO and amyloid-ß plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SAßOs are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SAßO nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer's disease.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Plaque, Amyloid , Single-Domain Antibodies , Animals , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/immunology , Single-Domain Antibodies/immunology , Single-Domain Antibodies/chemistry , Mice , Plaque, Amyloid/metabolism , Alzheimer Disease/metabolism , Humans , Brain/metabolism , Brain/pathology , Blood-Brain Barrier/metabolism , Mice, Transgenic , Camelids, New World , Disease Models, Animal
16.
NPJ Digit Med ; 7(1): 176, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956410

ABSTRACT

AI-enabled ECGs have previously been shown to accurately predict patient sex in adults and correlate with sex hormone levels. We aimed to test the ability of AI-enabled ECGs to predict sex in the pediatric population and study the influence of pubertal development. AI-enabled ECG models were created using a convolutional neural network trained on pediatric 10-second, 12-lead ECGs. The first model was trained de novo using pediatric data. The second model used transfer learning from a previously validated adult data-derived algorithm. We analyzed the first ECG from 90,133 unique pediatric patients (aged ≤18 years) recorded between 1987-2022, and divided the cohort into training, validation, and testing datasets. Subgroup analysis was performed on prepubertal (0-7 years), peripubertal (8-14 years), and postpubertal (15-18 years) patients. The cohort was 46.7% male, with 21,678 prepubertal, 26,740 peripubertal, and 41,715 postpubertal children. The de novo pediatric model demonstrated 81% accuracy and an area under the curve (AUC) of 0.91. Model sensitivity was 0.79, specificity was 0.83, positive predicted value was 0.84, and the negative predicted value was 0.78, for the entire test cohort. The model's discriminatory ability was highest in postpubertal (AUC = 0.98), lower in the peripubertal age group (AUC = 0.91), and poor in the prepubertal age group (AUC = 0.67). There was no significant performance difference observed between the transfer learning and de novo models. AI-enabled interpretation of ECG can estimate sex in peripubertal and postpubertal children with high accuracy.

19.
Psychol Trauma ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976387

ABSTRACT

OBJECTIVE: Bisexual women experience higher rates of sexual assault (SA) and posttrauma distress compared to monosexual women. We examined the patterns of reactions to SA disclosure (positive and two types of negative) and bisexual minority stress (antibisexual stigma from heterosexual and lesbian/gay people, internalized binegativity) experienced by young bisexual women who experienced adult SA. We also examined differences in assault-related experiences, posttraumatic stress disorder and depression symptoms, and hazardous drinking based on the identified patterns. METHOD: The current sample was drawn from two parent samples of women and included survivors who had disclosed an adult SA: (a) n = 149 bisexual women (98% cisgender, ages 18-35, 87.9% White) recruited via Amazon's Mechanical Turk and (b) n = 81 cisgender bisexual women (ages 18-25, 84% White) recruited via online ads. Latent profile analyses and analyses of variance were conducted. RESULTS: Analyses identified four latent profiles characterized by: (a) low stigmatizing responses, (b) high negative SA disclosure reactions, (c) high antibisexual stigma, and (d) highest stigmatizing responses. The fourth profile had higher posttraumatic stress disorder and depression symptoms and hazardous drinking compared to the other profiles. CONCLUSIONS: Results suggest women in the profile characterized by highest negative reactions to SA disclosure and highest bisexual minority stress (antibisexual stigma and internalized binegativity) may experience greatest distress postassault. Results highlight the importance for researchers, policymakers, and clinicians to consider and address both SA-related and identity-related stigma among bisexual survivors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

20.
Adv Radiat Oncol ; 9(7): 101514, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38948917

ABSTRACT

Purpose: The attack by Hamas on Israeli civilians (October 7, 2023) triggered the ongoing war, which could be detrimental to cancer care in general and radiation therapy (RT) in particular. To assure continuity of care within the Radiation Oncology Department of Samson Assuta Ashdod University Hospital (SAAUH), which borders on Gaza, patient-centric measures were redoubled by our institution. This study describes the impact of these measures on patients' perception and their willingness to continue RT, despite fear of war. Methods and Materials: A survey questionnaire was designed to detect changes in attitude and treatment adherence during war. It was offered to the patients undergoing RT at SAAUH. A Pearson correlation between the items relating to desire to continue the therapy was calculated. Smallest space analysis was conducted to illustrate the association between the variables. Results: Forty-seven patients enrolled in this study reported a significantly lower feeling of personal safety during wartime in comparison with the confidence in the professionalism of the staff (paired samples t test, t(43) = 4.61; P < .001). Simultaneously, patients perceived that the impact of the national situation on their health was very low (mean of 1.59 on a scale of 1-6). Both the Pearson correlation test and smallest space analysis revealed that the desire to continue treatment in general and to continue treatment at the same department were significantly related to trust in the staff's professionalism. Conclusions: Fear of war can pose a major pitfall in providing daily RT care. This obstacle may be potentially overridden by creating deep, trusting relationships between the patients and the medical staff.

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