Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia.

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower than those of AML without deletion 7/7q, this observation was not significant. Low ASNS expression correlated with improved overall survival (46 versus 54 weeks, respectively, p = 0.011), whereas higher ASNS levels were associated with better response to venetoclax-based therapy. Protein correlation analysis demonstrated association between ASNS and proteins involved in methylation and DNA repair. In conclusion, while ASNS expression was not lower in patients with deletion 7/7q as initially predicted, ASNS levels were highly variable across AML patients. Further studies are needed to assess whether patients with low ASNS expression are susceptible to asparaginase-based therapy due to their inability to augment compensatory ASNS expression upon asparagine depletion.

Oligodendrocyte-selective deletion of the eIF2α kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.

After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. Oligodendrocyte (OL) loss and white matter damage drive functional consequences and determine recovery potential after thoracic contusive SCI. We examined acute (<48 h post-SCI) and chronic (6 weeks post-SCI) effects of conditionally deleting Perk from OLs prior to SCI. While Perk transcript is expressed in many types of cells in the adult spinal cord, its levels are disproportionately high in OL lineage cells. Deletion of OL-Perk prior to SCI resulted in: (1) enhanced acute phosphorylation of eIF2α, a major PERK substrate and the critical mediator of the integrated stress response (ISR), (2) enhanced acute expression of the downstream ISR genes Atf4, Ddit3/Chop, and Tnfrsf10b/Dr5, (3) reduced acute OL lineage-specific Olig2 mRNA, but not neuronal or astrocytic mRNAs, (4) chronically decreased OL content in the spared white matter at the injury epicenter, (5) impaired hindlimb locomotor recovery, and (6) reduced chronic epicenter white matter sparing. Cultured primary OL precursor cells with reduced PERK expression and activated ER stress response showed: (1) unaffected phosphorylation of eIF2α, (2) enhanced ISR gene induction, and (3) increased cytotoxicity. Therefore, OL-Perk deficiency exacerbates ISR signaling and potentiates white matter damage after SCI. The latter effect is likely mediated by increased loss of Perk-/- OLs.

Computer vision for automated seizure detection and classification: A systematic review.

Computer vision (CV) shows increasing promise as an efficient, low-cost tool for video seizure detection and classification. Here, we provide an overview of the fundamental concepts needed to understand CV and summarize the structure and performance of various model architectures used in video seizure analysis. We conduct a systematic literature review of the PubMed, Embase, and Web of Science databases from January 1, 2000 to September 15, 2023, to identify the strengths and limitations of CV seizure analysis methods and discuss the utility of these models when applied to different clinical seizure phenotypes. Reviews, nonhuman studies, and those with insufficient or poor quality data are excluded from the review. Of the 1942 records identified, 45 meet inclusion criteria and are analyzed. We conclude that the field has shown tremendous growth over the past 2 decades, leading to several model architectures with impressive accuracy and efficiency. The rapid and scalable detection offered by CV models holds the potential to reduce sudden unexpected death in epilepsy and help alleviate resource limitations in epilepsy monitoring units. However, a lack of standardized, thorough validation measures and concerns about patient privacy remain important obstacles for widespread acceptance and adoption. Investigation into the performance of models across varied datasets from clinical and nonclinical environments is an essential area for further research.

Brief virtual intervention associated with increased social engagement and decreased negative affect among people aging with HIV.

Virtual Villages-online communities that deliver supports to promote aging in place-are proposed to mitigate isolation and support the health of aging populations. Using a community-engaged approach, we developed and pilot-tested a Virtual Village intervention tailored for people living with HIV (PLWH) aged 50+ . The intervention employed a Discord server featuring social interaction, regional and national resources, expert presentations, and mindful meditation exercises. In 2022, a sample of PLWH aged 50+ from three U.S. study sites participated in a four-week pilot. Pre- and post-intervention surveys assessed participants' demographic characteristics; degree of loneliness, social connectedness, HIV-related stigma, and technology acceptance; mental wellbeing and physical health outcomes; and user experience. Participants (N = 20) were socioeconomically and racially/ethnically diverse, aged 51-88 years, and predominantly identified as gay or bisexual men (75%). Paired t-tests revealed a significant increase in participants' mean social engagement scores and a significant decrease in participants' mean negative affect scores, following the intervention. User experience scores were acceptable and participants reported a positive sense of connectedness to the Virtual Village community. Results suggest that a virtual community can be accessible to older PLWH and may enhance social engagement and improve aspects of mental wellbeing.

A community-academic partnered approach to designing a Virtual Village to address the needs of older adults living with HIV.

ABSTRACTMany older adults living with HIV face unique challenges, including comorbidities, loneliness, and isolation. This community-academic partnered study elicited viewpoints from older adults living with HIV about the characteristics of a digital environment ("Virtual Village") to combat against loneliness and isolation. We utilized Choice-Based Conjoint Analyses to determine preferred attributes of a Virtual Village. We also conducted focus groups and interviews with older adults living with HIV and used an iterative, data-driven approach to systematically identify emergent themes. Participants (N = 82) were aged 50-82 years and racially/ethnically diverse. The majority were men (78%), gay (66%), and lived with HIV for ≥15 years (83%). Cost was the factor that most drove participants' preference for joining a Virtual Village. Thematic concerns included lack of technological confidence, internet access, potential for harassment in digital environments, privacy, and preference for in-person interactions. Praises centered on convenience and making connections across geographic distances. Participants emphasized the need for purposive strategies to form a cohesive and supportive community for older adults living with HIV. A moderated environment was recommneded to create a safe, structured, and comfortable digital environment for older adults living with HIV. A Virtual Village should be viewed as a bridge to in-person interactions.

Economic and social determinants of health care utilization during the first wave of COVID-19 pandemic among adults in Ghana: a population-based cross-sectional study.

BACKGROUND: The COVID-19 pandemic had socioeconomic effects in Africa. This study assessed the social and economic determinants of healthcare utilization during the first wave of COVID-19 among adults in Ghana. METHODS: Information about individuals residing in Ghana was derived from a survey conducted across multiple countries, aiming to evaluate the impact of the COVID-19 pandemic on the mental health and overall well-being of adults aged 18 and above. The dependent variable for the study was healthcare utilization (categorized as low or high). The independent variables were economic (such as financial loss, job loss, diminished wages, investment/retirement setbacks, and non-refunded travel cancellations) and social (including food scarcity, loss of financial support sources, housing instability, challenges affording food, clothing, shelter, electricity, utilities, and increased caregiving responsibilities for partners) determinants of health. A multinomial logistic regression was conducted to identify factors associated with healthcare utilization after adjusting for confounders (age, gender, access to medical insurance, COVID-19 status, educational background, employment, and marital status of the participants). RESULTS: The analysis included 364 responses. Individuals who encountered a loss of financial support (AOR: 9.58; 95% CI: 3.44-26.73; p < 0.001), a decrease or loss of wages (AOR: 7.44, 95% CI: 3.05-18.16, p < 0.001), experienced investment or retirement setbacks (AOR: 10.69, 95% CI: 2.60-43.88, p = 0.001), and expressed concerns about potential food shortages (AOR: 6.85, 95% CI: 2.49-18.84, p < 0.001) exhibited significantly higher odds of low healthcare utilization during the initial phase of the pandemic. Contrastingly, participants facing challenges in paying for basic needs demonstrated lower odds of low healthcare utilization compared to those who found it easy to cover basic expenses (AOR: 0.19, 95% CI: 0.06-0.67, p = 0.001). CONCLUSION: Economic and social factors were associated with low healthcare utilization in Ghana during the first wave of the pandemic. Investment or retirement loss and financial support loss during the pandemic had the largest effect on healthcare utilization. Further research is needed to understand the connection between concerns about food shortages, welfare losses during pandemics and healthcare utilization during pandemics in Ghana.

Prenatal hydrocolpos: imaging findings and differential diagnosis.

Prenatal hydrocolpos is characterized by fluid distension of the vagina. Hydrocolpos can be caused by multiple underlying etiologies and often demonstrates overlapping imaging features compared to other cystic abdominal and pelvic lesions. The purpose of the current pictorial essay is to provide a systematic prenatal magnetic resonance imaging (MRI) approach to differentiating the primary etiologies leading to hydrocolpos. After discussing the fundamental embryological processes involved in vaginal development, the current essay discusses the most common causes of hydrocolpos with their associated prenatal and postnatal imaging features. An approach to distinguishing the more common differential diagnoses is provided. Given the implications of parental counseling and postnatal management, this essay provides an important approach for narrowing differential diagnoses based on prenatal imaging.

Treatment of Chronic Insomnia in Adults.

Insomnia affects 30% of the U.S. population, with 5% to 15% meeting criteria for chronic insomnia. It can negatively impact quality of life, decrease productivity, increase fatigue and drowsiness, and put patients at higher risk of developing other health problems. Initial treatment focuses on nonpharmacologic therapies such as cognitive behavior therapy, which improves negative thought patterns and behaviors through sleep restriction, stimulus control, and relaxation techniques. Other nonpharmacologic treatments include exercise, mindfulness, and acupuncture. If these approaches are ineffective, pharmacologic agents may be considered. Medications such as benzodiazepines and Z-drugs are often prescribed for insomnia but should be avoided, if possible, due to short- and long-term risks associated with their use. Melatonin receptor agonists are safer and well tolerated but have limited effectiveness. Dual orexin receptor antagonists are effective in patients who have sleep maintenance insomnia or difficulty with sleep onset. Evidence for the use of antihistamines to treat insomnia is generally lacking, but doxylamine is effective for up to four weeks.

Arrhythmias and Sudden Cardiac Death.

Ventricular tachyarrhythmias remain a major cause of sudden cardiac arrest (SCA) that leads to sudden cardiac death (SCD). Primary prevention strategies to prevent SCD include promoting a healthy lifestyle, following United States Preventive Service Task Force recommendations related to cardiovascular disease, and controlling comorbid conditions. For a patient experiencing SCA, early cardiopulmonary resuscitation and defibrillation should be performed. Implantable cardioverter defibrillators are more effective at secondary prevention compared with drug therapy but medications such as amiodarone, beta-blockers, and sotalol may be helpful adjuncts to reduce the risk of SCD or improve a patient's symptoms (eg, palpitations and inappropriate defibrillator shocks).

Proteomics for optimizing therapy in acute myeloid leukemia: venetoclax plus hypomethylating agents versus conventional chemotherapy.

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, using machine learning algorithms, we determined a set of 14 proteins, among those 109, that were able to accurately recommend therapy, making it feasible for clinical application. Next, we identified a group of patients who did not benefit from either VH or CC and proposed target-based approaches to improve outcomes. Finally, we calculated that the clinical use of our proteomic strategy would have led to a change in therapy for 30% of patients, resulting in a 43% improvement in OS, resulting in around 2600 more cures from AML per year in the United States.

Proyecto Facil: Using the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) as a Diagnostic Tool to Improve Access to Human Immunodeficiency Virus Pre-Exposure Prophylaxis (PrEP) via Telemedicine.

Following the underutilization of pre-exposure prophylaxis (PrEP) among Latinx men who have sex with men (MSM) and transgender women in Southern California and the growing use of the delivery of PrEP through telemedicine, the California Department of Public Health implemented a telemedicine component to their already existing assistance program. We used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to identify and characterize factors inhibiting the successful implementation of the telemedicine program through in-depth, online stakeholder interviews and online community focus groups with Latinx MSM and trans women in southern California. Obstacles reported by stakeholders were complicated enrollment process, preference for in-person care, more appealing private sector models of PrEP, while community members reported low awareness of the program, fear of complications due to immigration status, challenges to fulfill enrollment requirements. Findings can used for the future improvement of the ongoing program, as well as other similar PrEP telemedicine programs.

Radiology Resident Ownership Scale (RROS): Adapting a Validated Measure of Patient Care Ownership to the Radiology Context.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a validated instrument to measure radiology residents' sense of psychological ownership of patient care. MATERIALS AND METHODS: A previously validated measure of patient care ownership was adapted through a two-step process of expert review and revision by six academic radiology faculty. An online, anonymous survey was distributed to 64 residents and fellows at the end of three consecutive four-week long rotations. We calculated Cronbach's α to determine the scale's internal consistency, performed exploratory factor analysis to identify possible subscales, and conducted bivariate and correlational analysis to establish construct validity. RESULTS: The 11-item ownership scale demonstrated good internal consistency (Cronbach's α = 0.93), and three subscales were identified corresponding to assertiveness, conscientiousness, and confidence/perceived competence. Sense of ownership was significantly associated with training level, prior experience in the type of rotation, stress, sleep, burnout, peer support, relationships with clinical staff, and recognition by department. We found no significant association between ownership and age, gender, type of rotation, site of rotation, type of residency, perceived interruption frequency, or remote work frequency. CONCLUSION: The radiology resident patient care ownership scale demonstrates good internal consistency and preliminary evidence of validity. After further validation, we expect the scale to be a valuable tool in evaluating interventions aimed at increasing radiology residents' sense of ownership.

Sleep disorder risk, perceived control over sleep, and mental health symptoms in paramedicine students.

Paramedics commonly experience both poor sleep and mental health symptoms. Clarifying whether sleep or mental health symptoms are a challenge prior to commencement of employment is important, as early prevention and intervention initiatives during training could support these workers. Paramedicine students (n=53) were included, with sleep disorder screening (obstructive sleep apnea, insomnia and restless legs syndrome), and mental health outcomes (depressive symptoms: Patient Health Questionnaire-9, and anxiety symptoms: General Anxiety Disorder-7). Data were analysed using robust regression models, adjusted for age, sex, and shift work status. Meeting criteria for a sleep disorder (n=21) was associated with higher scores for anxiety (8.2 [95% CI: 5.9-10.5] v 4.6, [3.4-5.8]) and depressive symptoms (11.1 [8.6-13.6] v 4.4 [3.1-5.7)] compared to those who did not meet the criteria for a sleep disorder (n=32). Depressive symptoms were lower in those with perceived control over sleep (5.2 [3.2-7.2] v 9.8 [7.7-11.8]). There was no interaction between sleep disorder risk and perceived control over sleep on mental health symptoms. Investigation and management of factors contributing to low perceived control over sleep, together with early screening and management of sleep disorders, are likely to be important priorities to support paramedic student wellbeing prior to commencing shift work.

Silencing long-descending inter-enlargement propriospinal neurons improves hindlimb stepping after contusive spinal cord injuries.

Spinal locomotor circuitry is comprised of rhythm generating centers, one for each limb, that are interconnected by local and long-distance propriospinal neurons thought to carry temporal information necessary for interlimb coordination and gait control. We showed previously that conditional silencing of the long ascending propriospinal neurons (LAPNs) that project from the lumbar to the cervical rhythmogenic centers (L1/L2 to C6), disrupts right-left alternation of both the forelimbs and hindlimbs without significantly disrupting other fundamental aspects of interlimb and speed-dependent coordination (Pocratsky et al., 2020). Subsequently, we showed that silencing the LAPNs after a moderate thoracic contusive spinal cord injury (SCI) resulted in better recovered locomotor function (Shepard et al., 2021). In this research advance, we focus on the descending equivalent to the LAPNs, the long descending propriospinal neurons (LDPNs) that have cell bodies at C6 and terminals at L2. We found that conditional silencing of the LDPNs in the intact adult rat resulted in a disrupted alternation of each limb pair (forelimbs and hindlimbs) and after a thoracic contusion SCI significantly improved locomotor function. These observations lead us to speculate that the LAPNs and LDPNs have similar roles in the exchange of temporal information between the cervical and lumbar rhythm generating centers, but that the partial disruption of the pathway after SCI limits the independent function of the lumbar circuitry. Silencing the LAPNs or LDPNs effectively permits or frees-up the lumbar circuitry to function independently.

Social media information and its association with the adoption of COVID-19 preventive measures in four Latin American countries.

Objective: The study aimed to assess the association between adherence to COVID-19 preventive measures and access to media information related to COVID-19. Methods: A multi-country, cross-sectional study using an online survey was conducted from June to December 2020. The sample included 1,457 participants from Argentina, Brazil, Chile, and Mexico. The outcome variable was self-reported adherence to preventive measures (handwashing, social distancing, self-isolation, use of face masks, and working from home). The explanatory variable was self-report of following media information related to COVID-19 (watching or reading the news, following social media coverage). Multivariable logistic regression analyses were conducted to determine the associations. Results: Following information on social media was positively associated with higher odds of practicing social distancing (AOR=5.39; 95%CI: 3.93-7.30), self-isolation (AOR=1.44; 95%CI: 1.08-1.92), use of face masks (AOR=16.84; 95%CI: 10.03-28.27), handwashing (AOR=6.95; CI 95%: 4.98-9.71), and working from home (AOR=1.85; 95% CI: 1.43-2.41). Differences in the use of social media for COVID-19 information were observed among the four countries. Conclusion: Following social media was positively associated with adherence to COVID-19 preventive measures in Latin America. Social media may be effectively used for COVID-19 behaviour modification in Latin America.

HPV vaccine acceptance is high among adults in Mexico, particularly in people living with HIV / Aceptación de la vacuna contra VPH es alta entre adultos en México, especialmente en personas con VIH

Abstract: Objective. To measure HPV vaccine acceptance in diverse Mexican adult popula­tions, taking into account HIV status. Materials and methods: A total of 1 329 men and women, with and without HIV, participated in one of three intervention studies, offering HPV vaccination, carried out in the states of Morelos, Tlaxcala and Mexico City; either the bivalent (Morelos n=103, Tlaxcala n=127) or quadrivalent HPV-vaccine (Mexico City n=1 099) was offered. Results: HPV vaccine was accepted by 80.3% of participants; acceptance was higher in people living with HIV than those without (84.4 vs. 78%, p=0.004). Women had greater HPV infection knowledge (p<0.0001) than men and slightly higher (p=0.4) vaccine acceptance. The main reason for vaccine non-acceptance among HIV-positive participants was their doctor recommended they not get vaccinated. Conclusion: Acceptance of HPV-vaccine was high in men and women regardless of HIV status. Even higher rates of acceptability may be achieved by educating healthcare providers to recommend HPV vaccine to their patients.

Resumen: Objetivo. Medir la aceptación de la vacuna de VPH en una muestra diversa de población adulta mexicana, teniendo en cuenta su estado de VIH. Material y métodos: 1 329 hombres y mujeres con y sin VIH participaron en tres estudios de intervención, realizados en los estados de Morelos, Tlaxcala y Ciudad de México. Se ofreció la vacuna bivalente (Morelos n=103, Tlaxcala n=127) o la cuadrivalente (Ciudad de México n=1 099) contra VPH. Resultados: La vacuna fue aceptada por 80.3% de los participantes; la aceptación fue mayor en personas que viven con VIH que en aquéllas que no (84.4 vs. 78%, p=0.004). Las mujeres (p<0.0001) tenían mayor conocimientos sobre VPH que los hombres y una aceptación de la vacuna ligeramente mayor (p=0.4). El motivo principal de la no aceptación de la vacuna entre personas con VIH fue que su médico recomendó que no se vacunaran. Conclusión: La aceptación de la vacuna contra el VPH fue alta en hombres y mujeres, independientemente del estado de VIH. Se pueden lograr mayores tasas de aceptabilidad educando a los proveedores de atención médica para que recomienden la vacuna contra el VPH a sus pacientes.

Healthcare professionals' awareness, knowledge, attitudes, perceptions and beliefs about Ebola at Gondar University Hospital, Northwest Ethiopia: a cross-sectional study

A poor understanding of Ebola Virus Disease (EVD) among Health Care Professionals (HCPs) may put our lives at risk. We aimed to assess the awareness, knowledge, attitudes, perceptions, beliefs of HCPs towards Ebola at Gondar University Hospital (GUH) in Northwest Ethiopia. We conducted a hospital based, cross-sectional survey among 245 randomly selected HCPs working at GUH from August-October, 2015. A validated, self-administered questionnaire was used to collect the data. We calculated descriptive statistics with P0.05 being statistically significant. Of the 245 participants, 211 (86.1%) completed the study. The majority had heard about EVD and used news media (62%) as a source of information. Still, many were afraid of getting EVD (56.4%; P=0.001). A significant number of HCPs thought EVD can cause paralysis like polio (45%) and can be treated with antibiotics (28.4%). In addition, 46.4% of the HCPs felt anger or fear towards Ebola infected patients (P=0.006). We identified poor knowledge and negative incorrect beliefs among doctors and allied health professionals. There is a need for intensive training for all HCPs reduce EVD risk