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1.
J Physiol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264228

RESUMEN

Pannexin 1 (PANX1) is an ion and metabolite membrane channel and scaffold protein enriched in synaptic compartments of neurons in the central nervous system. In addition to a well-established link between PANX1 and synaptic plasticity, we recently identified a role for PANX1 in the regulation of dendritic spine stability. Notably, PANX1 and its interacting proteins are linked to neurological conditions involving dendritic spine loss. Understanding the dual role of PANX1 in synaptic function and morphology may help to shed light on these links. We explore potential mechanisms, including PANX1's interactions with postsynaptic receptors and cytoskeleton regulating proteins. Finally, we contextualize PANX1's dual role within neurological diseases involving dendritic spine and synapse dysfunction.

2.
Psychol Trauma ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073388

RESUMEN

OBJECTIVE: Pediatric traumatic injury (PTI) is associated with a high risk for psychiatric sequelae. Most trauma centers do not adequately address the emotional needs of children and their caregivers. Technology-based programs offer a low-cost and low-burden opportunity to track and potentially enhance families' emotional recovery following PTI. This feasibility pilot project was designed to examine caregivers' usage of and feedback on a text message-based symptom monitoring service. METHOD: Participants included 25 caregivers of PTI patients under age 12. Caregivers received up to four texts daily for 30 days postdischarge from the automated system: one symptom-based question to capture the current mental health status of the caregiver and child, respectively, and a corresponding educational tip each time a symptom was endorsed. Data analyses describe the number of questions to which caregivers responded on behalf of themselves and their children. A semistructured qualitative interview was used to assess caregivers' reactions and suggested improvements for the service. RESULTS: Almost all caregivers (91.1%) responded to at least one text message, and two thirds (66.6%) responded to over half of the messages. Themes from the qualitative interviews indicated that caregivers perceived the timing and content of the text messaging service facilitated their own and their child's emotional recovery following PTI. Caregivers suggested that the service could be improved by providing an option to interact directly with mental health care providers. CONCLUSIONS: Text message-based symptom monitoring services offer an opportunity to bridge the gap in mental health services during the acute recovery phase for families of traumatically injured children. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Mol Ther ; 32(7): 2094-2112, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38796704

RESUMEN

Sialidosis (mucolipidosis I) is a glycoprotein storage disease, clinically characterized by a spectrum of systemic and neurological phenotypes. The primary cause of the disease is deficiency of the lysosomal sialidase NEU1, resulting in accumulation of sialylated glycoproteins/oligosaccharides in tissues and body fluids. Neu1-/- mice recapitulate the severe, early-onset forms of the disease, affecting visceral organs, muscles, and the nervous system, with widespread lysosomal vacuolization evident in most cell types. Sialidosis is considered an orphan disorder with no therapy currently available. Here, we assessed the therapeutic potential of AAV-mediated gene therapy for the treatment of sialidosis. Neu1-/- mice were co-injected with two scAAV2/8 vectors, expressing human NEU1 and its chaperone PPCA. Treated mice were phenotypically indistinguishable from their WT controls. NEU1 activity was restored to different extent in most tissues, including the brain, heart, muscle, and visceral organs. This resulted in diminished/absent lysosomal vacuolization in multiple cell types and reversal of sialyl-oligosacchariduria. Lastly, normalization of lysosomal exocytosis in the cerebrospinal fluids and serum of treated mice, coupled to diminished neuroinflammation, were measures of therapeutic efficacy. These findings point to AAV-mediated gene therapy as a suitable treatment for sialidosis and possibly other diseases, associated with low NEU1 expression.


Asunto(s)
Dependovirus , Modelos Animales de Enfermedad , Terapia Genética , Vectores Genéticos , Mucolipidosis , Neuraminidasa , Animales , Dependovirus/genética , Terapia Genética/métodos , Mucolipidosis/terapia , Mucolipidosis/genética , Neuraminidasa/genética , Neuraminidasa/metabolismo , Ratones , Vectores Genéticos/genética , Vectores Genéticos/administración & dosificación , Humanos , Lisosomas/metabolismo , Ratones Noqueados , Transducción Genética , Expresión Génica
4.
Trials ; 25(1): 326, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38755688

RESUMEN

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. METHODS: RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. DISCUSSION: This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.


Asunto(s)
COVID-19 , Ensayos Clínicos Fase II como Asunto , Disfunción Cognitiva , Estudios Multicéntricos como Asunto , SARS-CoV-2 , Humanos , COVID-19/complicaciones , Disfunción Cognitiva/terapia , Disfunción Cognitiva/psicología , Disfunción Cognitiva/diagnóstico , Estudios Prospectivos , Síndrome Post Agudo de COVID-19 , Ensayos Clínicos Controlados Aleatorios como Asunto , Estimulación Transcraneal de Corriente Directa , Cognición , Resultado del Tratamiento , Terapia Cognitivo-Conductual/métodos , Calidad de Vida
5.
Cell Rep ; 43(5): 114117, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38630590

RESUMEN

Endoplasmic reticulum-plasma membrane (ER-PM) junctions mediate Ca2+ flux across neuronal membranes. The properties of these membrane contact sites are defined by their lipid content, but little attention has been given to glycosphingolipids (GSLs). Here, we show that GM1-ganglioside, an abundant GSL in neuronal membranes, is integral to ER-PM junctions; it interacts with synaptic proteins/receptors and regulates Ca2+ signaling. In a model of the neurodegenerative lysosomal storage disease, GM1-gangliosidosis, pathogenic accumulation of GM1 at ER-PM junctions due to ß-galactosidase deficiency drastically alters neuronal Ca2+ homeostasis. Mechanistically, we show that GM1 interacts with the phosphorylated N-methyl D-aspartate receptor (NMDAR) Ca2+ channel, thereby increasing Ca2+ flux, activating extracellular signal-regulated kinase (ERK) signaling, and increasing the number of synaptic spines without increasing synaptic connectivity. Thus, GM1 clustering at ER-PM junctions alters synaptic plasticity and worsens the generalized neuronal cell death characteristic of GM1-gangliosidosis.


Asunto(s)
Señalización del Calcio , Retículo Endoplásmico , Gangliósido G(M1) , Gangliosidosis GM1 , Receptores de N-Metil-D-Aspartato , Animales , Humanos , Ratones , Calcio/metabolismo , Membrana Celular/metabolismo , Espinas Dendríticas/metabolismo , Modelos Animales de Enfermedad , Retículo Endoplásmico/metabolismo , Gangliósido G(M1)/metabolismo , Gangliosidosis GM1/metabolismo , Gangliosidosis GM1/patología , Plasticidad Neuronal , Neuronas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/metabolismo , Masculino , Femenino
6.
Perspect Sex Reprod Health ; 56(2): 158-170, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38623631

RESUMEN

BACKGROUND: Transgender and gender diverse youth experience multiple disproportionate adverse sexual health outcomes. Sexual health education teaches knowledge, attitudes, and skills for promoting sexual health, including reducing risk for sexually transmitted infection, HIV acquisition, and unintended pregnancy. Provision of sexual health education may be protective, but research remains scarce. METHODS: We conducted a multi-stage thematic analysis of 33 in-depth interviews among transgender and gender diverse youth (ages 15-24) living in the southeastern United States on their sexual health education experiences. RESULTS: Our study participants described school-based sexual health education as unhelpful due to a lack of relevant information, inadequately prepared teachers, and a perceived negative tone toward sexuality. They reported relying on online sources of sexual health information, finding relevant content and community despite some limitations. Participants desired content and pedagogy that expands beyond binary and white-centric presentations of sexuality and gender and sought resources that provide relevant, accurate, and judgment-free information while holding positive framing around sexuality and gender. CONCLUSION: There is much work needed to improve the breadth, quality, and relevance of school-based sexual health education. Sexual health education can improve by strengthening critical media literacy skills of youth; raising staff cultural competency on gender, race, and sexual identity through training and supports; using culturally relevant and inclusive curricula; and partnering with community-based organizations. Transgender and gender diverse youth would benefit from sexual health education from multiple sources which is queer-friendly, affirms their existence, and provides information on gender, race, and sexuality in positive and expansive ways.


Asunto(s)
Educación Sexual , Personas Transgénero , Humanos , Adolescente , Femenino , Masculino , Educación Sexual/métodos , Personas Transgénero/psicología , Sudeste de Estados Unidos , Adulto Joven , Salud Sexual/educación , Conocimientos, Actitudes y Práctica en Salud , Investigación Cualitativa
7.
Health Educ J ; 83(1): 52-64, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38481968

RESUMEN

Objective: School Health Profiles (Profiles) is a national surveillance system operated by the US Centers for Disease Control and Prevention. A school-based system of surveys, Profiles monitors school health policies and practices in US states and other jurisdictions through questionnaires completed by school principals and lead health education teachers. This study used the Profiles principal survey to identify trends in US schools' implementation of diversity-related learning opportunities (i.e., opportunities to learn about people who are different from them) in secondary classroom and extracurricular settings. Methods: Logistic regression models using data from three cycles of School Health Profiles from 35 US states examined trends in the percentages of secondary schools offering students diversity-related learning opportunities in the following settings, each measured by using dichotomous yes/no response options: a) clubs; b) lessons in class; and c) special events (e.g., multicultural week, family night) sponsored by the school or community organisations. Results: During 2014-2018, no states experienced decreases in opportunities for students to learn about people who are different from them; most states demonstrated no significant change. Conclusion: Findings suggest efforts are needed to strengthen capacity for and prioritisation of policies, programmes, and practices promoting diversity and culturally relevant education in schools, and in turn, promote positive health and educational outcomes for youth.

8.
Chembiochem ; 25(8): e202400056, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38386898

RESUMEN

Enzymatic modifications of small molecules are a common phenomenon in natural product biosynthesis, leading to the production of diverse bioactive compounds. In polyketide biosynthesis, modifications commonly take place after the completion of the polyketide backbone assembly by the polyketide synthases and the mature products are released from the acyl-carrier protein (ACP). However, exceptions to this rule appear to be widespread, as on-line hydroxylation, methyl transfer, and cyclization during polyketide assembly process are common, particularly in trans-AT PKS systems. Many of these modifications are catalyzed by specific domains within the modular PKS systems. However, several of the on-line modifications are catalyzed by stand-alone proteins. Those include the on-line Baeyer-Villiger oxidation, α-hydroxylation, halogenation, epoxidation, and methyl esterification during polyketide assembly, dehydrogenation of ACP-bound short fatty acids by acyl-CoA dehydrogenase-like enzymes, and glycosylation of ACP-bound intermediates by discrete glycosyltransferase enzymes. This review article highlights some of these trans-acting proteins that catalyze enzymatic modifications of ACP-bound small molecules in natural product biosynthesis.


Asunto(s)
Sintasas Poliquetidas , Policétidos , Sintasas Poliquetidas/metabolismo , Proteína Transportadora de Acilo/química , Policétidos/química
9.
JGH Open ; 8(1): e13022, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38268959

RESUMEN

Background and Aim: Functional bowel disorders (FBDs), including irritable bowel syndrome (IBS) and others, are conditions without a physically identifiable etiology that, as a result, are difficult to treat. Alternatives to traditional medical interventions are needed because IBS patients require more of physician time and higher healthcare spending. The goal of this study was to determine the efficacy of alternative lifestyle interventions for patients with FBDs seen in an integrative medicine (IM) clinic at an academic medical center. Methods: We performed a retrospective chart review to determine whether patients with FBDs had improvement in symptoms following predominantly nutrition-based IM interventions that included recommendations for dietary supplements and elimination diets. We measured symptoms before and after intervention (average time between measurements 8.75 months) using a medical symptoms questionnaire (MSQ) commonly used to quantify symptom change in IM clinics. Results: Digestive tract symptoms, as measured by the MSQ, improved significantly in patients (n = 57) with FBDs following IM intervention. The MSQ Digestive Tract subtotal for FBD patients decreased from 10.2 (SD, 5.4) to 7.2 (SD, 5.2) (P < 0.001) after IM intervention. Conclusions: Patients in an IM clinic had improved digestive tract symptoms scores following IM intervention. Because nutrition-based interventions were the primary intervention recommended by IM providers, primary care physicians and gastroenterologists may wish to consider referring FBD patients to registered dietitian-nutritionists (RDNs) skilled in implementing elimination diets.

10.
Psychol Trauma ; 16(3): 504-512, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37166922

RESUMEN

OBJECTIVE: Violent injuries have become increasingly more common in the United States. Individuals experiencing violent injury are at increased risk for the development of posttraumatic stress disorder (PTSD) as compared to those experiencing nonviolent injury. Social support is touted as a protective factor against various psychiatric symptoms (i.e., PTSD), though little is known about the relation between PTSD symptoms and social support in traumatic injury populations. The aims of the present paper were twofold: (1) examine the prevalence of PTSD as a function of injury type (2) explore differences in levels of social support as a function of injury type and (3) explore the association between injury type and later PTSD symptoms as moderated by baseline social support. METHOD: Participants were 553 adults from a level-one trauma center in the Southeast United States who experienced a violent injury or nonviolent injury and completed measures of social support at baseline as well as PTSD symptoms at the 30-day follow-up timepoint. The study utilized data from both the baseline timepoint (i.e., upon admission to the trauma surgery unit), as well as a 30-day follow-up timepoint. RESULTS: Results demonstrated that those endorsing nonviolent injury reported lower levels of social support and PTSD symptoms. Social support predicted later PTSD symptoms until injury type was included as a covariate in the model. Social support did not moderate the relationship between injury type and later PTSD symptoms. CONCLUSIONS: Findings highlight the interrelatedness of key risk variables (i.e., injury type) with protective factors in influencing the trajectory of psychopathology postinjury. Violence intervention and interruption programs may have the capacity to fill patient needs when social support networks are insufficient. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Trastornos por Estrés Postraumático , Adulto , Humanos , Trastornos por Estrés Postraumático/psicología , Apoyo Social , Agresión , Violencia , Sudeste de Estados Unidos/epidemiología
11.
J Trauma Acute Care Surg ; 96(4): 650-657, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37339343

RESUMEN

BACKGROUND: Few studies have examined mental health symptom trajectories and engagement in mental health follow-up in relation to mechanism of injury. This study examined differences in engagement between survivors of nonviolent and violent injury in the Trauma Resilience and Recovery Program (TRRP), a stepped-care, technology-enhanced model that provides evidence-based mental health screening and treatment to patients admitted to our Level I trauma service. METHODS: This study analyzed data from 2,527 adults enrolled in TRRP at hospital bedside between 2018 and 2022, including 398 patients (16%) with a violent injury and 2,129 patients (84%) with a nonviolent injury. Bivariate and hierarchical logistic regression analyses examined relations between injury type (violent vs. nonviolent) engagement in TRRP and mental health symptoms at 30 day follow-up. RESULTS: Engagement in services at bedside was similar across survivors of violent and nonviolent traumatic injury. Patients with violent injury had higher levels of posttraumatic stress disorder and depressive symptoms 30 days postinjury but were less likely to engage in mental health screening. Among patients who screened positive for posttraumatic stress disorder and depression, patients with violent injury were more likely to accept treatment referrals. CONCLUSION: Patients with a violent traumatic injury have higher levels of mental health needs yet face greater barriers to accessing mental health services following their injury relative to those with a nonviolent injury. Effective strategies are needed to ensure continuity of care and access to mental health care to promote resilience and emotional and functional recovery. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.


Asunto(s)
Servicios de Salud Mental , Resiliencia Psicológica , Trastornos por Estrés Postraumático , Adulto , Humanos , Salud Mental , Agresión , Trastornos por Estrés Postraumático/psicología
12.
J Adolesc Health ; 74(4): 720-728, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38127017

RESUMEN

PURPOSE: To examine trends and racial and ethnic disparities in early adolescent suicidal thoughts and behaviors in the years immediately prior to the COVID-19 pandemic. METHODS: This study used pooled data from Centers for Disease Control and Prevention's middle school Youth Risk Behavior Survey (n = 127,912) between 2015 and 2019. Three dichotomized measures of suicide-related behaviors were assessed: suicidal thoughts, planning, and attempts. Weighted prevalence estimates with 95% confidence intervals were calculated for each survey year. Linear trends examined disparities in the prevalence of suicidal thoughts and behaviors, overall and by student demographic characteristics. Main effects odds ratios compared estimates among racial and ethnic minority adolescents with non-Hispanic White students, controlling for sex and grade. RESULTS: Significant linear increases were observed for the percentage of middle school students who reported seriously thinking about suicide (18.2%-22.3%), ever making a suicide plan (11.8%-14.7%), and ever attempting suicide (6.9%-9.3%). Racial and ethnic minority students, other than non-Hispanic Asian, showed higher odds of suicidal thoughts and behaviors compared with non-Hispanic White students. DISCUSSION: Findings indicate a need for comprehensive suicide prevention to address health equity and disparities in suicide-related behaviors among middle school-aged adolescents.


Asunto(s)
Conducta del Adolescente , Ideación Suicida , Humanos , Adolescente , Niño , Intento de Suicidio , Etnicidad , Pandemias , Grupos Minoritarios , Asunción de Riesgos , Estudiantes
13.
Cells ; 12(24)2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38132176

RESUMEN

In the skin, repeated incidents of ischemia followed by reperfusion can result in the breakdown of the skin and the formation of a pressure ulcer. Here we gently applied paired magnets to the backs of mice to cause ischemia for 1.5 h and then removed them to allow reperfusion. The sterile inflammatory response generated within 4 h causes a stage 1 pressure ulcer with an elevation of the gap junction protein Cx43 in the epidermis. If this process is repeated the insult will result in a more severe stage 2 pressure ulcer with a breakdown of the epidermis 2-3 days later. After a single pinch, the elevation of Cx43 in the epidermis is associated with the inflammatory response with an increased number of neutrophils, HMGB1 (marker of necrosis) and RIP3 (responsible for necroptosis). Delivering Cx43 specific antisense oligonucleotides sub-dermally after a single insult, was able to significantly reduce the elevation of epidermal Cx43 protein expression and reduce the number of neutrophils and prevent the elevation of HMGB1 and RIP3. In a double pinch model, the Cx43 antisense treatment was able to reduce the level of inflammation, necroptosis, and the extent of tissue damage and progression to an open wound. This approach may be useful in reducing the progression of stage 1 pressure ulcers to stage 2.


Asunto(s)
Proteína HMGB1 , Úlcera por Presión , Ratones , Animales , Conexina 43/metabolismo , Conexinas/metabolismo , Isquemia
14.
bioRxiv ; 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-38014061

RESUMEN

Sialidosis is a glycoprotein storage disease caused by deficiency of the lysosomal sialidase NEU1, which leads to pathogenic accumulation of sialylated glycoproteins and oligosaccharides in tissues and body fluids. The disease belongs to the group of orphan disorders with no therapy currently available. Here, we have tested the therapeutic potential of AAV-mediated gene therapy for the treatment of sialidosis in a mouse model of the disease. One-month-old Neu1 -/- mice were co-injected with two scAAV2/8 vectors, expressing NEU1 and its chaperone PPCA, and sacrificed at 3 months post-injection. Treated mice were phenotypically indistinguishable from their WT controls. Histopathologically, they showed diminished or absent vacuolization in cells of visceral organs, including the kidney, as well as the choroid plexus and other areas of the brain. This was accompanied by restoration of NEU1 activity in most tissues, reversal of sialyl-oligosacchariduria, and normalization of lysosomal exocytosis in the CSF and serum of treated mice. AAV injection prevented the occurrence of generalized fibrosis, which is a prominent contributor of disease pathogenesis in Neu1 -/- mice and likely in patients. Overall, this therapeutic strategy holds promise for the treatment of sialidosis and may be applicable to adult forms of human idiopathic fibrosis with low NEU1 expression.

15.
J Neurochem ; 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38014645

RESUMEN

As the COVID-19 pandemic persists, SARS-CoV-2 infection is increasingly associated with long-term neurological side effects including cognitive impairment, fatigue, depression, and anxiety, colloquially known as "long-COVID." While the full extent of long-COVID neuropathology across years or even decades is not yet known, we can perhaps take direction from long-standing research into other respiratory diseases, such as influenza, that can present with similar long-term neurological consequences. In this review, we highlight commonalities in the neurological impacts of influenza and COVID-19. We first focus on the common potential mechanisms underlying neurological sequelae of long-COVID and influenza, namely (1) viral neurotropism and (2) dysregulated peripheral inflammation. The latter, namely heightened peripheral inflammation leading to central nervous system dysfunction, is emerging as a shared mechanism in various peripheral inflammatory or inflammation-associated diseases and conditions. We then discuss historical and modern examples of influenza- and COVID-19-associated cognitive impairment, depression, anxiety, and fatigue, revealing key similarities in their neurological sequelae. Although we are learning that the effects of influenza and COVID differ somewhat in terms of their influence on the brain, as the impacts of long-COVID grow, such comparisons will likely prove valuable in guiding ongoing research into long-COVID, and perhaps foreshadow what could be in store for individuals with COVID-19 and their brain health.

16.
Channels (Austin) ; 17(1): 2253102, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37807670

RESUMEN

Many neurological conditions exhibit synaptic impairments, suggesting mechanistic convergence. Additionally, the pannexin 1 (PANX1) channel and signaling scaffold is linked to several of these neurological conditions and is an emerging regulator of synaptic development and plasticity; however, its synaptic pathogenic contributions are relatively unexplored. To this end, we explored connections between synaptic neurodevelopmental disorder and neurodegenerative disease susceptibility genes discovered by genome-wide association studies (GWASs), and the neural PANX1 interactome (483 proteins) identified from mouse Neuro2a (N2a) cells. To identify shared susceptibility genes, we compared synaptic suggestive GWAS candidate genes amongst autism spectrum disorders, schizophrenia, Parkinson's disease, and Alzheimer's disease. To further probe PANX1 signaling pathways at the synapse, we used bioinformatics tools to identify PANX1 interactome signaling pathways and protein-protein interaction clusters. To shed light on synaptic disease mechanisms potentially linking PANX1 and these four neurological conditions, we performed additional cross-analyses between gene ontologies enriched for the PANX1 synaptic and disease-susceptibility gene sets. Finally, to explore the regional specificity of synaptic PANX1-neurological condition connections, we identified brain region-specific elevations of synaptic PANX1 interactome and GWAS candidate gene set transcripts. Our results confirm considerable overlap in risk genes for autism spectrum disorders and schizophrenia and identify potential commonalities in genetic susceptibility for neurodevelopmental disorders and neurodegenerative diseases. Our findings also pinpointed novel putative PANX1 links to synaptic disease-associated pathways, such as regulation of vesicular trafficking and proteostasis, warranting further validation.


Asunto(s)
Conexinas , Proteínas del Tejido Nervioso , Enfermedades Neurodegenerativas , Animales , Ratones , Biología Computacional , Conexinas/genética , Conexinas/metabolismo , Estudio de Asociación del Genoma Completo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo
17.
J Sch Health ; 93(12): 1061-1069, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37867403

RESUMEN

BACKGROUND: COVID-19 screening testing (ST) can detect asymptomatic or pre-symptomatic cases, allowing for prompt identification of cases and close contacts. This study examined parents' and school staffs' knowledge and attitudes toward to a pilot school-based ST program in a school district in southern Arizona. METHODS: In May 2021, online surveys to parents and school staff were administered to examine attitudes toward ST and impacts of the COVID-19 pandemic. Unweighted percent estimates were calculated, and bivariate differences were examined by demographics. Associations were assessed using chi-square tests and logistic regression. RESULTS: The survey had response rates of 10% (606/6085) and 22% (187/849) among parents and staff, respectively. Approximately one-third of responding parents (35%) would or already allow their child to participate in school-based ST, 37% would not participate; 28% were unsure. Among responding staff, 46% would or already participate in ST, 33% would not; 21% were unsure. The top concern (38%) among responding staff was taking job-related leave if testing positive. CONCLUSION: Schools work to balance the needs of students, families, and staff by implementing supportive and flexible policies and practices founded on buy-in and acceptance from their communities.


Asunto(s)
COVID-19 , Niño , Humanos , Estados Unidos , COVID-19/diagnóstico , COVID-19/epidemiología , Pandemias , Instituciones Académicas , Prueba de COVID-19 , Padres
18.
J Pediatr Psychol ; 48(11): 960-969, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37794767

RESUMEN

OBJECTIVE: Over 120,000 U.S. children are hospitalized for traumatic injury annually, a major risk factor for behavioral health problems such as acute/posttraumatic stress disorder (PTSD) and depression. Pediatric trauma centers (PTCs) are well positioned to address the recent mandate by the American College of Surgeons Committee on Trauma to screen and refer for behavioral health symptoms. However, most PTCs do not provide screening or intervention, or use varying approaches. The objective of this mixed-methods study was to assess PTCs' availability of behavioral health resources and identify barriers and facilitators to service implementation following pediatric traumatic injury (PTI). METHODS: Survey data were collected from 83 Level I (75%) and Level II (25%) PTC program managers and coordinators across 36 states. Semistructured, qualitative interviews with participants (N = 24) assessed the feasibility of implementing behavioral health education, screening, and treatment for PTI patients and caregivers. RESULTS: Roughly half of centers provide behavioral health screening, predominantly administered by nurses for acute stress/PTSD. Themes from qualitative interviews suggest that (1) service provision varies by behavioral health condition, resource, delivery method, and provider; (2) centers are enthusiastic about service implementation including screening, inpatient brief interventions, and follow-up assessment; but (3) require training and lack staff, time, and funding to implement services. CONCLUSIONS: Sustainable, scalable, evidence-based service models are needed to assess behavioral health symptoms after PTI. Leadership investment is needed for successful implementation. Technology-enhanced, stepped-care approaches seem feasible and acceptable to PTCs to ensure the availability of personalized care while addressing barriers to sustainability.


Asunto(s)
Problema de Conducta , Trastornos por Estrés Postraumático , Humanos , Niño , Estados Unidos , Estudios de Seguimiento , Centros Traumatológicos , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/etiología
19.
J Am Coll Surg ; 237(6): 810-825, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37815166

RESUMEN

BACKGROUND: Annually, over 600,000 adults served in US trauma centers (≥20%) develop posttraumatic stress disorder (PTSD) and/or depression in the first year after injury. American College of Surgeons guidelines include screening and addressing mental health recovery in trauma centers. Yet, many trauma centers do not monitor and address mental health recovery, and it is a priority to learn how to implement evidence-informed mental health programs in trauma centers. STUDY DESIGN: This report describes our application of the Exploration, Preparation, Implementation, Sustainment model to implement the Trauma Resilience and Recovery Program (TRRP) in 3 Level I and II trauma centers to address patients' mental health needs. TRRP is a scalable and sustainable stepped model of care-one of the few in the US-that provides early intervention and direct services after traumatic injury. RESULTS: Trauma centers are well positioned to accelerate patients' mental health recovery via early identification, education, screening, and referrals to mental health agencies that provide best-practice care. We found that TRRP was acceptable to the 3 partnering trauma centers we studied. Early engagement of patient, provider, and hospital administration stakeholders enhanced buy-in during the early stages of the implementation process and promoted sustainability. Active processes to support monitoring, evaluation, and adaptation were critical. CONCLUSIONS: Our work demonstrates the feasibility of implementing and adapting TRRP, a cost-efficient and sustainable stepped care intervention, in Level I and II trauma centers. Several factors should be carefully considered by trauma centers seeking to integrate behavioral health interventions into their trauma program.


Asunto(s)
Trastornos por Estrés Postraumático , Adulto , Humanos , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/diagnóstico , Salud Mental
20.
J Sch Health ; 93(9): 788-798, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37670599

RESUMEN

BACKGROUND: School-based health education can provide students with learning experiences that improve knowledge, attitudes, and perceptions (KAP) and behaviors regarding physical activity and nutrition. METHODS: We conducted a 2-phase systematic review. Phase 1 was a review of reviews (ie, systematic reviews or meta-analyses) that were published 2010-2018. Phase 2 was a search for individual articles published 2010-2020 addressing topics relevant to our review; we searched for articles that had not been part of a sufficiently relevant or recent review or that had been part of a review that concluded that too few articles were available to assert sufficient evidence. RESULTS: Forty-three studies were assessed: 20 randomized controlled trials and 23 quasi-experimental designs. Collectively, interventions had a favorable impact on students' PA and nutrition KAP, but behavioral and secondary outcome results (eg, body mass index) were mixed. CONCLUSIONS: Using the evidence-based health education strategies identified in this review can help contribute to improvements in students' KAP and behaviors.


Asunto(s)
Educación en Salud , Estado Nutricional , Humanos , Índice de Masa Corporal , Ejercicio Físico , Estudiantes
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