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Despite advances in prevention and treatment, the transmission of human immunodeficiency virus remains a significant problem in the United States, especially among men who have sex with men (MSM). Alcohol use can promote risky sexual decisions, and alcohol expectancies may influence the role of alcohol in decision making. The present secondary analysis tests the moderating role of sexual alcohol expectancies (SAEs) in the relation between daily alcohol intoxication and sexual behavior in a sample of 248 moderate- to heavy-drinking MSM. SAEs were assessed with the Sexual Alcohol Expectancies Questionnaire at baseline, followed by two 23-day bursts of ecological momentary assessment including self-initiated morning assessments of sexual behavior and the prior night's perceived intoxication, as well as nine daily random alcohol assessments. Multilevel modeling showed that SAEs moderated a curvilinear association between intoxication and anal intercourse with a condom such that the relation between daily intoxication and anal intercourse with a condom is a more pronounced inverted u-shape among individuals with strong SAEs, and this moderation effect was not seen for condomless anal intercourse (CAI). While SAEs do appear to influence the association between intoxication and sexual behavior in MSM, they do not appear to moderate the association between alcohol intoxication and CAI.
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Non-catheter related arterial thromboembolism in the neonatal population is rare and carries a significant risk of organ damage or limb loss. Thrombolysis, whether systemic or catheter- directed, is reserved either for limb or life-threatening thrombosis due to risk of bleeding especially in premature neonates. In this case, an infant male born at 34 weeks and 4 days gestational age presented with limb-threatening clot in the distal right subclavian artery and proximal right axillary artery with no known cause. After discussion of risks and benefits of various treatment options, he received thrombolysis treatment with low dose recombinant TPA via an umbilical artery catheter. There was complete resolution of the thrombus with this treatment and the patient had no significant bleeding while receiving treatment. Further investigation is needed to identify the patient population that will benefit from catheter-directed thrombolytic therapy and how to best monitor these patients.
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Fibrinolíticos , Trombosis , Recién Nacido , Humanos , Masculino , Trombosis/etiología , Terapia Trombolítica/efectos adversos , Catéteres/efectos adversos , Pierna/irrigación sanguínea , Resultado del TratamientoRESUMEN
Alpha-1 antitrypsin (AAT) is the canonical serine protease inhibitor of neutrophil-derived proteases and can modulate innate immune mechanisms through its anti-inflammatory activities mediated by a broad spectrum of protein, cytokine, and cell surface interactions. AAT contains a reactive methionine residue that is critical for its protease-specific binding capacity, whereby AAT entraps the protease on cleavage of its reactive centre loop, neutralises its activity by key changes in its tertiary structure, and permits removal of the AAT-protease complex from the circulation. Recently, however, the immunomodulatory role of AAT has come increasingly to the fore with several prominent studies focused on lipid or protein-protein interactions that are predominantly mediated through electrostatic, glycan, or hydrophobic potential binding sites. The aim of this review was to investigate the spectrum of AAT molecular interactions, with newer studies supporting a potential therapeutic paradigm for AAT augmentation therapy in disorders in which a chronic immune response is strongly linked.
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Apolipoproteínas/metabolismo , Caspasas/metabolismo , Proteínas del Sistema Complemento/metabolismo , Citocinas/metabolismo , alfa 1-Antitripsina/metabolismo , Sitios de Unión/genética , COVID-19/metabolismo , COVID-19/virología , Glicosilación , Humanos , Mutación , Unión Proteica , Dominios Proteicos , SARS-CoV-2/fisiología , alfa 1-Antitripsina/química , alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/metabolismoRESUMEN
Proper placental perfusion is essential for fetal exchange of oxygen, nutrients, and waste with the maternal circulation. Impairment of uteroplacental vascular function can lead to pregnancy complications, including preeclampsia and intrauterine growth restriction (IUGR). Potassium channels have been recognized as regulators of vascular proliferation, angiogenesis, and secretion of vasoactive factors, and their dysfunction may underlie pregnancy-related vascular diseases. Overexpression of one channel in particular, the small-conductance calcium-activated potassium channel 3 (SK3), is known to increase vascularization in mice, and mice overexpressing the SK3 channel (SK3(T/T) mice) have a high rate of fetal demise and IUGR. Here, we show that overexpression of SK3 causes fetal loss through abnormal placental vascularization. We previously reported that, at pregnancy day 14, placentas isolated from SK3(T/T) mice are smaller than those obtained from wild-type mice. In this study, histological analysis reveals that SK3(T/-) placentas at this stage have abnormal placental morphology, and microcomputed tomography shows that these placentas have significantly larger and more blood vessels than those from wild-type mice. To identify the mechanism by which these vascularization defects occur, we measured levels of vascular endothelial growth factor (VEGF), placental growth factor, and the soluble form of VEGF receptor 1 (sFlt-1), which must be tightly regulated to ensure proper placental development. Our data reveal that overexpression of SK3 alters systemic and placental ratios of the angiogenic factor VEGF to antiangiogenic factor sFlt-1 throughout pregnancy. Additionally, we observe increased expression of hypoxia-inducing factor 2α in SK3(T/-) placentas. We conclude that the SK3 channel modulates placental vascular development and fetal health by altering VEGF signaling.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Neovascularización Fisiológica , Placenta/metabolismo , Proteínas Gestacionales/metabolismo , Proteínas/metabolismo , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Femenino , Muerte Fetal , Retardo del Crecimiento Fetal/metabolismo , Proteínas de la Membrana , Ratones , Placenta/irrigación sanguínea , Placenta/diagnóstico por imagen , Factor de Crecimiento Placentario , Preeclampsia/metabolismo , Embarazo , Transducción de Señal , Microtomografía por Rayos XRESUMEN
BACKGROUND: Hazardous drinking has been associated with chronic pain in community and medical samples. The purpose of this study was to develop a novel, integrated mobile health intervention that improves pain management and reduces hazardous drinking that may be implemented in primary care settings. METHODS: Forty-eight participants with moderate or greater chronic pain and hazardous drinking were recruited from primary care clinics and through social media sites. Following baseline assessment, participants were randomized to a counselor-supported smartphone app intervention (INTV) or a counselor delivered treatment-as-usual control condition (CTL). RESULTS: Results supported the feasibility and acceptability of the smartphone app intervention. Participants found it easy to use, reported high levels of satisfaction, and showed high levels of engagement with the app. Between-group effect size estimates at follow-up showed small effects for the intervention on pain ratings. However, using clinically meaningful change thresholds of 30% and 50% improvement in pain scores, 38% and 25% respectively of those in the INTV condition showed reductions compared to 20% and 12.5% respectively in the CTL condition. Effect size estimates did not indicate intervention superiority on alcohol outcomes as participants in both conditions showed considerable reductions in drinking over the course of the study. CONCLUSIONS: Results supported the view that a mobile health intervention delivered via smartphone with electronic coaching is a feasible and acceptable method of addressing chronic pain among those who engage in hazardous drinking. Future work should test the efficacy of this approach in a fully powered trial.
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Dolor Crónico , Consejeros , Telemedicina , Humanos , Dolor Crónico/terapia , Etanol , Proyectos PilotoRESUMEN
Research supports abnormal inhibitory visual motion processing in adults with remitted and current depression, but all studies to date have used paradigms with simple grating stimuli. Global motion processing, where multiple motion signals must be integrated, has not been explored in depression, nor have inhibitory processes within that domain. Depressed participants (n = 46) and healthy controls (n = 28) completed a direction discrimination task featuring a random dot pattern stimulus. Various signal (rightward or leftward dots) to noise (dots with randomly assigned directions) ratios modulated task difficulty. Metrics of global center surround suppression and facilitation were calculated. Accuracy in the baseline condition (i.e., no surrounding annulus) was not significantly different between depressed and healthy participants. Global center surround suppression and facilitation were not significantly different between healthy and depressed participants overall. When limiting the sample to unmedicated individuals, depressed participants (n = 27) showed a reduced global center surround suppression effect compared to controls, and there was no difference in global center surround facilitation. While global motion processing is intact in depression, abnormal center surround suppression effects in depression do extend to global motion stimuli. These alterations may be mitigated by the psychotropic medications taken by some subjects in our depressed sample. Future studies should explore the mechanisms underlying these effects.
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Benchmarking , Depresión , Adulto , Humanos , Estado de Salud , Voluntarios Sanos , Movimiento (Física)RESUMEN
BACKGROUND: Treatment trials for borderline personality disorder (BPD) have consistently demonstrated that approaches that are diagnostically tailored are superior to those which are not. Currently, gold standard treatments for BPD are highly intensive, lengthy, and specialized, leading to a critical gap between the supply and demand of effective, evidence-based treatment for patients who receive a diagnosis of BPD. Psychoeducation, which is a common component of most treatments known to be effective, is a low-cost, low-burden intervention proven to relieve symptoms. The present study builds on psychoeducation research, assessing online video prescriptions as a means of disseminating information patients need to know about their diagnosis and care. METHODS: This article presents the study protocol for a safety, feasibility, and preliminary efficacy trial of psychoeducational video prescriptions and online assessment with feedback for newly diagnosed individuals with BPD. We aim to recruit 100 adults recently diagnosed with BPD to be randomly assigned to receive videos about BPD or videos about non-BPD mental health topics that are matched in length in the first step of the study. All participants will complete daily surveys about their emotions, interpersonal interactions, and behaviors, as well as self-report assessments and cognitive tests at 4 different time points. Half of the participants in the intervention group will receive feedback on their symptom ratings and cognitive test performance to assess whether there is incremental value in tailoring this online set of interventions with individualized feedback unique to each participant. This study aims to assess the effects of BPD-focused psychoeducational videos with and without personalized feedback, on BPD and depressive symptom severity as well as core mechanisms of the disorder such as loneliness, rejection sensitivity, cognitive control difficulties, and self-clarity. Results will inform efforts to progress to a larger, more definitive trial. TRIAL REGISTRATION: Clinical trials registration: The protocol is registered with ClinicalTrials.gov NCT05358925.
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Trastorno de Personalidad Limítrofe , Adulto , Humanos , Trastorno de Personalidad Limítrofe/diagnóstico , Trastorno de Personalidad Limítrofe/terapia , Trastorno de Personalidad Limítrofe/psicología , Proyectos Piloto , Resultado del Tratamiento , Relaciones Interpersonales , Autoinforme , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: HIV transmission remains a significant health concern for men who have sex with men (MSM) in the United States. Heavy episodic drinking (HED) is related to increased rates of condomless anal intercourse (CAI) among MSM, though evidence suggests that this association may vary by individual difference factors. The present secondary analysis tested whether sexual alcohol expectancies (SAEs) moderate the associations between frequency of HED and anal intercourse (AI) with and without a condom among moderate-to-heavy drinking HIV- MSM. METHODS: Two hundred and forty-eight moderate-to-heavy drinking MSM completed self-report questionnaires including the Sexual Behavior Questionnaire, the Modified Daily Drinking Questionnaire, and the Sexual Alcohol Expectancies Questionnaire. RESULTS: Negative binomial regressions indicated that SAEs moderated the association between frequency of HED and AI with a condom, but not between the frequency of HED and condomless AI (CAI). CONCLUSIONS: These results suggest that stronger SAEs play a role in alcohol-related sexual behavior among MSM, but do not provide evidence that SAEs are associated with increased risk for HIV transmission through CAI.
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How do we resolve conflicting ideas about how to protect our health during a pandemic? Prior knowledge influences our decisions, potentially creating implicit cognitive conflict with new, correct information. COVID-19 provides a natural condition for investigating how an individual's health-specific knowledge (e.g., understanding mask efficacy) and their personal context (e.g., outbreak proximity) influence their protective health behavior endorsement, as information about the virus, its spread, and lethality has changed over time. Using a dual-process-model framework, we investigated the role cognitive conflict has on health decision-making. We used a computer mouse-tracking paradigm alongside geographical information systems (GIS) as a proxy for context. The results support a contextualized-deficit-model framework in which relevant knowledge and context-based factors help individuals override cognitive conflict to make more preventative health decisions. Findings from this study may provide evidence for a more effective way for experts to combat non-adherence due to conflicting health information.
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Face recognition is impaired in autism spectrum disorders (ASDs), but the reason for this remains unclear. One possibility is that impairments in the ability to visually detect faces might be a factor. As a preliminary study in this vein, we measured face detection ability as a function of visual contrast level in 13 individuals with ASD, aged 13-18, and 18 neurotypical controls (NCs) in the same age range. We also measured contrast sensitivity, using sinusoidal grating stimuli, as a control task. Individuals with ASD did not differ from controls in face detection (p > 0.9) or contrast detection (p > 0.2) ability. Performance on contrast and face detection was significantly correlated in ASD but not in NC. Results suggest that the ability to visually detect faces is not altered in ASD overall, but that alterations in basic visual processing may affect face detection ability in some individuals with ASD.
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Non-invasive respiratory support (NRS) outside of the ICU has played an important role in the management of COVID-19 pneumonia. There is little data to guide selection of NRS modality. We present outcomes of NRS outside the ICU and discuss the effects of NRS on gas exchange with implications for management.