Engineered dityrosine-bonding of the RSV prefusion F protein imparts stability and potency advantages.

Viral fusion proteins facilitate cellular infection by fusing viral and cellular membranes, which involves dramatic transitions from their pre- to postfusion conformations. These proteins are among the most protective viral immunogens, but they are metastable which often makes them intractable as subunit vaccine targets. Adapting a natural enzymatic reaction, we harness the structural rigidity that targeted dityrosine crosslinks impart to covalently stabilize fusion proteins in their native conformations. We show that the prefusion conformation of respiratory syncytial virus fusion protein can be stabilized with two engineered dityrosine crosslinks (DT-preF), markedly improving its stability and shelf-life. Furthermore, it has 11X greater potency as compared with the DS-Cav1 stabilized prefusion F protein in immunogenicity studies and overcomes immunosenescence in mice with simply a high-dose formulation on alum.

Comparative effectiveness of a mindfulness-based intervention (M-Body) on depressive symptoms: study protocol of a randomized controlled trial in a Federally Qualified Health Center (FQHC).

BACKGROUND: Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city. METHODS: In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18-65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months. DISCUSSION: If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018.

Mindfulness and Valued Living in the Face of Racism­Related Stress.

Objectives: Racism-related stress is associated with significant mental health costs, necessitating the development of coping strategies to mitigate the negative sequelae. Mindfulness and valued living (MVL)-based strategies may be uniquely beneficial in addressing the negative effects of racism-related stress for people of color (POC) by decreasing internalized messages, while increasing self-compassion, coping flexibility, and engagement in values-based actions. It is imperative that clinicians applying or recommending MVL strategies to POC for coping with racism-related stress understand the complex nature of racism and, given that complexity, consider how MVL may need to be adapted to be effective. This paper offers guidance to clinicians seeking to use MVL strategies with clients of color to cope with racism-related stress. Methods: We provide a brief contextual literature review on the nature of racism, mental health impacts of racism-related stress for POC, and selected models of coping with racism-related stress. We also review existing mindfulness literature in relation to coping with racism-related stress, while offering considerations for adapting MVL strategies specifically for coping with racism-related stress. Results: Altogether, the research points to the promise of MVL strategies as beneficial interventions for coping with racism-related stress, although more research is warranted. We recommend that clinicians consider the suggestions outlined to present MVL strategies to clients in culturally responsive, validating ways. Conclusions: Further research is needed to evaluate links between MVL strategies and mental health, and to evaluate whether discrimination-specific adaptations are beneficial in mitigating the mental health impacts of racism-related stress.

Atención integral a una mujer con úlcera neoplásica latero cervical: un caso clínico en Atención Primaria / Comprehensive care for a woman with laterocervical neoplastic ulcer: a clinical case in primary care

El aumento de episodios oncológicos en la salud supone un incremento en las heridas de etiología neoplásica, las cuales tienen un abordaje diferente del de otro tipo de heridas. En el artículo se describe el caso clínico de una mujer de 71 años que presentaba una lesión neoplásica en la zona latero cervical derecha, a la que se le realizó un plan integral de cuidados de Enfermería con la intención de efectuar un abordaje holístico. La valoración permitió detectar un riesgo de baja autoestima situacional como diagnóstico enfermero, que fue abordado en el plan de cuidados junto a los problemas de colaboración: úlcera neoplásica latero cervical y dolor agudo secundario a la lesión neoplásica. Para el plan de cuidados se utilizaron las taxonomías NOC y NIC: Curación de la herida por segunda intención (NOC: 1103), Cuidados de las heridas (NIC: 3660) y Cuidado de las heridas: ausencia de cicatrización (NIC: 3664); Control del dolor (NOC: 1605) y Manejo del dolor (NIC: 1400); Aceptación: Estado de salud (NOC: 1300) y Apoyo emocional (NIC: 5270). Hasta la muerte de la paciente se cumplieron los objetivos generales de un abordaje terapéutico dirigidos a mejorar la calidad de vida del sujeto, optimizar su autoestima y su paz espiritual

The increase of oncological episodes in health represents an increase in the wounds with neoplastic etiology, which need a different approach from that used for other type of wounds. This article describes the clinical case of a 71-year-old woman who presented a neoplastic lesion in her right laterocervical area; a comprehensive Nursing Care plan was conducted with holistic approach as objective. Assessment allowed to detect the risk of situational low self-esteem as Nursing Diagnosis, which was addressed in the Nursing Plan alongside collaborative problems: laterocervical neoplastic ulcer and acute pain secondary to the neoplastic lesion. NOC and NIC taxonomies were used for the Care Plan: Wound healing: secondary intention (NOC: 1103), Wound care (NIC: 3660) and Wound care: Non-healing (NIC: 3664); Pain control (NOC: 1605) and Pain management (NIC: 1400); Acceptance: Health Status (NOC: 1300) and Emotional Support (NIC: 5270). Until the patient’s death, the general objectives were met regarding a treatment approach targeted to improving the patient’s quality of life, optimizing her self-esteem and her spiritual peace

Specification of select hypothalamic circuits and innate behaviors by the embryonic patterning gene dbx1.

The hypothalamus integrates information required for the production of a variety of innate behaviors such as feeding, mating, aggression, and predator avoidance. Despite an extensive knowledge of hypothalamic function, how embryonic genetic programs specify circuits that regulate these behaviors remains unknown. Here, we find that in the hypothalamus the developmentally regulated homeodomain-containing transcription factor Dbx1 is required for the generation of specific subclasses of neurons within the lateral hypothalamic area/zona incerta (LH) and the arcuate (Arc) nucleus. Consistent with this specific developmental role, Dbx1 hypothalamic-specific conditional-knockout mice display attenuated responses to predator odor and feeding stressors but do not display deficits in other innate behaviors such as mating or conspecific aggression. Thus, activity of a single developmentally regulated gene, Dbx1, is a shared requirement for the specification of hypothalamic nuclei governing a subset of innate behaviors. VIDEO ABSTRACT.

Omega-3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers.

SCOPE: Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity. However, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans. METHODS AND RESULTS: The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-wk randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465 mg eicosapentaenoic acid (EPA) + 375 mg docosahexaenoic acid (DHA)) at "low" (1/day, 900 mg) or "high" (4/day, 3600 mg) dose in healthy individuals (N = 60; age 18-45; BMI 18-30; 43% female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6 ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (p = 0.03) but not low-dose EPA + DHA compared to placebo. Although there was no statistically significant impact of EPA + DHA on individual inflammatory responses (tumor necrosis factor-α (TNF-α), IL-6, monocyte chemotactic protein (MCP-1), IL-1 receptor agonist (IL-1RA), IL-10, C-reactive protein (CRP), serum amyloid A (SAA)), there was a pattern of lower responses across all biomarkers with high-dose (nine of nine observed), but not low-dose EPA + DHA. CONCLUSION: EPA + DHA at 3600 mg/day, but not 900 mg/day, reduced fever and had a pattern of attenuated LPS induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.

Noncanonical autophagy promotes the visual cycle.

Phagocytosis and degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible for bulk degradation of cellular components, but its role in POS degradation is not well understood. We report that the morning burst of RPE phagocytosis coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated form. LC3 associated with single-membrane phagosomes containing engulfed POS in an Atg5-dependent manner that required Beclin1, but not the autophagy preinitiation complex. The importance of this process was verified in mice with Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing. These mice also exhibited decreased photoreceptor responses to light stimuli and decreased chromophore levels that were restored with exogenous retinoid supplementation. These results establish that the interplay of phagocytosis and autophagy within the RPE is required for both POS degradation and the maintenance of retinoid levels to support vision.

Spiritual interventions in psychotherapy: evaluations by highly religious clients.

Spiritual and religious interventions in psychotherapy have increasingly received research attention, particularly with highly religious clients. This study examined client opinions about and experiences with religious interventions in psychotherapy. A sample of 152 clients at a counseling center of a university sponsored by the Church of Jesus Christ of Latter-Day Saints (LDS) completed a survey with ratings of specific religious interventions concerning appropriateness, helpfulness, and prevalence. Out-of-session religious interventions were considered more appropriate by clients than in-session religious interventions, but in-session interventions were rated as more helpful. Specific interventions considered both appropriate and helpful by the LDS participants included referencing scriptural passages, teaching spiritual concepts, encouraging forgiveness, involving religious community resources, and conducting assessments of client spirituality. Some religious interventions were perceived as inappropriate or not helpful, and clients provided explanations for why religious interventions can be either effective or ineffective in psychotherapy.