Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation. METHODS AND ANALYSIS: This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg-1 min-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test. ETHICS AND DISSEMINATION: The trial protocol was approved by the local Institutional Review Board (#20-30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.govNCT04901169.

Metabolism and gene sequence variation in Turicella otitidis implies its adaptability and pathogenicity in extra-otic infection: a systematic review.

Turicella otitidis belongs to the Corynebacteriaceae family and is a normal inhabitant of the ear and exists in a commensal relationship with its host. In children, T. otitidis is frequently associated with otitis media. The emergence of Turicella otitidis as a pathogen is concerning, particularly due to the limited availability of data on its pathogenic properties. The objective of this study is to conduct a systematic review of T. otitidis infections occurring in both the ear and other anatomical sites, and to summarize the differences in metabolism and genome sequences between isolates obtained from the ear and blood.

Coronary Artery Aneurysms as a Cause of Acute Coronary Syndrome Presentation - A Focused Review.

Coronary artery aneurysms (CAA) are defined as a dilation of a coronary vessel greater than 1.5 times the diameter of a local reference vessel. While CAAs tend to be incidental findings on imaging, they result in complications, such as thrombosis, embolization, ischemia, arrhythmias, and heart failure. Among symptomatic cases, chest pain has been the most common manifestation of CAAs. This necessitates an understanding of CAAs as a cause of acute coronary syndrome (ACS) presentation. However, due to the unclear pathophysiology of CAAs and their variable presentation complicated by similar ACS conditions, there is no clear strategy for CAA management. In this article, we will discuss the contribution of CAAs to ACS presentations and review the current management options for CAAs.

Relationship of health-related social needs and hospital readmissions in patients following a hospitalization for atrial fibrillation.

Atrial fibrillation (AF) has a high economic burden on the healthcare system with rehospitalizations as the most significant contributing factor necessitating an understanding of aspects related to hospitalizations to minimize economic costs and improve patient outcomes. Our study aims to assess whether all-cause 30-day hospital readmission following AF-specific hospitalization is associated with health-related social needs (HRSN) using the Nationwide Readmissions Database (NRD). All hospitalization data were abstracted from the 2015-2019 NRD, including hospitalizations for patients at least 18 years of age with a primary discharge diagnosis of AF. For each hospitalization, we identified secondary diagnoses for five HRSN domains including employment, family, housing, psychosocial, and socioeconomic status. Primary outcomes included all-cause 30-day readmission rates. Secondary outcomes included all-cause 90-day readmissions and diagnosis on readmissions. An estimated 1,807,460 index hospitalizations in the United States included a primary discharge diagnosis of AF. Of these, 97.3 % included a diagnosis in only one HRSN domain with the most frequently diagnosed HRSN domain being housing (54.5 %) followed by socioeconomic (29.4 %), family (10.0 %), employment (6.1 %), and psychosocial (2.8 %). Index hospitalizations that included any HRSN diagnosis had 2.2-times greater unadjusted odds of all-cause 30-day readmission (95 % CI: 2.1 to 2.3-times greater, p < .001). Index hospitalizations that included an HRSN diagnosis were associated with higher rates of 90-day readmission due to conduction disorder and COPD. In conclusion, there is a significant association between HRSN and hospital readmissions in patients with AF. Further research is required to explain the true nature of this relationship with a specific emphasis on housing insecurity.

Hypersensitivity Pneumonitis With and Without Autoimmune Features: A Clinical Comparative Analysis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by an immunological reaction to repeated inhalational exposure to antigens. The etiology and exact immunopathology are poorly understood. Autoimmunity overlapping with HP has been described but the role of concomitant autoimmunity in the clinical course and outcome of the HP is not clearly established. In this study, we examined patients diagnosed with HP and compare them to patients with concomitant HP and autoimmunity. METHODS: Patients were retrospectively screened from a single-center ILD registry. Patients > 18 years with an established multidisciplinary diagnosis of HP were included in the study. Patients with HP without autoimmune features and patients with HP with autoimmune features (HPAF) were assessed. We compared the demographics, clinical characteristics, treatment, and outcomes between the two groups. We used a Cox proportional hazards model to compare lung transplant-free survival outcomes of patients with HPAF to those with non-HPAF HP patients. RESULTS: Of 73 patients with HP, 43 were diagnosed with HPAF. Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to non-HPAF HP patients [48.8 vs 23.3%, p = 0.028, Crude odds ratio (cOR) = 3.14]. Symptomatically, those with HPAF reported a higher prevalence of arthritis as compared to non-HPAF HP (20.9 vs 3.3%, p = 0.040, cOR = 7.68). No significant differences between pulmonary function tests, oxygen requirements, mortality, and lung transplantation rates were found between the two groups. There was no statistically significant difference in transplant-free survival (p = 0.836). CONCLUSION: Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to patients with non-HPAF HP. The clinical characteristics and outcomes did not differ between the two groups and concomitant autoimmunity among the HP group did not portend a poorer prognosis.

A new dawn in internal medicine education curriculum-a project by the residents, with the residents, for the residents.

The academic half-day (AHD) curriculum is an alternative to the noon conference (NC) approach. To date, there is little literature evaluating the transition from NC to AHD in internal medicine residency programs. We investigated the effectiveness of AHD by comparing in-training exam (ITE) and American Board of Internal Medicine (ABIM) certifying exam scores of residents before and after implementation of AHD. In 2019, we transitioned to the AHD curriculum. Averages of three consecutive years of NC (2016-2018) and AHD (2019-2021) were used for statistical testing to determine ITE and ABIM score changes. The class of 2018 experienced both approaches. Cohen's d effect sizes were calculated to assess the magnitude of change in ITE and ABIM scores between NC (2016-2018) and AHD (2019-2021) cohorts. Residents' performance significantly improved (P < 0.05) on ABIM scores (513.80 ± 48.34) on average from 2019 to 2021 compared to ABIM scores (452.42 ± 49.72) on average from 2016 to 2018 with a large effect size of 1.27. Similarly, a significant (P = 0.005) improvement in ITE scores was observed from 2019 to 2021 with implementation of AHD compared to preceding NC scores (2016-2018) with a moderate effect size of 0.52. Participating residents in AHD sessions had higher ITE and ABIM scores compared to those in hourly NC didactic sessions with significantly improved resident attendance and overall satisfaction.

Prevalence of Post-Heart Transplant Malignancies: A Systematic Review and Meta-Analysis.

The prevalence of different cancers after heart transplant (HT) is unclear due to small and conflicting prior studies. Herein, we report a systematic review and meta-analysis to highlight the prevalence and pattern of malignancies post-HT. We conducted an extensive literature search on PubMed, Scopus, Cochrane databases for prospective or retrospective studies reporting malignancies after HT. The proportions from each study were subjected to random effects model that yielded the pooled estimate with 95% confidence intervals (CI). Fifty-five studies comprising 60,684 HT recipients reported 7759 total cancers during a mean follow-up of 9.8 ± 5.9 years, with an overall incidence of 15.3% (95% CI = 12.7%-18.1%). Mean time from HT to cancer diagnosis was 5.1 ± 4 years. The most frequent cancers were gastrointestinal (7.6%), skin (5.7%), and hematologic/blood (2.5%). Meta-regression showed no association between incidence of cancer and mean age at HT (coeff: -0.008; P = 0.25), percentage of male recipients (coeff: -0.001; P = 0.81), donor age (coeff: -0.011; P = 0.44), 5-year (coeff: 0.003; P = 0.12) and 10-year (coeff: 0.02; P = 0.68) post-transplant survival. There is a substantial risk of malignancies in HT recipients, most marked for gastrointestinal, skin, and hematologic. Despite their occurrence, survival is not significantly impacted.

Implementation of Multiple Evidence-Based Heart Failure Therapies.

Despite the advancements in the management of heart failure, acute heart failure is one of the most common causes of mortality and morbidity. In light of the financial burden imposed by heart failure hospitalizations on the health care system, this area remains the focus of research, clinical advances, and policy changes aimed at improving the quality of care and outcomes. Despite practice guidelines, high-quality trial data, and consensus statements, barriers to therapy remain. The barriers related to physician, patient, economic, health care system, and logistical factors prevent widespread adoption of available therapeutics. In this review article, we outline guidelines directed therapies for heart failure, challenges associated with their implementation, and potential solutions to these challenges to help reduce mortality and improve clinical outcomes in this patient population.

Oxytocin receptor behavioral effects and cell types in the bed nucleus of the stria terminalis.

Oxytocin is a neuropeptide that can produce anxiolytic effects and promote social approach. However, emerging evidence shows that under some conditions, oxytocin can instead induce anxiety-related behaviors. These diverse effects of oxytocin appear to be mediated by circuit-specific actions. Recent data showed that inhibition of oxytocin receptors (OTRs) in the bed nucleus of the stria terminalis (BNST) was sufficient to increase social approach and decrease social vigilance in female California mice (Peromyscus californicus) exposed to social defeat stress. As a member of the G-protein coupled receptor family, OTRs can induce distinct downstream pathways by coupling to different G-protein isoforms. We show that infusion of carbetocin, a biased OTR-Gq agonist, in the BNST reduced social approach in both female and male California mice. In both females and males, carbetocin also increased social vigilance. To gain insight into cell types that could be mediating this effect, we analyzed previously published single-cell RNAseq data from the BNST and nucleus accumbens (NAc). In the NAc, we and others showed that OTR activation promotes social approach behaviors. In the BNST, Oxtr was expressed in over 40 cell types, that span both posterior and anterior subregions of the BNST. The majority of Oxtr-expressing neurons were GABAergic. In the anterior regions of BNST targeted in our carbetocin experiments, Cyp26b1-expressing neurons had high average Oxtr expression. In the NAc, most Oxtr+ cells were D1 dopamine receptor-expressing neurons and interneurons. These differences in Oxtr cell type distribution may help explain how activation of OTR in BNST versus NAc can have different effects on social approach and social vigilance.

Milk-Derived Proteins and Peptides in Head and Neck Carcinoma Treatment.

Research investigating milk-derived proteins has brought to light the potential for their use as novel anticancer agents. This paper aims to systematically review studies examining the effectiveness of milk-derived proteins in the treatment of head and neck cancer. A systematic literature search of Medline, Evidence-Based Medicine, and Web of Science databases including papers published from all dates was completed. Inter-rater reliability was high during the title, abstract, and full-text screening phases. Inclusion criteria, exclusion criteria, and data extraction were based on the PICOS tool and research questions. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria. Eligible in vitro and in vivo studies (n = 8/658) evaluated lactoferrin, α-lactalbumin, and its complexes, such as HAMLET, BAMLET and lactalbumin-oleic acid complexes, as well as lactoperoxidase, whey, and casein. Their effectiveness in the treatment of head and neck cancer cells lines found that these compounds can inhibit tumour growth modulate cancer gene expression, and have cytotoxic effects on cancer cells. However, the exact mechanisms by which these effects are achieved are not well understood. Systematically designed, large, optimally controlled, collaborative studies, both in vitro and in vivo, will be required to gain a better understanding of their potential role in the treatment of head and neck cancer.

Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without fibrosis.

Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice (Acomys) are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the Acomys genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney.

Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus.

The pathogen Staphylococcus aureus can readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment. Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants. The compounds, which we term 'antibiotic-chemoattractants', consist of a formylated peptide (known to act as chemoattractant for neutrophil recruitment) that is covalently linked to the antibiotic vancomycin (known to bind to the bacterial cell wall). We use a combination of in vitro assays, cellular assays, infection-on-a-chip and in vivo mouse models to show that the compounds improve the recruitment, engulfment and killing of S. aureus by neutrophils. Furthermore, optimizing the formyl peptide sequence can enhance neutrophil activity through differential activation of formyl peptide receptors. Thus, we propose antibiotic-chemoattractants as an alternate approach for antibiotic development.

Posttraumatic Stress Disorder Subsequent to Apparent Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) is prevalent among veterans with a history of traumatic brain injury (TBI); however, the relationship between TBI and PTSD is not well understood. We present the case of a 31-year-old male veteran with PTSD who reported TBI before entering the military. The reported injury appeared to be mild: He was struck on the head by a baseball, losing consciousness for ∼10 seconds. Years later, he developed severe PTSD after combat exposure. He was not receiving clinical services for these issues but was encountered in the context of a research study. We conducted cognitive, autonomic, and MRI assessments to assess brain function, structure, and neurophysiology. Next, we compared amygdala volume, uncinate fasciculus diffusion, functional connectivity, facial affect recognition, and baroreceptor coherence with those of a control group of combat veterans (n = 23). Our veteran's MRI revealed a large right medial-orbital prefrontal lesion with surrounding atrophy, which the study neuroradiologist interpreted as likely caused by traumatic injury. Comparison with controls indicated disrupted structural and functional connectivity of prefrontal-limbic structures and impaired emotional, cognitive, and autonomic responses. Detection of this injury before combat would have been unlikely in a clinical context because our veteran had reported a phenomenologically mild injury, and PTSD is a simple explanation for substance abuse, sleep impairment, and psychosocial distress. However, it may be that right prefrontal-limbic disruption imparted vulnerability for the development of PTSD and exacerbated our veteran's emotional response to, and recovery from, PTSD.

Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance.

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.

The Effect of Vertically Yoked Prisms on Binocular Vision and Accommodation.

SIGNIFICANCE: Vertically yoked prisms have been used in treatment of binocular vision dysfunction despite minimal supporting evidence. In people with normal binocular vision, the impact on phorias has been assessed but not the impact on accommodation, accommodation vergence interactions, or the horopter. We found that vertically yoked prisms have minor effects during short-term wear in young adults. PURPOSE: The purpose of this study was to determine effects of vertically yoked prisms on accommodative response and several binocular vision tasks. METHODS: There were 45 participants aged 18 to 24 years. The 23 myopes wore distance-corrected soft contact lenses. In a random arrangement, each person wore spectacles containing planopower lenses with either 8 Δ base-up, 4 Δ base-up, zero, 4 Δ base-down, and 8 Δ base-down prisms. Before spectacle wear, baseline measurements of near heterophoria, accommodation response, negative and positive relative accommodations, fusional vergence, and Nonius-horopter spatial perception were taken. Measurements were repeated after a 40-minute wear, spectacles were removed, and tests were performed 20 minutes later. On a 22-participant subset, on a separate occasion, measurements of heterophoria, accommodation response, and relative accommodation were made immediately after spectacles were fitted. RESULTS: Most changes relative to baseline were not significant. Where effects occurred, these were nearly all associated with prism presence rather than adaptation. There were significant effects on accommodation response, but these seem to be refraction effects produced by pantoscopic tilt-induced power changes rather than perceptual effects altering accommodation. There were statistically significant effects on negative relative accommodation (P < .01), with zero prism giving more negative relative accommodation than 8 Δ base-down prisms. Tendencies were noted for prisms to move horopter limits toward the observer. Effects were small and likely not of clinical relevance. CONCLUSIONS: Vertically yoked prisms have minor effects on accommodation and binocular vision, at least during short-term wear in young adults with normal binocular vision.

Chemical biology of glycoproteins: From chemical synthesis to biological impact.

Recent advances have demonstrated the feasibility and robustness of chemical synthesis for the production of homogeneously glycosylated protein forms (glycoforms). By taking advantage of the unmatchable flexibility and precision provided by chemical synthesis, the quantitative effects of glycosylation were obtained using chemical glycobiology approaches. These findings greatly advanced our fundamental knowledge of glycosylation. More importantly, analysis of these findings has led to the development of glycoengineering guidelines for rationally improving the properties of peptides and proteins. In this chapter, we present the key experimental steps for chemical biology studies of protein glycosylation, with the aim of facilitating and promoting research in this important but significantly underexplored area of biology.

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss.

BACKGROUND AND OBJECTIVE: Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH)2 D3 , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD). MATERIALS AND METHODS: Wild-type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH)2 D3 , followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2 D3 was quantified by ELISA. Effect of vitamin D on basal IL-1α expression in mice was determined by topical administration to the gingiva of wild-type mice, followed by qRT-PCR. RESULTS: Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH)2 D3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25-hydroxylases (CYP27A1 and CYP2R1), as well as 1-α hydroxylase, enabling conversion of vitamin D to both 25(OH)D3 and 1,25(OH)2 D3 . Topical application of both vitamin D3 and 1,25(OH)2 D3 to the gingiva of mice led to rapid inhibition of IL-1α expression, a prominent pro-inflammatory cytokine associated with inflammation, which also exhibited more than a 2-fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH)2 D3 treatment, as determined by RNA-seq. CONCLUSION: Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease.

The Health and Well-being of Children and Adolescents Accessing In-Patient Psychiatry: A Brief Report.

OBJECTIVE: People with mental illness have high rates of physical illness that are not detected and that shorten their lifespan. Health behaviours are central to physical health, and many children and adolescents with psychiatric illness may be at risk for poor physical health. The purpose for this study was to explore the self-reported health behaviours and well-being of pediatric psychiatric patients and their association with mental health problems. METHODS: Pediatric patients hospitalized for psychiatric care were invited to complete a survey containing items on amount of physical activity, nutrient intake and sleep, a standardized perceived stress scale, and the Strengths and Difficult Questionnaire. RESULTS: Informed consent was provided by 161 patients who completed the survey. Youth reported: engaging in very little physical activity, eating fruits and vegetables about 2-3 times per week, not sleeping well and very high perceived stress. DISCUSSION: Implications for practice include increasing opportunities for and monitoring of health behaviours in youth hospitalized for psychiatric illness. Further research is needed to explore interventions designed to improve the physical health and mental well-being of youth with psychiatric illness and possibly the inpatient environment.

OBJECTIF: Les personnes souffrant de maladie mentale ont des taux élevés de maladie physique qui ne sont pas détectés et qui réduisent leur durée de vie. Les comportements liés à la santé sont au centre de la santé physique, et bien des enfants et adolescents souffrant de maladie psychiatrique peuvent être à risque d'une mauvaise santé physique. Le but de cette étude était d'explorer les comportements liés à la santé et au bien-être auto-déclarés par des patients psychiatriques pédiatriques et leur association aux problèmes de santé mentale. MÉTHODES: Les patients pédiatriques hospitalisés pour des soins psychiatriques ont été invités à remplir un sondage dont les items portaient sur la quantité d'activité physique, l'apport en nutriments et le sommeil, une échelle normalisée du stress perçu, et un questionnaire sur les forces et difficultés. RÉSULTATS: Un consentement éclairé a été donné par les 161 patients qui ont rempli le sondage. Les adolescents déclaraient très peu d'activité physique, mangeaient fruits et légumes environ 2 à 3 fois par semaine, ne dormaient pas bien et leur perception du stress était très élevée. DISCUSSION: Les implications pour la pratique sont notamment de plus grandes possibilités d'améliorer et de surveiller les comportements liés à la santé chez les adolescents hospitalisés pour une maladie psychiatrique. Il faut plus de recherche pour explorer les interventions destinées à améliorer la santé physique et le bien-être mental des adolescents souffrant de maladie psychiatrique et possiblement, l'environnement des patients hospitalisés.

O-GalNAcylation of RANTES Improves Its Properties as a Human Immunodeficiency Virus Type 1 Entry Inhibitor.

Many human proteins have the potential to be developed as therapeutic agents. However, side effects caused by direct administration of natural proteins have significantly slowed expansion of protein therapeutics into the clinic. Post-translational modifications (PTMs) can improve protein properties, but because of significant knowledge gaps, we are considerably limited in our ability to apply PTMs to generate better protein therapeutics. Here, we seek to fill the gaps by studying the PTMs of a small representative chemotactic cytokine, RANTES. RANTES can inhibit HIV-1 infection by competing with it for binding to receptor CCR5 and stimulating CCR5 endocytosis. Unfortunately, RANTES can induce strong signaling, leading to severe inflammatory side effects. We apply a chemical biology approach to explore the potential of post-translationally modified RANTES as safe inhibitors of HIV-1 infection. We synthesized and systematically tested a library of RANTES isoforms for their ability to inhibit inflammatory signaling and prevent HIV-1 infection of primary human cells. Through this research, we revealed that most of the glycosylated variants have decreased inflammation-associated properties and identified one particular glyco variant, a truncated RANTES containing a Galß1-3GalNAc disaccharide α-linked to Ser4, which stands out as having the best overall properties: relatively high HIV-1 inhibition potency but also weak inflammatory properties. Moreover, our results provided a structural basis for the observed changes in the properties of RANTES. Taken together, this work highlights the potential importance of glycosylation as an alternative strategy for developing CCR5 inhibitors to treat HIV-1 infection and, more generally, for reducing or eliminating unwanted properties of therapeutic proteins.