Mental Health and Wellbeing in Young People in the UK during Lockdown (COVID-19).

This study aimed to assess the levels of mental wellbeing and potential for clinical need in a sample of UK university students aged 18-25 during the COVID-19 pandemic. We also tested the dose-response relationship between the severity of lockdown restrictions and mental wellbeing. We carried out a prospective shortitudinal study (one month between baseline and follow up) during the pandemic to do this and included 389 young people. We measured a range of facets of mental wellbeing, including depression, depressogenic cognition (rumination), wellbeing, stress and sleep disturbance. Our primary outcome was 'probable depression' as indexed by a score of ≥10 on the patient health questionnaire (PHQ-8). The prevalence of probable depression was significantly higher than pre-pandemic levels (55%) and did not decrease significantly over time (52%). Higher levels of lockdown severity were prospectively associated with higher levels of depressive symptoms. Nearly all students had at least one mental wellbeing concern at either time point (97%). The evidence suggests that lockdown has caused a wellbeing crisis in young people. The associated long-term mental, social, educational, personal and societal costs are as yet unknown but should be tracked using further longitudinal studies.

The effect of divalent metal cations on the αv integrin binding site is ligand and integrin specific.

The binding of orthosteric ligands to integrins requires the presence of divalent metal cations bound to metal ion-binding sites located in the I domains of the integrin α and ß subunits. In this study the influence of the type and concentration of divalent metal cation present was investigated on a single arginyl-glycinyl-aspartic acid (RGD) ligand across the αv integrin sub-family and single αv integrin (αvß6) with different ligands. These relationships were determined using radioligand binding studies completed with [3H] ligands and purified αv integrin protein preparations. The binding of [3H]compound 1 to the RGD site on individual αv integrins demonstrated a unique profile in relation to the type and concentration of divalent metal cation present. The use of physiological concentrations of Mg2+ and Ca2+ in simulated lung fluid altered the αv integrin selectivity profile of [3H]compound 1 in terms of affinity and the level of receptor occupancy. In addition, different RGD ligands for the αvß6 integrin behaved differently under the same divalent metal cation conditions. In conclusion, this study demonstrates the need to determine the individual relationship between RGD ligands and the integrins they may engage in vivo, especially when determining selectivity profiles for potential RGD-mimetic small molecule therapeutics, with organ and disease state also considered.

Immigrant Health in the United States: A Trajectory Toward Change.

INTRODUCTION: Immigrants have a negative health trajectory due to interactions between immigration policies and the totality of the immigration experience. Despite the enactment of the Patient Protection and Affordable Care Act in 2010, an association with the sociopolitical environment and its influence on chronic disease prevalence remains. The purpose of this review was to provide evidence for existing health disparities among immigrants based on ethnicity, immigration status, country of origin, duration in the United States. The sociopolitical environment affecting immigrant health and opportunities to change the course toward ameliorating health disparities is discussed. METHOD: Using PRISMA guidelines, the literature focused on immigrants, disease prevalence, health care access, and policy. Twenty-nine articles were selected for this review. RESULTS: Chronic disease prevalence is associated with the restrictive immigration and health care policies among all immigrant groups. DISCUSSION: Recent evidence and the current immigration debate signify an opportunity to explore strategies to improve health outcomes among immigrants.

Characterisation of a novel, high affinity and selective αvß6 integrin RGD-mimetic radioligand.

The alpha-v beta-6 (αvß6) integrin has been identified as playing a key role in the activation of transforming growth factor-ß (TGFß) that is hypothesised to be pivotal in the development of cancer and fibrotic diseases. Therefore, the αvß6 integrin is an attractive therapeutic target for these debilitating diseases and a drug discovery programme to identify small molecule αvß6 selective arginyl-glycinyl-aspartic acid (RGD)-mimetics was initiated within GlaxoSmithKline. The primary aim of this study was to pharmacologically characterise the binding to αvß6 of a novel clinical candidate, compound 1, using a radiolabelled form. Radioligand binding studies were completed with [(3)H]compound 1 against the human and mouse soluble protein forms of αvß6 to determine accurate affinity estimates and binding kinetics. The selectivity of compound 1 for the RGD integrin family was also determined using saturation binding studies (αvß1, αvß3, αvß5, αvß8, α5ß1 and α8ß1 integrins) and fibrinogen-induced platelet aggregation (αIIbß3 integrin). In addition, the relationship between divalent metal cation type and concentration and αvß6 RGD site binding was also investigated. Compound 1 has been demonstrated to bind with extremely high affinity and selectivity for the αvß6 integrin and has the potential as a clinical tool and therapeutic for investigating the role of αvß6 in a range of disease states both pre-clinically and clinically. In addition, this is the first study that has successfully applied radioligand binding to the RGD integrin field to accurately determine the affinity and selectivity profile of a small molecule RGD-mimetic.

Social Ecology of Adherence to Hypertension Treatment in Latino Migrant and Seasonal Farmworkers.

PURPOSE: This study explored Latino migrant/seasonal farmworkers' (MSFWs') adherence to hypertension treatment. DESIGN: A cross-sectional correlational study was conducted. METHOD: Forty-five Latino MSFWs from two farmworker health clinics completed Spanish versions of the Morisky Medication Adherence Scale, the Blood Pressure Knowledge Scale and Blood Pressure Self-Care Scale, the Perceived Stress Scale, the Acculturation Rating Scale for Mexican Americans-II, the Short Assessment of Health Literacy for Spanish-Speaking Adults, health care access questions, and blood pressure measurements. RESULTS: MSFWs had poor medication adherence (51%). Blood pressure knowledge, perceived stress, acculturation, health literacy, and health care access accounted for 49% of the variance in blood pressure self-care. Higher acculturation level and health literacy were associated with better blood pressure control (p = .01). DISCUSSION: MSFWs had poor medication adherence and blood pressure control. Blood pressure knowledge and acculturation played a role in blood pressure self-care. IMPLICATIONS: Culturally appropriate educational programs are needed to help MSFWs' adherence to hypertension treatment.

Valence-to-core-detected X-ray absorption spectroscopy: targeting ligand selectivity.

X-ray absorption spectroscopy (XAS) can provide detailed insight into the electronic and geometric structures of transition-metal active sites in metalloproteins and chemical catalysts. However, standard XAS spectra inherently represent an average contribution from the entire coordination environment with limited ligand selectivity. To address this limitation, we have investigated the enhancement of XAS features using valence-to-core (VtC)-detected XAS, whereby XAS spectra are measured by monitoring fluorescence from valence-to-core X-ray emission (VtC XES) events. VtC emission corresponds to transitions from filled ligand orbitals to the metal 1s core hole, with distinct energetic shifts for ligands of differing ionization potentials. VtC-detected XAS data were obtained from multiple valence emission features for a series of well-characterized Mn model compounds; taken together, these data correspond to a VtC resonant XES (VtC RXES) plane. For comparison, standard total fluorescence yield (TFY) XAS and nonresonant XES data were obtained. Dramatic intensity variations and the appearance of new features were observed in the pre-edge region by detecting at different VtC emission energies. The TFY XAS, nonresonant XES, and VtC RXES data were all modeled within a density functional theory approach. While the TFY XAS and nonresonant XES data are readily interpreted by theory, the VtC RXES cannot be reproduced within such a simplified model. Nonetheless, dramatic changes in the experimental spectra are observed that have the potential to further the information content and selectivity of XAS. Potential applications and required theoretical developments are discussed.