Functional Expression of Programmed Death-Ligand 1 (B7-H1) by Immune Cells and Tumor Cells

The programmed death-1 (PD-1) and its ligand PD-L1 (B7-H1) signaling pathway has been the focus of much enthusiasm in the fields of tumor immunology and oncology with recent FDA approval of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies durvalumab, atezolimuab, and avelumab. These therapies, referred to here as PD-L1/ PD-1 checkpoint blockade therapies, are designed to block the interaction between PD-L1, expressed by tumor cells, and PD-1, expressed by tumor-infiltrating CD8+ T cells, leading to enhanced antitumor CD8+ T cell responses and tumor regression. The influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined for antitumor CD8+ T cell responses. Although PD-L1 expression by tumor cells has been used as a biomarker in selection of patients for PD-L1/PD-1 checkpoint blockade therapies, patients whose tumor cells lack PD-L1 expression often respond positively to PD-L1/PD-1 checkpoint blockade therapies. This suggests that PD-L1 expressed by non-malignant cells may also contribute to antitumor immunity. Here, we review the functions of PD-L1 expressed by immune cells in the context of CD8+ T cell priming, contraction, and differentiation into memory populations, as well as the role of PD-L1 expressed by tumor cells in regulating antitumor CD8+ T cell responses

CD80 Expressed by CD8+ T Cells Contributes to PD-L1-Induced Apoptosis of Activated CD8+ T Cells

Tumor cells are capable of limiting antitumor CD8+ T cell responses through their cell surface expression of PD-L1. In addition to PD-1 expressed by CD8+ T cells, PD-L1 also binds to CD80 expressed by CD8+ T cells. The influence of the PD-L1/CD80 interaction on CD8+ T cell function has not been fully characterized, so we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1-induced apoptosis of activated CD8+ T cells. We found that CD8+ T cells that lacked CD80 expression got activated to the same extent as wild-type CD8+ T cells, but when cultured with anti-CD3 and PD-L1/Fc protein, activated CD8+ T cells that lacked CD80 expression survived better than activated wild-type CD8+ T cells. These findings indicate that PD-L1 induces apoptosis in activated CD8+ T cells in part by signaling through CD80. Thus, in the design and implementation of checkpoint blockade therapies that target PD-L1, it is essential that both binding partners for PD-L1, PD-1, and CD80 are considered

The experiences and support needs of consultant psychiatrists following a patient-perpetrated homicide

Aims and method: To investigate the experiences and support needs of consultant psychiatrists following a patient-perpetrated homicide, an anonymous online survey was sent to all consultant psychiatrists registered as members of the UK's Royal College of Psychiatrists. / Results: Of the 497 psychiatrists who responded, 165 (33%) had experienced a homicide by a patient under their consultant care. Most respondents reported negative impacts on their clinical work (83%), mental and/or physical health (78%) or personal relationships (59%), and for some (9–12%) these were severe and long lasting. Formal processes such as serious incident inquiries were commonly experienced as distressing. Support was mainly provided by friends, family and colleagues rather than the employing organisation. / Clinical implications: Mental health service providers need to provide support and guidance to psychiatrists following a patient-perpetrated homicide to help them manage the personal and professional impact. Further research into the needs of other mental health professionals is needed

Psychiatrists' Experience of a Peer Support Group for Reflecting on Patient Suicide and Homicide: A Qualitative Study

There is a lack of support for mental health professionals who experience a patient suicide or homicide. This is despite a high likelihood of such an occurrence and the heavy professional and personal toll the experience can take. We conducted 15 interviews with members of a facilitated peer support group run for consultant psychiatrists who have experienced a patient homicide or suicide. Our interviews explored the trauma of the experience as well as the effectiveness of the group in helping the clinician heal. Our results echoed previous research that the experience can be profoundly traumatic. A professionally facilitated, consultant-only peer group specifically dedicated to suicide and homicide were the key components helping participants to process their grief. Mental health trusts should consider setting up facilitated peer support groups for clinicians who experience patient suicide or homicide

Maternal feeding practices predict weight gain and obesogenic eating behaviours in young children : a prospective study

Background&nbsp;Maternal feeding practices have been proposed to play an important role in early child weight gain and obesogenic eating behariours. However, to date longitudinal investigations in young children exploring these relationships have been lacking. The aim of the present study was to explore prospective relationships between maternal feeding practices, child weight gain and obesogenic eating behaviours in 2-year-old children. The competing hypothesis that child eating behaviours predict changes in maternal feeding practices was also examined.Methods&nbsp;A sample of 323 mother (mean age = 35 years, + 0.37) and child dyads (mean age = 2.03 years, + 0.37 at recruitment) were participants. Mothers completed a questionnaire assessing parental feeding practices and child eating behaviours at baseline and again one year later. Child BMI (predominantly objectively measured) was obtained at both time points.Results&nbsp;Increases in child BMI z-scores over the follow-up period were predicted by maternal instrumental feeding practices. Furthermore, restriction, emotional feeding, encouragement to eat, weight-based restriction and fat restriction were associated prospectively with the development of obesogenic eating behaviours in children including emotional eating, tendency to overeat and food approach behaviours (such as enjoyment of food and good appetite). Maternal monitoring, however, predicted decreases in food approach eating behaviours. Partial support was also observed for child eating behaviours predicting maternal feeding practices.Conclusions&nbsp;Maternal feeding practices play an important role in the development of weight gain and obesogenic eating behaviours in young children and are potential targets for effective prevention interventions aiming to decrease child obesity.<br /

Une étude exploratoire. Interaction entre les dyades mère-nourrisson et père-nourrisson chez les couples à faible revenu

Vingt-neuf parents à faible revenu et leurs nourrissons ont participé à une recherche exploratoire portant sur les interactions parent-nourrisson et décrivant le niveau d'interactions, les similarités et les différences au sein des dyades mère-nourrisson et père-nourrisson. L'échelle de mesure Nursing Child Assessment Teaching Scale, un instrument d'observation standardisé de 73 items, a été utilisée pour mesurer les interactions. Les résultats ont montré que bien que la majorité (69%) des dyades parent-nourrisson n'ont pas démontré de comportements interactifs à risque, près de 31% de l'échantillon étaient désorganisés dans leurs interactions. De plus, les résultats ont démontré que bien que les deux parents étaient sensibles et répondaient aux signaux de leurs nourrissons, les mères étaient plus aptes que les pères à répondre à la détresse de leurs nourrissons alors que les nourrissons étaient plus clairs et répondaient mieux aux pères qu'aux mères. Avec cette information, les cliniciens et les chercheurs peuvent mieux comprendre les interactions au sein du contexte familial et renforcer les programmes d'intervention visant à maintenir et à améliorer les interactions parent-nourrisson.Interaction between low-income mother-infant and father-infant pairs: an exploratory study Twenty-nine low-income parents and their infants participated in an explanatory study about parent-infant interaction — describing the level of interaction and the similarities and differences in mother-infant and father infant pairs. The Nursing Child Assessment Teaching Scale, a 73-item standardized observation instrument, was used to measure interaction. Results showed that although the majority (69%) of parent-infant dyads did not demonstrate risky interactive behaviors, nearly 31% of the sample was disorganized in their interactions. Further, results showed that while both mothers and fathers were sensitive and responsive to their infants' cues, mothers were more apt to respond to their infants' distress than fathers, and infants were clearer and more responsive with their fathers than with their mothers. With this information clinicians and researchers can better understand interactions within a family context and strengthen intervention programs aimed at maintaining and improving parent-infant interactions.Una investigación exploratoria. Interacción entre los pares madre-niño lactante y padre-niño lactante en las parejas a ingreso modesto Veinte-nueve padres con ingreso modesto y sus niños lactantes participaron en una investigación exploratoria sobre las interacciones padre-niño lactante y el nivel de interacciones, las similitudes y las diferencias en el seno de las dyadas madre-niño lactante y padre-niño lactante. Para medir las interacciones se utilizó un instrumento de observación standardizado de 73 elementos, la escala de medida Nursing Child Assessment Teaching Scale. Los resultados indican que aunque la mayoridad (69%) de las dyadas padre-niño lactante no demuestran comportamientos interactivos con riesgo, cerca de 31% de la muestra estaban desorganisados en sus interacciones. Además, los resultados demuestraron que aunque los dos padres eran sensibles y respondian a los señales de sus niños lactantes, las madres estaban más aptas que los padres a responder al desemparo de sus niños cuando los niños estaban más tranquilos y respondian mejor a los padres que a las madres. Con esta información, los clínicos y los investigadores pueden comprender mejor las interacciones en el seno del contexto familial y reforzar programas de intervención aspirando mantener y mejorar las interacciones padre-niño lactante

Effects of forest management practices on treefrog oviposition site choice

Abstract only availableGlobally, amphibian populations are declining faster than those of birds or mammals. Habitat destruction is considered the primary cause of these declines; however, what remains partly unexplored is the idea that some species may be more greatly affected than others by deforestation. Treefrogs (Family: Hylidae), because of their mobility, may be expected to circumvent disturbed habitats; however, because of their dependency on arboreal habitat, they may be adversely affected by different forms of forest management. As part of the LEAP (Land-Use Effects on Amphibian Populations) study, four forest management practices—clearcut with coarse woody debris (CWD) removed, clearcut with CWD retained, thinning of 25% basal area, and uncut forest—were implemented at four wetlands at the Savannah River Site. In May 2005, we placed wading pools 25 m into each treatment and allowed them to fill with rainwater. To monitor time to first oviposition event and to determine the number of events per treatment, pools were checked daily, eggs were counted, and tadpoles were raised to confirm that all eggs were indeed those of hylids. We measured water depth, canopy cover, and surrounding vegetation. These data will be analyzed to determine if suitable calling/breeding habitat (microhabitat) is a more reliable predictor of oviposition than treatment (macrohabitat). At three of the four wetlands, first oviposition events occurred in the thinning treatments, and second events occurred in the clearcuts with CWD retained. We found that more oviposition events also occurred in the thinning treatments (43%) and the clearcuts with CWD retained (33%) than in the clearcuts with CWD removed (13%) or the uncut forest controls (10%). One explanation for these findings is that hylids have evolved to locate openings in the forest canopy which could indicate a wetland or a fallen tree whose uprooting has caused an ephemeral pool to form.Life Sciences Undergraduate Research Opportunity Progra

Coping with psychological distress during COVID-19: a cautionary note of self-criticalness and personal resilience among healthcare workers

PURPOSE: The COVID-19 pandemic resulted in immense pressure on healthcare workers (HCWs) and healthcare systems worldwide. The current multi-centre evaluation sought to explore the association between coping behaviours and levels of psychological distress among HCWs working during the initial onset of COVID-19. DESIGN/METHODOLOGY/APPROACH: Between April and July 2020 HCWs at three urban hospitals in England were invited to complete an online survey measuring personal and professional characteristics, psychological distress and coping. A principal component analysis (PCA) identified components of coping and structural equation modelling (SEM) was used to test the relationship between components of coping and psychological distress. FINDINGS: A total of 2,254 HCWs participated (77% female, 67% white, 66% in clinical roles). Three components for coping were retained in the PCA analysis: external strategies, internal strategies and self-criticalness/substance use. SEM indicated that internally based coping was associated with lower levels of psychological distress, whereas externally based coping and self-criticalness were associated with greater psychological distress. The final model accounted for 35% of the variance in psychological distress. ORIGINALITY/VALUE: This multi-centre evaluation provides unique insight into the level of psychological distress among HCWs during the initial onset of the COVID-19 pandemic (2020) and associated coping strategies. Addressing self-criticalness and supporting cognitive-based internal coping strategies among HCWs may protect against prolonged exposure to psychological distress. Findings highlight the importance of developing a culture of professional resilience among this vital workforce as a whole rather than placing pressure on an individual's personal resilience

Functional Expression of Programmed Death-Ligand 1 (B7-H1) by Immune Cells and Tumor Cells

The programmed death-1 (PD-1) and its ligand PD-L1 (B7-H1) signaling pathway has been the focus of much enthusiasm in the fields of tumor immunology and oncology with recent FDA approval of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies durvalumab, atezolimuab, and avelumab. These therapies, referred to here as PD-L1/PD-1 checkpoint blockade therapies, are designed to block the interaction between PD-L1, expressed by tumor cells, and PD-1, expressed by tumor-infiltrating CD8+ T cells, leading to enhanced antitumor CD8+ T cell responses and tumor regression. The influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined for antitumor CD8+ T cell responses. Although PD-L1 expression by tumor cells has been used as a biomarker in selection of patients for PD-L1/PD-1 checkpoint blockade therapies, patients whose tumor cells lack PD-L1 expression often respond positively to PD-L1/PD-1 checkpoint blockade therapies. This suggests that PD-L1 expressed by non-malignant cells may also contribute to antitumor immunity. Here, we review the functions of PD-L1 expressed by immune cells in the context of CD8+ T cell priming, contraction, and differentiation into memory populations, as well as the role of PD-L1 expressed by tumor cells in regulating antitumor CD8+ T cell responses