An Early Reduction in Treg Cells Correlates with Enhanced Local Inflammation in Cutaneous Leishmaniasis in CCR6-Deficient Mice

Resistance to Leishmania major infection is dependent on the development of a cell-mediated Th1 immune response in resistant C57BL/6 mice whereas Th2-prone BALB/c mice develop non-healing lesions after infection. The chemokine receptor CCR6 is shared by anti-inflammatory regulatory T cells and pro-inflammatory Th17 cells. In a recent study we showed that C57BL/6 mice deficient in CCR6 exhibited enhanced footpad swelling and impaired T helper cell migration indicated by reduced recruitment of total T helper cells into the skin after infection and a reduced delayed type hypersensitivity reaction. Based on these findings we tested whether the lack of CCR6 alters Treg or Th17 cell responses during the course of Leishmania major infection. When we analyzed T cell subsets in the lymph nodes of CCR6-deficient mice, Th17 cell numbers were not different. However, reduced numbers of Treg cells paralleled with a stronger IFNγ response. Furthermore, the early increase in IFNγ-producing cells correlated with increased local tissue inflammation at later time points. Our data indicate an important role of CCR6 for Treg cells and a redundant role for Th17 cells in a Th1 cell-driven anti-parasitic immune response against Leishmania major parasites in resistant C57BL/6 mice

Psychometric properties of the Late-Life Function and Disability Instrument: a systematic review

Background: The choice of measure for use as a primary outcome in geriatric research is contingent upon the construct of interest and evidence for its psychometric properties. The Late-Life Function and Disability Instrument (LLFDI) has been widely used to assess functional limitations and disability in studies with older adults. The primary aim of this systematic review was to evaluate the current available evidence for the psychometric properties of the LLFDI. Methods: Published studies of any design reporting results based on administration of the original version of the LLFDI in community-dwelling older adults were identified after searches of 9 electronic databases. Data related to construct validity (convergent/divergent and known-groups validity), test-retest reliability and sensitivity to change were extracted. Effect sizes were calculated for within-group changes and summarized graphically. Results: Seventy-one studies including 17,301 older adults met inclusion criteria. Data supporting the convergent/divergent and known-groups validity for both the Function and Disability components were extracted from 30 and 18 studies, respectively. High test-retest reliability was found for the Function component, while results for the Disability component were more variable. Sensitivity to change of the LLFDI was confirmed based on findings from 25 studies. The basic lower extremity subscale and overall summary score of the Function component and limitation dimension of the Disability component were associated with the strongest relative effect sizes. Conclusions: There is extensive evidence to support the construct validity and sensitivity to change of the LLFDI among various clinical populations of community-dwelling older adults. Further work is needed on predictive validity and values for clinically important change. Findings from this review can be used to guide the selection of the most appropriate LLFDI subscale for use an outcome measure in geriatric research and practice

SARS-CoV-2 Infection and the Risk of Suicidal and Self-Harm Thoughts and Behaviour:A Systematic Review

OBJECTIVE: The COVID-19 pandemic has had a complex impact on risks of suicide and non-fatal self-harm worldwide with some evidence of increased risk in specific populations including women, young people, and people from ethnic minority backgrounds. This review aims to systematically address whether SARS-CoV-2 infection and/or COVID-19 disease confer elevated risk directly. METHOD: As part of a larger Living Systematic Review examining self-harm and suicide during the pandemic, automated daily searches using a broad list of keywords were performed on a comprehensive set of databases with data from relevant articles published between January 1, 2020 and July 18, 2021. Eligibility criteria for our present review included studies investigating suicide and/or self-harm in people infected with SARS-CoV-2 with or without manifestations of COVID-19 disease with a comparator group who did not have infection or disease. Suicidal and self-harm thoughts and behaviour (STBs) were outcomes of interest. Studies were excluded if they reported data for people who only had potential infection/disease without a confirmed exposure, clinical/molecular diagnosis or self-report of a positive SARS-CoV-2 test result. Studies of news reports, treatment studies, and ecological studies examining rates of both SARS-CoV-2 infections and suicide/self-harm rates across a region were also excluded. RESULTS: We identified 12 studies examining STBs in nine distinct samples of people with SARS-CoV-2. These studies, which investigated STBs in the general population and in subpopulations, including healthcare workers, generally found positive associations between SARS-CoV-2 infection and/or COVID-19 disease and subsequent suicidal/self-harm thoughts and suicidal/self-harm behaviour. CONCLUSIONS: This review identified some evidence that infection with SARS-CoV-2 and/or COVID-19 disease may be associated with increased risks for suicidal and self-harm thoughts and behaviours but a causal link cannot be inferred. Further research with longer follow-up periods is required to confirm these findings and to establish whether these associations are causal

Evaluation of Precision Livestock Technology and Human Scoring of Nursery Pigs in a Controlled Immune Challenge Experiment

The objectives were to determine the sensitivity, specificity, and cutoff values of a visual-based precision livestock technology (NUtrack), and determine the sensitivity and specificity of sickness score data collected with the live observation by trained human observers. At weaning, pigs (n = 192; gilts and barrows) were randomly assigned to one of twelve pens (16/pen) and treatments were randomly assigned to pens. Sham-pen pigs all received subcutaneous saline (3 mL). For LPS-pen pigs, all pigs received subcutaneous lipopolysaccharide (LPS; 300 µg/kg BW; E. coli O111:B4; in 3 mL of saline). For the last treatment, eight pigs were randomly assigned to receive LPS, and the other eight were sham (same methods as above; half-and-half pens). Human data from the day of the challenge presented high true positive and low false positive rates (88.5% sensitivity; 85.4% specificity; 0.871 Area Under Curve, AUC), however, these values declined when half-and-half pigs were scored (75% sensitivity; 65.5% specificity; 0.703 AUC). Precision technology measures had excellent AUC, sensitivity, and specificity for the first 72 h after treatment and AUC values were \u3e0.970, regardless of pen treatment. These results indicate that precision technology has a greater potential for identifying pigs during a natural infectious disease event than trained professionals using timepoint sampling

Systematic review of the impact of the COVID-19 pandemic on suicidal behaviour amongst health and social care workers across the world

BackgroundThe COVID-19 pandemic has had an impact on the mental health of healthcare and social care workers, and its potential effect on suicidal thoughts and behaviour is of particular concern.MethodsThis systematic review identified and appraised the published literature that has reported on the impact of COVID-19 on suicidal thoughts and behaviour and self-harm amongst healthcare and social care workers worldwide up to May 31, 2021.ResultsOut of 37 potentially relevant papers identified, ten met our eligibility criteria. Our review has highlighted that the impact of COVID-19 has varied as a function of setting, working relationships, occupational roles, and psychiatric comorbidities.LimitationsThere have been no completed cohort studies comparing pre- and post-pandemic suicidal thoughts and behaviours. It is possible some papers may have been missed in the search.ConclusionsThe current quality of evidence pertaining to suicidal behaviour in healthcare workers is poor, and evidence is entirely absent for those working in social care. The clinical relevance of this work is to bring attention to what evidence exists, and to encourage, in practice, proactive approaches to interventions for improving healthcare and social care worker mental health

Comparison of Enzymatic and Non-Enzymatic Means of Dissociating Adherent Monolayers of Mesenchymal Stem Cells

The dissociation of adherent mesenchymal stem cell (MSC) monolayers with trypsin and enzyme-free dissociation buffer was compared. A significantly lower proportion of viable cells were obtained with enzyme-free dissociation buffers compared to trypsin. Subsequently, the dissociated cells were re-seeded on new cell culture dishes and were subjected to the MTT assay 24 h later. The proportion of viable cells that reattached was significantly lower for cells obtained by dissociation with enzyme-free dissociation buffer compared to trypsin. Frozen–thawed MSC displayed a similar trend, yielding consistently higher cell viability and reattachment rates when dissociated with trypsin compared to enzyme-free dissociation buffer. It was also demonstrated that exposure of trypsin-dissociated MSC to enzyme-free dissociation buffer for 1 h had no significant detrimental effect on cell viability