Prioritisation of diabetes-related footcare amongst primary care healthcare professionals

Aims and objectives To assess primary healthcare professionals’ priority for managing diabetic foot disease (DFD) over the progressive course of the condition compared to other aspects of diabetes care. Background DFD affects up to 60 million people globally. Evidence suggests that comprehensive preventative footcare may reduce serious complications of DFD, such as amputation. Design A cross-sectional quantitative study reported according to STROBE statement. Methods General Practitioners (GPs) and Credentialled Diabetes Educators (CDEs) working within Australian primary care were invited to complete an online survey, to obtain information about preventative and early intervention footcare priorities and practices. Ten GPs and 84 CDEs completed the survey. Results On diagnosis of type 2 diabetes, haemoglobin A1c (HbA1c) review was identified to be one of the top three priorities of care by 57 (61%) of participants whilst at 20-year history of diabetes 73 (78%) participants indicated its priority. Foot assessments became a priority for 78% (n = 73) of participants and podiatry referrals a priority for 53% (n = 50) of participants only when a “foot concern” was raised. Referrals to specialist high-risk foot podiatrists or services were a first priority for 56% (n = 53), when the person had significant amputation risk factors. Conclusion Diabetes-related preventative footcare assessments and management remain a low priority amongst primary healthcare professionals. Preventative care for asymptomatic complications, such as DFD, may be overlooked in favour of monitoring HbA1c or medication management. Limited prioritisation of footcare in primary care is concerning given the risks for amputation associated with DFD. Relevance to clinical practice This study reveals the need for primary healthcare decision makers and clinicians to ensure preventative footcare is a focused priority earlier in the diabetes care continuum. Collaborative and widespread promotion of the importance of proactive rather than reactive footcare practices is required to support prevention of foot ulcers and amputation

A Tale of Two Tails: Exploring Stellar Populations in the Tidal Tails of NGC 3256

We have developed an observing program using deep, multiband imaging to probe the chaotic regions of tidal tails in search of an underlying stellar population, using NGC 3256's 400 Myr twin tidal tails as a case study. These tails have different colours of $u - g = 1.05 \pm 0.07$ and $r - i = 0.13 \pm 0.07$ for NGC 3256W, and $u - g = 1.26 \pm 0.07$ and $r - i = 0.26 \pm 0.07$ for NGC 3256E, indicating different stellar populations. These colours correspond to simple stellar population ages of $288^{+11}_{-54}$ Myr and $841^{+125}_{-157}$ Myr for NGC 3256W and NGC 3256E, respectively, suggesting NGC 3256W's diffuse light is dominated by stars formed after the interaction, while light in NGC 3256E is primarily from stars that originated in the host galaxy. Using a mixed stellar population model, we break our diffuse light into two populations: one at 10 Gyr, representing stars pulled from the host galaxies, and a younger component, whose age is determined by fitting the model to the data. We find similar ages for the young populations of both tails, ($195^{-13}_{+0}$ and $170^{-70}_{+44}$ Myr for NGC 3256W and NGC 3256E, respectively), but a larger percentage of mass in the 10 Gyr population for NGC 3256E ($98^{+1}_{-3}\%$ vs $90^{+5}_{-6}\%$). Additionally, we detect 31 star cluster candidates in NGC 3256W and 19 in NGC 2356E, with median ages of 141 Myr and 91 Myr, respectively. NGC 3256E contains several young (< 10 Myr), low mass objects with strong nebular emission, indicating a small, recent burst of star formation.Comment: Accepted for publication in MNRAS. 16 pages, 19 figure

Early-Life Socioeconomic Status and Adult Physiological Functioning: A Life Course Examination of Biosocial Mechanisms

A growing literature has demonstrated a link between early-life socioeconomic conditions and adult health at a singular point in life. No research exists, however, that specifies the life course patterns of socioeconomic status (SES) in relation to the underlying biological processes that determine health. Using an innovative life course research design consisting of four nationally representative longitudinal datasets that collectively cover the human life span from early adolescence to old age (Add Health, MIDUS, NSHAP, and HRS), we address this scientific gap and assess how SES pathways from childhood into adulthood are associated with biophysiological outcomes in different adult life stages. For each dataset, we constructed standardized, composite measures of early-life SES and adult SES and harmonized biophysiological measurements of immune and metabolic functioning. We found that the relative importance of early-life and adult SES varied across young-, mid-, and late-adulthood, such that early-life SES sets a life course trajectory of socioeconomic well-being and operates through adult SES to influence health as adults age. We also documented evidence of the detrimental health effects of downward mobility and persistent socioeconomic disadvantage. These findings are the first to specify the life course patterns of SES that matter for underlying biophysiological functioning in different stages of adulthood. The study thus contributes new knowledge critical for improving population health by identifying the particular points in the life course in which interventions might be most effective in preventing disease and premature mortality

Social relationships and physiological determinants of longevity across the human life span

Although much evidence has accrued in research over the past 20 years on the strong causal associations between social relationships and health and longevity, important gaps remain in our understanding of the mechanisms, timing, and duration of these associations. This study integrates social and biological disciplinary perspectives and research to examine how social relationships “get under the skin” to affect physiological well-being as individuals age. By combining data from and harmonizing measurement across four large nationally representative, population-based, contemporary surveys using an innovative longitudinal life course design, this study provides previously unidentified evidence on the biological and life course mechanisms linking social relationship patterns with health. As such, our findings advance explanations of the emergence and progression of diseases across the human life span

What Accounts for the Factors of Psychopathology? An Investigation of the Neurocognitive Correlates of Internalising, Externalising, and the p-Factor

Neurocognitive deficits have been consistently associated with a wide range of psy-chopathology and are proposed to not only be a consequence of the development of psychopathology but also directly involved in its aetiology. However, there is no clear understanding of what neurocog-nitive processes are particularly important to mental health. In this paper, we explored the association between neurocognitive abilities and the factors derived from structural models of psychopathol-ogy. Four hundred participants from a representative community sample completed measures of symptomology and substance use, as well as 8 neurocognitive tasks. We found a correlated-factors model, with internalising and externalising as the higher-order factors, and a single-factor model with only the p-factor, to be good fits for the data. Tasks that measured the speed of processing were significantly associated with internalising, externalising, and the p-factor, and accounted for significant amounts of unique variance in the factors after accounting for the common variance of the other tasks. Tasks that measured working memory, shifting, and inhibition were not significantly associated with psychopathology factors. Our findings suggest that neurocognitive abilities may not be differentially associated with psychopathology factors, but that speed of processing is a common correlate of the factors. We emphasise the importance of examining neurocognitive abilities and psychopathology on the individual level

Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer

Background: Previously we identified a DNA damage response–deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. Methods: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines, which represent DDRD-positive and -negative, were used to study the effects of chemokine release on peripheral blood mononuclear cell (PBMC) migration and the mechanism of immune signaling activation. Finally, we studied the association between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as detected by IHC. All statistical tests were two-sided. Results: We found that DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration (Fisher’s exact test P < .001) and that DDRD cells expressed the chemokines CXCL10 and CCL5 3.5- to 11.9-fold more than DNA damage response–proficient cells (P < .01). Conditioned medium from DDRD cells statistically significantly attracted PBMCs when compared with medium from DNA damage response–proficient cells (P < .05), and this was dependent on CXCL10 and CCL5. DDRD cells demonstrated increased cytosolic DNA and constitutive activation of the viral response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in a cell cycle–specific manner. Finally, we demonstrated that S-phase DNA damage activated expression of PD-L1 in a STING-dependent manner. Conclusions: We propose a novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production. Activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD tumors. We provide a rationale for exploration of DDRD in the stratification of patients for immune checkpoint–based therapies

Interaction of smoking and obesity susceptibility loci on adolescent BMI: The National Longitudinal Study of Adolescent to Adult Health

Background Adolescence is a sensitive period for weight gain and risky health behaviors, such as smoking. Genome-wide association studies (GWAS) have identified loci contributing to adult body mass index (BMI). Evidence suggests that many of these loci have a larger influence on adolescent BMI. However, few studies have examined interactions between smoking and obesity susceptibility loci on BMI. This study investigates the interaction of current smoking and established BMI SNPs on adolescent BMI. Using data from the National Longitudinal Study of Adolescent to Adult Health, a nationally-representative, prospective cohort of the US school-based population in grades 7 to 12 (12–20 years of age) in 1994–95 who have been followed into adulthood (Wave II 1996; ages 12–21, Wave III; ages 18–27), we assessed (in 2014) interactions of 40 BMI-related SNPs and smoking status with percent of the CDC/NCHS 2000 median BMI (%MBMI) in European Americans (n = 5075), African Americans (n = 1744) and Hispanic Americans (n = 1294). Results Two SNPs showed nominal significance for interaction (p < 0.05) between smoking and genotype with %MBMI in European Americans (EA) (rs2112347 (POC5): β = 1.98 (0.06, 3.90), p = 0.04 and near rs571312 (MC4R): β 2.15 (−0.03, 4.33) p = 0.05); and one SNP showed a significant interaction effect after stringent correction for multiple testing in Hispanic Americans (HA) (rs1514175 (TNNI3K): β 8.46 (4.32, 12.60), p = 5.9E-05). Stratifying by sex, these interactions suggest a stronger effect in female smokers. Conclusions Our study highlights potentially important sex differences in obesity risk by smoking status in adolescents, with those who may be most likely to initiate smoking (i.e., adolescent females), being at greatest risk for exacerbating genetic obesity susceptibility

SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression towards cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic and therapeutic targets in patients with liver fibrosis

DETECT schools study protocol: A prospective observational cohort surveillance study investigating the impact of COVID-19 in Western Australian schools

Introduction: Amidst the evolving COVID-19 pandemic, understanding the transmission dynamics of the SARS-CoV-2 virus is key to providing peace of mind for the community and informing policy-making decisions. While available data suggest that school-aged children are not significant spreaders of SARS-CoV-2, the possibility of transmission in schools remains an ongoing concern, especially among an aging teaching workforce. Even in low-prevalence settings, communities must balance the potential risk of transmission with the need for students\u27 ongoing education. Through the roll out of high-throughput school-based SARS-CoV-2 testing, enhanced follow-up for individuals exposed to COVID-19 and wellbeing surveys, this study investigates the dynamics of SARS-CoV-2 transmission and the current psychosocial wellbeing impacts of the pandemic in school communities. Methods: The DETECT Schools Study is a prospective observational cohort surveillance study in 79 schools across Western Australia (WA), Australia. To investigate the incidence, transmission and impact of SARS-CoV-2 in schools, the study comprises three “modules”: Module 1) Spot-testing in schools to screen for asymptomatic SARS-CoV-2; Module 2) Enhanced surveillance of close contacts following the identification of any COVID-19 case to determine the secondary attack rate of SARS-CoV-2 in a school setting; and Module 3) Survey monitoring of school staff, students and their parents to assess psycho-social wellbeing following the first wave of the COVID-19 pandemic in WA. Clinical Trial Registration: Trial registration number: ACTRN1262000092297