Visual short-term memory binding deficit with age-related hearing loss in cognitively normal older adults

Age-related hearing loss (ARHL) has been posited as a possible modifiable risk factor for neurocognitive impairment and dementia. Measures sensitive to early neurocognitive changes associated with ARHL would help to elucidate the mechanisms underpinning this relationship. We hypothesized that ARHL might be associated with decline in visual short-term memory binding (VSTMB), a potential biomarker for preclinical dementia due to Alzheimer’s disease (AD). We examined differences in accuracy between older adults with hearing loss and a control group on the VSTMB task from a single feature (shapes) condition to a feature binding (shapes-colors) condition. Hearing loss was associated with a weaker capacity to process bound features which appeared to be accounted for by a weaker sensitivity for change detection (A’). Our findings give insight into the neural mechanisms underpinning neurocognitive decline with ARHL and its temporal sequence

What matters in Cardiovascular Research? Scientific discovery driving clinical delivery

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Corporate Governance for Sustainability

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features

The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFβ signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFβ signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFβ signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC’s with born to be bad traits

Impact of COVID-19 on acute appendicitis presentation, management and pathology findings in adult and paediatric populations

BackgroundWe investigated the impact of the COVID-19 pandemic on trends of presentation, management and pathology findings in patients who underwent an appendicectomy for suspected acute appendicitis.MethodThe retrospective study reviewed patients (n = 939 adults and n = 329 children) who had an appendicectomy performed for suspected acute appendicitis and histopathology assessment in the Belfast Health and Social Care Trust, Northern Ireland. Pre-COVID-19 (March 2019 to February 2020) and COVID-19 Year 1 (March 2020 to February 2021) data were compared. Chi-squared tests were applied to compare timeframes.Results513 adult appendicectomies were performed in the immediate year pre-COVID-19, compared to 426 in COVID-19 Year 1, representing a 17% reduction. No such reduction was seen within the paediatric population, likely related to a change in regional paediatric referral criteria during the pandemic. When comparing COVID-19 Year 1 with pre-pandemic, fewer patients presented with &lt;24 hours of symptoms (45% v 53%, p = 0.005), and there was greater use of pre-operative computed tomography imaging in adults (63.2% v 48.7%, p&lt;0.001). Fewer adult and paediatric cases of simple acute appendicitis and non-diagnostic specimens, with relative increased proportions of perforated acute appendicitis, were observed in COVID-19 Year 1 compared with pre-pandemic. No absolute increase in perforated acute appendicitis cases was observed in adults.ConclusionYear 1 of the COVID-19 pandemic was associated with delayed presentation of acute appendicitis in adults and children. In adults, an overall reduction in appendicectomy operations, increased use of pre-operative diagnostic imaging, and fewer specimens showing simple acute appendicitis or non-diagnostic features, collectively support appropriate restriction of surgery for those patients with a more certain acute appendicitis diagnosis.<br/

The Impact of the Mediterranean Diet on the Cognitive Functioning of Healthy Older Adults: A Systematic Review and Meta-Analysis

Evidence from epidemiologic studies suggests a relation between the Mediterranean diet (MeDi) and cognitive function, but results are inconsistent. Prior reviews have not provided pooled data from meta-analysis of longitudinal studies and randomized controlled trials (RCTs), or they included younger adult participants. This systematic review and meta-analysis examines the impact of the MeDi on the cognitive functioning of healthy older adults. Fifteen cohort studies with 41,492 participants and 2 RCTs with 309 and 162 participants in intervention and control groups, respectively, were included. The primary outcome of interest was cognitive function, divided into domains of memory and executive function. Meta-analysis of cohort studies revealed a significant association between MeDi and older adults' episodic memory (n = 25,369, r = 0.01, P = 0.03) and global cognition (n = 41,492, r = 0.05, P ≤ 0.001), but not working memory (n = 1487, r = 0.007, P = 0.93) or semantic memory (n = 1487, r = 0.08, P = 0.28). Meta-analysis of RCTs revealed that compared with controls, the MeDi improved delayed recall (n = 429, P = 0.01), working memory (n = 566, P = 0.03), and global cognition (n = 429, P = 0.047), but not episodic memory (n = 566, P = 0.15), immediate recall (n = 566, P = 0.17), paired associates (n = 429, P = 0.20), attention (n = 566, P = 0.69), processing speed (n = 566, P = 0.35), or verbal fluency (n = 566, P = 0.12). The strongest evidence suggests a beneficial effect of the MeDi on older adults' global cognition. This article discusses the influence of study design and components of the MeDi on cognitive function and considers possible mechanisms

Association of Age-Related Hearing Loss With Cognitive Function, Cognitive Impairment, and Dementia: A Systematic Review and Meta-analysis

Importance Epidemiologic research on the possible link between age-related hearing loss (ARHL) and cognitive decline and dementia has produced inconsistent results. Clarifying this association is of interest because ARHL may be a risk factor for outcomes of clinical dementia. Objectives To examine and estimate the association between ARHL and cognitive function, cognitive impairment, and dementia through a systematic review and meta-analysis. Data Sources and Study Selection A search of PubMed, the Cochrane Library, EMBASE, and SCOPUS from inception to April 15, 2016, with cross-referencing of retrieved studies and personal files for potentially eligible studies was performed. Keywords included hearing, cognition, dementia, and Alzheimer disease. Cohort and cross-sectional studies published in peer-reviewed literature and using objective outcome measures were included. Case-control studies were excluded. Data Extraction and Synthesis One reviewer extracted and another verified data. Both reviewers independently assessed study quality. Estimates were pooled using random-effects meta-analysis. Subgroup and meta-regression analyses of study-level characteristics were performed. Main Outcomes and Measures Hearing loss measured by pure-tone audiometry only and objective assessment measures of cognitive function, cognitive impairment, and dementia. Cognitive function outcomes were converted to correlation coefficients (r value); cognitive impairment and dementia outcomes, to odds ratios (ORs). Results Forty studies from 12 countries met our inclusion criteria. Of these, 36 unique studies with an estimated 20 264 unique participants were included in the meta-analyses. Based on the pooled maximally adjusted effect sizes using random-effects models, a small but significant association was found for ARHL within all domains of cognitive function. Among cross-sectional studies, a significant association was found for cognitive impairment (OR, 2.00; 95% CI, 1.39-2.89) and dementia (OR, 2.42; 95% CI, 1.24-4.72). Among prospective cohort studies, a significant association was found for cognitive impairment (OR, 1.22; 95% CI, 1.09-1.36) and dementia (OR, 1.28; 95% CI, 1.02-1.59) but not for Alzheimer disease (OR, 1.69; 95% CI, 0.72-4.00). In further analyses, study, demographic, audiometric, and analyses factors were associated with cognitive function. Vascular dysfunction and impaired verbal communication may contribute to the association between hearing loss and cognitive decline. Conclusions and Relevance Age-related hearing loss is a possible biomarker and modifiable risk factor for cognitive decline, cognitive impairment, and dementia. Additional research and randomized clinical trials are warranted to examine implications of treatment for cognition and to explore possible causal mechanisms underlying this relationship

The Impact of Adherence to the Traditional Mediterranean Diet and Sex Differences on Global Cognitive Functioning: a Systematic Review and Meta-analysis

Contradictory findings in reviews that assess the relationship between the Mediterranean Diet (MedDiet) and cognitive functioning have been attributed to heterogeneity in the criteria used to assess MedDiet and cognition, and differences in the location or cultural habits of the populations studied. Few reviews have examined the relationship between dietary adherence and cognition or considered the impact of sex differences. This systematic review and meta-analysis examines the relationship between adherence to the MedDiet and cognitive functioning of healthy older adults (50+). We included isolated data from Mediterranean regions and considered differential outcomes based on sex. A search of PubMed, Cochrane Library, EMBASE, Scopus and Web of Science from 2011 to 2018 identified five longitudinal cohort studies (n = 3368) and one randomized controlled trial (RCT; n = 239 intervention; n = 95 controls). The primary outcome of interest was global cognitive functioning. Meta-analysis of cohort studies revealed a significant association between MedDiet adherence and cognitive functioning (n = 3368, r = 0.09, p = 0.012), an effect greater than previously reported. Meta-regression demonstrated that the effect size was stronger with improved quality of study reporting (p = 0.01). Sex did not impact cognitive outcomes, but sex differences in levels of adherence were reported in individual studies. There might be a stronger association between MedDiet and cognitive functioning for older adults from Mediterranean countries compared to other geographical locations, perhaps due to higher adherence and/or longer exposure over the life course. Results are compared to those of prior meta-analyses, and the impact of sources of heterogeneity is considered. The potential influence of sex and gender, as biological and social constructs, on dietary adherence is discussed