Elder abuse by family caregivers is an often-overlooked phenomenon that affects many older adults. Especially, retirement-aged children caring for their oldest-old parents with dementia may be at greater risk of engaging in harmful or abusive behaviors, given their own age-related health issues and other competing caregiving demands. Most of the elder abuse literature has focused on general demographic predictors of elder abuse, regarding the caregiver, care recipient, and the care environment. Less attention has been paid towards relationship factors, which may play a large role among these parent-child dyads. This study examined how relationship factors are associated with potentially harmful caregiver behaviors , which have been identified as “early warning signs” for elder abuse. Relationship factors of interest include positive and negative relationship quality measured by caregivers’ mean scores on the support and conflict subscales on the Quality of Relationship Inventory (QRI). We conducted in-depth interviews with 88 caregivers (65+) who are caring for their parents with dementia (90+) as the part of the Boston Aging Together Study. Regression models revealed that relationship conflict was significantly associated with higher levels of PHCB, accounting for caregiver, care recipient, and care environment characteristics. The creation of screeners to identify “high conflict” care dyads could prove useful in the early detection and intervention of potential elder abuse cases, given that caregivers may be more willing to report negative aspects of their relationship  than more obviously harmful or abusive behaviors.


Vascular risk factors including hypertension, diabetes and dyslipidaemia promote diverse pathological mechanisms in the brain leading to cerebral hypoperfusion and ultimately cognitive decline in people. Medial temporal, medial frontal and anterior cingulate atrophy has been closely associated with diabetes and medial temporal lobe atrophy is associated with hypertension in people with Alzheimer’s disease (AD).To assess if hypertension, diabetes and dyslipidaemia have differential effects on different brain locations using brain imaging in people with AD.18F] fluorodeoxyglucose- positron emission tomography (FDG-PET) data of 970 participants from two large Phase III multi-centre clinical trials of a novel tau aggregation inhibitor drug Leuco-Methylthioninium (LMTX)meeting research criteria for mild to moderate AD. Vascular risk factor data including hypertension, diabetes and dyslipidaemia were collected and quantification of FDG PET hypo-metabolism was done by calculating Standardized Uptake Value Ratio(SUVR).The current study is based on [Hypertension, diabetes and dyslipidaemia were found to have differential effects on brain locations in people with AD. When people with hypertension, diabetes and dyslipidaemia were compared to those without, mean SUVR was increased significantly in both left and right parietal and occipital lobes and decreased in left and right anterior cingulate gyri in hypertensives. SUVR was significantly higher in both left and right temporal lobes in diabetics andlower in both left and right anterior cingulate gyri in people with dyslipidaemia.Vascular risk factors including hypertension, diabetes and dyslipidaemia have differential effects on different brain regions, measured using SUVR analysis of FDG-PET.The FDG-PET data was taken from participants of two large phase III clinical trials sponsored by TauRx Therapeutics (Singapore). TauRx Therapeutics has contributed towards my studentship during my PhD but the data related to drug used in the clinical tria


Novel opportunities to examine how life experiences connect to health and mortality through biological aging have increased due to the affordability of genomic analysis. Although epidemiological studies suggest associations between stress and accelerated biological aging, most if not all measures in the past have been global, data cross-sectional, and from primarily white samples. As part of a completed measurement study, a diverse sample  provided detailed stress measures, including EMA and lifetime stress assessments, and consented to future analysis of their blood samples. We successfully used decade-old blood samples to estimate methylation-based epigenetic clocks and examined them within the context of various stress measures as a preliminary phase of a future longitudinal study. Additional whole genome sequencing will also allow for future work that incorporate continuous measures of genomic ancestry when examining lifetime discrimination-related stress, rather than simply testing for demographic group differences.


Electrocardiography and high-sensitivity cardiac troponin testing are routinely applied as the initial step for clinical evaluation of patients with suspected non-ST-segment elevation myocardial infarction. Once diagnosed, patients with non-ST-segment elevation myocardial infarction are commenced on antithrombotic and secondary preventative therapies before undergoing invasive coronary angiography to determine the strategy of coronary revascularisation. However, this clinical pathway is imperfect and can lead to challenges in the diagnosis, management, and clinical outcomes of these patients. Computed tomography coronary angiography (CTCA) has increasingly been utilised in the setting of patients with suspected non-ST-segment elevation myocardial infarction, where it has an important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia. CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory. In addition, CTCA provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease and highlights alternative or incidental diagnoses for those with cardiac troponin elevation. However, the routine application of CTCA has yet to demonstrate an impact on subsequent major adverse cardiovascular events. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction. We here review the current evidence relating to the clinical application of CTCA in patients with non-ST-segment elevation myocardial infarction and highlight the areas where CTCA is likely to have an increasing important role and impact for our patients. It accounts for 6% of all Emergency Department attendances in the UK, resulting in approximately 350,000 hospitalisations each year. In contemporary practice, the application of high-sensitivity cardiac troponin assays for the diagnosis of myocardial infarction is central to clinical pathways for acute chest pain. This has resulted in marked improvements in the detection of not only myocardial infarction but also myocardial injury, substantially altering the prevalence of the diagnoses of unstable angina and myocardial infarction. Moreover, high-sensitivity cardiac troponin assays can expedite the exclusion of myocardial infarction through so-called ‘rule-out’ pathways. Indeed, less than one in five patients are ultimately diagnosed with an acute coronary syndrome. However, because of their high sensitivity, these assays also have issues of specificity, and a large proportion of cardiac troponin elevations are unrelated to atherosclerotic plaque disruption or even not myocardial infarction.Acute chest pain is one of the commonest presentations to the Emergency Department, with half of the patients subsequently being hospitalised for assessment of suspected acute coronary syndrome. Furthermore, neither cardiac troponin concentration thresholds nor background cardiovascular risk factors are sufficient to identify underlying mechanisms of myocardial injury nor determine the subtypes of myocardial infarction. Therefore, invasive coronary angiography plays a pivotal role in the management of high-risk patients with acute chest pain, including those with cardiac troponin elevation.The differentiation between the various mechanisms responsible for myocardial injury and distinctive subtypes of myocardial infarction is critical because those with a classic or Type 1 myocardial infarction attributable to atherosclerotic plaque disruption are more likely to benefit from intensive pharmacotherapy and coronary revascularisation. Interestingly, only a half or less of patients admitted with cardiac troponin elevation are diagnosed with Type 1 myocardial infarction. Moreover, CTCA is cost-effective and reduces length of stay in patients with acute chest pain and without cardiac troponin elevation. To exclude underlying obstructive coronary artery disease, the European Society of Cardiology guidelines recommend CTCA for those with chronic coronary syndrome and a lower likelihood of the presence of haemodynamically significant stenosis, and for those with suspected acute coronary syndrome and a normal or inconclusive cardiac troponin concentration. However, it remains unclear whether patients with non-ST-segment elevation myocardial infarction would also benefit from CTCA by improving their downstream management and treatment. This review will examine the latest advances in CTCA in patients with acute chest pain, discuss the potential application of CTCA in those with suspected non-ST-segment elevation myocardial infarction, and highlight potential future developments in this area.Computed tomography coronary angiography (CTCA) has diagnostic accuracy and prognostic performance comparable to invasive coronary angiography in the diagnosis of obstructive coronary artery disease. It is associated with enhancing clinical diagnosis, better targeting of treatments, and improving clinical outcomes in patients with stable chest pain. Finally, an elevation in cardiac troponin in the absence of symptoms or signs of ischaemia is termed myocardial injury and can be acute  or chronic (persistently elevated). Although non-ischaemic aetiologies account for the majority of cardiac troponin elevations, differentiating and classifying myocardial injury and myocardial infarction are not always straightforward even among a panel of experts with pre-specified guidance.Any elevation of a cardiac troponin concentration above the 99th centile upper reference limit defines myocardial injury. Under such a pre-requisite, myocardial infarction is diagnosed by a rise and fall in cardiac troponin in the context of clinical symptoms or electrocardiographic signs suggestive of myocardial ischaemia. Based on underlying pathophysiology contributing to oxygen supply–demand imbalance, myocardial infarction is further subclassified into five types: atherothrombosis (Type 1), acute mismatch between oxygen supply and demand unrelated to atherosclerotic plaque disruption (Type 2), cardiac death presumably due to myocardial ischaemia (Type 3), and consequences of coronary procedures (Types 4 and 5). Currently, cardiac magnetic resonance imaging is recommended in patients with cardiac troponin elevation of undetermined aetiology. Based on the pattern of injury and dysfunction, it may distinguish myocardial infarction from myocardial injury, or alter a location of the infarct-related artery in non-ST-segment elevation myocardial infarction. However, the pattern of myocardial injury on imaging is not always specific for a disease or pathophysiological process, and the availability of cardiac magnetic resonance imaging service is limited.The presence of coronary atherosclerosis is a pre-requisite for Type 1 myocardial infarction and a common observation in Type 2 myocardial infarction. Although assessing coronary artery anatomy may aid in the distinction between myocardial injury and myocardial infarction, invasive coronary angiography has many limitations, especially when the infarct size is small. In those with cardiac troponin elevation in the absence of obstructive coronary artery disease, CTCA has greater sensitivity for the detection of atherosclerotic plaques and the identification of the infarct-related artery than invasive coronary angiography. Conversely, CTCA demonstrates that three-quarters of patients with cardiac troponin elevation and low clinical suspicion for acute coronary syndrome have no or minimal atherosclerotic plaques. Consequently, the likelihood of Type 1 myocardial infarction is extremely low when all coronary arteries are free from atherosclerotic plaques. Finally, it also offers an opportunity to evaluate other cardiothoracic structures and recognise alternative causes of myocardial injury. Therefore, CTCA provides important information to help guide the diagnosis and classification of aetiologies for myocardial injury  trial. In this trial, 1023 out of 2147 patients with non-ST-segment elevation acute coronary syndrome  underwent CTCA before invasive coronary angiography. Using invasive coronary angiography as the gold standard, the negative-predictive value for CTCA to exclude any diameter stenosis ≥50% was 91%. Among 24 patients who were falsely excluded by CTCA, only three had a lesion with diameter stenosis ≥50% in a major epicardial coronary artery by invasive coronary angiography. The positive-predictive value for CTCA to identify diameter stenosis ≥50% was 88%. Among 92 patients who were falsely included by CTCA, 17 had a non-diagnostic scan and 19 had previous coronary stenting. The negative-predictive value for patients with cardiac troponin elevation, an ischaemic electrocardiographic change, and a GRACE score >140 was 89%, 95%, and 95%, respectively. The overall negative- and positive-predictive values of CTCA remained similar when considering diameter stenosis ≥70% as the cut-off. Thus, CTCA has very similar diagnostic performance to invasive coronary angiography in the setting of non-ST-segment elevation myocardial infarction. It has excellent negative-predictive value and rarely misses an obstructive atherosclerotic lesion in a major epicardial coronary artery.CTCA has excellent diagnostic performance compared to invasive coronary angiography in patients with stable chest pain and a low-to-intermediate pre-test probability of coronary artery diameter stenosis ≥50%.Non-ST-segment elevation myocardial infarction represents three-quarters of all contemporary myocardial infarctions, but many do not have obstructive coronary artery disease at the time of invasive coronary angiography. Implementation of CTCA was associated with a slight increase in the immediate use of invasive coronary angiography. However, around 50% of patients were directly discharged from the Emergency Department after CTCA, and fewer patients required subsequent non-invasive functional testing for myocardial ischaemia, resulting in shorter lengths of stay and a reduced cost at the Emergency Department. Similarly, compared with routine functional ischaemia testing, CTCA was associated with a higher rate of invasive coronary angiography and subsequent coronary revascularisation but again shorter lengths of stay.Prior to the advent of high-sensitivity cardiac troponin testing, randomised controlled trials of low-risk patients with acute chest pain reported that rates of invasive coronary angiography and coronary revascularisation within usual clinical care were low at less than 6 and 3%, respectively .42 ImpIn the era of high-sensitivity cardiac troponin testing, three randomised controlled trials have evaluated the clinical effectiveness of CTCA in patients presenting with suspected or diagnosed non-ST-segment elevation myocardial infarction . The Bet In the overall RAPID-CTCA trial population, the rate of invasive coronary angiography was lower with CTCA than with standard of care (54% vs  61%) although there was no difference in the rates of coronary revascularisation. For those with cardiac troponin elevation in the RAPID-CTCA trial, the findings remained consistent, suggesting CTCA allows for the better selection of patients for coronary revascularisation even in higher risk patients. In the CARMENTA trial, both cardiac magnetic resonance imaging and CTCA reduced the proportion of patients referred to invasive coronary angiography during index hospitalisation  and at one year (88 and 70% vs  100%). In contrast, the diagnostic yield for the presence of diameter stenosis ≥70% was greater with CTCA than with cardiac magnetic resonance imaging or standard of care . Thus, these three trials demonstrate that CTCA reduces the requirement for invasive coronary angiography without affecting the use of coronary revascularisation especially in patients with suspected non-ST-segment elevation myocardial infarction. This has implications for resource management in hospitals where CTCA can help efficiently identify those who require invasive coronary angiography and access to coronary revascularisation.Reflecting the lower risk trial population, only a minority of patients in the BEACON trial underwent invasive coronary angiography (13–17%) or coronary revascularisation (7–9%), and the 30-day rates of these procedures were unaffected by CTCA.There is always a concern that the introduction of new tests will lead to so-called test inflation where new or incidental findings will lead to further testing. Indeed, in low-risk and asymptomatic populations, this is an inherent concern. However, in general, CTCA was associated with a reduced need for downstream or layering of testing in patients with non-ST-segment elevation myocardial infarction. In keeping with the rates of invasive coronary angiography, CTCA was associated with a reduced requirement for downstream non-invasive ischaemia testing. This was seen across all three trials and resulted in similar lengths of stay. Overall, these trials would suggest that CTCA has no or minimal impact on length of stay but does reduce the need for downstream non-invasive ischaemia testing without impacting on overall healthcare costs  in the RAPID-CTCA trial and 0.64  in the CARMENTA trial.Downstream clinical event rates are clearly determined by the length of follow-up and the risk of patients included in the trials. The follow-up duration of the BEACON trial was 30 days, and there was only one death and four possible recurrent acute coronary syndromes in 500 patients. The one-year event rate of death or myocardial infarction was comparable between the RAPID-CTCA (6%) and the CARMENTA (4%) trials. Nevertheless, patients with cardiac troponin elevation in the RAPID-CTCA trial appeared to have the highest risk as the one-year rate of death or myocardial infarction reached 8%.Overall, contemporary trials enrolling higher risk patients including those with non-ST-segment elevation myocardial infarction have suggested that early CTCA can lead to accelerated management and tailored investigations and treatments but does not have a major impact on near- and short-term major adverse cardiovascular events. The high sensitivity and negative-predictive value of high-sensitivity cardiac troponin assays have meant that there is little scope for CTCA to identify unrecognised cases of non-ST-segment elevation myocardial infarction. Thus, there is no opportunity to prevent recurrent immediate or intermediate clinical events for those already diagnosed with non-ST-segment elevation myocardial infarction. However, CTCA does have a role in identifying those with cardiac troponin elevation who do not have Type 1 myocardial infarction and thereby improves on specificity for the diagnosis of non-ST-segment elevation myocardial infarction. However, those clinical variables may not always represent a target that could be modified to improve outcomes, and the recommended risk scores and models do not always have good long-term discriminative performance. In contrast, cardiac imaging can potentially identify treatable targets, recommending treatment selection, as well as providing more powerful risk stratification.Initial risk stratification is essential in the clinical pathway for non-ST-segment elevation myocardial infarction in order to allocate appropriate therapies proportionate to the projected risk. Currently recommended risk stratification schemes using clinical variables offer good predictive value for near- and short-term outcomes. a finding that was recently reaffirmed in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial. For patients with suspected or diagnosed non-ST-segment elevation myocardial infarction, similar excellent risk prediction is seen with CTCA. In the VERDICT trial, the long-term (a median of 4.2 years) follow-up of 978 patients who underwent CTCA suggested that the presence of diameter stenosis ≥50% by CTCA was associated with an increased risk of major adverse cardiovascular events independent of cardiac troponin elevation. In addition, the presence of diameter stenosis ≥50% in left main coronary artery, proximal left anterior descending artery, or two or more vascular territories by CTCA identified patients at the highest risk of long-term adverse outcomes. Finally, among those without diameter stenosis ≥50% by CTCA, the subsequent findings of invasive coronary angiography did not further distinguish patients at increased risk.In patients with stable chest pain, CTCA-defined risk stratification is superior to functional testing for myocardial ischaemia, On the other hand, most cardiac troponin elevations are related to either Type 2 myocardial infarction or myocardial injury. Again, the differentiation between Type 1 myocardial infarction, Type 2 myocardial infarction, and myocardial injury can be challenging, and the optimal investigations and treatments for these conditions remain to be established. This has led to the design of several clinical studies investigating the use of CTCA in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction  is currently recruiting patients with intermediate risk and a cardiac troponin concentration within three times upper reference limit to evaluate the effect of coronary calcium scoring on diagnosis and management for patients in the observe zone. Another two studies, the Coronary CT Angiography for Improved Assessment of Suspected Acute Coronary Syndrome With Inconclusive Diagnostic Work-up  and the Prospective RandOmised Trial of Emergency Cardiac CT  will throw light on the effectiveness of CTCA in patients with a ‘non-diagnostic’ cardiac troponin concentration under the current clinical pathway.The atherosclerotic plaque burden measured by calcium score is a simple gauge for long-term cardiovascular outcomes independent of diameter stenosis, Beyond qualitative assessment, semi-automated quantification allows for a reproducible and detailed breakdown of atherosclerotic plaque morphology  study showed that two-thirds of patients with Type 2 myocardial infarction had coronary artery disease of any severity, of which half had not been identified previously. In addition, many of them were not treated with preventative therapies, suggesting missed treatment opportunities. Further substudies of the DEMAND-MI study and the DEFINing the PrEvalence and Characteristics of Coronary Artery Disease Among Patients With TYPE 2 Myocardial Infarction Using CT-FFR  study will use CTCA-based techniques to explore the prevalence of coronary artery disease, haemodynamically significant stenosis, and plaque characteristics among patients with Type 2 myocardial infarction. This information will increase our understanding of pathogenesis of Type 2 myocardial infarction and suggest potential treatment opportunities.Additional computational fluid dynamics and advanced molecular imaging may enhance the identification of adverse features that are culprit for incident acute coronary syndrome. the specificity of CTCA in discriminating anatomical (≥50% diameter stenosis) or functional  obstruction remains imperfect. Fractional flow reserve derived from CTCA is a promising approach that improves discrimination of those at higher risk for future events. However, its use has not resulted in further improvement of major adverse cardiovascular events in patients with stable chest pain. The CArdiac cT in the treatment of acute CHest pain-2 (CATCH-2) trial showed that additional computed tomography perfusion imaging further reduced the utilisation of invasive coronary angiography in low-risk patients with acute chest pain, but it was underpowered to evaluate clinical outcomes. These findings are not definitive, and the role of CTCA-derived fractional flow reserve or computed tomography myocardial perfusion remains to be established in non-ST-segment elevation myocardial infarction. Ultimately, any advanced computed tomography-based functional assessment will need to demonstrate incremental diagnostic and prognostic value over CTCA in the value-based health care.Although CTCA is excellent at identifying normal coronary arteries and avoiding unnecessary invasive coronary angiography, Thus, the greatest opportunity for CTCA to improve long-term clinical outcomes in those with acute chest pain may be in those who have myocardial infarction excluded but may still be at a high risk of future long-term cardiovascular events. Two ongoing randomised controlled trials, the Randomized Evaluation of Coronary Computed Tomographic Angiography in Intermediate-risk Patients Presenting to the Emergency Department With Chest Pain  and the Troponin in Acute Chest Pain to Risk Stratify and Guide EffecTive Use of Computed Tomography Coronary Angiography  trials, will determine the effectiveness of CTCA on long-term (≥3 years) major adverse cardiovascular events in such patients.The principal advantage of CTCA is to identify unrecognised coronary atherosclerosis regardless of stenosis severity as an opportunity to apply preventative interventions, such as antiplatelet and statin therapies. The benefit of such interventions take many years to accrue as demonstrated in patients with stable chest pain.In patients with suspected non-ST-segment elevation myocardial infarction, electrocardiography and high-sensitivity cardiac troponin testing will remain the initial step for clinical evaluation, and invasive coronary angiography is still the routine clinical tool to determine the strategy of coronary revascularisation. CTCA has an increasingly important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia especially among those with low or intermediate risk. Moreover, CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory, provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease, and can highlight alternative or incidental diagnoses for patients with non-ST-segment elevation myocardial infarction. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction.


Men using cholesterol-lowering statin medications have been found to have lower risks of both advanced and fatal prostate cancer in multiple registry-based studies and prospective cohort studies. Statin use has also been associated with longer survival among men already diagnosed with prostate cancer. Mechanisms responsible for purported anti-cancer effects of statins are not well understood but may offer insight into prostate cancer biology.We summarise epidemiological data from studies of statins and prostate cancer and discuss to what extent these findings can be interpreted as causal. Additionally, lipid-mediated and non-lipid-mediated mechanisms that may contribute to potential anti-cancer effects of statins are reviewed. Finally, we consider treatment settings and molecular subgroups of men who might benefit more than others from statin use in terms of prostate cancer-specific outcomes.Data from prospective observational studies generally reported a lower risk of fatal prostate cancer among statin users. There is some evidence for serum cholesterol-lowering as an indirect mechanism linking statins with advanced and fatal prostate cancer. Window-of-opportunity clinical trials show measurable levels of statins in prostate tissue highlighting potential for direct effects, whilst observational data suggest possible statin-driven modulation of prostate microenvironment inflammation. Additionally, emerging data from registry studies support a potential role for statins within the context of androgen deprivation therapy and anti-androgen treatment.Prospective and registry-based studies support a lower risk of advanced and fatal prostate cancer in statin users relative to non-users, as well as better outcomes among prostate cancer patients. The few randomised-controlled trials conducted so far have short follow-up, lack identified molecular subgroups, and do not provide additional support for the observational results. Consequently, additional evidence is required to determine which men may experience greatest benefit in terms of prostate cancer-specific outcomes and how statin effects may vary according to molecular tumour characteristics. Statins are competitive antagonists of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, whose activity is rate-limiting for the biosynthesis of cholesterol and derivatives via the mevalonate pathway. While the evidence supporting the role for statins in cardiovascular disease prevention is unequivocal , mountinThis review discusses epidemiological evidence supporting a potential role for statins in prostate cancer prevention, particularly prevention of fatal disease. Whilst underlying mechanisms behind statin effects in cancer are currently unclear, we review evidence from epidemiological studies that may support existing theories and provide greater understanding of prostate cancer biology. This is followed by an evaluation of data exploring the timing of statin use alongside, and potential synergy with, androgen deprivation therapies (ADT). Finally, we review current data regarding which patients may benefit more from statin use. Our companion review discusses mechanistic evidence of anti-tumour effects of statins from laboratory studies .Following the first report of a stronger association of pre-diagnosis statin use with advanced, metastatic and fatal prostate cancer , the majTwo prospective cohort studies addressed this question by following cancer-free men long term. Findings from the Health Professionals Follow-up Study, with 801 fatal prostate cancers diagnosed amongst 44,126 men during 24 years of follow-up, showed a 24% lower rate of fatal prostate cancer in pre-diagnosis statin users vs. non-users (hazard ratio (HR) 0.76; 95% CI 0.60–0.96) [In addition, registry-based studies have explored effects of pre- and post-diagnosis statin use on prostate cancer-specific mortality. A UK registry study reported that the association between post-diagnosis statin use and prostate cancer-specific mortality was strongest amongst pre-diagnosis statin users  . In contGiven that any clinical trial of statins is more feasible among men already diagnosed with prostate cancer, it is informative to evaluate the effect of post-diagnosis statin use on prostate cancer-specific outcomes. Indeed, all three aforementioned studies reported similar magnitudes of association between post-diagnosis statin use and reduced prostate cancer-specific mortality. Specifically, the Finnish Randomised Study of Screening for Prostate Cancer showed that post-diagnosis statin use was associated with a 20% (95% CI 0.65–0.98) lower rate of prostate cancer-specific mortality, with stronger associations among those using higher doses of statins and for longer durations . The magBefore taking next steps, a central question is whether bias from confounding and other sources may affect reported associations between statin use and prostate cancer outcomes as they do in studies of other commonly used medications . For exaAppropriate analytic methods as well as prospective study designs help reduce potential sources of bias. Prospective cohort studies address confounding through adjustments for detailed measures of modifiable and non-modifiable risk factors for prostate cancer and competing causes of death, with registry studies using medical diagnoses and medications as proxies. As it is ultimately unknowable if confounding and bias was successfully controlled in observational studies, results from existing randomised trials need to be considered.The Cholesterol Treatment Trialists’ Collaboration pooled data from 27 major randomised-controlled trials of statin therapy, including 1877 incident prostate cancers and 211 prostate cancer deaths over a median follow-up of 4.8 years, with null results  . A doublIdentification of mechanisms linking statins and prostate cancer could provide a biological rationale to support epidemiological associations. Unfortunately, the mechanisms responsible for purported statin anti-cancer effects are still unclear though two broad categories have been proposed: lipid-mediated and non-lipid-mediated, for which we have summarised the epidemiological evidence below. Our companion review considers mechanistic evidence from laboratory studies .Statins have a pronounced effect on serum lipid levels, reducing low density lipoprotein (LDL) cholesterol by 30–60%, total cholesterol by 23–28% , and triIn a meta-analysis of six studies, the association between high versus low categories of total serum cholesterol and high-grade or advanced prostate cancer  tended to be slightly more pronounced than for total prostate cancer  . SeveralAn additional consideration is that serum lipid levels may not reflect tumour lipid levels. In a randomised-controlled trial, 160 men were treated with radical prostatectomy after randomisation to high-intensity atorvastatin (80 mg daily) or placebo for at least 28 days . MetabolOne approach to teasing apart the mechanism is to compare associations of statin versus non-statin cholesterol-lowering drugs with prostate cancer, though this can be challenging due to the overlap in use of statin and non-statin cholesterol-lowering medications and therefore necessitates large studies. A registry study from the Canadian province of Saskatchewan  found thSeveral studies have found measurable statin levels within the prostate tissue itself. The ability of statins to access the prostate supports the potential for direct physiological effects of statins unrelated to systemic lowering of circulating cholesterol and other lipid species. Two window-of-opportunity trials measured statin concentrations in prostate tissue after roughly 4 weeks of statin treatment. A Canadian pilot trial randomised men with localised prostate cancer to 80 mg fluvastatin for 4–12 weeks prior to their scheduled radical prostatectomy. Fluvastatin was detected in prostate tissue of 10 (36%) of 28 patients evaluated, and mean intraprostatic fluvastatin concentration in these ten patients was 9.7 ng/g or 24 nM, while mean serum fluvastatin levels were tenfold higher (200 nM) . AnotherReduction of systemic and local inflammation is one of the best described non-cholesterol-lowering effect of statin use. Results from secondary analyses of cardiovascular disease clinical trials demonstrate that statins lower plasma levels of the inflammatory biomarker C-reactive protein , 35 in aTwo prostate cancer chemoprevention trials, REDUCE and the Prostate Cancer Prevention Trial (PCPT), provided opportunities for assessing the association of statin use with benign prostate inflammation among men undergoing study-mandated, PSA-independent prostate biopsies. REDUCE, which recruited men with elevated baseline PSA but a negative prostate biopsy, found lower risk of chronic histological inflammation of negative biopsies in statin users versus non-users  and suggested lower odds of severe acute histological inflammation  . By contA window-of-opportunity clinical trial which administered atorvastatin to 158 men scheduled to undergo radical prostatectomy in Finland examined intraprostatic inflammation as a secondary endpoint. Among men with high-grade disease randomised to atorvastatin, histological inflammation score was slightly lower . FinallyAlthough potential mechanisms discussed above are grouped into lipid-mediated and non-lipid-mediated categories, it is important to note that statins have pleiotropic effects, and so these may not be mutually exclusive. Mechanisms are challenging to tease apart in epidemiological studies, and country-specific prescribing patterns and differences in treatment protocols may hinder direct comparison of findings from various studies.One major consideration is whether it is appropriate to analyse statins together as a class or whether their effects and mechanisms need to be considered according to the statin type or subgroup. While many studies reported the prevalence of use of various statin types and doses (previously summarised in ), most wIn addition to statin type, few observational studies have been able to accurately account for variations in serum cholesterol levels throughout statin therapy. The previously mentioned ARIC study by Mondul et al. performed a stratified analysis by pre-statin serum cholesterol level  and found similar associations between statin use and fatal prostate cancer in both groups . MurtolaGiven a cardiovascular risk profile that places most men with prostate cancer at high cardiovascular event risk , these mAs a first step towards answering this question, several studies explored the association between post-diagnosis statin use and prostate cancer-specific mortality, stratified by tumour characteristics at diagnosis. An analysis of the Health Professionals Follow-up Study reported that post-diagnosis statin use was not associated with lower prostate cancer-specific mortality overall , but found an inverse association among men diagnosed with higher stage prostate cancer , not present among men with stage T1 disease  . An obseTMPRSS2:ERG fusion (ERG) status [Examining associations with subgroups defined by pathological and molecular features could highlight not only the most statin sensitive prostate tumours but could also bring to light new molecular targets that may be susceptible to other treatment modalities. Efforts to identify molecular biomarkers of prostate tumours that may be particularly susceptible to statins are now underway, which would enable more precise identification of men predicted to benefit. Within the prospective Health Professionals Follow-up Study, we reported a lower risk of PTEN-null prostate cancer among cancer-free men who used statins compared to non-users  and no association between statin use and PTEN-intact prostate cancer  . The ass) status . As ERG ) status , height ) status , physica) status , and lyc) status  further As statins are associated with reduced risk of advanced prostate cancer and androgen deprivation therapy (ADT) is the main treatment for this patient subgroup, it is not surprising that recent investigations have focused on statins in the context of patients managed with ADT Table . A 2017 By inhibiting androgen synthesis in the testes, ADTs lower systemic androgen levels, limiting androgen signalling pathways driving prostate cancer survival and proliferation. However, tumour progression inevitably occurs in spite of low availability of circulating androgens through a variety of documented mechanisms including intratumoral androgen synthesis from cholesterol . As suchWith a view to understanding which point in clinical progression that the tumour may be most sensitive to statins, a number of studies reporting lower prostate cancer-specific mortality in statin users Table  performeAside from blocking intratumour cholesterol ester accumulation, which may primarily affect advanced tumours with the necessary enzymatic machinery to synthesise intratumoral androgens, an alternative hypothesis as to why statins may synergise with ADT lies in their potential effect on adrenal androgens such as dehydroepiandrosterone (DHEAS), a precursor to the more potent dihydroxytestosterone (DHT) and testosterone. As adrenal androgens continue to be synthesised despite orchiectomy or pharmaceuticals that modulate gonadotropin-releasing hormone, which largely target testicular androgen synthesis, they are thought to be one of the mechanisms of tumour resistance to ADT . A pre-sSecond generation anti-androgens, including abiraterone acetate, interfere with the androgen signalling axis in multiple organs including the adrenal glands as well as the prostate itself. As such, the aforementioned downregulation of adrenal androgens by statins suggests a mechanism whereby statins could complement downregulation of adrenal androgens by abiraterone to improve prostate cancer outcomes. As statins compete with abiraterone for SLCO-mediated influx there were initial concerns that statins may be antagonistic to abiraterone and therefore interfere with treatment efficacy. However, a US hospital-based cohort study found a trend towards longer duration of abiraterone response among men with CRPC using statins  . The retTo date, the observational data summarised in our review shows a narrowing of focus for the promise of statin for prevention of all prostate cancer to prevention of fatal prostate cancer. Results showing an inverse association between statins and fatal prostate cancer risk are promising. While this is particularly encouraging given these patients currently have limited effective treatments and shorter survival times, biomarkers may help identify and subsequently target the molecular subgroups that are most likely to benefit from statin therapy. Given that statins are comparatively safe, in addition to support for improved prostate cancer-related outcomes in statin users, it could be argued that most men with prostate cancer should receive a statin. A central consideration here is that men with prostate cancer, particularly those receiving ADT , are at It is critical that these questions be evaluated using randomised-controlled trials. With advances in molecular profiling of prostate cancer, resulting biomarkers may aid in more efficient selection of participants for clinical trials of statins as well as become appropriate intermediate endpoints in such trials.As one of the world’s most prescribed medications, statins are well-established and clinically safe drugs. For prevention and treatment of prostate cancer, as summarised in this review, the most pronounced and robust associations have been observed between statin use and outcomes related to advanced prostate cancer. A key consideration is the high burden of cardiovascular disease among men with prostate cancer , 71, witOur review shows that statins are not a cure-all, but the hype surrounding this class of drugs is understandable. Prostate cancer research motivated by potential statin effects has advanced our understanding of prostate cancer biology with regards to both cholesterol and lipid metabolism (see partner review of mechanistic data)  as well With many observational studies supporting the hypothesis that statins may protect against fatal prostate cancer, there is hope that statins could form part of a multipronged therapeutic strategy. Ultimately, the focus should be on testing this hypothesis in patients using randomised-controlled trials. Furthermore, translational research integrating epidemiological data and lab-based investigations could help identify biomarkers of statin sensitivity. Such biomarkers would be beneficial to define molecular subgroups for subsequent examination in observational and trial-based settings.


Exercise intensity has been suggested to influence acute appetite-regulating gut hormone responses after exercise. High intensity interval training (HIIT) with near maximal to maximal intensity or sprint interval training (SIT) with supramaximal intensity might induce greater effects on gut hormones compared to moderate intensity continuous training (MICT), while current findings were inconsistent regarding the effects of these popular training methods.This systematic review and meta-analysis aimed to synthesis the findings in the literature and explore the impact of exercise modality on acylated ghrelin (AG), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).After searching the major databases  to find articles published up to May 2022, twelve studies that compared hormone responses to HIIT/SIT and MICT were identified and included in the analysis.A random-effects meta-analysis showed that HIIT/SIT and MICT decreased AG concentration and increased GLP-1 and PYY concentration compared with no exercise control group, while interval training protocols, especially SIT protocols, elicited greater effect sizes in suppressing AG levels at all of the analysed time points and PYY immediately post-exercise compared to MICT.Acute SIT with lower exercise volume appears to be a more advantageous approach to decrease plasma AG concentration and potentially suppress hunger to a greater extent compared to MICT, despite the similar effects of HIIT/SIT compared to MICT in increasing anorectic hormones . Future studies are needed to further investigate the impact of moderators  on the variability of changes in gut hormones after interval trainings.


Immunization programs are key preventive interventions and have largely contributed to reducing the burden of infectious diseases and decreasing related morbidity, mortality and healthcare costs. The study aimed to investigate coverage regarding diphtheria, tetanus, and acellular pertussis (dTap) - Inactivated Poliomyelitis Vaccine (IPV) and Human Papilloma Virus (HPV) vaccine and attitudes towards vaccinations among undergraduate university students in Southern Italy.This cross-sectional study was conducted among 327 students through an anonymous online questionnaire and included socio-demographic characteristics, attitudes towards vaccinations overall and specifically on dTap-IPV and HPV, reasons for having received or not vaccinations and willingness to receive vaccinations.One third of the students were concerned about serious adverse effects of vaccines and 95% believed that vaccines for uncommon diseases are useless. During adolescence, 89% of the sample received the mandatory dTap-IPV vaccine booster. Among unvaccinated students, 45% were unwilling to get vaccinated against dTap-IPV because they believed not to be at risk of infection (59%) and had lack of recommendation (35.3%). Regarding vaccination against HPV, 67% had received the recommended schedule. Among those who did not receive it, 34% were unwilling to get vaccinated because they did not feel at risk of HPV infection (41%). Interestingly, 16% of the sample disclosed some barriers to access vaccination centers. Moreover, 30% declared that HPV vaccination was discouraged by healthcare professionals (HCPs).Vaccination uptake is worryingly low and national objective coverage seems not still achieved. Likewise, risk perception of vaccine-preventable diseases was low and it seems negatively impact on the intention to get vaccinated. Improving vaccine confidence among HCPs is crucial as they have been shown to have the potential to influence patient vaccination uptake.Skilled communication with a trusted HCP could increase acceptance of vaccine during adolescence and address vaccine hesitancy.Strategies to disseminate information on vaccines should be established to increase mandatory and recommended vaccines coverage.


The Appalachian region is often characterized by poor health outcomes and economic depression. Health centers (HCs) are community-based and patient-directed organizations that deliver comprehensive, culturally competent, high-quality primary healthcare services in high need areas, including Appalachia, where economic, geographic, or cultural factors can hinder access to healthcare services.The study compares the clinical quality performance in preventive care and chronic disease management between Appalachian HCs and their non-Appalachian counterparts.Using 2015 Uniform Data System (UDS) health center data, bivariate and multivariate linear regression analyses examine the association of Appalachian HC with performance on preventive and chronic care clinical quality measures (CQMs).In the multivariate analysis, patients served at Appalachian HCs are more likely to receive colorectal cancer screening and pediatric weight assessment and counseling than at non-Appalachian HCs. No statistically significant differences in performance observed among other CQMs. The percentage of Medicaid patients and total physician FTEs have positive associations with preventive care in colorectal and cervical cancer screening, pediatric weight assessment and counseling, and tobacco screening and cessation intervention as well as chronic disease management of aspirin therapy for ischemic vascular disease and hypertension control in the multivariate model.Overall Appalachian HCs perform as well as or better than non-Appalachian HCs in delivering preventive and chronic care services. Further examination of clinical quality improvement programs, insurance payer mix, and practice size among Appalachian HCs could advance the replication of clinical quality success for clinics in similar underserved communities. The Appalachian region is a geographically and culturally distinctive region of the U.S. extending from New York to Alabama characterized by largely rural geography and resiliency assets that include strong social cohesion, family ties, social support, and spiritual belief.7Health centers (HCs) are community-based and patient-directed organizations that deliver comprehensive primary health care services and receive federal grant funding from the Health Resources and Services Administration (HRSA). HCs provide services in high-need areas, including Appalachia, where economic, geographic, or cultural factors hinder access to affordable primary care services. Annually, HCs are required to report clinical quality measures (CQMs) into HRSA’s Uniform Data System (UDS). This study uses the national 2015 UDS data to examine the differences in clinical quality performance in preventive care and chronic disease management between the Appalachian HCs and their non-Appalachian counterparts.The HRSA’s 2015 UDS data contain health center organizational-level data for patient sociodemographic, services provision, workforce, clinical quality measures, cost, and revenues.This cross-sectional study examines six preventive care and three chronic care CQMs reported in the UDS. The preventive measures consist of the following:cervical cancer screening: percentage of women aged 21–64 years who received timely Pap tests to screen for cervical cancer;colorectal cancer (CRC) screening: percentage of patients aged 50 to 75 years who had appropriate screening for colorectal cancer, which could be a colonoscopy within the last 10 years, a flexible sigmoidoscopy within the last 5 years, or an annual fecal occult blood test (FOBT), including the fecal immunochemical (FIT) test;body mass index (BMI) screening and follow-up plan: percentage of patients aged 18 and older with a documented BMI during the most recent visit or within the 6 months prior to that visit and when the BMI is outside of normal parameters, a follow-up plan is documented;weight assessment and counseling for nutrition and physical activity for children and adolescents: percentage of patients aged 3–17 years who had evidence of BMI percentile documentation and who had documentation of counseling for nutrition and who had documentation of counseling for physical activity during the measurement year;tobacco use and screening and cessation intervention: percentage of patients aged 18 years and older who were screened for tobacco use at least once during the measurement year or prior year and who received cessation counseling intervention and/or pharmacotherapy if identified as a tobacco user; andscreening for depression and follow-up plan: percentage of patients aged 12 years and older screened for clinical depression using an age appropriate standardized tool and follow-up plan documented.The chronic disease management clinical quality measures are as follows:aspirin therapy for patients with ischemic vascular disease;blood pressure control (as defined by hypertensive patients with a blood pressure less than 140/90); andrate of uncontrolled diabetes, that is, diabetic patients with a hemoglobin A1c (HbA1c) > 9%.Bivariate and multivariate linear regression analyses examined the association between being an Appalachian health center and performance on preventive and chronic care clinical quality measures. Other covariates in the regression model include patient characteristics, total number of physician full-time equivalent (FTE) as a proxy for practice size, and patient-centered medical home (PCMH) recognition status. HRSA has supported HC’s implementation of PCMH practice transformation to improve clinical quality through effective care coordination and holistic care. Patient characteristics were composed of percentage of racial/ethnic minority patients, percentage of patients at or below 100% of the federal poverty level (FPL), and percentage of Medicaid patients. Statistical analyses were conducted using SAS version 9.3.In In the multivariate linear regression analysis as exhibited in Our findings demonstrate that patients receiving health care in Appalachian HCs experience quality of preventive and chronic care on par with patients served at non- Appalachian HCs. In particular, receiving care at Appalachian HCs is not associated with lower cervical cancer screening rate, which suggests Appalachian HCs are making strides towards addressing risk factors associated with receipt of cervical cancer screening such as lack of routine source of medical care, self-image insecurity, cultural stigma, as well as misperceptions about health and cancer.10Of particular interest are findings of positive associations between Appalachian HC and preventive CQMs of CRC screening and pediatric weight assessment and counseling. The CRC screening CQM performance in Appalachia HCs may reflect targeted clinical quality improvement initiatives by HCs and professional organizations to expand CRC screening modalities beyond colonoscopy, address financial barriers, and enhance trust in patient–provider relationships towards screening recommendation adherence.The primary limitation of this study is that findings from 2015 UDS cross-sectional data do not allow for causal inferences. In addition, the Appalachian HC definition includes any HC with a clinical service delivery site in an Appalachian county, which may potentially lead to the inclusion of primary care service sites in border counties incorporated into CQM data reported at the HC organizational level.Overall, Appalachian HCs perform better than or comparable to their non-Appalachian counterparts in delivering preventive and chronic care services. Additionally, study findings suggest that HCs may be providing effective primary care that helps offset health care related disparities expected in Appalachia communities. In particular, barriers to Appalachian health disparities can be overcome by culturally competent care delivered in organizations such as HCs that utilize PCMH model of care with strong care coordination and case management to improve CQMs in Appalachian communities.What is already known about the subject? Health disparities in the Appalachian region reflect broader trends in rural America, which include higher prevalence of obesity, diabetes, hypertension, cancer mortality, lower life expectancy, and lower adoption of preventive screening.What is added by this report? The Appalachian health centers performed better or comparable than their non-Appalachian counterparts in delivering high quality primary care in preventive and chronic disease management.What are the implications? Future research on clinical quality improvement programs, insurance payer mix, and practice size among Appalachian health centers could advance the replication of clinical quality success for clinics in similar underserved communities.


Individuals differ in the extent to which they represent their goals as hoped-for versus feared states. We examined the role of such goal representations for how everyday affective experiences and goal pursuit are intertwined. When goals are represented as hoped-for states, we expected stronger associations between daily positive affect and goal pursuit. In contrast, when goals are represented as feared states, we expected stronger associations between daily negative affect (particularly fear) and goal pursuit. We used seven days of repeated daily life assessments from 238 older individuals . At baseline, participants reported three goals they planned to pursue over the study period and the extent to which each goal referred to something they hoped-for or feared. During the daily life assessments, participants reported their current affective states and momentary goal pursuit  three times per day . Multilevel analyses regarding participants’ most salient goal provide initial evidence supporting the expected interactions of goal representations on everyday affect–goal pursuit links. Specifically, individuals with a strong hope-focus in their goals engaged in more goal pursuit when positive affect was up than individuals whose goals were low in hope-focus. In contrast, those with feared goals engaged in more goal pursuit when reporting increased fear. Findings are discussed in the context of the possible selves literature. Future analyses will examine lead-lag effects to address the temporal order underlying affect-goal pursuit associations.


Despite concerns regarding the risks of ionizing radiation from computed tomography (CT) imaging, the rates of abdominal pelvic CT (APCT) utilization in the emergency department (ED) continues to increase for patients with inflammatory bowel disease (IBD).To determine the factors that drive decisions on when to perform APCT imaging in the ED for patients with IBD and to determine if differences exist between physician specialties.We performed a quantitative, web-based survey between November 2021 and August 2022. Structured questions for Crohn’s disease (CD) and ulcerative colitis (UC) were developed with input from stakeholders in gastroenterology, surgery, and emergency medicine. Surveys were disseminated to Canadian physicians in each of the three specialities through personal emails, and by newsletter from national specialty organizations. Between specialty comparisons were performed by Chi-squared and Fisher exact tests where appropriate.A total of 208 participants responded to our survey: median age 44 years (IQR 37-50), 132 (63%) male, and 141 (68%) in an academic practice. Survey participants included 81 (39%) gastroenterologists, 35 (17%) surgeons and 92 (44%) emergency physicians.There were significant differences between specialties in the perceived rates of positive findings from APCT imaging. In UC, gastroenterologists felt inflammation alone was more common than emergency physicians and bowel obstruction and septic complications less common than surgeons and emergency physicians. In CD, surgeons felt bowel obstructions, septic complications and bowel perforations were more common compared with gastroenterologists and emergency physicians.There were significant differences between specialties in the types of clinical presentations that drove decisions to arrange APCT imaging . In UC, gastroenterologists were less likely to order APCT imaging for diarrhea with rectal bleeding, abdominal pain without peritoneal findings and fever than surgeons and emergency physicians. In CD, there were similar practice patterns between specialities except gastroenterologists were less likely to order APCT imaging for diarrhea with rectal bleeding than surgeons.Our survey identified key differences between physician specialties in the perceived rates of positive findings from APCT imaging and practice patterns of CT utilization. These findings will help to guide the development of future multidisciplinary consensus guidelines for the appropriateness of CT imaging in the ED for patients with IBD.NoneNone Declared


Antenatal depression and antenatal anxiety adversely affect several obstetric and foetal outcomes, and increase the rate of postnatal mental illness. Thus, to tackle these challenges the need for social support during pregnancy is vital.This study examined the association between domains of social support and antenatal depressive and anxiety symptoms among Australian women.Our study used data obtained from the 1973–78 cohort of the Australian Longitudinal Study on Women’s Health (ALSWH), focusing upon women who reported being pregnant (n=493). Depression and anxiety were assessed using the Center for Epidemiological Studies Depression (CES-D-10) scale, and the 9-item Goldberg Anxiety and Depression scale (GADS) respectively. The 19 item-Medical Outcomes Study Social Support index (MOSS) was used to assess social support. A binary logistic regression model was used to examine the associations between domains of social support and antenatal depressive and anxiety symptoms.After adjusting for potential confounders, our study found that the odds of antenatal depressive symptoms was about four and threefold higher among pregnant women who reported low emotional/informational support  and low social support   respectively compared with their counterpart. In addition, the odds of antenatal anxiety symptoms was seven times higher among pregnant women who reported low affectionate support/positive social interaction .Low emotional support and low affectionate support have a significant association with antenatal depressive and anxiety symptoms respectively. As such, targeted screening of expectant women for social support is essential.No significant relationships.


Despite efforts by the WHO to support local surveillance strategies in developing countries, there is a lack of robust public health surveillance frameworks. As a result, early infectious disease outbreak detection and response remain a significant challenge for local health systems in low-resource settings such as sub-Saharan African countries. In contrast, the growing digital infrastructure, especially in the mobile phone sector, and the global availability of extensive digital data offer promising solutions to enhance and strengthen epidemiological surveillance. Yet, there is little insight into concepts of utilisation and transfer into local public health practice. Using Tanzania as an example, a novel electronic surveillance and early outbreak alert framework is being developed that links signals on emerging diseases with relevant contextual Open Data for rapid outbreak risk assessment. The concept focuses on haemorrhagic fever diseases, specifically dengue virus disease, which is increasingly spreading in sub-Saharan Africa. A data stack framework forms the core of the system, which augments electronic information on the occurrence of acute haemorrhagic fever syndrome, e.g., collected via mobile phone-based surveillance tools, with openly available socio-ecological context data specific to dengue. Preliminary results on the data and information flow within the surveillance framework are presented and strategies for an automated indicator-based risk assessment for dengue outbreaks will be discussed, supplemented by an agent-based simulation framework to model possible short-term outbreak scenarios. In addition, adequate data inputs, identified through an appraisal of various data sources available for Tanzania, are outlined. The framework could serve as a blueprint for designing locally implementable early warning and decision support systems integrated with existing digital surveillance infrastructure.• Digital health surveillance and Open Data offer great potential for early outbreak detection and supporting health decisions but require tailored solutions to benefit low-resource settings.• Building on existing digital surveillance infrastructure, the framework may serve as a blueprint for designing an enhanced surveillance and decision support system for infectious disease outbreaks.


Coping styles refer to cognitive and behavioral patterns used to manage the demands of stressors. This study aimed to characterize associations between coping styles and cognitive functioning across non-Hispanic Black and non-Hispanic White older adults. Cross-sectional data comes from the Michigan Cognitive Aging Project . Coping styles are measured with COPE inventory. Global cognition was a composite of five cognitive domain factor scores derived from a comprehensive battery. Results show that Black older adults reported more emotion-focused coping than Whites, but there were no differences in problem-focused coping. Less emotion-focused and greater problem-focused coping were each more strongly associated with better global cognition among Black older adults, who showed disproportionately worse cognitive performance in the context of less adaptive coping. Coping style may be a particularly important psychosocial resource for cognitive health among Black older adults who may have less access to compensatory resources than Whites.


Cell senescence and inflammation are interconnected mediators of aging and age-related disease. Recent advances in molecular and cellular profiling methods and research models are aiding in our ability to decipher mechanisms through which senescent cells drive inflammatory dysfunction, and inversely, to discover mechanisms through which aging immune cells may drive senescence, inflammation, and pathology. This symposium will feature exciting advances that span the emerging conceptual framework of how senescence and inflammation influence mammalian aging. Dr. Birgit Schilling will discuss the use of advanced mass spectrometric methods for profiling the senescent cell proteome, which reveal new insights into protein pathways and mechanisms of aging and disease. Dr. Matt Yousefzadeh will share how endogenous DNA damage can invoke cellular senescence, which enhances inflammation in both a cell autonomous and non-autonomous manner to drive tissue dysfunction and impact health. Dr. Daniel Tyrrell will discuss discovery of a novel population of age-associated CD8 T-cells that enhance local tissue senescence and inflammation and promote atherosclerosis. Dr. Xu Zhang will share a characterization of senescent cells in skeletal muscle using single-cell RNA-sequencing and the potential recruitment of immune cells by senescent fibroadipogenic progenitors. Dr. Marissa Schafer will discuss cell senescence as a mediator of age-related brain inflammatory cell composition and senescent cell targeting as a strategy to prevent cognitive decline. Importantly, discoveries discussed in this symposium may reveal new avenues for therapeutic development, to ultimately improve human healthspan.


We can understand the ecology and evolution of plant thermal niches through thermal performance curves (TPCs), which are unimodal, continuous reaction norms of performance across a temperature gradient. Though there are numerous plant TPC studies, plants remain under-represented in syntheses of TPCs. Further, few studies quantify plant TPCs from fitness-based measurements , limiting our ability to draw conclusions from the existing literature about plant thermal adaptation. We describe recent plant studies that use a fitness-based TPC approach to test fundamental ecological and evolutionary hypotheses, some of which have uncovered key drivers of climate change responses. Then, we outline three conceptual questions in ecology and evolutionary biology for future plant TPC studies: (i) Do populations and species harbour genetic variation for TPCs? (ii) Do plant TPCs exhibit plastic responses to abiotic and biotic factors? (iii) Do fitness-based TPCs scale up to population-level thermal niches? Moving forward, plant ecologists and evolutionary biologists can capitalize on TPCs to understand how plasticity and adaptation will influence plant responses to climate change. Variation in plant performance across temperatures are illustrated with a thermal performance curve (TPC), where performance peaks at a benign temperature and decreases to zero as temperature becomes cooler or warmer. Thermal performance curves have been useful for understanding evolution and plasticity, especially in response to climate change. However, most plant TPCs in the literature are based on physiological traits of single leaves, rather than individual fitness which would more directly approximate how populations might respond to changes in temperature. We describe what has been done and necessary next steps that utilize TPCs to determine how plants will respond to climate change. Temperature is among the most important global drivers of productivity and biodiversity  to geothThermal performance curves are unimodal, continuous reaction norms of performance, defined as any metric of an organism’s ability to function, across a temperature gradient ; Fig. 1AHere, we convey the value of fitness-based TPCs for addressing key questions in plant ecology and evolutionary biology. By fitness-based TPCs, we mean TPCs that are quantified through performance traits that are measured at the individual level or above . We do not discuss TPCs characterized by short-term, subindividual traits (e.g. photosynthesis) or the physiological or molecular mechanisms underlying such TPCs as these topics are already well-studied (Mollugo verticillata (Mimulus), species with broader TPCs experienced greater temperature variation across their ranges relative to species with narrower TPCs  evolved narrower thermal performance breadth  rely on measurements of the same individuals across multiple temperatures and can take only a few minutes to quantify e.g. , fitnessGiven that these fitness proxies typically do not encompass the full life cycle, a key knowledge gap is whether fitness-based TPCs capture the relationship between temperature and the long-term growth rates of natural populations . M. verticillata. Second, using populations spanning the northern half of the geographic range of M. cardinalis, Two studies have combined species distribution models (SDMs) with TPCs to investigate the hierarchical nature of niche breadth and predict how plant populations and species will respond to climate change. First, Mimulus species with greater genetic variation for thermal tolerance have evolved broader TPCs. They were unable to fit TPCs to each genotype (represented by full-sibling seed families) to evaluate whether species with greater genetic variation for TPC parameters have evolved broader TPCs, because hierarchical TPC models that could simultaneously estimate multiple genotype-level TPCs from a population-level average TPC were not yet available. Rather, they focused on genetic variation for thermal reaction norms at the two lowest and the two highest experimental temperatures. They found that species with broader TPCs had greater among-genotype variation in slopes of reaction norms at both the cold (15–20 °C) and hot (40–45 °C) ends of the temperature gradient. Future work is needed to evaluate whether plant populations have sufficient genetic variation for TPC parameters to respond to climate change, and to further develop modelling approaches that can account for variation at multiple biological levels  is ≥1, indicating demographic stability or growth, whereas a TPC describes a performance metric for a biological entity . While extreme temperature events may drive short-term acclimation responses at the subindividual level (In the strictest sense, the thermal niche represents the set of temperatures across which population growth rate (Daphnia (Previous work has estimated TPCs using population growth rate as the response variable in short-lived organisms including Daphnia . Such stin situ. Ultimately, we hope that this viewpoint paves the way for including plants in future syntheses of TPCs and deepening our understanding of the ecological and evolutionary determinants of plant responses to climate change.Thermal performance curves are an ideal tool for fundamental and applied research in plant ecology and evolution. Here, we have described plant TPC studies that have tested hypotheses about plant adaptation and plasticity, with important implications for predicting responses to climate change. Several hypotheses, however, remain untested, including those about the roles of genetic variation in the evolution of niche space at the population level and beyond, controls of biotic interactions on realized niche space, and whether fitness-based TPCs determined in experimental settings can be scaled up to represent population-level niche space


This symposium uses data from the National Social Life, Health & Aging Project to examine how and for whom older adults’ social relationships and experiences changed with the advent of the COVID-19 pandemic. Zhang et al. examine video call usage among older adults with hearing impairment and how this might mitigate loneliness. They find that although this population reported greater loneliness during the pandemic, video calls attenuated this relationship in a dose-response manner. Wilder et al. evaluate 2015 resilience and socioeconomic status as predictors of older adults’ reports that the pandemic led to a positive change in their lives. Results revealed greater odds of reporting a positive impact of the pandemic for those with higher education, adjusting for resilience. Compernolle et el. assess differences by cognitive status in changes in mental health from pre- to during the pandemic. Higher 2015 cognitive functioning was associated with greater pandemic loneliness, with decreased pandemic emotional support partly explaining this association. Copeland & Liu investigate the role of 2015 personal networks in receiving instrumental and emotional support during the pandemic, finding that larger and denser pre-pandemic confidant networks each predicted higher odds of receiving various types of support during the pandemic. Wong et al. explore whether and for whom relationship quality changed since the pandemic started. Two-thirds of partnered respondents reported unchanged relationship quality, and Black respondents were more likely to report improved relationship quality. These investigations highlight sub-group differences in older adults’ changes in experiences, behavior, and well-being since the pandemic began.


Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Due to an increased risk of developing colorectal cancer, regular surveillance for dysplastic lesions via colonoscopy is recommended. Invisible dysplasia is the abnormal development of cells noted on pathology with no visible lesion seen during colonoscopy. Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease leading to progressive stricturing and fibrosis of the bile ducts. There is significant association between PSC and IBD, as up to 80% of patients with PSC having underlying IBD. Drug induced liver injury (DILI) is a common cause of acute liver failure in most Western countries. Most cases of DILI are self-limited, with resolution of laboratory and clinical findings after cessation of the offending agent.To describe a case of invisible colonic malignancy and possible idiosyncratic drug-induced liver injury from vedolizumab (VDZ) in a patient with ulcerative colitis (UC), PSC and autoimmune hepatitis (AIH) overlap syndrome.Patient consent was obtained. Information from electronic records was extracted, including admission notes and procedural reports. A literature review was performed using Pubmed.A 32-year-old Caucasian female with UC on VDZ with PSC and AIH had multiple colonoscopies performed demonstrating multifocal low-grade dysplasia. However, she remained resistant to surgery. She presented to clinic with tea-coloured urine, fatigue, and scleral icterus. Investigations revealed conjugated hyperbilirubinemia with elevation in hepatocellular liver enzymes. Imaging was consistent with large duct PSC, and liver biopsy showed grade 2 chronic hepatitis raising the possibility of large bile duct obstruction. She underwent liver transplant assessment and VDZ was held. Her bilirubin and liver enzymes recovered. Given multiple colonoscopies showing multifocal dysplastic changes and the patient declining other biologics, she would ultimately undergo total proctocolectomy with end ileostomy. Pathology demonstrated mucinous adenocarcinoma with a signet ring component.Both mucinous adenocarcinoma and signet ring carcinoma are more aggressive malignancies associated with poor prognosis. Found more often in younger patients, they are often diagnosed in later stages with lymphovascular invasion. Here, there was no evidence of metastases in any of the 40 lymph nodes examined, which indicated more favourable prognosis.The mechanism by which VDZ potentially causes liver injury is unknown. Multiple therapies for PSC-AIH overlap and IBD were entertained as causative agents. However, significant improvement in clinical symptoms and serologic parameters following cessation of VDZ was temporally suggestive.This case simultaneously highlights the importance of both timely colectomy in IBD patients with high-risk features during surveillance and early recognition and cessation of potential causative medications which induce liver injury.NoneNone Declared


Within Ohio’s MyCare demonstration, two distinct care management models were selected by the participating MyCare Ohio health plans (MCOPs): fully-delegated waiver care management and waiver service coordination. The purpose of this presentation is to describe the components of care management operating in MyCare Ohio. Qualitative interviews with n=91 Area Agency on Aging (AAA) and n=131 MCOP care management personnel were audio-recorded, transcribed, and checked for accuracy prior to thematic coding in Dedoose. Results indicate that comprehensive care management is the core element of MyCare Ohio. Fully-delegated care management models were viewed by participants as beneficial to reducing confusion for members however ‘scope creep’ challenged the already strained AAAs. Effective teamwork was identified for waiver service coordination models but the division of labor and communication needed between the AAA and MCOP care management personnel created tensions. The discussion will focus on practice recommendations for training, caseloads, and support staff.


Teaching Point: Intravertebral venous collateral formation can occur in thoracic venous obstruction syndrome and mimic metastatic bone lesions on contrast-enhanced imaging: vanishing bone metastases. Intravertebral venous collateral formation can occur in thoracic venous obstruction syndrome and mimic metastatic bone lesions on contrast-enhanced imaging.A 60-year-old man was admitted to the emergency department complaining of headaches, dyspnea and deterioration of consciousness during the past few days. He has a history of esophageal cancer treated with surgery and adjuvant radiochemotherapy. Clinical examination revealed swelling of the face, neck and upper limbs, as well as turgidity of the jugular veins and stridor.A contrast enhanced computed tomography (CT) scan of the neck and chest was performed. It showed a superior vena cava obstruction with various venous collaterals  and 2 11.Multiple high-density bone lesions were also detected in several cervical and thoracic vertebral bodies . These fSpine magnetic resonance imaging (MRI) performed two days later didn’t reveal any vertebral signal abnormalities . Nor werTherefore, we can conclude that the dense intravertebral images on the contrast-enhanced CT imaging resulted well from contrast accumulation in intravertebral venous collaterals .Venous dilatation and relative blood stagnation can be present when the superior vena cava is obstructed. Most frequent venous collateral pathways are via the azygos, hemiazygos, intercostal veins and vertebral venous plexuses. In some cases, intravertebral collaterals can also be involved. These intraosseous venous collaterals are located in the vertebral bodies and drain into vertically oriented veins in the spinal subarachnoid space 45.4Therefore, stagnation of intravenous contrast material in these intravertebral collaterals can mimic condensing bone metastases on CT scans after contrast administration , hence tIn literature, there are limited number of case reports describing such vanishing bone metastases. One of the first descriptions of this peculiar aspect was in 2009 by Jesinger and colleagues .Vanishing metastases appear to be an underdescribed entity and should not be confused for malignant lesions.


Anxiety disorders (ADs) are pervasive, detrimental, and associated with numerous psychiatric disorders; however, their etiology and effective treatment strategies are not yet fully explored.We aimed to study whether the symptom severity of ADs is related to mindfulness and metacognition among adults. In addition, we wanted to compare metacognition and mindfulness between patients with ADs and healthy controls (HC).Two hundred participants were enrolled in this study. Structured clinical interview, sociodemographic form, Five Facet Mindfulness Questionnaire-Short Form (FFMQ-S), Metacognition Questionnaire-30 (MCQ-30), and Hamilton Anxiety Rating Scale (HAM-A) were administered. Multivariate analysis of covariance (MANCOVA) was conducted to compare the groups in terms of mindfulness and metacognition. Correlation and multiple linear regression analyses were performed to measure the association between anxiety symptom severity, mindfulness, and metacognition.The main finding indicates that Positive Beliefs about Worry are associated with reduced symptom severity of ADs. Furthermore, the results suggest that HC have more Positive Beliefs about Worry and Nonjudging of Inner Experience compared to patients with ADs, who use Negative Beliefs about Uncontrollability and Danger and Need to Control Thoughts to a greater extent.This study suggests that dysfunctional metacognitive beliefs may influence symptom severity of ADs among adults. We advise that focusing on reducing maladaptive metacognitions may be beneficial while treating ADs in adultsNo significant relationships.


The pancreas exhibits remarkable inherent cellular plasticity in response to injury. To prevent inflammatory injury or death, acinar cells can undergo transient acinar-to-ductal metaplasia (ADM) by suspending normal cell functions and adopting characteristics of ductal cells. However, persistent ADM in the setting of chronic pancreatitis predisposes to pancreatic cancer. Less frequently, acinar cells have also been found to undergo acinar-to-adipocyte transdifferentiation, but the mechanisms and clinical significance of this process are largely unknown. Recent studies have identified that the Hippo signaling pathway and its effectors are vital for pancreatic development and function.YAP is highly expressed in normal pancreatic ducts and transiently in acinar cells undergoing ADM, suggesting a dual role for YAP in (1) the homeostatic maintenance of pancreatic ductal cells, and (2) the regenerative response to injury in acinar cells. However, little is known about the cell type-specific effects of YAP/TAZ on pancreas homeostasis and regeneration.Yap/Taz in both acinar cells and ductal cells using the previously described CluCreERT mouse line. We also established a pancreatic ductal cell-derived organoid system. The efficiency of in vitro Cre recombinase induction was confirmed in Yapfl/fl;Tazfl/fl;CluCre-ERT;LSL-tdTomato (YTKO) ductal organoids.We investigated the homeostatic functions of Yap and Taz in the pancreas by conditionally ablating We observed severe atrophy and a pancreatitis-like phenotype in the pancreata of YTKO mice following tamoxifen induction. At later time-points, YTKO pancreata were progressively remodeled – the exocrine pancreas was almost entirely replaced by adipose tissue and large hyperplastic ductal structures. We will perform further lineage tracing experiments to determine whether infiltrating adipose cells derive directly from transdifferentiating acinar cells. YTKO pancreatic ductal organoids exhibited disrupted survival and proliferation, evidenced by increased expression of cleaved Caspase3 and decreased EdU incorporation compared to vehicle-treated controls.Although some flexibility in cell fate potential is beneficial for the regenerative capacity of the pancreas, dramatic changes in cellular identity can have disastrous consequences. Overall, this study revealed that disruptions in Hippo signaling in the adult murine pancreas led to failure of regeneration and the complete remodeling of the exocrine pancreas, and has shed light on the previously uncharacterized role of Hippo signaling in acinar-to-adipocyte transdifferentiation. The potential contribution of fatty infiltration of the pancreas to the pathogenesis of diabetes mellitus and pancreatic cancer merits further exploration.CIHR, OtherFonds de recherche du Quebec - Sante (FRQS)None DeclaredCELLULAR & MOLECULAR GASTROENTEROLOGY


The coated alloy was co-cultured with bone marrow mesenchymal stem cells and showed excellent biocompatibility and osteoinductivity in vitro. A further exploration of the underlying mechanism by quantitative real-time polymerase chain reaction and western blotting revealed that the enhancement effects are related to the upregulation of genes and proteins  involved in the Wnt/β-catenin pathway. In vivo experiments showed that the TiCu/TiCuN coating significantly promoted osteoporotic fracture healing in a rat femur fracture model, and has good in vivo biocompatibility based on various staining results. Our study confirmed that TiCu/TiCuN-coated Ti promotes osteoporotic fracture healing associated with the Wnt pathway. Because the coating effectively accelerates the healing of osteoporotic fractures and improves bone quality, it has significant clinical application prospects.Osteoporosis results in decreased bone mass and insufficient osteogenic function. Existing titanium alloy implants have insufficient osteoinductivity and delayed/incomplete fracture union can occur when used to treat osteoporotic fractures. Copper ions have good osteogenic activity, but their dose-dependent cytotoxicity limits their clinical use for bone implants. In this study, titanium alloy implants functionalized with a TiCu/TiCuN coating by arc ion plating achieved a controlled release of copper ions   Osteoporosis is a common orthopaedic disease characterized by bone microstructure destruction and bone loss. As the bone quality declines, the bone microstructure is destroyed. The bones become very fragile over time, and eventually, fractures can occur in response to minimal external force. Osteoporotic fractures are difficult to treat. Because of the decline in bone quality, postoperative fractures that do not heal or delayed healing can occur. Fracture healing generally occurs in three phases: inflammation, osteogenesis and bone remodelling . Bone reThe implants currently used to fix fractures are mainly made of stainless steel, medical titanium alloy or cobalt chromium molybdenum alloy, and have high mechanical strength, excellent biocompatibility and maintain optimal stability , 6. HoweCopper is an indispensable trace element in the human body and is involved in most metabolic reactions as an important coenzyme . In addiin vitro corrosion resistance tests. Further in vitro and in vivo studies are needed to assess osteogenic activity.Titanium nitride (TiN) is a very hard and stable material , 18, witin vivo by promoting Wnt/β-catenin signalling pathway, and promote the formation of callus at the fracture site, thereby accelerating fracture healing ; the Science and Technology Commission of Shanghai Municipality [22YF1422900 and 21002411200]; the Shanghai Municipal Key Clinical Specialty, China [shslczdzk06701]; Huangpu District Industrial Support Fund [XK2020009]; the National Facility for Translational Medicine (Shanghai), China [TMSZ-2020-207]; and the Shanghai Engineering Research Center of Orthopedic Innovative Instruments and Personalized Medicine Instruments and Personalized Medicine [19DZ2250200].Conflicts of interest statement. The authors have no conflicts of interest relevant to this article.rbac092_Supplementary_DataClick here for additional data file.


Acute upper limb ischemia in a patient with thoracic outlet syndrome is a rare but serious clinical disorder. If the disease is not treated promptly due to underdiagnosis, it could lead to distal artery embolization and limb-threatening ischemia. Revascularizing upper extremity arteries in a timely manner could rescue ischemic limbs and improve the patient’s quality of life. We reported here a case of a patient who presented with bilateral upper limb ischemia caused by arterial thoracic outlet syndrome.A 63-year-old woman who presented with sudden bilateral upper extremity cold, numbness, pulselessness, and altered temperature sensation was first diagnosed with arterial thoracic outlet syndrome. The patient had performed a lot of pull-up and lat pull-down exercises in the 2 months prior to the onset of the above symptoms. Color Doppler ultrasonography showed thrombosis in the right axillary artery and left subclavian and axillary artery. The patient received Rotarex mechanical thrombectomy combined with drug-coated balloon percutaneous transluminal angioplasty (PTA) to complete revascularization of the upper extremities and achieved a full recovery finally.Complete endovascular revascularization for treating arterial thoracic outlet syndrome is a minimally invasive and effective method, especially for upper extremity ischemic lesions caused by nonbone compression. Arterial thoracic outlet syndrome (TOS) is a group of disorders manifested with upper extremity ischemia or aneurysmlike disease caused by external compression of subclavian or axillary arteries at the thoracic outlet . ArteriaDecompression of the thoracic outlet is the classic therapy, including cervical rib excision, release of scalenus, and vascular thrombectomy and reconstruction . HoweverWe report a rare case of acute ischemia of bilateral upper extremities caused by arterial thoracic outlet syndrome. Rotarex mechanical thrombectomy combined with a drug-coated balloon was used to reconstruct the upper extremity blood flow, and finally, the patient fully recovered.A 63-year-old female patient presented with acute bilateral upper extremity cold, pulselessness, and altered temperature sensation. The patient described that she had performed a lot of pull-up and lat pull-down exercises in the 2 months prior to the onset of the above symptoms. The physical examination showed that typically marked bilateral upper extremity ischemia manifesting with radial and ulnar artery blood flow were out of palpable and cold sensation in upper limbs. The patient was diagnosed with arterial thoracic outlet syndrome after clinical provocation tests  and computed tomography (CT)  results The patient received anticoagulant and antiplatelet therapy after hospitalization. An 8F Rotarex  mechanical thrombectomy system was used to reduce the thrombus burden in the axillary artery and the subclavian artery. To decrease the risk of ectopic embolization, we adopted a strategy of slowly pushing the Rotarex catheter from proximal to distal end of the artery. Before the aspiration of thrombus in the distal artery, we performed repeated aspiration in the proximal artery aiming to reduce the amount of thrombus fully. Then, 3-, 5-, and 8-mm Mustang balloon catheters   were useArterial thoracic outlet syndrome is usually present with upper extremity ischemia or aneurysm caused by chronic external compression of the subclavian artery or axillary artery when passing through the defined anatomical space called thoracic outlet. Bony abnormalities such as abnormal cervical rib and first rib, anomalous development of anterior scalene muscle, and other soft tissues contribute to subclavian/axillary artery stenosis, occlusion, thrombosis, and aneurysm. The innovation of endovascular technology makes it possible to treat arterial thoracic outlet syndrome through a more minimally invasive surgical approach.First, the diagnosis of arterial TOS needs to be carefully distinguished. Patients with arterial TOS usually present with obvious symptoms of limb ischemia such as cold feeling, pulseless, and altered temperature sensation. In addition to pain, numbness, and paresthesia, some neurogenic TOS patients also manifested intermittent finger paresthesia, discoloration, and coldness in the absence of thromboembolism in the subclavian artery. The ischemic manifestations of the upper extremities are mainly attributed to vasospasm mediated by sympathetic nerve plexus compression rather than true arterial TOS , 13. ColThe congenital abnormality of anterior scalene muscle, cervical rib, the first rib, and other factors lead to the compression of the subclavian/axillary artery, resulting in intimal hyperplasia, thrombosis, and aneurysm in arterial TOS. Traditional surgery requires thoracic outlet decompression, artery release, thrombectomy, and subclavian–axillary artery bypass grafting, causing extremely traumatic injury and bleeding. The advancement of endovascular intervention provides new treatment possibilities. Pantoja et al.  comparedRotarex thrombectomy combined with drug-coated balloon dilation achieved good initial clinical results and a satisfactory arterial patency rate in treating arterial TOS; however, a strict case screening is required. For arterial TOS caused by bone compression, it is still necessary to decompress the neurovascular bundle first . Further


This study examined Alzheimer’s disease (AD) knowledge and its predictors among Korean Americans (KAs). A total of 268 KAs in the Greater Washington metropolitan area participated in the study and completed a cross-sectional survey. Using the Alzheimer’s Disease Knowledge Scale (ADKS), overall and domain knowledge was assessed. Multiple regression analyses were conducted with predictors including exposure to AD, social engagement, sources and frequency of health-related information, stigmatic beliefs , English proficiency, and education. KAs reported 59% accuracy in overall AD knowledge. They were most knowledgeable about assessment and diagnosis domain and least knowledgeable about caregiving domain. Regression analyses showed that having more education is associated with greater overall and certain domain knowledge. Having more pity stigmatic beliefs is related to greater knowledge in both life impact and caregiving domains while having less pity stigmatic beliefs is associated with more risk factor knowledge; having less social distance stigmatic beliefs is associated with greater life impact knowledge; and having less antipathy stigmatic beliefs is related to better caregiving knowledge. Our findings revealed areas of misconceptions and knowledge gaps in KAs which need to be addressed in educational interventions. Different knowledge status across the domains demonstrates a multi-dimensional nature of AD knowledge. Multivariate findings confirmed the robust role of education in AD knowledge. Effect of different AD stigmatic beliefs on certain AD knowledge domains suggests ways of how stigma change can be efficient for the purpose of increasing AD domain knowledge in KAs.


COVID-19 raises serious concerns regarding its unknown consequences for health, including psychiatric long term outcomes. Historically, influenza virus has been responsible for pandemics associated with schizophrenia. Epidemiological studies showed increased risk for schizophrenia in children of mothers exposed to the 1957 influenza A2 pandemic. Controversy remains concerning the mechanisms of pathogenesis underlying this risk.We aim to review the evidence for the association between influenza infection and schizophrenia risk, the possible pathogenic mechanisms underlying and correlate these findings with the schizophrenia hypothesis of neurodevelopment.We reviewed literature regarding evidence from epidemiological, translational animal models and serological studies using medline database.The biological mechanisms likely to be relevant account to the effects of infection-induced maternal immune activation, microglial activation, infection-induced neuronal autoimmunity, molecular mimicry of the influenza virus, neuronal surface autoantibodies and psychosis with potential infectious antecedents. Influenza infection may fit into the theory of the neurodevelopment of schizophrenia as a factor that alters the normal maturation processes of the brain (possible second or third hit).Influenza infection has multiple pathogenic pathways in both pre and post natal processes that might increase the risk of schizophrenia or psychosis. The existing evidence regarding the relationship between influenza virus and psychosis might help us draw similar long-term concerns of COVID-19.No significant relationships.


Little is known how adults’ memories of parental acceptance-rejection in childhood influence their behavior toward their aging parents. Grounded in interpersonal acceptance-rejection theory (IPARTheory), this study attempts to better understand how early parent-child relationships affect adult offspring who provide care to their parents in later life. Data were collected from 41 adult offspring. Findings revealed that adults who felt rejected by their parents in childhood reported fewer positive caregiving behaviors toward their now aging parents, were less satisfied with social activities with their parents, spent less time with them or visited them less frequently, and revealed less overall concern for their aging parents. Results were consistent with IPARTheory’s expectations that if parents reject their children, then parents place their own dependent old age at the risk of counter rejection: As you sow, so shall you reap. Such findings may help researchers, clinicians, and practitioners better understand the well-being of aging adults.