Association between self-reported visual symptoms (suggesting cataract) and self-reported fall-related injury among adults aged ≥ 65 years from five low- and middle-income countries.

BACKGROUND: Cataracts may increase risk for falls but studies on this topic from low- and middle-income countries (LMICs) are scarce. Therefore, we examined the cross-sectional association between self-reported visual symptoms (suggesting cataract) and self-reported injurious falls in nationally representative samples of adults aged ≥ 65 years from five LMICs (China, Ghana, India, Mexico, and Russia). METHODS: Data from the WHO Study on global AGEing and adult health (SAGE) were analysed. Self-reported information on past 12-month fall-related injury and cataract based on symptoms were collected. Multivariable logistic regression and meta-analyses were conducted to assess associations. RESULTS: Data on 13,101 people aged ≥ 65 years were analysed [mean (SD) age 72.5 (11.3) years; 45.2% males]. The overall prevalence of self-reported fall-related injury and visual symptoms (suggesting cataract) were 4.9% and 29.4%, respectively. There was a positive association between self-reported visual symptoms (suggesting cataract) and fall-related injury (i.e., OR > 1) in all five countries but statistical significance was reached in three: China (OR = 1.60; 95% CI = 1.08-2.35), India (OR = 1.96; 95% CI = 1.15-3.35), and Russia (OR = 3.58; 95% CI = 2.06-6.24). The pooled OR including all five countries based on a meta-analysis was OR = 1.88 (95% CI = 1.32-2.68). CONCLUSIONS: Self-reported visual symptoms (suggesting cataract) were associated with higher odds for self-reported injurious falls among older adults in LMICs. Expanding availability of cataract surgery in LMICs may also have the additional benefit of reducing falls among older people.

Association between back and neck pain and workplace absenteeism in the USA: the role played by walking, standing, and sitting difficulties.

PURPOSE: There is a paucity of literature identifying factors that influence the back and neck pain (BNP)-workplace absenteeism relationship. Therefore, this study aimed to investigate the association between BNP and workplace absenteeism and potential mediating variables in a large sample of the US population. METHODS: Nationally representative data collected in 2019 from the RAND American Life Panel (ALP) were used for this retrospective study. Workplace absenteeism was defined as the number of days of absence in the past 12 months for health-related reasons (count variable), while BNP corresponded to the presence of back pain due to spinal stenosis, back pain due to other causes, or neck pain (dichotomous variable). Control variables included sex, age, ethnicity, marital status, education, occupation, annual family income, health insurance, obesity, and diabetes. There were eight influential variables (depression, anxiety, sleep disorder, alcohol dependence, opioid dependence, walking difficulty, standing difficulty, and sitting difficulty). The association between BNP and workplace absenteeism was analyzed using a negative binomial regression model. RESULTS: There were 1,471 adults aged 22-83 years included in this study (52.9% of men; mean [standard deviation] age 44.5 [13.0] years). After adjusting for control variables, BNP was positively and significantly associated with workplace absenteeism (incidence rate ratio = 1.40, 95% confidence interval: 1.07-1.83). Walking, standing, and sitting difficulties individually explained between 24 and 43% of this association. CONCLUSIONS: Workplace interventions focusing on the management of BNP and overcoming difficulties in walking, standing, and sitting, potentially utilizing exercise, therapy, and ergonomic interventions, may prevent absenteeism.

Prevalence and correlates of multiple suicide attempts among adolescents aged 12-15 years from 61 countries in Africa, Asia, and the Americas.

Suicide is the fourth leading cause of death worldwide in young people aged 15-19 years. However, little is known about the correlates of multiple suicide attempts in adolescents, especially from a global perspective. Therefore, the aim of the present study was to investigate the association of putative physical, behavioral, and social correlates with multiple suicide attempts among adolescents aged 12-15 years from 61 countries. Data from the Global school-based Student Health Survey (2009-2017) were analyzed. Multiple suicide attempts was classified as having attempted suicide at least twice in the past 12 months. Multivariable logistic regression analyses were conducted to assess the potential correlates. Data on 162,994 adolescents [mean (SD) age 13.8 (0.9) years; 50.8% boys] were analyzed. The overall prevalence of multiple suicide attempts was 4.4% [range 1.2% (Laos) to 13.8% (Ghana)]. Among those who had attempted suicide at least once in the past 12 months, in the overall sample, food insecurity, smoking, alcohol consumption, cannabis use, amphetamine use, sedentary behavior, sexual intercourse, sleep problems, loneliness, no close friends, and bullying victimization were all independently associated with higher odds for multiple suicide attempts although some regional differences were observed. Our study results indicate potential target factors that could be addressed amongst those who had attempted suicide in the past to reduce future suicide attempts and possibly completed suicides. Furthermore, it is possible that region-specific interventions are necessary.

Physical multimorbidity and incident urinary incontinence among community-dwelling adults aged ≥50 years: findings from a prospective analysis of the Irish Longitudinal Study on Ageing.

BACKGROUND: There are no prospective studies on the association between multimorbidity and urinary incontinence (UI), while mediators in this association are unknown. Thus, we aimed to (i) investigate the longitudinal association between multimorbidity and UI in a large sample of Irish adults aged ≥50 years and (ii) investigate to what extent physical activity, polypharmacy, cognitive function, sleep problems, handgrip strength and disability mediate the association. METHODS: Data on 5,946 adults aged ≥50 years old from the Irish Longitudinal Study on Aging were analysed. The baseline survey was conducted between 2009 and 2011 and follow-up after 2 years was conducted. Information on self-reported occurrence of UI in the past 12 months and lifetime diagnosis of 14 chronic conditions were obtained. Multivariable logistic regression and mediation analysis were conducted. RESULTS: After adjustment for potential confounders, compared to having no chronic conditions at baseline, having three (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.30-2.48) and four or more (OR = 1.86; 95% CI = 1.32-2.60), chronic conditions were significantly associated with incident UI. Mediation analysis showed that polypharmacy, sleep problems and disability explained 22.7, 17.8 and 14.7% of the association between multimorbidity (i.e. two or more chronic conditions) and incident UI, respectively. CONCLUSION: A greater number of chronic conditions at baseline were associated with a higher risk for incident UI at 2-year follow-up among adults aged ≥50 years in Ireland. Considering the effects of different medications on UI and improving sleep quality and disability among people aged ≥50 years with multimorbidity may reduce the incidence of UI.

Ejaculation Disorders in Male Patients with Cancer: A Systematic Review and Meta-Analysis of Prevalence.

PURPOSE: Ejaculatory dysfunction (EjD) and erectile dysfunction after cancer treatment are clinically important complications, but their exact prevalence by various kinds of cancer site and type of treatment is unknown. The aim of this systematic review and meta-analysis was to examine the available evidence and provide pooled estimates for prevalence of EjD and erectile dysfunction in relation to all cancer sites and identify characteristics associated with EjD in cancer patients. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of cross-sectional and case-control studies. We searched 4 electronic databases (Medline®, CINAHL, PsychInfo and Embase®) until July 22, 2020. All retrospective or prospective studies reporting the prevalence of EjD in male patients with cancer were included in this review. A random effects meta-analysis was conducted calculating prevalence proportions with 95% confidence intervals. Prevalence proportions were calculated for the incidences of EjD by cancer site and type of treatment. RESULTS: A total of 64 studies (a total of 10,057 participants) were included for analysis. The most common cancer sites were bladder, colon, testis and rectum. The prevalence rates of EjD after surgical intervention ranged from 14.5% (95% CI 2.2-56.3) in colon cancer to 53.0% (95% CI 23.3-80.7) in bladder cancer. The prevalence rates of erectile dysfunction ranged from 6.8% (95% CI 0.8-39.1) in bladder cancer to 68.7% (95% CI 55.2-79.6) in cancer of the rectum. CONCLUSIONS: In a large study-level meta-analysis, we looked at a high prevalence of EjD and erectile dysfunction at various cancer sites and across different treatment types. Prospective studies of EjD and erectile dysfunction after various kinds of cancer treatments are warranted.

The CADENCE pilot trial - Promoting physical activity in bladder cancer survivors: A protocol paper.

BACKGROUND: Participation in physical activity has been found to be beneficial for mental and physical health outcomes among cancer survivors. However, to date no intervention exists specifically to promote physical activity among bladder cancer survivors. In light of this knowledge a home-based exercise intervention was co-created for those recently diagnosed with bladder cancer. AIM: The aim of the present study, financially supported by Action Bladder Cancer UK [1], is to pilot the home-based exercise intervention tailored specifically for bladder cancer survivors (i.e. from the point of diagnosis) to improve physical and mental health outcomes (during treatment and beyond) in this population. METHODS: This study will use a randomised controlled trial design. Arm one will consists of the 14 week home-based exercise intervention and arm two usual care (15 participants will be randomised to each arm). Baseline data collection will take place shortly after clinical diagnosis of bladder cancer, and follow-up approximately 7 weeks and then again approximately 14 weeks after commencement of the intervention. At each data collection point data will be collected from participants relating to demographics, physical and mental health. Participants will aslo be asked to wear an Actigraph Accelerometer at each data collection point for seven consecutive days. Immediately after baseline data collection participants in the intervention arm will be given the home-based exercise booklet. ETHICS AND DISSEMINATION: Ethical approval was obtained for the present study via The London- City and East Research Ethics Committee (ID:291676). Results of this study will be disseminated through peer-reviewed publications and scientific presentations.

Prevalence of erectile dysfunction in male survivors of cancer: a systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: Prevalence of erectile dysfunction (ED) in male survivors of cancer across cancer types has not been systematically analysed. AIM: To estimate the prevalence of ED in all types of cancer and identify characteristics associated with ED in survivors of cancer. DESIGN AND SETTING: Systematic review and meta-analysis (MA) of cross-sectional studies. METHOD: MEDLINE, CINAHL, PsycINFO, and EMBASE were searched, targeting reports published from inception to 1 February 2020. All retrospective or prospective studies reporting prevalence of ED in male patients with cancer and using a validated tool for detection of ED were included. A random-effects MA model was used to pool prevalence of ED as absolute estimates at three different stages, that is, 'healthy', 'at diagnosis', and 'after treatment'. A univariate MA regression including the three-level group variable as the only independent variable was used to assess the difference in ED prevalence across the three groups. Further MAs were conducted for studies involving patients at diagnosis and after treatment, and statistical inferences were made with setting for multiple testing controlling for a false discovery rate (FDR) <0.05. RESULTS: In total, 1301 studies were assessed for inclusion. Of these, 141 were potentially eligible and subsequently scrutinised in full text. Finally, 43 studies were included with a total of 13 148 participants. Overall, pooled data of the included studies showed an ED prevalence of 40.72% (95% confidence interval [CI] = 31.80 to 50.29) in patients with cancer, with prevalences of 28.60% (95% CI = 12.10 to 53.83) at time of diagnosis and 42.70% (95% CI = 32.97 to 53.03) after treatment, with significant difference between these two stages and across cancer locations, controlling for an FDR <0.05. CONCLUSION: Erectile dysfunction was particularly high in male survivors of cancer and was associated with cancer treatment, cancer site, and age.

Correlates of symptoms of anxiety and depression and mental wellbeing associated with COVID-19: a cross-sectional study of UK-based respondents.

BACKGROUND: The aim was to assess the impact of COVID-19 self-isolation/social distancing on mental health, and potential correlates, among a sample of the UK population. METHODS: A cross-sectional study. Mental health was measured using the Beck Anxiety and Depression Inventory. Mental wellbeing was measured using The Short Warwick-Edinburgh Mental Well-being Scale. Data collected on predictors included sex, age, marital status, employment, annual income, region, current smoking, current alcohol consumption, physical multimorbidity, any physical symptoms experienced during self-isolation/social distancing, and the number of days of self-isolation/social distancing. The association between potential predictors and poor mental health was studied using a multivariable logistic regression. RESULTS: 932 participants were included. Factors associated with poor mental health were sex (reference: male; female: OR=1.89, 95%CI=1.34-2.68), age (18-24 years: reference;45-54 years: OR=0.27, 95%CI=0.14-0.53; 55-64 years: OR=0.24, 95%CI=0.12-0.47; 65-74years: OR=0.10, 95% CI=0.05-0.22; and ≥75years: OR=0.08,95% CI=0.03-0.24),annual income (<£15,000: reference; £25,000-<£40,000: OR=0.54, 95% CI=0.31-0.93; £40,000-<£60,000: OR=0.39, 95% CI=0.22-0.69; and ≥£60,000: OR=0.38, 95% CI=0.21-0.67), current smoking (yes: OR=2.59, 95%CI=1.62-4.20), and physical multimorbidity (OR=2.35, 95%CI=1.61-3.46). CONCLUSIONS: In this sample of UK adults self-isolating/social distancing females, younger age groups, those with a lower annual income, current smokers and those with physical multimorbidity were associated with higher levels of poor mental health.

Challenges in the Practice of Sexual Medicine in the Time of COVID-19 in the United Kingdom.

BACKGROUND: On 23rd March 2020, the UK government released self-isolation/social distancing guidance to reduce the risk of transmission of SARS-CoV-2. The influence such guidance has on sexual activity is not known. AIM: To investigate levels and correlates of sexual activity during COVID-19 self-isolation/social distancing in a sample of the UK public. METHODS: This paper presents preplanned interim analyses of data from a cross-sectional epidemiological study, administered through an online survey. OUTCOMES: Sexual activity was measured using the following question: "On average after self-isolating how many times have you engaged in sexual activity weekly?" Demographic and clinical data were collected, including sex, age, marital status, employment, annual household income, region, current smoking status, current alcohol consumption, number of chronic physical conditions, number of chronic psychiatric conditions, any physical symptom experienced during self-isolation, and number of days of self-isolation/social distancing. The association between several factors (independent variables) and sexual activity (dependent variable) was studied using a multivariable logistic regression model. RESULTS: 868 individuals were included in this study. There were 63.1% of women, and 21.8% of adults who were aged between 25 and 34 years. During self-isolation/social distancing, 39.9% of the population reported engaging in sexual activity at least once per week. Variables significantly associated with sexual activity (dependent variable) were being male, a younger age, being married or in a domestic partnership, consuming alcohol, and a higher number of days of self-isolation/social distancing. CLINICAL IMPLICATIONS: In this sample of 868 UK adults self-isolating owing to the COVID-19 pandemic, the prevalence of sexual activity was lower than 40%. Those reporting particularly low levels of sexual activity included females, older adults, those not married, and those who abstain from alcohol consumption. STRENGTH AND LIMITATIONS: This is the first study to investigate sexual activity during the UK COVID-19 self-isolation/social distancing. Participants were asked to self-report their sexual activity potentially introducing self-reporting bias into the findings. Second, analyses were cross-sectional and thus it is not possible to determine trajectories of sexual activity during the current pandemic. CONCLUSION: Interventions to promote health and well-being during the COVID-19 pandemic should consider positive sexual health messages in mitigating the detrimental health consequences in relation to self-isolation/social distancing and should target those with the lowest levels of sexual activity. Jacob L, Smith L, Butler L, et al. Challenges in the Practice of Sexual Medicine in the Time of COVID-19 in the United Kingdom. J Sex Med 2020;17:1229-1236.

Treatment of Human Lens Epithelium with High Levels of Nanoceria Leads to Reactive Oxygen Species Mediated Apoptosis.

Nanoceria (cerium oxide nanoparticles) have been shown to protect human lens epithelial cells (HLECs) from oxidative stress when used at low concentrations. However, there is a lack of understanding about the mechanism of the cytotoxic and genotoxic effects of nanoceria when used at higher concentrations. Here, we investigated the impact of 24-hour exposure to nanoceria in HLECs. Nanoceria's effects on basal reactive oxygen species (ROS), mitochondrial morphology, membrane potential, ATP, genotoxicity, caspase activation and apoptotic hallmarks were investigated. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) studies on isolated mitochondria revealed significant uptake and localization of nanoceria in the mitochondria. At high nanoceria concentrations (400 µg mL-1), intracellular levels of ROS were increased and the HLECs exhibited classical hallmarks of apoptosis. These findings concur with the cells maintaining normal ATP levels necessary to execute the apoptotic process. These results highlight the need for nanoceria dose-effect studies on a range of cells and tissues to identify therapeutic concentrations in vitro or in vivo.

Ethylene glycol coated nanoceria protects against oxidative stress in human lens epithelium.

Chronic diseases are rising in incidence and prevalence because of increases in life expectancy in many parts of the world coupled with advances in medicine which manage disease progression, rather than curing and alleviating the causes. Cataract is one such chronic condition. Identifying a therapeutic intervention that is successful in reversing or preventing cataracts may have applications for other chronic diseases of protein misfolding, such as diabetes and Alzheimer's disease as these have similar causation factors, notably oxidative stress and/or glycation. Cerium oxide nanoparticles (nanoceria) which have antioxidant, radioprotective and enzyme-mimetic properties have the potential to lead to an effective non-surgical treatment. However, nanoceria stability in physiological media is poor thus hindering their effective use in biomedical applications. Here we report a highly efficient one-pot synthesis of nanoceria (2-5 nm) coated with ethylene glycol, that is colloidally stable in physiological media and exhibits multiwavelength photoluminescence. The formulation, up to concentrations of 200 µg ml-1, was not toxic to human lens epithelial cells and had no adverse effect on the cellular morphology or proliferation rate. More significantly, these nanoceria showed protective effects against oxidative stress induced by hydrogen peroxide in lens epithelial cells. Electron microscopy studies show the internalization and cytoplasmic localization of the nanoceria was found to be largely in the perinuclear region.

SENIEUR status of the originating cell donor negates certain 'anti-immunosenescence' effects of ebselen and N-acetyl cysteine in human T cell clone cultures.

BACKGROUND: Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. METHODS: T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. RESULTS: In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. CONCLUSIONS: The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit.

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation.

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 ± 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1ß and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1ß and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation.

The effects of inspiratory muscle training on plasma interleukin-6 concentration during cycling exercise and a volitional mimic of the exercise hyperpnea.

It is unknown whether the respiratory muscles contribute to exercise-induced increases in plasma interleukin-6 (IL-6) concentration, if this is related to diaphragm fatigue, and whether inspiratory muscle training (IMT) attenuates the plasma IL-6 response to whole body exercise and/or a volitional mimic of the exercise hyperpnea. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of 1) passive rest, 2) cycling exercise at estimated maximal lactate steady state power (EX), and 3) volitional hyperpnea at rest, which mimicked the breathing and respiratory muscle recruitment patterns achieved during EX (HYPEX). Plasma IL-6 concentration remained unchanged during passive rest. The plasma IL-6 response to EX was reduced following IMT (main effect of intervention, P = 0.039) but not PLA (P = 0.272). Plasma IL-6 concentration increased during HYPEX (main effect of time, P < 0.01) and was unchanged postintervention. There was no evidence of diaphragm fatigue (measured by phrenic nerve stimulation) following each trial. In conclusion, plasma IL-6 concentration is increased during EX and HYPEX and this occurred in the absence of diaphragm fatigue. Furthermore, IMT reduced the plasma IL-6 response to EX but not HYPEX. These findings suggest that the respiratory muscles contribute to exercise-induced increases in plasma IL-6 concentration in the absence of diaphragm fatigue and that IMT can reduce the magnitude of the response to exercise but not a volitional mimic of the exercise hyperpnea.

An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells.

BACKGROUND: The research literature has documented age-related increases in genetic damage, including oxidative DNA damage, in human T lymphocytes, in vitro and ex vivo. Such damage has the potential to interfere with the ability of the T cells to proliferate at times when they need to, such as when antigen challenged. The consequence of this could be a sub-optimal immune response in vivo. CONTEXT AND PURPOSE: The purpose of the research reported in this paper was to investigate the impact of two antioxidants, which can be administered in vivo, Ebselen and N-acetyl L-cysteine, on the age-related increase in genetic damage, and on T cell proliferation and lifespan. In vitro human T cell clones, ex vivo peripheral blood mononuclear cells or T cells were supplemented with different concentrations of antioxidants, under standard conditions and for different periods of time. A range of assays were then applied in order to determine any impact of the antioxidants. RESULTS: 30 µM ebselen or 7.5 mM N-acetyl L-cysteine supplementation resulted in a significantly higher intracellular GSH: GSSG ratio. This increased ratio was accompanied by reduced levels of oxidative DNA damage in established CD4+ human T cell clones, from a young or a middle-aged donor. Additionally, cultures of primary human peripheral blood mononuclear cells and CD4+ T cells from donors aged 25-30 or 55-60 years were also supplemented with these agents. Cells from all sources exhibited increased proliferation, and in the case of the T cell clones, an increase in cumulative population doublings. Neither ebselen nor N-acetyl L-cysteine had such effects on clones supplemented from the midpoint of their in vitro lifespan. CONCLUSIONS: Ebselen and N-acetyl L-cysteine, under certain conditions, may have anti-immunosenescent potential in T cells in in vitro clonal and ex vivo polyclonal culture models.

An investigation of the effects of MitoQ on human peripheral mononuclear cells.

MitoQ is a ubiquinone derivative targeted to mitochondria which is known to have both antioxidant and anti-apoptotic properties within mammalian cells. Previous research has suggested that the age-related increase in oxidative DNA damage in T lymphocytes might contribute to their functional decline with age. This paper describes the impact of mitoQ on unchallenged or oxidatively challenged ex vivo human peripheral blood mononuclear cells from healthy 25-30 or 55-60 year old volunteers. When cells were challenged with hydrogen peroxide (H(2)O(2)), following mitoQ treatment (0.1-1.0 µM), the ratio of reduced to oxidized forms of glutathione increased, the levels of oxidative DNA damage decreased and there was an increase in the mitochondrial membrane potential. Low levels of mitoQ (0.1 or 0.25 µM) had no impact on endogenous DNA damage, whilst higher levels (0.5 and 1.0 µM) of mitoQ significantly reduced endogenous levels of DNA damage. The results of this investigation suggest that mitoQ may have anti-immunosenescent potential.

Family communication, genetic testing and colonoscopy screening in hereditary non-polyposis colon cancer: a qualitative study.

OBJECTIVE: Genetic testing and colonoscopy is recommended for people with a strong history of colorectal cancer (CRC). However, families must communicate so that all members are aware of the risk. The study aimed to explore the factors influencing family communication about genetic risk and colonoscopy among people with a strong family history of CRC who attended a genetic clinic with a view to having a genetic test for hereditary non-polyposis colon cancer (HNPCC). METHODS: Interviews were held with 30 people with a high familial risk of colon cancer. The transcripts were transcribed verbatim and analysed using Interpretative Phenomenological Analysis. RESULTS: The family context, family history and perceptions about family duties and responsibilities were important motivators for communication about risk, genetic testing and colonoscopy and influenced participation in genetic testing and screening programmes. Participants reported usually communicating openly with their relatives about genetic risk and colonoscopy. Individuals felt a duty towards affected relatives and to their own children. The influence of the spouse and other relatives, particularly those affected by CRC, was also important. Colonoscopy was perceived to be embarrassing, unpleasant and sometimes painful. While there was sometimes anxiety about the result of the colonoscopy the results were usually reassuring. CONCLUSIONS: The family context and the experience of the family history can have an impact on communication, genetic testing and screening in HNPCC and this should be explored during counselling. Some individuals might benefit from support in communicating with relatives about genetic risk. Ways of improving the individual's experience of colonoscopy should also be examined.

Cancer genetics: consultants' perceptions of their roles, confidence and satisfaction with knowledge.

RATIONALE, AIMS AND OBJECTIVES: Genetic testing for susceptibility for common cancers is widely available. Cancer specialists and specialists in other areas may have a role in identifying and referring patients who would benefit from a consultation with a specialist in genetics. This study aimed to find out which consultants believed that genetic testing was relevant to their practice. We also wanted to determine their views of their roles in relation to genetic testing, their confidence in these roles, and the value of different educational tools. METHODS: This was a self-completed, cross-sectional, postal survey of all the consultants in Northern Ireland (n=520, response rate=59.3%) identified from the Central Services Agency list. RESULTS: Three hundred and ninety questionnaires were returned (44%). A total of 28.6% did not complete the questionnaire stating that genetics was not relevant to their practice. Few consultants reported having consultations related to genetic disease, receiving training in genetics and referring to genetics services. There was some dissatisfaction with their current knowledge of genetics and they believed that guidelines and educational tools may be useful. The respondents lacked confidence in undertaking some of their roles. Through their responses to the cancer scenarios, these consultants showed that they would offer appropriate advice and referrals. Many consultants did not know if family history information should be provided to insurance companies. CONCLUSIONS: Some consultants may require further training to enable them to fulfil their roles in relation to genetics. Tools or guidelines to assist with referral decisions may also be useful. Consultants may need clearer guidance regarding the provision of family history information to insurance companies.

Genetic consultations in primary care: GPs' responses to three scenarios.

OBJECTIVE: This study investigated general practitioners' responses to three scenarios in which patients consulted regarding genetic conditions. DESIGN: Self-completed postal study. Setting. Primary care in Northern Ireland. SUBJECTS: Questionnaire were distributed to all the GPs in Northern Ireland (n = 1079). A total of 541 GPs participated (50%). MAIN OUTCOME MEASURES: Responses to three scenarios in which patients consulted regarding their family history and risk of bowel cancer, breast cancer, and cystic fibrosis. RESULTS: Most GPs correctly identified the patients' risk of bowel cancer, recommended regular colonoscopy, advised lifestyle changes, and did not refer to the genetic clinic. GPs who were qualified for longer were more likely to recommend colonoscopy and less likely to advise lifestyle changes. With the breast cancer patient GPs adopted a cautious approach; most would refer to the genetic and mammography clinics. With the cystic fibrosis example, most correctly identified the patient's risk of carrying the gene, would refer to the genetic clinic, and would encourage the patient to discuss the risk with his partner. In general, doctors were unsure, but would pass on genetic information to insurance companies if requested. CONCLUSION: The study suggests that, in most cases, general practitioners correctly identify at-risk individuals but there may still be some uncertainty regarding referrals. The results suggest that ways of educating GPs should be explored. Educational interventions should be linked to a greater understanding of factors involved in referral (including the influence of gender and experience). The guidelines provided to GPs in relation to the provision of genetic information to insurance companies may need to be reviewed in some countries.

Engineering anticancer T cells for extended functional longevity.

Like other somatic cells, human T lymphocytes have a finite replicative capacity in vitro, and, by implication and consistent with the limited data available, in vivo as well. An accumulation of dysfunctional T cells may be detrimental under conditions of chronic antigenic stress (chronic infection, cancer, autoimmunity). Using T cells from young donors to model the process of T cell clonal expansion in vitro under these conditions reveals age-associated increasing levels of oxidative DNA damage and microsatellite instability (MSI), coupled with decreasing DNA repair capacity, telomerase induction and telomere length, decreased levels of expression of the T cell costimulator CD28 and consequently reduced secretion of the T cell growth factor interleukin-2 (IL-2). However, data from similar experiments using T cell clones (TCCs) derived from extremely healthy very elderly donors ("successfully aged") indicate that DNA repair is better maintained, MSI less prevalent, and (already short) telomere lengths are maintained. Nonetheless, oxidative DNA damage is seen to the same extent, and clonal longevity is also similar in these clones. DNA damage levels are reduced by culture in 5% oxygen, but longevity is not improved. This may be because of the requirement for intermittent reactivation via receptor pathways dependent on free radical production in T cells. These recent findings from our international immunosenescence research consortium suggest that strategies other than telomere maintenance, better protection against free radicals, or improved DNA repair will be required for functional longevity extension of human TCCs. To obtain sufficient cells for adoptive immunotherapy of cancer, alternative avenues need exploration; currently, these include enforced expression of certain heat shock proteins and proteasome components, and interference with the expression of negative regulatory receptors expressed by T cells.