Depressive symptomatology and the prevalence of cardiovascular risk factors among older men and women from Cyprus; the MEDIS (Mediterranean Islands Elderly) epidemiological study

Aims. The purpose of this paper is to explore the link between symptoms of depression and the prevalence of cardiovascular risk factors in older adults. Methods. During 2005, 136 older men and 164 women from various parts of Cyprus agreed to participate in the study. The sampling was random and multistage (according to age–sex distribution of the referent population). All participants were living in the community and not in institutions. Among several socio‐demographic, bioclinical, lifestyle and dietary characteristics, depressive symptoms were assessed using the short version of the Geriatric Depression Scale (GDS). Results. Participants without signs of depression, typically, have fewer cardiovascular risk factors (i.e. hypertension, hypercholesterolemia, diabetes and obesity) than those with moderate or severe symptoms. Even when behavioural variables (e.g. diet, smoking, exercise) are statistically controlled, participants that are higher than others on depression are more likely to have hypertension and/or hypercholesterolemia than those with lower scores. Every one‐unit increase in GDS score (range 0–15) is associated with a 12% higher likelihood of having an additional cardiovascular disease risk factor. Conclusions. Symptoms of depression are positively associated with the number of cardiovascular risk factors in ‘healthy’ older adults, irrespective of lifestyle behaviours (e.g. smoking, dietary intake and physical activity). Relevance to clinical practice. Healthcare providers should consider the implications of both the presence and nature of this relationship in their continuing care of older adults.     

Recovery of shoulder abduction in traumatic brachial plexus palsy: a systematic review and meta-analysis of nerve transfer versus nerve graft

Brachial plexus palsy is a surgically manageable condition. Re-animating the shoulder is a high priority for restoring upper extremity function. Methods for reinnervating injured nerves include the transfer of a healthy nerve or fascicle distal to the site of injury, or grafting a healthy sensory nerve to restore motor function. Studies aiming to compare these two techniques for restoring shoulder abduction have yielded conflicting results. We conducted a systematic review and meta-analysis following the PRISMA guidelines. We reviewed the PubMed database for studies comparing nerve transfer and nerve grafting for shoulder abduction published by December 2018. Outcomes using the Medical Research Scale (MRC) for muscle strength were assessed using a random effects model meta-analysis. Five studies comprising a total of 212 patients (n = 158, nerve transfer; n = 54, nerve grafts) were used for the analysis. The rate of functional recovery of shoulder function was slightly better for nerve transfer (n = 114/158, 72%) than for nerve graft patients (n = 36/54, 67%). However, this was not statistically significant (OR 1.34, 95% CI 0.27–6.72, I2 = 62.9%). Nerve transfer and grafting are similarly effective in terms of shoulder abduction. Future prospective studies are needed to validate our results and identify the optimal shoulder re-animation strategy in patients with brachial plexus injuries.     

Palliative chemotherapy in elderly patients with common metastatic malignancies: A Hellenic Cooperative Oncology Group registry analysis of management, outcome and clinical benefit predictors

INTRODUCTION: Cancer in the elderly is a common health issue in developed societies. We sought to present epidemiology, management and outcome data on fit elderly patients with common metastatic cancers and to identify predictors of clinical benefit from palliative chemotherapy. METHODS: All patients aged >65 years who were diagnosed with metastatic breast, colorectal or non-small cell lung carcinomas and managed with palliative chemotherapy in the context of Hellenic Cooperative Oncology Group (HeCOG) clinical trials or protocols were eligible for electronic data retrieval and analysis. Common eligibility criteria included adequate performance status (ECOG 0-3), organ function and absence of severe co-morbidity forbidding cytotoxic chemotherapy. RESULTS: One thousand three hundred and seventy-two fit patients (PS 0-1 in 73%) with a median age of 70 years diagnosed with metastatic breast (n=250), colorectal (n=621) or lung cancer (n=501) received chemotherapy from 1991 until 2006. Most patients received modern full-dose chemotherapy regimens including platinum, taxanes, anthracyclines, fluoropyrimidines, oxaliplatin or irinotecan. Mild to moderate co-morbidity was present in 35%. At a median follow-up of 3 years, objective responses were seen in 41% of patients with breast cancer, 25% with colorectal cancer and 31% with lung cancer, while median survival was 21, 16 and 9.4 months, respectively. Grade 3 or 4 toxicity was seen in a quarter of patients, the most common being neutropenia (14%), diarrhoea (6%), neurotoxicity (4%), fatigue, nausea and febrile neutropenia (each 2%). In multivariate analysis, diagnosis of colorectal or lung cancer, metastases in multiple organ sites, presence of liver/brain/peritoneal deposits, impaired PS and low baseline serum albumin levels were prognostic factors for adverse outcome. The same factors excluding metastatic sites and with the addition of anemia predicted for resistance to chemotherapy. Toxicity was more likely in females with low serum albumin and renal dysfunction. A six-variable geriatric assessment for palliation (GAP) score that included tumour type, sites of metastatic dissemination, impaired PS, low serum albumin and anemia classified elderly patients to groups with low, intermediate and high risk for disease progression and death (relative risks of 1.59 and 2.50 for resistance to therapy and 1.87 and 3.12 for death in the intermediate and high-risk groups). CONCLUSIONS: Our data indicate that relatively fit elderly patients with advanced cancer safely tolerate modern chemotherapy and enjoy disease control in a manner comparable to younger patients. Our GAP score, if further validated, offers promise for geriatric application in combination to comprehensive geriatric assessment tools for the optimisation of palliative therapy on an individualised basis.     

A conserved trimerization motif controls the topology of short coiled coils

In recent years, short coiled coils have been used for applications ranging from biomaterial to medical sciences. For many of these applications knowledge of the factors that control the topology of the engineered protein systems is essential. Here, we demonstrate that trimerization of short coiled coils is determined by a distinct structural motif that encompasses specific networks of surface salt bridges and optimal hydrophobic packing interactions. The motif is conserved among intracellular, extracellular, viral, and synthetic proteins and defines a universal molecular determinant for trimer formation of short coiled coils. In addition to being of particular interest for the biotechnological production of candidate therapeutic proteins, these findings may be of interest for viral drug development strategies.     

Hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption

Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema.     

Molecular cloning of the mouse homologue of Rab3c

Small GTP-binding proteins of the Rab subfamily are key regulators of intracellular vesicle transport. Here we report the isolation of a cDNA clone encoding the complete Rab3c isoform from mouse embryo using a degenerative PCR-based approach. Multiple sequence alignment revealed that the predicted amino acid sequence was identical to the previously identified rat Rab3c isoform and 98% identical to the published bovine Rab3c GTPase from brain. Furthermore by in situ hybridisation, Rab3c mRNA was detectable within various regions of the brain, cartilage and highly enriched within intestinal villi of foetal tissues. Chondrocytes in the hypertrophic zone, but not reserve or proliferative zones, expressed high levels of Rab3c. This pattern of expression corresponds with the genesis of matrix vesicles during endochondral ossification.In all, our results suggest that in addition to its functional role during regulated secretion in brain, Rab3c may play a part in matrix vesicle trafficking during skeletal development.     

Forty-years (1961-2001) of all-cause and coronary heart disease mortality and its determinants: the Corfu cohort from the Seven Countries Study

AIMS: This study examined risk factors in relation to 40-year all-cause and coronary heart disease mortality in the Corfu cohort of the Seven Countries Study. METHODS: The population studied in this analysis consisted of 529 rural middle-aged men enrolled in 1961. Multivariate analysis was performed using the proportional hazards Cox model with all-cause as well as coronary heart disease death as end points and age, blood pressure, serum total cholesterol, smoking, physical activity, body mass index, skinfold thickness, vital capacity and forced expiratory volume as predictors. RESULTS: The 40-year all-cause mortality rate was 87.1% (461 deaths/529 individuals at entry), while the CHD mortality rate was 22.7% (120 deaths/529 individuals at entry). The proportion of CHD deaths varied from 16 to 28.5% of all deaths during the period investigated. Age (hazard ratio (HR)=1.08, P<0.001), smoking (HR=1.40, P<0.01), diastolic blood pressure (HR=1.01, P<0.05), and forced expiratory volume (HR=0.97, P<0.05) were independently associated with 40-year all-cause mortality. Moreover, age (HR=1.093, P<0.001), smoking (HR=1.596, P<0.05), and body mass index (HR=1.05, P<0.05) were independently associated with 40-year CHD mortality. CONCLUSION: Among the investigated cardiovascular risk factors, age, smoking, physical activity, skinfold thickness, diastolic blood pressure, and forced expiratory volume seem to be associated with all-cause mortality, while age, smoking, and body mass index were consistently associated with 40-year CHD mortality.     

The interplay between haemodynamic load, brain natriuretic peptide and left atrial size in the early stages of essential hypertension

OBJECTIVE: Left atrial (LA) enlargement is an index of adverse cardiovascular events. We sought to investigate any possible correlation between haemodynamic load, neurohumoral factors and LA size in the early stages of essential hypertension. METHODS: We studied 94 consecutive middle-aged subjects, with newly diagnosed stage I-II essential hypertension without left ventricular (LV) hypertrophy and 34 age and sex-matched normotensive individuals. Ambulatory blood pressure (BP) monitoring, plasma levels of brain natriuretic peptide (BNP), metabolic profile and left atrial volume index (LAVI), an echocardiographic measurement of LA volume indexed for the body surface area, constituted the work-up of all subjects. RESULTS: Hypertensive compared with normotensive subjects had significantly increased office and ambulatory systolic and diastolic BP (P < 0.0001 for all cases) as well as body mass index and waist-to-hip ratio (P < 0.05 for both cases). BNP levels were greater in hypertensive compared with normotensive subjects but were not statistically significant (20.4 versus 17.1 pg/ml, P = NS). Hypertensive compared with normotensive subjects also had significantly increased LV mass index (105 versus 84 g/m, P < 0.0001), LA diameter (39 versus 36 mm, P < 0.0001), and LAVI (22 versus 19 ml/m, P < 0.05). In the hypertensive population, LAVI exhibited significant positive relationships with office systolic BP, ambulatory pulse pressure, LV mass index and BNP. In multiple linear regression analysis only LV mass index and BNP were significantly associated with LAVI (beta = 0.298, P = 0.030 and beta = 0.322, P = 0.009, respectively). CONCLUSIONS: Increased LAVI, closely associated with LV mass index and BNP, was still found in the early stages of essential hypertension. However, the clinical significance of these findings remains to be elucidated in future studies.     

An integrated assessment of family history on the risk of developing acute coronary syndromes (CARDIO2000 study)

OBJECTIVE: In this work we assessed a risk score for developing a first event of acute coronary syndrome (ACS) based on the family history of the cardiovascular risk factors. METHODS AND RESULTS: The studied population consisted of 848 randomly selected middle-aged patients with first event of ACS and 1078 sex-age-region matched controls admitted to the same hospitals for minor operations and without any clinical suspicion of cardiovascular disease in their life. A Family History Score (FHS) was developed based on the presence of coronary heart disease, hypertension, hypercholesterolaemia and diabetes mellitus, among first-degree relatives of the participants after adjusting for the family size. The evaluation of FHS was based on conditional logistic regression analysis, after controlling for demographic variables as well as for the mutual confounding effects of other risk factors. Family history of CHD, hypercholesterolaemia and diabetes was highly associated with the development of the disease. The introduced FHS was also highly associated with the development of ACS among participants who had no family history of CHD (odds ratio = 10.9, p < 0.001), whereas it was not associated with the development of the disease among participants who had a family history of CHD (odds ratio = 1.41, p = 0.543). CONCLUSIONS: The suggested FHS could be a useful tool in the primary prevention of ACS, as well as in detecting and understanding associations between genetic vulnerability and cardiovascular risk factors.