Correlations between HIV-1 clades and HIV-1 antibody neutralization sensitivity: significant for vaccine development?

The correlates of protection against HIV-1 infection or disease progression are still unknown which causes an immense challenge for HIV-1 vaccine design. Existing effective vaccines against other viruses generate antibodies that either block the initial infection or contribute to the eradication of the virus before it can cause disease. For HIV-1, a protective vaccine capable of eliciting protective neutralizing antibodies does not exist and the difficulties for the generation of such a vaccine are multiple. Conserved elements on the viral envelope glycoprotein, the target of HIV-specific neutralizing antibodies, seem to be poorly immunogenic and attempts to generate an immunogen that can elicit broadly reactive neutralizing antibodies have remained largely without success. In addition, the envelope of HIV-1 is highly variable with respect to amino acid sequence, length of the variable loops, and glycosylation pattern. To cope with the high sequence variation, vaccine-elicited clade-specific neutralizing antibodies have been suggested as an attractive alternative and recent studies have revealed some evidence for the existence of HIV-1 clade-specific humoral immune responses. Here, we will review these recent findings and hypothesize on the nature of clade-specific humoral immunity also in light of their relevance for HIV-1 vaccine development.     

Interference between PARPs and SIRT1: a novel approach to healthy ageing?

Poly(ADP-ribosyl) polymerases (PARPs) have traditionally been linked to chromosome maintenance and DNA repair. Recent findings identify PARPs as key modulators of metabolism through their influence on SIRT1 activity, hinting to a possible role of PARPs as longevity regulators.     

Potential coeliac disease in Type 1 diabetes mellitus: Does a positive antibody lead to increased complications?

Background and aimsCoeliac disease (CD) is more common in people with Type 1 diabetes and is associated with poorer glycaemic control, lipid profiles, nephropathy and retinopathy. Potential CD (positive serology but normal duodenal biopsy) is associated with neuropathy but patients with coexisting Type 1 diabetes were excluded. The aim was to determine whether potential CD is associated with increased microvascular complications in patients with Type 1 diabetes.Methods and resultsFour groups were recruited; 1) patients with Type 1 diabetes and potential CD, 2) patients with Type 1 diabetes and newly identified CD, 3) patients with Type 1 diabetes alone and 4) patients with CD alone. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined.As many as 76 individuals were included in the study: 22 in group 1, 14 in group 2, 24 in group 3 and 16 in group 4. There were no differences in age, gender, BMI and diabetes duration between the groups. Patients in group 1 had significantly lower total cholesterol compared to group 3 (p = 0.003) but higher than group 2 (p = 0.027). There were no significant differences in HbA1c, HDL cholesterol, cholesterol:HDL ratio, creatinine, quality of life scores or prevalence of neuropathy between individuals in group 1 and the other groups.ConclusionsThis is the first study to assess the effects of potential CD in patients with Type 1 diabetes. It appears that an enteropathy is required as well as antibody positivity in order to increase the risk of diabetes related complications. This pilot data requires further longitudinal validation.     

Nursing homes: a suitable alternative to hospital care for older people in the UK?

Over the past two decades nursing homes have become the major supplier of long-stay care for frail older people in the UK. Demographic projections indicate that the volume of nursing home places will continue to increase to keep pace with demand and that the population of homes will become steadily more dependent. Little systematic research exists to indicate how nursing home care compares with hospital care; the evidence that does exists tends to be restricted to local studies and thus is not generalizable. Local studies indicate that in both care settings there are shortfalls in terms of meeting basic quality of care standards. Despite this, there is obvious potential for nursing homes to act as an alternative to hospitalization, provided that there is suitable access for residents to specialist care and, for example, appropriate administration of medicines. Proposed changes in government policy will introduce more uniform standards in nursing homes and associated inspection structures and procedures. However, further research is needed to ascertain the clinical and consumer value of different interventions in nursing homes, and the cost-benefit of enhancing provision available in terms of preventing or forestalling demand on hospitals or reducing hospital length of stay. In the light of the commitment to develop evidence based practice, it is important that such research is urgently advanced to eliminate poor practice. In our rights conscious society, future generations of older people are unlikely to be as tolerant of substandard care.     

Goals for the care of frail older adults: do caregivers and clinicians agree?

PURPOSE: Establishing shared treatment goals for patients may improve the quality of care by facilitating achievement of appropriate and desired outcomes. The purpose of this study was to describe types of family caregiver and physician treatment goals for frail elderly patients who had a high prevalence of cognitive impairment, and to ascertain the level of agreement between family caregivers and physicians on principal treatment goals. SUBJECTS AND METHODS: We surveyed family caregivers and physicians for 200 consecutive older adults who were initially evaluated at the outpatient geriatric assessment center of a major teaching hospital. Treatment goals for patients were measured after a comprehensive geriatric assessment. RESULTS: Goals commonly chosen as most important by family caregivers and physicians pertained to day-to-day functioning (61 [31%] family caregivers, 81 [41%] physicians), behavior and emotional health (56 [28%] family caregivers, 50 [25%] physicians), and safety (40 [20%] family caregivers, 29 [15%] physicians). Although a substantial proportion of family caregiver and physician pairs shared at least one goal (157 [79%] of 200), agreement on presence or absence of individual categories of goals was poor (kappas from -0.19 to 0.28), and agreement on the most important goal was also poor (kappa 0.20). CONCLUSIONS: Agreement on treatment goals between family caregivers and physicians for patients at the study site was low. These results suggest that encounters between family caregiver and physician may need improvement. Further research is needed to assess whether lack of agreement is found in other settings, persists over time, and affects achievement of goals and optimal health outcomes.     

Is the clinical presentation different between men and women admitting to the sleep laboratory?

Objectives  Sleep and sleep disorders are different in several important ways between men and women. We aimed to investigate gender differences in initial symptoms and associating medical diseases of patients admitting to our sleep clinic. Methods  Ninety-one patients, 20 women (22%) and 71 men (78%), admitting consecutively to the sleep clinic were studied. A detailed sleep and medical history of the patients was recorded. All patients were questioned for Epworth Sleepiness Scale (ESS) and underwent an entire night of diagnostic polysomnography. Apnea–hypopnea index (AHI) was identified as the total number of apnea and hypopnea per hour of sleep. Hypopnea was defined as a decrease of airflow by at least 50% and desaturations were defined as ≥4% decrease in oxygen saturation. Results  The mean values for age, body mass index, blood pressures and ESS score did not significantly differ between men and women, but AHI (events/h) was significantly higher in men (29.1 ± 22.7) than women (17.9 ± 17.7, p < 0.05). Snoring was the most common symptom in both men (95%) and women (90%). Among the main presenting complaints, only morning headache (12 of women 60%, 31 of men 43%, p = 0.04) and dry mouth on awakening (ten of women 50%, 57 of men 80%, p = 0.02) showed a significant difference between the two genders, while among the medical diseases only hypothyroidism (four of women 20% and three of men 4%, p = 0.03) and depression (nine of women 45% and 16 of men 22%, p = 0.02) were seen as statistically higher in women than in men. Conclusions  Primary care physicians should be aware of obstructive sleep apnea (OSA) in women and the importance of referring women for sleep studies when they complain of symptoms associated with OSA, even if other non-specific symptoms such as morning headaches are reported. Also, hypothyroidism and depression are accompanied with sleep disorders especially in women.     

The relationship between tumors and the lymphatics: what more is there to know?

Ten years ago the relationship between tumors and the lymphatic system was perceived to be rather passive. Since then, the dramatic increase in our understanding of the molecular biology of lymphatic endothelial cells and the regulation of lymphangiogenesis has revealed that tumors can actively interact with the lymphatics by inducing lymphangiogenesis. In turn, this interaction promotes the entry of tumor cells into the lymphatic vasculature and their subsequent transport to regional lymph nodes, a process that stimulates the formation of metastases. Tumor-induced lymphangiogenesis has thus emerged as an important new target in the fight against metastatic cancer. Nevertheless, there is still much to be learned about the relationship between tumors and the lymphatics that will have important ramifications for the design of clinical trials aimed at the application of anti-lymphangiogenesis therapies in the management of cancer. This Lymphangiogenesis Review focuses on these issues.     

How to assess frailty and the need for care? Report from the Study of Health and Drugs in the Elderly (SHADES) in community dwellings in Sweden

Knowledge about the need for care of elderly individuals in community dwellings and the factors affecting their needs and support is limited. The aim of this study was to characterize the frailty of a population of elderly individuals living in community dwellings in Sweden in relation to co-morbidity, use of drugs, and risk of severe conditions such as malnutrition, pressure ulcers, and falls. In 2008, 315 elderly individuals living in community dwellings were interviewed and examined as part of the SHADES-study. The elderly demonstrated co-morbidity (a mean of three diseases) and polypharmacy (an average of seven drugs). More than half the sample was at risk for malnutrition, one third was at risk for developing pressure ulcers, and nearly all (93%) had an increased risk of falling and a great majority had cognitive problems. Age, pulse pressure, body mass index, and specific items from the modified Norton scale (MNS), the Downton fall risk index (DFRI), and the mini nutritional assessment (MNA-SF) were related to different outcomes, defining the need for care and frailty. Based on the results of this study, we suggest a single set of items useful for understanding the need for care and to improve individual based care in community dwellings.