Sympathetic activity, assessed by power spectral analysis of heart rate variability, in white-coat, masked and sustained hypertension versus true normotension

OBJECTIVE: To assess, in a population-based approach, sympathetic nervous system activity by the use of power spectral analysis of heart rate variability, in normotension, white-coat hypertension, masked hypertension and sustained hypertension. METHODS: The electrocardiographic RR interval was registered in the supine and standing positions and the low-frequency and high-frequency components of its variability were quantified. Cut-off values of 140/90 mmHg for conventional blood pressure and 135/85 mmHg for daytime ambulatory blood pressure were used to define the four blood pressure groups. RESULTS: After exclusion of patients with diabetes, myocardial infarction or treated hypertension, 1485 subjects with complete data remained for the analysis in the supine position. Age averaged 39 +/- 14 years; 54% were women. Conventional and ambulatory blood pressure averaged, respectively, 122 +/- 16/79 +/- 11 mmHg and 124 +/- 12/77 +/- 8 mmHg. After adjusting for demographic, anthropometric and lifestyle characteristics, the low-frequency to high-frequency ratio (geometric mean) averaged 0.81 in normotension and was significantly higher in white-coat hypertension (1.11; P < 0.001), based on a higher low-frequency component and a lower high-frequency component (P < 0.01). This ratio was not significantly different between normotension, masked hypertension (0.97) and sustained hypertension (0.93). The adjusted standing-to-supine ratio of the high-frequency component (geometric mean) was significantly higher in sustained hypertension (0.50) than in normotension (0.39; P < 0.01), but not in white-coat (0.40) and masked hypertension (0.45). CONCLUSION: The findings at rest are compatible with increased sympathetic activity and decreased parasympathetic modulation in white-coat hypertension, with normal autonomic cardiac regulation in masked and sustained hypertension. In addition, sustained hypertension is characterized by a blunted decrease of the high-frequency component on standing.     

Does age at the onset of narcolepsy influence the course and severity of the disease?

ObjectiveThe aim of the study is to compare the course and severity of narcolepsy in relation to different ages at the disease onset.MethodsClinical interviews with the completion of the Stanford questionnaire, Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT) were evaluated in 105 patients (44 males, 61 females, mean age 45.4 ± 19.2, BMI 29.2 ± 5.8) suffering from narcolepsy.ResultsThe severity of the disease was judged by clinical complaints, ESS value and MSLT results. No relations with the age at onset and clinical tetrad were found, however, smoking may be associated with an increased risk of hypnagogic hallucinations. There was no correlation between the number of sleep and cataplectic attacks and the age at onset, nor did subjective ESS show any significant dependence. However, earlier onset of the disease correlated with shorter MSLT mean latency. A correlation was found between the BMI and narcolepsy sleepiness rating in the elderly and between degree of education attained and subjective complaints.ConclusionsThe clinical severity of narcolepsy does not depend on the age at onset.     

Laparoscopic Sleeve Gastrectomy without an Over-Sewing of the Staple Line

Background  In the past few years, laparoscopic sleeve gastrectomy (LSG) became a widely used bariatric method. Based on results of recent LSG studies, LSG is being increasingly used even as a single bariatric method. On contrary with some other reports, we do not reinforce the LSG staple line with over-sewing. Our pilot study presents treatment outcomes and results 18 months after LSG. Methods  Sixty-one consecutive morbidly obese (MO) patients (19 male and 42 female) who underwent LSG from January 2006 to May 2008 were included into the study. The mean age, height, and weight were 37.3 years (29–57), 168 cm (151–187), and 118 kg (97–181), respectively, while mean body mass index (BMI) was 41.8 (36.1–60.4). LSG started at 6 cm from pylorus and ended at the angle of Hiss. For gastric sleeve calibration 38F, intragastric tube was used. All 61 LSG were performed without over-sewing of the staple line. In the last 24 cases, the staple line was covered with Surgicel™ strips, which were however placed without any fixation to the underlying gastric tissue. Results  Mean operating time was 105 min (80–170) and no conversion to open surgery. An 18-month follow-up was recorded in 39 MO patients. The mean weight loss was 31.3 (range, 21–67 kg) and mean % excess BMI loss reached 72% (range, 64–97%). Neither leak nor disruptions of the staple line and/or sleeve dilatation were recorded. Conclusion  LSG is an effective and safe bariatric procedure with low incidence of complications and mortality in our experience.     

Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice

Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed to aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized 1% OVA solution on 3 consecutive days to investigate the development of an inflammatory response. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. OVA-specific IgG1 production in both MEHP groups was significantly increased. OVA-specific IgE and IgG2a were not increased significantly. A dose-dependent increase in inflammatory cells was observed in BAL fluid, leading to significantly higher lymphocyte and eosinophil numbers in the OVA+0.4 mg/m(3) MEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested a T(H)2 profile of MEHP. In conclusion, MEHP acted as a T(H)2 adjuvant after inhalation. However, it is suggested that the inflammation in the MEHP groups was primarily mediated by an IgG1-dependent mechanism. To address implications for humans, a margin-of-exposure was estimated based on the lack of significant effects on IgE production and inflammation after exposures to 0.03 mg/m(3) MEHP observed in the present study and estimated human exposure levels.     

Transitions for older people with intellectual disabilities and behaviours that challenge others: A rapid scoping review

Background

People with intellectual disabilities and behaviours that challenge others are living longer. This review aimed to explore what is known about the health and social care needs, experiences, service interventions and resources of and for this population as they transition to different care contexts in the UK.

Method

A rapid scoping review of published and unpublished literature was conducted based on collaborative working with key stakeholders and using systematic methods of data searching, extraction and analysis.

Results

Consistent social work support, skilled staff, suitable accommodation, creative engagement with individuals and families to plan ahead, and timely access to quality healthcare are all required to promote successful transitions as people age, and to avoid unwanted/inappropriate transitions at points of crisis.

Conclusions

More research is needed to assess the types of services that this population can and do access as they age, the quality of those services, and the extent to which local commissioners are planning ahead for people with intellectual disabilities and behaviours that challenge others.     

Activation of B cell apoptotic pathways in the course of Francisella tularensis infection

Francisella tularensis is a facultative intracellular, gram-negative bacterium that induces apoptosis in macrophages and B cells. Here we show apoptotic pathways that are activated in the Ramos human B cell line in the course of F. tularensis infection. Live bacteria F. tularensis FSC200 activate caspases 8, 9 and 3, as well as Bid; release cytochrome c and apoptosis-inducing factor from mitochondria; and induce depolarization of mitochondrial membrane potential in the Ramos cell line, thus leading these cells to apoptosis. Unlike live bacteria, killed F. tularensis FSC200 bacteria activated only caspase 3, and did not cause apoptosis of Ramos cells as measured by annexin V. Killed bacteria also caused accumulation of anti-apoptotic protein Bclx_L in mitochondrial membranes. Thus, live F. tularensis activates both caspase pathways (receptor-mediated and intrinsic) as well as caspase-independent mitochondrial death.     

Socioeconomic inequalities in homicide mortality: a population-based comparative study of 12 European countries

Recent research has suggested that violent mortality may be socially patterned and a potentially important source of health inequalities within and between countries. Against this background the current study assessed socioeconomic inequalities in homicide mortality across Europe. To do this, longitudinal and cross-sectional data were obtained from mortality registers and population censuses in 12 European countries. Educational level was used to indicate socioeconomic position. Age-standardized mortality rates were calculated for post, upper and lower secondary or less educational groups. The magnitude of inequalities was assessed using the relative and slope index of inequality. The analysis focused on the 35–64 age group. Educational inequalities in homicide mortality were present in all countries. Absolute inequalities in homicide mortality were larger in the eastern part of Europe and in Finland, consistent with their higher overall homicide rates. They contributed 2.5?% at most (in Estonia) to the inequalities in total mortality. Relative inequalities were high in the northern and eastern part of Europe, but were low in Belgium, Switzerland and Slovenia. Patterns were less consistent among women. Socioeconomic inequalities in homicide are thus a universal phenomenon in Europe. Wide-ranging social and inter-sectoral health policies are now needed to address the risk of violent victimization that target both potential offenders and victims.     

The role of chronic inflammation in cutaneous fibrosis: fibroblast growth factor receptor deficiency in keratinocytes as an example

Fibrosis is associated with a variety of skin diseases and causes severe aesthetic and functional impairments. Functional studies in rodents, together with clinical observations, strongly suggest a crucial role of chronic injury and inflammation in the pathogenesis of fibrotic diseases. The phenotype of mice lacking fibroblast growth factor (FGF) receptors 1 and 2 in keratinocytes supports this concept. In these mice, a defect in keratinocytes alone initiated an inflammatory response, which in turn caused keratinocyte hyperproliferation and dermal fibrosis. As the mechanism underlying this phenotype, we identified a loss of FGF-induced expression of claudins and occludin, which caused abnormalities in tight junctions with concomitant deficits in epidermal barrier function. This resulted in severe transepidermal water loss and skin dryness. In turn, activation of keratinocytes and epidermal γδ T cells occurred, which produced IL-1 family member 8 and S100A8 and S100A9. These cytokines attracted immune cells and activated fibroblasts, resulting in a double paracrine loop through production of keratinocyte mitogens by dermal cells. In addition, a profibrotic response was induced in fibroblasts. Our results highlight the importance of an intact epidermal barrier for the prevention of inflammation and fibrosis and the role of chronic inflammation in the pathogenesis of fibrotic diseases.