Poor perception of dyspnoea in children with undiagnosed asthma.

The aim of the present study was to establish the differences in dyspnoea perception between children with undiagnosed and diagnosed asthma. A cross-sectional community-based study was performed, which included a parental questionnaire on the child's respiratory health and testing of airway reversibility and bronchial hyperresponsiveness (BHR). "Diagnosed asthma" was defined by a physician's diagnosis of asthma. "Undiagnosed asthma" was defined by the presence of asthma symptoms combined with either airway reversibility or BHR without a physician's diagnosis of asthma. Only children with a positive BHR test were selected for further analysis. Perception of dyspnoea was assessed using the Borg scale and the visual analogue scale (VAS), plotted against the percentage fall in forced expiratory volume in one second and expressed as the slope of the regression line. Of the initial 1,758 participating children, 70 had undiagnosed asthma and 38 had diagnosed asthma. The Borg and VAS slopes in children with undiagnosed asthma were less steep than those of children with diagnosed asthma (Borg: 0.07 and 0.14, respectively; VAS: 0.06 and 0.11, respectively). Among children with bronchial hyperresponsiveness, those without a parent's report of physician's diagnosis of asthma had a worse perception of dyspnoea than children with diagnosed asthma.     

Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons

Background  

The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.     

DNA methylation testing for endometrial cancer detection in urine,cervicovaginal self-samples and cervical scrapes

Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally- and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P < .01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%. Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection. Our study shows the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. This approach has great potential to screen patient populations at risk for endometrial cancer.     

Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial

We performed a randomized, double-blind, placebo-controlled trial in 555 patients with unstable angina who were hospitalized in coronary care units. Patients received one of four possible treatment regimens: aspirin (325 mg four times daily), sulfinpyrazone (200 mg four times daily), both, or neither. They were entered into the trial within eight days of hospitalization and were treated and followed for up to two years (mean, 18 months). The incidence of cardiac death and nonfatal myocardial infarction, considered together, was 8.6 per cent in the groups given aspirin and 17.0 per cent in the other groups, representing a risk reduction with aspirin of 51 per cent (P = 0.008). The corresponding figures for either cardiac death alone or death from any cause were 3.0 per cent in the groups given aspirin and 11.7 per cent in the other groups, representing a risk reduction of 71 per cent (P = 0.004). Analysis by intention to treat yielded smaller risk reductions with aspirin of 30 per cent (P = 0.072), 56 per cent (P = 0.009), and 43 per cent (P = 0.035) for the outcomes of cardiac death or nonfatal acute myocardial infarction, cardiac death alone, and all deaths, respectively. There was no observed benefit of sulfinpyrazone for any outcome event, and there was no evidence of an interaction between sulfinpyrazone and aspirin. Considered together with the results of a previous clinical trial, these findings provide strong evidence for a beneficial effect of aspirin in patients with unstable angina.     

Long-term restoration of the human T-cell compartment after thymectomy during infancy: a role for thymic regeneration?

Thymectomy during early childhood is generally thought to have serious consequences for the establishment of the T-cell compartment. In the present study, we investigated the composition of the T-cell pool in the first 3 decades after thymectomy during infancy due to cardiac surgery. In the first 5 years after thymectomy, naive and total CD4(+) and CD8(+) T-cell numbers in the blood and T-cell receptor excision circle (TREC) levels in CD4(+) T cells were significantly lower than in healthy age-matched controls. In the first years after thymectomy, plasma IL-7 levels were significantly elevated and peripheral T-cell proliferation levels were increased by ～ 2-fold. From 5 years after thymectomy onward, naive CD4(+) and CD8(+) T-cell counts and TRECs were within the normal range. Because TREC levels are expected to decline continuously in the absence of thymic output, we investigated whether normalization of the naive T-cell pool could be due to regeneration of thymic tissue. In the majority of individuals who had been thymectomized during infancy, thymic tissue could indeed be identified on magnetic resonance imaging scans. Whereas thymectomy has severe effects on the establishment of the naive T-cell compartment during early childhood, our data suggest that functional regrowth of thymic tissue can limit its effects in subsequent years.     

Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4

DNA double-strand break (DSB) repair by nonhomologous end joining (NHEJ) requires the assembly of several proteins on DNA ends. Although biochemical studies have elucidated several aspects of the NHEJ reaction mechanism, much less is known about NHEJ in living cells, mainly because of the inability to visualize NHEJ repair proteins at DNA damage. Here we provide evidence that a pulsed near IR laser can produce DSBs without any visible alterations in the nucleus, and we show that NHEJ proteins accumulate in the irradiated areas. The levels of DSBs and Ku accumulation diminished in time, showing that this approach allows us to study DNA repair kinetics in vivo. Remarkably, the Ku heterodimers on DNA ends were in dynamic equilibrium with Ku70/80 in solution, showing that NHEJ complex assembly is reversible. Accumulation of XRCC4/ligase IV on DSBs depended on the presence of Ku70/80, but not DNA-PK(CS). We detected a direct interaction between Ku70 and XRCC4 that could explain these requirements. Our results suggest that this assembly constitutes the core of the NHEJ reaction and that XRCC4 may serve as a flexible tether between Ku70/80 and ligase IV.     

Relation between migraine and size of echocardiographic intrapulmonary right-to-left shunt

An increased prevalence of intrapulmonary right-to-left shunt (RLS) has been shown in patients with migraine. The aim of this study was to determine whether the size of intrapulmonary RLS was associated with migraine with aura (MA+) and migraine without aura (MA-) in subjects screened for hereditary hemorrhagic telangiectasia. A total of 462 consecutive subjects were screened for hereditary hemorrhagic telangiectasia and underwent transthoracic contrast echocardiography. A pulmonary shunt was established when contrast appeared in the left atrium after 4 cardiac cycles. Shunt size was assessed semiquantitatively as small (<30 microbubbles), moderate (30 to 100 microbubbles), or large (>100 microbubbles). A headache questionnaire was completed by 420 subjects (91%). Two independent neurologists diagnosed migraine according to the International Headache Society criteria. Of 420 screened subjects (mean age 43.4 ± 15.4 years, 61.4% women), 44 (10.5%) had MA+ and 45 (10.7%) had MA-. MA+ was an independent predictor for an intrapulmonary RLS (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.36 to 6.47, p=0.006) in multivariate analysis. MA- was not correlated with RLS (OR 1.21, 95% CI 0.56 to 2.64, p=0.60). When comparing patients with MA+ to those without migraine in a multivariate analysis, the presence of an intrapulmonary shunt predicted MA+ (OR 2.5, 95% CI 1.2 to 5.2, p=0.01), as did female gender (OR 3.15, 95% CI 1.29 to 7.65, p<0.01). The correlation of MA+ and RLS could be entirely attributed to large intrapulmonary shunts (OR 7.61, 95% CI 3.11 to 18.61, p<0.001), as small (OR 0.6, 95% CI 0.13 to 2.78, p=0.52) and moderate (OR 1.33, 95% CI 0.35 to 5.02, p=0.68) shunts did not appear to be risk factors for MA+. In conclusion, patients with large intrapulmonary RLS have an increased risk for MA+.