Family health narratives : midlife women’s concepts of vulnerability to illness

Perceptions of vulnerability to illness are strongly influenced by the salience given to personal experience of illness in the family. This article proposes that this salience is created through autobiographical narrative, both as individual life story and collectively shaped family history. The paper focuses on responses related to health in the family drawn from semi-structured interviews with women in a qualitative study exploring midlife women’s health. Uncertainty about the future was a major emergent theme. Most respondents were worried about a specified condition such as heart disease or breast cancer. Many women were uncertain about whether illness in the family was inherited. Some felt certain that illness in the family meant that they were more vulnerable to illness or that their relatives’ ageing would be mirrored in their own inevitable decline, while a few expressed cautious optimism about the future. In order to elucidate these responses, we focused on narratives in which family members’ appearance was discussed and compared to that of others in the family. The visualisation of both kinship and the effects of illness, led to strong similarities being seen as grounds for worry. This led to some women distancing themselves from the legacies of illness in their families. Women tended to look at the whole family as the context for their perceptions of vulnerability, developing complex patterns of resemblance or difference within their families

Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.

Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease

Patients with IgA nephropathy exhibit high systemic PDGF-DD levels

Background. Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. Methods. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. Results. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 ± 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 ± 0.86 ng/ml) compared to healthy controls (1.17 ± 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Conclusions. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative G

Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism

In alcohol-dependent (AD) patients, alcohol cues induce strong activations in brain areas associated with alcohol craving and relapse, such as the nucleus accumbens (NAc) and amygdala. However, little is known about the influence of depressive symptoms, which are common in AD patients, on the brain’s reactivity to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has been associated with alcohol dependence, craving and depression, but its influence on neural alcohol cue reactivity has not been tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs) using functional magnetic resonance imaging and assessed the influence of depressive symptoms and peripheral DAT methylation in these responses. We show that alcoholics with low Beck’s Depression Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala than those with mild/moderate depression scores (n=9), though subjective perception of craving was higher in those with mild/moderate depression scores. We corroborated a higher DAT methylation in AD patients than HCs, and showed higher DAT methylation in AD patients with mild/moderate than low depression scores. Within the AD cohort, higher methylation predicted craving and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we show that amygdala cue reactivity correlated with craving and DAT methylation only in AD patients with low depression scores. These findings suggest that depressive symptoms and DAT methylation are associated with alcohol craving and associated brain processes in alcohol dependence, which may have important consequences for treatment. Moreover, peripheral DAT methylation may be a clinically relevant biomarker in AD patients

Evaluation of temporomandibular disorders before and after orthognathic surgery: therapeutic considerations on a sample of 76 patients

Temporomandibular disorders may be associated with dental and facial malformations. The aim of this study is to record the prevalence of TMDs in patients scheduled for orthognathic surgery, reporting the development of TMDs and symptoms during the entire period of the treatment, and demonstrating the benefits of a team effort on this population. MATERIALS AND METHODS: Assessment of temporomandibular status was performed using the RDC/TMD criteria at T0 (prior to orthodontic therapy), T1 (3 months after the surgery), and T2 post-therapeutic cycle (6 to 12 months postoperatively). A total of 76 participants were included in the study; all the patients underwent surgical treatment: 12 had bilateral sagittal split osteotomy, 6 with condylar position devices; 64 had Le Fort I + bilateral sagittal split osteotomy, and 15 with condylar position devices. Results were evaluated with a paired-sample t-test and segmentation analysis. RESULTS: Forty-seven patients were affected by TMDs. At T0, 25 patients experienced TMJ pain, 27 had muscular pain, 31 suffered headaches, 42 had disc dislocation with reduction, and 5 were affected by disc dislocation without reduction. Thirty-five patients had occlusal signs of parafunctions, 8 reported tinnitus, and 7 dizziness. At T1, TMJ pain changed from 33.3% to 4.44%, muscular pain changed from 35.5% to 11.1%, headaches improved from 40% to 6.67%, and disc dislocation from 55.2% to 17.7%. Segmentation analysis highlighted improvement after therapy; 57 patients were considered recovered, 14 improved, none were considered stable, whereas 5 patients demonstrated some worsening, 3 of whom had not presented disc dislocation before surgery. At T2, 71 patients were considered completely recovered or improved. CONCLUSIONS: Our data indicates beyond any doubt that both functional status and pain levels related to TMDs can be significantly improved with a multi-disciplinary approach. We concluded that surgeon's intervention need to be modified in the presence of presurgical TMDs

Measurement of the CMS Magnetic Field

The measurement of the magnetic field in the tracking volume inside the superconducting coil of the Compact Muon Solenoid (CMS) detector under construction at CERN is done with a fieldmapper designed and produced at Fermilab. The fieldmapper uses 10 3-D B-sensors (Hall probes) developed at NIKHEF and calibrated at CERN to precision 0.05% for a nominal 4 T field. The precise fieldmapper measurements are done in 33840 points inside a cylinder of 1.724 m radius and 7 m long at central fields of 2, 3, 3.5, 3.8, and 4 T. Three components of the magnetic flux density at the CMS coil maximum excitation and the remanent fields on the steel-air interface after discharge of the coil are measured in check-points with 95 3-D B-sensors located near the magnetic flux return yoke elements. Voltages induced in 22 flux-loops made of 405-turn installed on selected segments of the yoke are sampled online during the entire fast discharge (190 s time-constant) of the CMS coil and integrated offline to provide a measurement of the initial magnetic flux density in steel at the maximum field to an accuracy of a few percent. The results of the measurements made at 4 T are reported and compared with a three-dimensional model of the CMS magnet system calculated with TOSCA.Comment: 4 pages, 5 figures, 15 reference

Expression of the chemokine receptor CCR6 in human renal inflammation

Background. Nodular inflammatory cell infiltrates with defined microarchitecture, i.e. tertiary lymphoid organs, develop in the tubulointerstitium during chronic renal inflammation. CCR6 and the corresponding ligand CCL20 are involved in the formation of gut-associated lymphatic tissue. We hypothesized that CCR6 might be involved in the formation of nodular infiltrates in the kidney. Methods. CCR6- and CD20-positive B cells were localized in renal biopsies with IgA nephropathy (n = 13), membranous nephropathy (n = 12), crescentic glomerulonephritis (cGN, n = 11) and chronic interstitial nephritis (n = 13), and in pre-implantation biopsies as controls (n = 8). The mRNA expression of CCR6 and the ligand CCL20 was quantified by real-time RT-PCR in 51 renal biopsies of the same disease entities. Results. In the pre-transplant biopsies, CCR6 was expressed by endothelial cells of peritubular and glomerular capillaries. In patients with glomerulonephritis, infiltrating cells were positive particularly in areas of nodular inflammatory cell accumulations. A major part of the CCR6-positive cells were CD20-positive B cells, but a part of the CD3-positive T cells were also found to be positive. The constitutive expression of CCR6 on the endothelium of glomerular capillaries was lost in biopsies with progressive injury. Tubular epithelial cells expressed CCR6 in inflamed kidneys, most commonly on the basolateral side. Conclusions. CCR6 and the corresponding ligand CCL20 might therefore be involved in the recruitment of T and B cells to organized nodular infiltrates in chronic renal inflammation. The functional role of endothelial CCR6 needs to be evaluated in further studie

A qualitative study of the experiences of people who identify themselves as having adjusted positively to a visible difference

Individual and group interviews explored experiences of positive adjustment among 12 people with a range of visible differences. Thematic analysis identified four main themes: importance of appearance; personal growth; relationships with others; and coping (factors in the coping theme considered to be paramount to positive adjustment were inner strength and positivity, active coping techniques, downward social comparisons, taking things day-by-day, spirituality and humour). The findings provide insight into behaviours and personal outlooks that may contribute to adaptive coping and have implications for future research and interventions aimed at those who exhibit poor adjustment to visible difference. The article reflects on the use of both individual and group interviews for research in this field