The effects of a hearing education program on recreational noise exposure,attitudes and beliefs toward noise,hearing loss,and hearing protector devices in young adults

Excessive recreational noise exposure in young adults might result in noise-induced hearing loss (NIHL) and tinnitus. Inducing behavioral change in young adults is one of the aims of a hearing conservation program (HCP). The goal of the current study was to evaluate the effect of a hearing education program after 6 months in young adults in relation to knowledge regarding their individual hearing status. The results of a questionnaire regarding the weekly equivalent recreational noise exposure, attitudes and beliefs toward noise, and hearing loss and hearing protector devices (HPDs) were compared between both sessions. Seventy-eight young adults completed the questionnaire concerning recreational noise exposure, youth attitude to noise scale (YANS), and beliefs about hearing protection and hearing loss (BAHPHL). Their hearing status was evaluated based on admittance measures, audiometry, transient-evoked otoacoustic emissions (TEOAEs), and distortion-product otoacoustic emissions (DPOAEs). The main analysis consisted of a mixed model analysis of variance with dependent variables of either the noise exposure or the scores on (subscales of) YANS and BAHPHL. The independent variables were hearing status and session one versus session two. There was a significant decrease in recreational noise exposure and several (sub) scales of YANS and BAHPHL between both the sessions. This behavioral change resulted in a more frequent use of HPDs in 12% of the participants. However, the behavioral change was not completely related to the knowledge of young adults’ individual hearing status. To prevent hearing damage in young people, investing in HCPs is necessary, apart from regulating sound levels and its compliance at various leisure-time activities. Also, the long-term effect of HCPs and their most cost-efficient repetition rates should be further investigated.     

Whole genome sequencing identifies variants associated with sarcoidosis in a family with a high prevalence of sarcoidosis

Clinical Rheumatology - We studied genetic risk factors associated with sarcoidosis within a family with a high prevalence of this disease. We studied 41 members of a family with a high rate of...     

Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.     

Seroprevalence of HBV (anti-HBc,HBsAg and anti-HBs) and HDV infections among 9006 women at delivery*

Abstract: Serum samples from 9006 women, who delivered in Switzerland in 1990 and 1991, were collected around the country. Of these women, 62.7% were Swiss and 37.3% originated from foreign countries. Samples were first screened for anti-HBc and those found positive were further tested for HBsAg, anti-HBs and anti-HDV Anti-HBc was found in 640 of the 9006 women (overall prevalence, 7.1%; Swiss, 3.3%; foreigners, 13.5%). Of these 640 positive samples, 61 (9.5%) were positive for HBsAg (without anti-HBs), 467 (73.0%) positive for anti-HBs (without HBsAg) and 8 (1.3%) positive for both HBsAg and anti-HBs. The remaining 104 were thus anti-HBc positive without HBsAg or anti-HBs. These 104 specimens with the so-called “isolated anti-HBc” reactivity represented 1.2% of the whole population or 16.3% of the 640 anti-HBc positive mothers. All were HBV DNA negative (PCR). Anti-HDV antibody was found in only five women. HBsAg was seen in 38 of the cord-blood samples from the anti-HBc positive mothers. In this large sampling, we observed a relatively high seroprevalence of HBV infection. Cases with isolated anti-HBc reactivity, being HBV DNA negative by PCR, were probably non-infectious at the time of blood collection.     

Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma

Human leukocyte antigen class I molecules expressed by tumor cells play a central role in the regulation of natural killer (NK) cell-mediated immune responses. The proteasome inhibitor bortezomib has demonstrated significant activity in multiple myeloma (MM). We hypothesized that treatment of MM with bortezomib results in the reduction of cell-surface expression of class I and thereby sensitizes MM to NK cell-mediated lysis. Here we report that bortezomib down-regulates class I in a time- and dose-dependent fashion on all MM cell lines and patient MM cells tested. Downregulation of class I can also be induced in vivo after a single dose of 1.0 mg/m(2) bortezomib. Bortezomib significantly enhances the sensitivity of patient myeloma to allogeneic and autologous NK cell-mediated lysis. Further, the level of decrease in class I expression correlates with increased susceptibility to lysis by NK cells. Clinically relevant bortezomib concentrations do not affect NK-cell function. Our findings have clear therapeutic implications for MM and other NK cell-sensitive malignancies in the context of both allogeneic and autologous adoptively transferred NK cells.     

No reduction of metabolic rate in food restricted Caenorhabditis elegans

Dietary restriction (DR) is the most consistent means of extending life span throughout the animal kingdom. Multiple mechanisms by which DR may act have been proposed but none are clearly predominant. We asked whether metabolic rate and stress resistance is altered in Caenorhabditis elegans in response to DR. DR was imposed in two complementary ways: by growing wild-type worms in liquid medium supplemented with reduced concentrations of bacteria and by using eat-2 mutants, which have a feeding defect. Metabolic rate was not reduced when we fed wild-type worms reduced food and was up-regulated in the eat-2 mutants in liquid culture, as assessed by oxygen consumption rate and heat production. The specific activity levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase showed small increases when we reduced food in wild-type worms, but restricted worms acquired no elevated protection against paraquat and hydrogen peroxide. eat-2 mutants showed elevated specific activities of SOD and catalase relative to wild type in liquid culture. These results indicate that the effects imparted by DR and the eat-2 mutation are not identical, and they contradict, at least in C. elegans, the widespread belief that CR acts by lowering the rate of metabolism.     

Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) have been reported after autologous transplantation (AT) for lymphoma. It is not clear whether myeloablative therapy used in conjunction with autologous transplantation contributes to the development of MDS/AML or whether the conventional chemotherapy preceding the transplant, and administered over a prolonged period, causes these secondary malignancies. To address this issue, we examined 188 patients with multiple myeloma (MM) who had received AT. 71 patients with no more than one cycle of standard chemotherapy were enrolled in our Total Therapy program, designed to avoid exposure to alkylating agents prior to peripheral blood stem cell mobilization (group 1). The median duration of pre-transplant therapy in group 1 was 7.6 months and significantly shorter than the 24 months of 117 patients (group 2) with more prolonged conventional therapy ( P  = 0.0001). All seven patients developing MDS post-transplantation belonged to group 2 ( P  = 0.02); the median durations from initial therapy and first transplant were 66 months (range 38–86) and 24 months (range 9–39), respectively. Our findings provide evidence that prolonged standard-dose alkylating agent therapy prior to transplantation, rather than autotransplant-supported myeloablative treatment, is associated with development of MDS/AML. Stem cell damaging alkylator treatment should be avoided, not to compromise PBSC collection, but also to reduce the risk of treatment-related MDS/AML.     

Cardiac arrhythmia following total correction of tetralogy of Fallot

41 patients after surgical correction of the tetralogy of Fall of aged 2-24 years (mean 11.2 y.) were followed for 12-65 months (mean 39.5 m.) for known or suspected dysrhythmias. 24-hour ambulatory ECG and exercise testing demonstrated nonsignificant ventricular ectopy (grade 0-1 according to a modified Lown classification) in 28 patients (group I) and significant (grade 2-5) ventricular dysrhythmias in the remaining 13 patients (group II). There were 2 cases of sudden late death in group II, whereas all patients in group I are alive. The victims of sudden death had no, other serious dysrhythmias and received no antiarrhythmic treatment. Ejection fraction of the functional part of the right ventricle estimated by radionuclide angiocardiography was not different in both groups whereas, global right ventricular ejection fraction differed nearly significantly (group I: 39.6 +/- 8.3%, group II: 31.9 +/- 10.4%, p = 0.052). Thus, a diminished global right ventricular ejection fraction caused by an extensive resection and large patch in the right ventricular outflow tract may be connected with the occurrence of higher grades of ventricular ectopy. These may lead to sudden late death.     

Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathways

Atheroma formation involves the movement of vascular smooth muscle cells (VSMC) into the subendothelial space. The aim of this study was to determine the involvement of PI3K and MAPK pathways and the importance of cross-talk between these pathways, in glucose-potentiated VSMC chemotaxis to serum factors. VSMC chemotaxis occurred in a serum gradient in 25 mmol/L glucose (but not in 5 mmol/L glucose) in association with increased phosphorylation (activation) of Akt and ERK1/2 in PI3K and MAPK pathways, respectively. Inhibitors of these pathways blocked chemotaxis, as did an mTOR inhibitor. VSMC expressed all class IA PI3K isoforms, but microinjection experiments demonstrated that only the p110beta isoform was involved in chemotaxis. ERK1/2 phosphorylation was reduced not only by MAPK pathway inhibitors but also by PI3K and mTOR inhibitors; when PI3K was inhibited, ERK phosphorylation could be induced by microinjected activated Akt, indicating important cross-talk between the PI3K and ERK1/2 pathways. Glucose-potentiated phosphorylation of molecules in the p38 and JNK MAPK pathways inhibited these pathways but did not affect chemotaxis. The statin, mevinolin, blocked chemotaxis through its effects on the MAPK pathway. Mevinolin-inhibited chemotaxis was restored by farnesylpyrophosphate but not by geranylgeranylpyrophosphate; in the absence of mevinolin, inhibition of farnesyltransferase reduced ERK phosphorylation and blocked chemotaxis, indicating a role for the Ras family of GTPases (MAPK pathway) under these conditions. In conclusion, glucose sensitizes VSMC to serum, inducing chemotaxis via pathways involving p110beta-PI3K, Akt, mTOR, and ERK1/2 MAPK. Cross-talk between the PI3K and MAPK pathways is necessary for VSMC chemotaxis under these conditions.