Roles of Cognitive Characteristics in Tinnitus Patients

To investigate the cognitive characteristics that affect the emotional and functional distress caused by tinnitus and to decide and test the model to explain their relations, 167 patients with tinnitus, who visited Samsung Medical Center, Seoul, Korea between March 2001 and May 2002 were recruited. To examine their features related to tinnitus, the following scales were administered; Tinnitus-related basic questionnaire including dysfunctional beliefs, Tinnitus Handicap Inventory, State-Trait Anxiety Inventory, Anxious Thought and Tendencies, Self-Consciousness Scale, and modified 'catastrophic thought' from Coping Strategies Questionnaire. The results showed that the duration of experiencing tinnitus was 4.7±7.1 yr, those who com-plained of hearing one sound were the most common (45.5%), and hearing sounds similarly described to whistling were the most common (22.5%). Also, there were significant correlations among tinnitus features, cognitive characteristics, and distresses from tinnitus. As a result of testing the model, Normed fit index, Incremental fit index, Tucker-Lewis index, and Comparative fit index were over .90, indicating that it is a good model, and Root mean square error of approximation showed a reasonable fit. Also, the direct effects of the trait or severity of tinnitus on distress did not appear to be significant, thus it appeared to be affecting indirectly through the cognitive characteristics. This result shows that cognitive interventions can be important for the psychological adaptations of tinnitus patients

Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden

We investigated effects of occupational physical activity on relative risk for prostate cancer. From Swedish nationwide censuses in 1960 and 1970, we defined two cohorts of men whose occupational titles allowed classification of physical activity levels at work in 1960 (n=1 348 971) and in 1970 (n=1 377 629). A third cohort included only men whose jobs required a similar level of physical activity in both 1960 and 1970 (n=673 443). The incidence of prostate cancer between 1971 and 1989 was ascertained through record linkage to the Swedish Cancer Register. A total of 43 836, 28 702, and 19 670 prostate cancers, respectively, occurred in the three cohorts. In all three cohorts, the relative risk for prostate cancer increased with decreasing level of occupational physical activity (P<0.001), using Poisson regression. Among men with the same physical activity levels in 1960 and 1970, the rate ratio was 1.11 for men with sedentary jobs as compared with those whose jobs had very high/high activity levels after adjustment for age at follow-up, calendar year of follow-up and place of residence (95% CI 1.05–1.17; P for trend <0.001). There was no association between occupational activity and prostate cancer mortality. Since we had no data on other potential risk factors the observed associations for both incidence and mortality might have been confounded. Further studies are needed to better understand the potential role of physical activity for prostate cancer

Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation

The urokinase plasminogen activator (uPA) receptor (uPAR) is a GPI-linked cell surface protein that facilitates focused plasmin proteolytic activity at the cell surface. uPAR has been detected in macrophages infiltrating the central nervous system (CNS) and soluble uPAR has been detected in the cerebrospinal fluid during a number of CNS pathologies. However, its expression by resident microglial cells in vivo remains uncertain. In this work, we aimed to elucidate the murine CNS expression of uPAR and uPA as well as that of tissue plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) during insults generating distinct and well-characterized inflammatory responses; acute intracerebral lipopolysaccharide (LPS), acute kainate-induced neurodegeneration, and chronic neurodegeneration induced by prion disease inoculation. All three insults induced marked expression of uPAR at both mRNA and protein level compared to controls (naïve, saline, or control inoculum-injected). uPAR expression was microglial in all cases. Conversely, uPA transcription and activity was only markedly increased during chronic neurodegeneration. Dissociation of uPA and uPAR levels in acute challenges is suggestive of additional proteolysis-independent roles for uPAR. PAI-1 was most highly expressed upon LPS challenge, whereas tissue plasminogen activator mRNA was constitutively present and less responsive to all insults studied. These data are novel and suggest much wider involvement of the uPAR/uPA system in CNS function and pathology than previously supposed. © 2009 Wiley-Liss, Inc

An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom were previously treated for Hodgkin lymphoma. To investigate MKL1 and B cell responses in HL pathogenesis, we generated Epstein Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the Hodgkin lymphoma treated patients had a phenotype close to healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for Hodgkin lymphoma in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B cell transformation and Hodgkin lymphoma pathogenesis

Metal-Organic Covalent Network Chemical Vapor Deposition for Gas Separation

The chemical vapor deposition (CVD) polymerization of metalloporphyrin building units is demonstrated to provide an easily up-scalable one-step method toward the deposition of a new class of dense and defect-free metal–organic covalent network (MOCN) layers. The resulting hyper-thin and flexible MOCN layers exhibit outstanding gas-separation performances for multiple gas pairs.United States. Army Research Office. Institute for Soldier Nanotechnologies (Contract DAAD-19-02D-0002)Luxembourg National Research Fun

The influences of Taiwan's generic grouping price policy on drug prices and expenditures: Evidence from analysing the consumption of the three most-used classes of cardiovascular drugs

<p>Abstract</p> <p>Background</p> <p>Controlling the growth of pharmaceutical expenditures is a major global challenge. Promotion of generic drug prescriptions or use is gaining increased support. There are substantial contextual differences in international experiences of implementing pharmaceutical policies related to generic drugs. Reporting these experiences from varied perspectives can inform future policy making. This study describes an experience of Taiwan, where patients with chronic (long-term) conditions are usually managed in hospitals and drugs are provided in this setting with costs reimbursed through the National Health Insurance (NHI). It investigates the effects of Taiwan's reimbursement rate adjustment based on chemical generic grouping in 2001. This research also demonstrates the use of micro-level longitudinal data to generate policy-relevant information. The research can be used to improve efficiency of health care resource use.</p> <p>Methods</p> <p>We chose the three most-used classes of cardiovascular drugs for this investigation: beta blocking agents, calcium channel blockers mainly with vascular effects, and plain ACE inhibitors. For each drug class, we investigated changes in daily expense, consumption volume, and total expenditures from a pre-action period to a corresponding post-action period. We compared an exposure or "intervention" group of patients targeted by the action with a comparisonor "control" group of patients not targeted by the action. The data sources are a longitudinal database for 200,000 NHI enrolees, corresponding NHI registration data of health care facilities, and an archive recording all historical data on the reimbursement rates of drugs covered by the NHI. We adopted a fixed effects linear regression model to control for unobserved heterogeneity among patient-hospital groups. Additional descriptive statistics were applied to examine whether any inappropriate consumption of drugs in the three classes existed.</p> <p>Results</p> <p>The daily drug expense significantly decreased from the pre-action period to the post-action period for the exposure group. The average magnitudes of the decreases for the three classes of drugs mentioned above were 14.8%, 5.8% and 5.8%, respectively. In contrast, there was no reduction for the comparison group. The number of days of the prescription increased significantly from the pre- to the post-action period for both exposure and comparison groups. The total expense also significantly increased for both patient groups. For the exposure group, the average magnitudes of the growth in the total expenditure for the three classes of drugs were 47.7%, 60.0% and 55.3%, respectively. For the comparison group, they were 91.6%, 91.6% and 63.2%, respectively. After the action, approximately 50% of patients obtained more than 180 days of prescription drugs for a six-month period.</p> <p>Conclusion</p> <p>The 2001 price adjustment action, based on generic grouping, significantly reduced the daily expense of each of the three classes of cardiovascular drugs. However, in response to this policy change, hospitals in Taiwan tended to greatly expand the volume of drugs prescribed for their regular patients. Consequently, the total expenditures for the three classes of drugs grew substantially after the action. These knock-on effects weakened the capability of the price adjustment action to control total pharmaceutical expenditures. This means that no saved resources were available for other health care uses. Such expansion of pharmaceutical consumption might also lead to inefficient use of the three drug classes: a large proportion of patients obtained more than one day of drugs per day in the post-action period, suggesting manipulation to increase reimbursement and offset price controls. We recommend that Taiwan's government use the NHI data to establish a monitoring system to detect inappropriate prescription patterns before implementing future policy changes. Such a monitoring system could then be used to deter hospitals from abusing their prescription volumes, making it possible to more effectively save health care resources by reducing drug reimbursement rates.</p

Development of a new mechano-chemical model in boundary lubrication

A newly developed tribochemical model based on thermodynamics of interfaces and kinetics of tribochemical reactions is implemented in a contact mechanics simulation and the results are validated against experimental results. The model considers both mechanical and thermal activation of tribochemical reactions instead of former thermal activation theories. The model considers tribofilm removal and is able to capture the tribofilm behaviour during the experiment. The aim of this work is to implement tribochemistry into deterministic modelling of boundary lubrication and study the effect of tribofilms in reducing friction or wear. A new contact mechanics model considering normal and tangential forces in boundary lubrication is developed for two real rough steel surfaces. The model is developed for real tribological systems and is flexible to different laboratory experiments. Tribochemistry (e.g. tribofilm formation and removal) and also mechanical properties are considered in this model. The amount of wear is calculated using a modified Archard’s wear equation accounting for local tribofilm thickness and its mechanical properties. This model can be used for monitoring the tribofilm growth on rough surfaces and also the real time surface roughness as well as changes in the λ ratio. This model enables the observation of in-situ tribofilm thickness and surface coverage and helps in better understanding the real mechanisms of wear

Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon

Summary Background Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans. Aims To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. Methods Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0–61 wt% (IPE-0–IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using 13C-labelled IPE variants. Results In vitro, IPE-27–IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE-27 led to greater 13C recovery in breath CO2 than IPE-54 (64.9 vs. 24.9%, P = 0.001). IPE-27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control. Conclusions IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet–gut microbiome–host metabolism axis in human

Additive Interaction of Hyperglycemia and Albuminuria on Risk of Ischemic Stroke in Type 2 Diabetes: Hong Kong Diabetes Registry

OBJECTIVE—The study aims to test whether biological interaction between hyperglycemia and albuminuria can explain the inconsistent findings from epidemiological studies and clinical trials about effects of hyperglycemia on stroke in type 2 diabetes