Comparing Prevalence of Sarcopenia Using Twelve Sarcopenia Definitions in a Large Multinational European Population of Community-Dwelling Older Adults.

OBJECTIVES: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. SETTING AND PARTICIPANTS: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. MEASUREMENTS: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). RESULTS: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) - all based on muscle mass and muscle strength - showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. CONCLUSION: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health.

MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs.

The PD-L1/PD-1 pathway is a critical component of the immunosuppressive tumor microenvironment in acute myeloid leukemia (AML), but little is known about its regulation. We investigated the role of the MUC1 oncoprotein in modulating PD-L1 expression in AML. Silencing of MUC1 in AML cell lines suppressed PD-L1 expression without a decrease in PD-L1 mRNA levels, suggesting a post-transcriptional mechanism of regulation. We identified the microRNAs miR-200c and miR-34a as key regulators of PD-L1 expression in AML. Silencing of MUC1 in AML cells led to a marked increase in miR-200c and miR-34a levels, without changes in precursor microRNA, suggesting that MUC1 might regulate microRNA-processing. MUC1 signaling decreased the expression of the microRNA-processing protein DICER, via the suppression of c-Jun activity. NanoString (Seattle, WA, USA) array of MUC1-silenced AML cells demonstrated an increase in the majority of probed microRNAs. In an immunocompetent murine AML model, targeting of MUC1 led to a significant increase in leukemia-specific T cells. In concert, targeting MUC1 signaling in human AML cells resulted in enhanced sensitivity to T-cell-mediated lysis. These findings suggest MUC1 is a critical regulator of PD-L1 expression via its effects on microRNA levels and represents a potential therapeutic target to enhance anti-tumor immunity.

The association between objectively measured physical activity and life-space mobility among older people.

The purpose of this cross-sectional study was to investigate the association between objectively measured physical activity and life-space mobility in community-dwelling older people. Life-space refers to the spatial area a person purposefully moves through in daily life (bedroom, home, yard, neighborhood, town, and beyond) and life-space mobility to the frequency of travel and the help needed when moving through different life-space areas. The study population comprised community-living 75- to 90-year-old people {n = 174; median age 79.7 [interquartile range (IQR) 7.1]}, participating in the accelerometer substudy of Life-Space Mobility in Old Age (LISPE) project. Step counts and activity time were measured by an accelerometer (Hookie "AM20 Activity Meter") for 7 days. Life-space mobility was assessed with Life-Space Assessment (LSA) questionnaire. Altogether, 16% had a life-space area restricted to the neighborhood when moving independently. Participants with a restricted life space were less physically active and about 70% of them had exceptionally low values in daily step counts (≤ 615 steps) and moderate activity time (≤ 6.8 min). Higher step counts and activity time correlated positively with life-space mobility. Prospective studies are needed to clarify the temporal order of low physical activity level and restriction in life-space mobility.

Three-dimensional image analysis of the temporal bone in patients with unilateral attic cholesteatoma.

We determined temporal bone anatomy in patients with unilateral attic cholesteatoma. We compared the affected and normal ears of ten patients with unilateral attic cholesteatoma using three-dimensionally reconstructed high-resolution computed tomography images of the temporal bone. We determined the eustachian tube angle, eustachian tube length, sizes of the tympanic orifice of the eustachian tube, the pars flaccida, and the mastoid cavity, and distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. No significant differences were found between the normal and affected ears with regard to the size of the eustachian tube orifice, eustachian tube length or distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. By contrast, the mastoid cavity and the eustachian tube angle were significantly larger in the normal ears than in the affected ears [mean, 6.99 cm(3) (S.D.,4.9 cm(3)) vs. 1.28 cm(3) (0.81 cm(3)) and 16.7° (4.12°) vs. 13.89° (5.30°), respectively]. The pars flaccida was significantly smaller in the normal ears [1.07 cm (0.31 cm)] than in the affected ears [2.19 cm (0.77 cm)]. The inherent anatomy of the eustachian tube may be particularly important in the formation of attic cholesteatomas.

Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila.

BACKGROUND: Drugs of abuse have a common property in mammals, which is their ability to facilitate the release of the neurotransmitter and neuromodulator dopamine in specific brain regions involved in reward and motivation. This increase in synaptic dopamine levels is believed to act as a positive reinforcer and to mediate some of the acute responses to drugs. The mechanisms by which dopamine regulates acute drug responses and addiction remain unknown. RESULTS: We present evidence that dopamine plays a role in the responses of Drosophila to cocaine, nicotine or ethanol. We used a startle-induced negative geotaxis assay and a locomotor tracking system to measure the effect of psychostimulants on fly behavior. Using these assays, we show that acute responses to cocaine and nicotine are blunted by pharmacologically induced reductions in dopamine levels. Cocaine and nicotine showed a high degree of synergy in their effects, which is consistent with an action through convergent pathways. In addition, we found that dopamine is involved in the acute locomotor-activating effect, but not the sedating effect, of ethanol. CONCLUSIONS: We show that in Drosophila, as in mammals, dopaminergic pathways play a role in modulating specific behavioral responses to cocaine, nicotine or ethanol. We therefore suggest that Drosophila can be used as a genetically tractable model system in which to study the mechanisms underlying behavioral responses to multiple drugs of abuse.

[Clinical studies of neonatal hyperbilirubinemia treated with blood exchange transfusion].

From April 1984 to November 1989, 194 cases of neonatal hyperbilirubinemia treated with blood exchange transfusions (BET) were studied. The patients included 127 male and 67 female neonates, with an age ranged from 13 hours to 16 days. The most common cause was idiopathic (52.6%), followed by G-6-PD deficiency (23.7%), and sepsis (12.9%). Most of the neonates received BET at the 4th day of birth (23.2%), but there were still 30 cases (15.5%) that received BET after 1 week of age. There were 17 cases (8.8%) with maximum serum bilirubin lower than 20 mg/dl before receiving BET, five of them were LBW infants; 11 cases (5.7%) were greater than 40 mg/dl. The mean of maximum serum bilirubin was 26.9 +/- 7.96 mg/dl. Most of the cases received BET once (145 cases) or twice (33 cases). There were two cases that received up to six BET's. One was G-6-PD deficiency and one idiopathic in etiology. No significant difference of BET frequency between sex or body weight (p greater than 0.05) was found. Newborns with higher serum bilirubin due to G-6-PD deficiency, received more BET (p less than 0.05). No significant differences of the pH value (7.33 +/- 0.08 vs 7.35 +/- 0.10) and bicarbonate values (21.20 +/- 3.99 vs 22.00 +/- 3.83 mM/L) occurred before and after blood exchange transfusion (p greater than 0.1). The serum calcium decreased significantly after BET (3.88 +/- 0.91 vs 3.15 +/- 6.97 mEq/L, p less than 0.05). There were 11 deaths in this series, the mortality rate was 5.7%. Three cases (1.5%) were dead within 6 hours after BET.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced recovery of cytomegalovirus in conventional tube cultures with a spin-amplified adsorption.

Low-speed centrifugation-mediated adsorption was evaluated as an enhancement of infectivity of clinical and laboratory strains of cytomegalovirus (CMV) occurring with cells grown in conventional culture tubes. The time required for reporting of primary isolates of CMV from urine specimens adsorbed onto monolayers of WI-38 cells in culture tubes was calculated. Of 668 specimens adsorbed by the stationary phase (SP) method, 98 were positive by cytopathic effect (CPE) that required an average of 16.8 days for recovery in culture. However, the appearance of CPE required a shorter average time of 11.9 days for 70 CMV strains isolated from 283 specimens adsorbed in tube cultures by the spin-amplified (SA) method. In another phase of clinical CMV recovery, urine specimens were adsorbed by the SA method onto cell cultures grown in both shell vials and test tubes. Of 594 specimens inoculated, a total of 74 were positive by either CPE in test tubes or immunostaining-localized early antigen in shell vials. Approximately one-third of these CMV isolates were recovered only by CPE from specimens adsorbed by the SA method in test-tube cultures. In a related study to further evaluate differences between adsorption methods, the AD-169 laboratory strain of CMV was adsorbed by SP and SA methods onto MRC-5 cells grown in both culture vessels. Early antigen detection by immunomicroscopy was found in the infected cells at least 2 to 4 days prior to the appearance of CPE, regardless of adsorption procedure. In both vessels, the replication of AD-169 virus in cultures adsorbed by the SA method consistently exceeded that of virus adsorbed by the SP procedure. CPE occurred 24 to 48 h earlier and progressed two to four times more extensively; early antigen was expressed two- to fourfold greater within 24 to 48 h postinfection; and foci of infected cells containing late antigen were two to four times greater in number at 1, 2, and 5 days postinfection. Overall, the replication and enhancement of infectivity of laboratory and clinical strains of CMV as determined by CPE and early and late antigen expression occurred most efficiently with specimens adsorbed by the SA method onto cultures grown in conventional tubes or shell vials.