20-Year prevalence projections for dementia and impact of preventive policy about risk factors

Incidence of dementia increases sharply with age and, because of the increase in life expectancy, the number of dementia cases is expected to rise dramatically over time. Some studies suggest that controlling some modifiable risk factors for dementia like diabetes or hypertension could lower its incidence. However, as treating these vascular factors would also reduce mortality risk, the actual impact of such public-health intervention on dementia prevalence is not known. Accounting for the impact of dementia and risk factors on mortality, the aim of this work was (1) to compute projections of age- and-sex specific prevalence of dementia in France from 2010 to 2030, (2) to evaluate how public-health interventions targeting risk factors for dementia could change these projections. Age-and-sex specific incidence of dementia and mortality of demented subjects were estimated from the Paquid population-based cohort using a semi-parametric illness-death model. Future global mortality rates and population sizes were obtained from national demographic projections. Under the assumption that life expectancy will increase by 3.5 years for men and 2.8 years for women by 2030, the number of subjects with dementia was estimated to increase by about 75 % from 2010 to 2030 with a 200 % increase after 90 years of age. Therapeutic intervention on the whole population reducing high blood pressure prevalence would lead to a decrease in both dementia incidence rates and mortality and would have a modest impact on the number of dementia cases. On the other hand, a preventive dementia treatment targeting ApoE4 carriers would probably not improve survival and hence would decrease dementia prevalence by 15–25 %.     

Histological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin,acute pinpoint lesions and established psoriasis plaques: An approach of vascular development chronology in psoriasis

BackgroundDysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies.ObjectiveTo analyse vascular development, angiogenesis and lymphangiogenesis markers expression in uninvolved skin in psoriatic patients (N), early psoriasis lesions or pinpoints (PP) and psoriasis plaques (PSO).MethodsSkin biopsies were taken in 17 patients in N and in PSO and/or PP. The mRNA steady-state level of angiogenesis and lymphangiogenesis markers was measured by RT-PCR. Immunohistochemistry was performed for von Willebrand factor, podoplanin, Ki-67 and VEGFR3. Blood (BV) and lymphatic (LV) vessels expansion was measured by computer-assisted morphometry.ResultsClinical and epidermal aspects indicated that PP are intermediate between N and PSO. While total BV area was already increased in PP similarly to PSO as compared to N, LV area in PP was intermediate between N and PSO. Mean LV size was identical in N and PP and increased in PSO, mean BV size in PP being intermediate between N and PSO. VEGF-A 189 variant was increased in PP as compared to N and PSO. As compared to N, angiogenesis markers (VEGF-A isoforms, PlGF, VEGFR2, NRP-1), VEGF-C and NRP-2 were similarly increased in PP and PSO. Keratin 16 and the lymphangiogenesis markers (VEGFR3, prox-1) were intermediate in PP.ConclusionThese data suggest that the expansion of lymphatic vessels occurs after blood vascular development in psoriasis. Expansion of BV in PP could be followed by vessel enlargement during progression to PSO, in parallel with a decreased VEGF-A 189/VEGF-A 121 balance in plaques.     

Partial regulation of serotonin transporter function by γ-synuclein

Human α-synuclein (α-Syn) is instrumental in maintaining homeostasis of monoamine neurotransmitters in brain, through its trafficking, and regulation of the cell surface expression and, thereby, activity of dopamine, serotonin and norepinephrine transporters. Here we have investigated whether other members of the synuclein family of proteins, γ-synuclein (γ-Syn) and β-synuclein (β-Syn) can similarly modulate the serotonin transporter (SERT). In Ltk⁻ cells co-transfected with SERT and γ-Syn, γ-Syn reduced [³H]5-HT uptake, in a manner dependent on its expression levels. The decrease in SERT activity was via decreased V_max of the transporter, without change in K_m, compared to cells expressing only SERT. By contrast, β-Syn co-expression failed to alter SERT uptake activity, and neither the V_max nor the K_m was changed in the presence of β-Syn. γ-Syn modulation of SERT was only partial, with a maximal ∼27% decrease in SERT activity seen even at high expression levels of γ-Syn. By contrast, α-Syn attenuated SERT activity by ∼65% at identical expression levels as γ-Syn. Co-immunoprecipitation studies showed the presence of heteromeric protein:protein complexes between γ-Syn or α-Syn and SERT, while β-Syn failed to physically interact with SERT. Both α-Syn and γ-Syn colocalized with SERT in rat primary raphae nuclei neurons. These studies document a novel physiological role for γ-Syn in regulating 5-HT synaptic availability and homeostasis, and may be of relevance in depression and mood disorders, where SERT function is dysregulated.     

Artificial metalloenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation

Most physiological and biotechnological processes rely on molecular recognition between chiral (handed) molecules. Manmade homogeneous catalysts and enzymes offer complementary means for producing enantiopure (single-handed) compounds. As the subtle details that govern chiral discrimination are difficult to predict, improving the performance of such catalysts often relies on trial-and-error procedures. Homogeneous catalysts are optimized by chemical modification of the chiral environment around the metal center. Enzymes can be improved by modification of gene encoding the protein. Incorporation of a biotinylated organometallic catalyst into a host protein (avidin or streptavidin) affords versatile artificial metalloenzymes for the reduction of ketones by transfer hydrogenation. The boric acid.formate mixture was identified as a hydrogen source compatible with these artificial metalloenzymes. A combined chemo-genetic procedure allows us to optimize the activity and selectivity of these hybrid catalysts: up to 94% (R) enantiomeric excess for the reduction of p-methylacetophenone. These artificial metalloenzymes display features reminiscent of both homogeneous catalysts and enzymes.     

Emergency Department influenza vaccination campaign allows increasing influenza vaccination coverage without disrupting time interval quality indicators

To evaluate the impact of an influenza vaccination (IV) coverage (IVC) in a vaccination campaign of an Emergency Department (EDVC) and its impact on ED time interval quality indicators. We conducted a 4 year observational study, with an intervention during the 4th year. IVC was calculated during pre-and early-epidemic periods. During the final period, a 12 weeks EDVC was implemented. Physicians and nurses were trained and sensitized in the importance of vaccination, and their role in the prevention of severe forms of influenza was reinforced. The vaccine was proposed by physicians and nurses, and delivered by them. Repeated measures ANOVA is a validated method for related not independent groups (https://statistics.laerd.com/statistical-guides/repeated-measures-anova-statistical-guide.php). Overall, IVC was 987/3191 (30.9%) with an increasing trend from 28.8 to 33.2%. In the fourth period, out of 868 patients identified with IV indication, 288 had already been vaccinated (IVC?33.2%). After excluding patients presenting criteria of exclusion, IV was proposed to 475 patients: 317 (66.7%) accepted. The vaccination rate after patient’s acceptance was 89.6% (288/317). At the end of the EDVC, influenza vaccination coverage was 572 (284?+?288)/868 (65.9%). The delay between arrival at the ED and seeing the triage nurse and physician as well as the overall ED length of stay were not modified during the study period and before and during EDVC. EDVC effectively doubled the influenza vaccination coverage, without modifying ED time interval quality indicators.     

Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial

BACKGROUND: Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients. METHODS: Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200-550 x 10(6) cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 x 10(6) IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74. RESULTS: CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 x 10(6) cells/l, respectively; P < 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P < 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a logistic regression analysis, odds of being responders to recall antigens was 8.5-fold higher in IL-2 recipients (P = 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively; P = 0.01). CONCLUSIONS: The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.     

Unusual pulmonary Enterocytozoon bieneusi microsporidiosis in an AIDS patient: case report and review

Enterocytozoon bieneusi is an agent of intestinal microsporidiosis leading to chronic diarrhoea in AIDS patients. Pulmonary involvement may occur but remains rare with only 4 cases reported in the literature. We report here the fifth case of pulmonary localization of E. bieneusi in a severe immunocompromized HIV-infected patient with intestinal and pulmonary symptoms.