On the unsteady behavior of turbulence models

Periodically forced turbulence is used as a test case to evaluate the predictions of two-equation and multiple-scale turbulence models in unsteady flows. The limitations of the two-equation model are shown to originate in the basic assumption of spectral equilibrium. A multiple-scale model based on a picture of stepwise energy cascade overcomes some of these limitations, but the absence of nonlocal interactions proves to lead to poor predictions of the time variation of the dissipation rate. A new multiple-scale model that includes nonlocal interactions is proposed and shown to reproduce the main features of the frequency response correctly

Apolipoprotein E Genotypes in Alzheimer's Disease in Central Algerian Population

Background: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder associated with cognitive decline and is the most common form of dementia in the elderly. Early-onset familial AD accounts for less than 1% of AD cases and develops before the age of 65 years because of mutations in either the APP gene or genes encoding presenilin 1 (PSEN1) or presenilin 2 (PSEN2). The majority of sporadic AD cases are referred to as late-onset AD (LOAD) because they occur late in life (>65 years). Apolipoprotein E (APOE) polymorphic alleles are the major genetic risk factor for AD. The human APOE gene exists as three polymorphic alleles, ε2, ε3, and ε4, with a worldwide frequency of 8%, 78%, and 13%, respectively, with ε4 reaching frequencies of 40% in AD patients. The purpose of this preliminary study was to determine ApoE genotype status since no previous association studies between LOAD and ApoE gene were available for the Central Algerian population. Methods: The cohort of our study was composed of 47 AD patients recruited from the Neurology Department of Frantz Fanon Hospital of Blida. Forty-seven controls with no type of dementia were also included in the study. All samples were genotyped for the ApoE Polymorphisms by PCR-RFLP method. Statistical studies can use the Fisher exact test or Chi-2 using the GraphPad Prism 7.0 software. Results: The results show that the genotype ɛ3/ɛ3 is most common in both groups followed by the heterozygous genotype ɛ3/ɛ4 which showed an increased frequency in patients compared to controls (27.66% vs. 12.77%, OR=3.66, IC=0.89-7.9, p=0,11). Although rare, all other possible genotypes have been observed in our cohort, namely ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4 and ɛ4/ɛ4. The ɛ2/ɛ4 genotype was observed only in AD patients, while the ɛ2/ɛ2 genotype was observed only in controls. As expected, the homozygous genotype ɛ4/ɛ4 was more frequent in AD patients, compared to controls (6.38% vs. 2.13%, respectively OR=2.64, IC=0.36-37.33; p=0,33). At the allelic level, ɛ4 allele was significantly associated with AD compared to controls (21,28% vs. 4,26% ; OR= 2.75, 95% CI= 1.109-6.35; p = 0.02, respectively), while the ɛ2 allele seems to be protective (4,26% vs. 9,57%, OR = 0.49 ; 95% CI=0.14-1.66 ; p=0,38, respectively), but without statistical significance. In population-based studies, the ApoEɛ4-AD association was weaker among African Americans (ε4/ε4, OR 5.7) and Hispanics (ε4/ε4, OR 2.2) and was stronger in the Japanese population (ε4/ε4, OR 33.1) compared with Caucasian cases (ε4/ε4, OR 12.5). The results obtained in our preliminary study indicate that the ApoEɛ4-AD association in the Central Algerian population is similar to that observed in the Mediterranean populations. Conclusion: We have presented, for the first time in the North Central Algerian population, the association of the ɛ4 allele with AD, which could be of great use in the diagnosis but also the follow-up of patients with this disease

Poorly differentiated thyroid carcinoma: a retrospective clinicopathological study

Poorly differentiated thyroid carcinoma (PDTC) is an independent thyroid cancer histotype. In spite of its scarcity, it represents the main cause of death from non-anaplastic follicular cell-derived thyroid cancer. However, given the newness of this entity, few data are available on its clinical behaviour and no explicit consensus sets its treatment. To report the experience of a tertiary medical centre in morocco with PDTC over a period of 7 years. Retrospective study selecting all patients treated for thyroid carcinoma in Nuclear Medicine Department of a tertiary medical centre in Casablanca over seven years period. Patient's files were reviewed for background data, clinico-pathological characteristics, treatment and outcome. Seven patients were included in the study. Patient's average age was 60 years old (30-81) including six women and one man. All patients underwent a total thyroidectomy completed by cervical lymph node dissection in 57% of cases. Mean primary tumour size was 4cm (1-9cm). Patients were classified pT3 in 70% of cases, pT1 and pT2 in 15% each. Vascular invasion was found in 85% of cases. Pathological subtypes found were "insular carcinoma" in 85% of cases. Radioiodine therapy (RIT) was indicated in all cases. Follow-up period ranged between 10 months and 6 years. It showed a complete remission in 57% of cases, persistent disease in 28% of cases and a progressive disease in 15% of cases with a local recurrence. To date, the survival rate is 85%. PDTC is an aggressive thyroid cancer histotype. Treatment remains surgical followed by RIT if the tumour is radioavid. Multimodality therapy is indicated depending on the case and close monitoring is always indicated given the high risk of relapse

Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>The secretory leukocyte protease inhibitor (SLPI) exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown</p> <p>Methods</p> <p>To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-β.</p> <p>Results</p> <p>The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-β and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. <it>In vitro</it>, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25^hiCD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-β to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation.</p> <p>Conclusion</p> <p>In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.</p

Characterization of the inflammatory cell infiltrate and expression of costimulatory molecules in chronic echinococcus granulosus infection of the human liver

Background: The local immune responses to chronic echinococcal infections in various organs are largely unknown. Since the liver is the most frequently involved organ in such infections in human we aimed to characterize the inflammatory as well as immune cell infiltrate around hydatid cysts in the liver and compared to common inflammatory processes of the liver. Method: Surgical samples from the liver of 21 cystic echinococcosis (CE) patients were studied and the distribution of different types of inflammatory and immune cells were determined by immunohistochemistry. Furthermore, expression levels of costimulatory CTLA4, CD28, CD80 and CD86 molecules were measured at RNA level by PCR. Liver biopsy samples from patients with steatohepatitis (SH, n = 11) and chronic hepatitis (CH, n = 11) were used as non-inflammatory and chronic inflammatory controls, respectively. The composition and density of the inflammatory and immune cell infiltrates have been compared by using morphometry. Results: CD3+ T cells predominated the inflammatory infiltrate in all pathological processes, while in CE samples CD20+ B cells, in CH samples CD68+ macrophages were also frequent. Both myeloperoxidase (MPO) + leukocytes and CD68+ macrophages were found to be significantly decreased in CE as compared to either SH or CH samples. Concerning T cell subtypes, only CD8+ T cells were found to be significantly decreased in SH samples. CD1a + dendritic cells were almost completely missing from CE biopsies unlike in any other sample types. There were no differences detected in the mRNA expression of costimulatory molecules except decreased expression of CD28 in CE samples. Conclusion: In the hydatid lesions of the liver of chronic echinococcal infections T cell-mediated immunity seems to be impaired as compared to other types of chronic inflammatory processes, suggesting an immunosuppressive role for Echinococcus granulosus, which deserve further attentions

Awareness of cognitive decline trajectories in asymptomatic individuals at risk for AD

Background: Lack of awareness of cognitive decline (ACD) is common in late-stage Alzheimer’s disease (AD). Recent studies showed that ACD can also be reduced in the early stages. Methods: We described different trends of evolution of ACD over 3 years in a cohort of memory-complainers and their association to amyloid burden and brain metabolism. We studied the impact of ACD at baseline on cognitive scores’ evolution and the association between longitudinal changes in ACD and in cognitive score. Results: 76.8% of subjects constantly had an accurate ACD (reference class). 18.95% showed a steadily heightened ACD and were comparable to those with accurate ACD in terms of demographic characteristics and AD biomarkers. 4.25% constantly showed low ACD, had significantly higher amyloid burden than the reference class, and were mostly men. We found no overall effect of baseline ACD on cognitive scores’ evolution and no association between longitudinal changes in ACD and in cognitive scores. Conclusions: ACD begins to decrease during the preclinical phase in a group of individuals, who are of great interest and need to be further characterized. Trial registration: The present study was conducted as part of the INSIGHT-PreAD study. The identification number of INSIGHT-PreAD study (ID-RCB) is 2012-A01731-42

Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease

Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer's disease (AD)

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

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