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

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A XFEM/Level set-based poroelastic framework for heterogeneous geomaterials

peer reviewe

A XFEM/Level set-based poroelastic framework for heterogeneous geomaterials

info:eu-repo/semantics/publishe

Techniques for wirebond free interconnection of piezoelectric ultrasound arrays operating above 50 MHz

Interconnects between high frequency ultrasound (HFUS) arrays and external circuitry may be difficult and expensive because of the small element pitch, as low as 15 µm, and the large number of piezoelectric elements, up to 256. The wire bonding commonly used can be time consuming and difficult to achieve on piezocomposite material because of the relatively soft filler material. Moreover, the minimum pitch is limited by the footprint requirement for the bonding head. This requires the creation of an electrical fan-out, in turn increasing the size of the array package; this interconnect technology is disadvantageous for medical applications such as ophthalmology and dermatology. This paper proposes a wirebond free bonding process for HFUS piezocomposite arrays operating at frequencies above 30 MHz. The suggested process is integration of ultrasound "chips" with a silicon (Si) wafer using state-of-the-art fabrication techniques and materials including anisotropic conductive film, through silicon vias, powder blasting and laser machining

Magnetic reconstructions at the surface of the B2 FeV alloy

Abstract. We present an ab initio study of the magnetic surface reconstructions of the B2 FeV alloy using a self-consistent tight-binding linearized muffin tin orbital method developed in the atomic spheres approximation. For (001) and (111), the surface reconstruction stabilizes configurations unstable in the bulk alloy. When Fe is at the (001) surface, a c(2 × 2) in-plane antiferromagnetic order is found to be the ground state with magnetic moments of −2.32µB and 2.27µB. Ap(1 × 1) ↓ ferromagnetic order is displayed in case of V toplayer with a magnetic moment of −1.83µB. At the (111) surface, we obtain for Fe toplayer two solutions p(1 × 1) ↑ and p(2 × 1). The configuration p(1×1) ↑ is found to be the ground state with a magnetic moment per atom of 2.34µB. For V toplayer, only the p(1 × 1) ↓ solution is obtained with a moment of −0.84µB. In all cases, the Fe-V coupling is always antiparallel like in the bulk. Our results are discussed and compared to experiments. PACS. 75.70.Rf Surface magnetism – 73.20.-r Electron states at surfaces and interfaces – 71.20.Be Transition metals and alloys