Raman spectroscopy to diagnose Alzheimer’s disease and dementia with Lewy bodies in blood

Accurate identification of Alzheimer’s disease (AD) is still of major clinical importance considering the current lack of non-invasive and low-cost diagnostic approaches. Detection of early-stage AD is particularly desirable as it would allow early intervention and/or recruitment of patients into clinical trials. There is also an unmet need for discrimination of AD from dementia with Lewy bodies (DLB), as many cases of the latter are misdiagnosed as AD. Biomarkers based on a simple blood test would be useful in research and clinical practice. Raman spectroscopy has been implemented to analyse blood plasma of a cohort that consisted of early-stage AD, late-stage AD, DLB and healthy controls. Classification algorithms achieved high accuracy for the different groups: early-stage AD vs healthy with 84% sensitivity, 86% specificity; late-stage AD vs healthy with 84% sensitivity, 77% specificity; DLB vs healthy with 83% sensitivity, 87% specificity; early-stage AD vs DLB with 81% sensitivity, 88% specificity; late-stage AD vs DLB with 90% sensitivity, 93% specificity; and lastly, early-stage AD vs late-stage AD 66% sensitivity and 83% specificity. G-score values were also estimated between 74-91%, demonstrating that the overall performance of the classification model was satisfactory. The wavenumbers responsible for differentiation were assigned to important biomolecules which can serve as a panel of biomarkers. These results suggest a cost-effective, blood-based biomarker for neurodegeneration in dementias

Circulation of Different Lineages of Dengue Virus 2, Genotype American/Asian in Brazil: Dynamics and Molecular and Phylogenetic Characterization

The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time, the introduction of American/Asian genotype into Brazil (lineage BR1) to 1988/89, followed by the introduction of lineages BR2 (1998–2000) and BR3 (2003–05). Our results show a delay between the introduction and detection of DENV-2 lineages in Brazil, reinforcing the importance and need for surveillance programs to detect and trace the evolution of these viruses. Additionally, Brazilian DENV-2 differed in genetic diversity, date of introduction and geographic origin and distribution in Brazil, and these are important factors for the evolution, dynamics and control of dengue.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Grant )Fundação de Amparo à Pesquisa do Estado de São PauloFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG grant

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

INTUSSUSCEPÇÃO EM CÃO – RELATO DE CASO

Um cão adulto foi diagnosticado com intussuscepção intestinal na rotina clínica no Hospital Veterinário Dix-Huit Rosado Maia (HOVET- UFERSA), Mossoró-RN. O animal apresentava histórico de apatia, anorexia e hematoquezia. O exame físico revelou palidez de mucosas, grau de desidratação moderado e notou-se dor à palpação, com um aumento longitudinal de consistência endurecida em um segmento intestinal. Para diagnóstico definitivo, foram realizados hemograma e ultrassonografia abdominal, que evidenciou intussuscepção intestinal. Optou-se pela enterectomia da região afetada. A recuperação pós-cirúrgica foi favorável e o paciente recebeu alta hospitalar no terceiro dia. O diagnóstico precoce associado à correção cirúrgica foram fundamentais para o sucesso do tratamento no caso de intussuscepção intestinal aqui relatado

Comportamento ingestivo de caprinos em caatinga raleada e enriquecida com capim corrente (Urochloa trichopus Stapf) e submetidos à suplementação

Objetivou-se avaliar o comportamento ingestivo de caprinos em pastejo e em confinamento, recebendo suplementação em caatinga raleada enriquecida com capim Urochloa trichopus Stapf. Os animais foram mantidos em pastejo das 8h às 16h, período em que foi avaliado, em intervalos de 10 minutos, o tempo de pastejo, ruminação e ócio de 24 caprinos mestiços F1 (Boer x SPRD) submetidos a 4 níveis de suplementação (0%, 0,5%, 1% e 1,5%). A avaliação do comportamento em confinamento foi realizada entre as 16h e as 8h, registrando-se as atividades dos animais em intervalos de 5 minutos durante o consumo de concentrado e a cada 10 minutos após o consumo, com três níveis de suplementação (0,5%, 1% e 1,5%). Utilizou-se o delineamento inteiramente casualizado, com 4 tratamentos e 6 repetições para comportamento em pastejo e 3 tratamentos e 6 repetições para comportamento em confinamento, e os dados foram analisados por regressão ao nível de 5% de probabilidade. A suplementação diminuiu o tempo de ingestão em pastejo e aumentou o tempo de ruminação. Em confinamento, a suplementação aumentou o tempo de ingestão e diminuiu o tempo gasto em ruminação

Bayesian coalescent and discrete phylogeography analyses of Brazilian DENV-2 based on envelope nucleotide sequence.

<p>Subtree of the maximum clade credibility tree was inferred using 144 DENV-2 envelope sequences (1,485 nt). The subtree containing isolates of the American/Asian genotype is displayed here. Time of the most recent common ancestor (MRCA) was estimated using the year of isolation as the calibration point, under the relaxed molecular clock, with the Tamura Nei Model, with discrete Gamma distribution and an estimated nucleotide substitution rate of 7.5⁻⁴. The posterior probabilities values ≥0.96 are represented by (*) and values ≥0.99 are represented by (**), inside the nodes. The years that the MRCA was estimated to exist are shown for some nodes with upper and lower intervals in parenthesis. The origin value of the reverse scale axis corresponds to year 2010. Using different colors, (legend shown on the left side), terminal branches were annotated based on geographic location of DENV-2 isolates. Internal nodes of the tree which presented modal state posterior probability ≥0.60 were also colored according to their most probable location states, inferred by discrete phylogeographical analysis. Brazilian lineages are delimited by square brackets. For clarity purposes some branches were collapsed. SJRP/2008 contains 11 isolates from São José do Rio Preto/São Paulo/Brazil (DENV-2/BR/BID-V3653/2008, -V3638/2008, -V3640/2008, -V3483/2008, -V3637/2008, -V3495/2008, -V3645/2008, -V3481/2008, -V3486/2008, -V3650/2008 and -V3648/2008); CU/US/KN 1997–2001 contains isolates from Cuba (Cuba115/97 and Cuba165/1997), Puerto Rico (US/BIC-V1387/1998) and Saint Kitts and Nevis (KN/BID-V2951/2001); VE/CO/GU/BZ/MX 1999–2009; PR 1986–1995 and PR 1994–2007 contain the same isolates as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059422#pone-0059422-g001" target="_blank">Figure 1</a> caption. Analyses were performed using programs from BEAST package v.1.6.1, BEAUTi, Tracer v.1.5.0, TreeAnotator v.1.6.1 and FigTree v.1.3.1 (B) Map of Brazil showing the macro-regions and states. The black pin indicates the approximate location of São José do Rio Preto/São Paulo/Brazil.</p

Amino acid differences in the envelope protein of Brazilian DENV-2 lineages.

1<p>- except HQ012515.BR59382/RN/1997 and HQ012518.BR66985/RJ/2000 (K).</p>2<p>- except DENV-2/BR/BID-V2386/2003, DENV-2/BR/BID-V2396/2006, JF804028.BR/DB015/2006 (V).</p

Phylogenetic analysis of DENV-2 based on the complete genome sequence.

<p>The evolutionary history was inferred using the Maximum Likelihood method, using the General Time Reversible model for nucleotide substitution with discrete Gamma distribution to model evolutionary rate differences among sites [4 categories (+<i>G</i>, parameter = 0.45)]. The tree with the highest log likelihood (−46330.60) is shown. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 91 nucleotide sequences with a total of 10,167 positions in the final dataset. A total of 1000 bootstrap replicates were run and values ≥99 are represented as percentage in respective nodes. The Brazilian DENV-2 lineages are shown in grey. For clarity purposes some branches were collapsed. VE/CO/GU/BZ/MX 1999–2009 contains isolates from Venezuela (VE61095/2007, DENV-2/VE/BID-V2944/2005, -V2424/2004, -V2492/200, -V2216/2003, -V2262/2006), Colombia (DENV-2/CO/BID-V3370/2004, -V3369/1999, -V1603/2004), Guatemala (FDA-GUA09/2009), Belize (BZ/BID-V2952/2002) and Mexico (DENV-2MX/BID-V3661, -V3714 and –V3768); PR 1986–1995 contains isolates from Puerto Rico (DENV-2/US/BID-V1356/1993, -V855/1992, -V1182/1989, -V1175/1988, -V1183/1990, -V1171/1987, -V1164/1986, DENV-2/PR/17DN/1995 and DENV-2/PR/6780DN/1994 ) and PR 1994–2007 also contains isolates from Puerto Rico (DENV-2/US/BID-V37DN/1994, -V1424/1996, -V1427/1999, -V1398/1997, -V1038/1998, -V1367/1995, -V1463/2000, V1472/2001, -V593/2005 and –V1412/2007). Evolutionary analyses were conducted in MEGA5.0.</p

The role of T-cells in neurobehavioural development: Insights from the immunodeficient nude mice

Mice homozygous for the nude mutation (Foxn1 ) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.