Dynamic feet distance: a new functional assessment during treadmill locomotion in normal and thoracic spinal cord injured rats

Of all the detrimental effects of spinal cord injury (SCI), one of the most devastating is the disruption of the ability to perform functional movement. Very little is known on the recovery of hindlimb joint kinematics after clinically-relevant contusive thoracic lesion in experimental animal models. A new functional assessment instrument, the dynamic feet distance (DFD) was used to describe the distance between the two feet throughout the gait cycle in normal and affected rodents. The purpose of this investigation was the evaluation and characterization of the DFD during treadmill locomotion in normal and T9 contusion injured rats, using three-dimensional (3D) instrumented gait analysis. Despite that normal and injured rats showed a similar pattern in the fifth metatarsal head joints distance excursion, we found a significantly wider distance between the feet during the entire gait cycle following spinal injury. This is the first study to quantify the distance between the two feet, throughout the gait cycle, and the biomechanical adjustments made between limbs in laboratory rodents after nervous system injury.This research was supported by the Project UID/CVT/00772/2013 from FCT.info:eu-repo/semantics/publishedVersio

Long-Term Evolution of SARS-CoV-2 in an Immunocompromised Patient with Non-Hodgkin Lymphoma

Recent studies have shown that persistent SARS-CoV-2 infections in immunocompromised patients can trigger the accumulation of an unusual high number of mutations with potential relevance at both biological and epidemiological levels. Here, we report a case of an immunocompromised patient (non-Hodgkin lymphoma patient under immunosuppressive therapy) with a persistent SARS-CoV-2 infection (marked by intermittent positivity) over at least 6 months. Viral genome sequencing was performed at days 1, 164, and 171 to evaluate SARS-CoV-2 evolution. Among the 15 single-nucleotide polymorphisms (SNPs) (11 leading to amino acid alterations) and 3 deletions accumulated during this long-term infection, four amino acid changes (V3G, S50L, N87S, and A222V) and two deletions (18-30del and 141-144del) occurred in the virus Spike protein. Although no convalescent plasma therapy was administered, some of the detected mutations have been independently reported in other chronically infected individuals, which supports a scenario of convergent adaptive evolution. This study shows that it is of the utmost relevance to monitor the SARS-CoV-2 evolution in immunocompromised individuals, not only to identify novel potentially adaptive mutations, but also to mitigate the risk of introducing "hyper-evolved" variants in the community.IMPORTANCE Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen. These findings show that the frequent oscillation in the immune status in immunocompromised individuals can trigger an accelerated virus evolution, thus consolidating this study model as an accelerated pathway to better understand SARS-CoV-2 adaptive traits and anticipate the emergence of variants of concern.This study was partially cofunded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Program (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Characterization of a large cluster of HIV-1 A1 infections detected in Portugal and connected to several Western European countries

HIV-1 subtypes associate with differences in transmission and disease progression. Thus, the existence of geographic hotspots of subtype diversity deepens the complexity of HIV-1/AIDS control. The already high subtype diversity in Portugal seems to be increasing due to infections with sub-subtype A1 virus. We performed phylogenetic analysis of 65 A1 sequences newly obtained from 14 Portuguese hospitals and 425 closely related database sequences. 80% of the A1 Portuguese isolates gathered in a main phylogenetic clade (MA1). Six transmission clusters were identified in MA1, encompassing isolates from Portugal, Spain, France, and United Kingdom. The most common transmission route identified was men who have sex with men. The origin of the MA1 was linked to Greece, with the first introduction to Portugal dating back to 1996 (95% HPD: 1993.6-1999.2). Individuals infected with MA1 virus revealed lower viral loads and higher CD4+ T-cell counts in comparison with those infected by subtype B. The expanding A1 clusters in Portugal are connected to other European countries and share a recent common ancestor with the Greek A1 outbreak. The recent expansion of this HIV-1 subtype might be related to a slower disease progression leading to a population level delay in its diagnostic.Supported by FEDER, COMPETE, and FCT by the projects NORTE-01-0145-FEDER-000013, POCI-01-0145-FEDER-007038 and IF/00474/2014; FCT PhD scholarship PDE/BDE/113599/2015; FCT contract FCT IF/00474/2014; European Funds through grant BEST HOPE (project funded through HIVERA, grant 249697) and by FCT PTDC/DTP-EPI/7066/2014. Global Health and Tropical Medicine Center are funded through FCT (UID/Multi/04413/2013). We would like to acknowledge all the patients and health care professionals from the Portuguese hospitals that contributed in some way to this study