Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the respiratory microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 respiratory microbiome studies by analyzing the upper (n = 58) and lower (n = 35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We find that time in the intensive care unit and type of oxygen support, as well as associated treatments such as antibiotic usage, explain the most variation within the upper respiratory tract microbiome, while SARS-CoV-2 viral load has a reduced impact. Specifically, mechanical ventilation is linked to altered community structure and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomics of the lower respiratory tract of COVID-19 patients identifies specific oral bacteria in physical association with proinflammatory immune cells, which show higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.
BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly
depends on host’s immune and genetic factors. Different Toll-like receptors (TLR)
variants have been described associated with leprosy, but with some lack of
replication across different populations.OBJECTIVES To evaluate the role of polymorphisms in genes TLR1,
TLR2 and TLR4 and susceptibility to leprosy
in a genetic case control study; to verify the association between genotypes of
these markers and the immunological profile in the serum of patients with
leprosy.METHODS Pre-designed TaqMan® assays were used to genotype markers at
TLR1 (rs4833095, rs5743551), TLR2 (rs7656411,
rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines
and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in
the serum of a subgroup of patients with and without leprosy reactions.FINDINGS Our results show an association between the T allele of rs3804099 at the
TLR2 gene and increased risk for leprosy per se [Odds ratio
(OR) = 1.296, p = 0,022]. In addition, evaluating the association between
different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine
serological levels, IL-17 appears as an immunological marker regulated by the
polymorphism of the three TLR genes evaluated, whereas different
TLR1 genotypes were associated with differential production of
IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as
CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and
IL-1β was related to TLR4 genotypes.MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory
role in the immunity against Mycobacterium leprae, by driving the
host’s production of key cytokines and chemokines involved in the pathogenesis of
this disease.
Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper (n=58) and lower (n=35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomic analysis of the lower respiratory tract of ventilated COVID-19 patients identified increased oral microbiota compared to controls. These oral microbiota were found physically associated with proinflammatory immune cells, which showed higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.
Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. Methods: We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. Results: No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). Conclusions: Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.
The purpose of this investigation was to compare ankle functional performance and ankle range of motion (ROM) between practitioners of resistance exercise (RE) with free-weights versus machines. Twenty-five men participated in this study. They were separated into two groups: (a) Free-weights; and (b) Machines. All subjects practiced regularly RE 5.3±0.7 d∙wk-1 and low aerobic training of 1.2±0.5 d∙wk-1 with a total time volume of 254.9±9.4 min∙wk-1. ROM measurements were taken in both ankles with a digital goniometer. Active ankle-dorsiflexion and plantar flexion range of motion were measured with subjects lying prone with an extended knee on a standard treatment table. The rising on the heel and the rising on toes were used to assess endurance of the ankle dorsiflexor and plantar flexor muscles, respectively. Ankle functional stability was assessed with the Single Leg Hop Test in both limbs. Ankle-dorsiflexion ROM showed a significant difference (Δ% left=21.1%; Δ% right=25.8%; P<0.01) between the Machines Group when compared to the Free-weights Group. Rising on the heel and rising on the toes showed no significant differences between the 2 groups (i.e., free-weights versus machines) (P>0.05). On the other hand, the Single Leg Hop Test (Δ% left=16.3%; Δ% right=15.4%; P<0.05) and number of jumps (Δ% left=27.9 %; Δ% right=26.1 %; P<0.05) recorded were lower in the Free-weights Group compared to the Machines Group. This study found a greater ankle-dorsiflexion ROM and performance during the Single Leg Hop Test in practitioners of RE with free-weights, showing a better control of sagittal plane movements.
Species delimitation in herbaceous bamboos has been complex and, in some genera, a great part of its diversity has been confirmed only based on genetic information, as is the case of the genus Raddia. It includes nine species, all occurring in Brazil, but only R. portoi predominates in dry forests of the Northeast associated with the Caatinga phytogeographic domain. This species is morphologically close to R. angustifolia, which is known for a single location in the Atlantic Forest in Southern Bahia, and is considered to be threatened by extinction. Besides problems with taxonomic focus, actions for its conservation are complicated because it is not certain if it must be considered an independent species or included in the more widespread R. portoi. In this study, we used coalescent multispecies (MSC) theory approaches combined with genetic structure analyses in an attempt to delimit these two species. Different analyses were congruent and the species delimitation using MSC inferred distinct lineages supporting their recognition as two species. These results solved the taxonomic doubts and also showed the power of these approaches to delimit species as lineages, even in groups with weak morphological divergence and low genetic variability, and also impacting our knowledge for conservation purposes.
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