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BACKGROUND: Knee osteoarthritis (KOA) is a prevalent condition, and its most frequent symptom is pain that often leads to disability. Pain sensitization is a core feature of KOA, and it can be measured through quantitative sensory testing protocols such as pain pressure threshold (PPT). However, there is a lack of understanding about the factors that may influence changes in PPTs in the KOA population. OBJECTIVE: To explore the clinical and functional factors associated with PPTs in a sample of people with chronic KOA pain and to compare models of local (knees) and remote (thenar regions) sites. DESIGN: Cross-sectional analysis of a prospective cohort. SETTING: Primary care in public institution. PARTICIPANTS: 113 adults with KOA. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Multivariable regression analyses evaluating demographic, clinical, and functional variables that could be associated with local and remote PPTs (main outcomes) were performed. RESULTS: Both thenar region (adjusted-R2 : 0.29) and knee (adjusted-R2 : 0.45) models had the same significant negative association with being a female, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain levels (thenar: ß: -0.15, p = .002; knee: ß: -0.2, p < .001), and the 10-Meter Walking Test (thenar: ß: -0.05, p = .038; knee: ß: -0.08, p = .004). A small significant positive association with depressive symptoms was identified in both models, which acted as a confounder for WOMAC pain and was likely affected by unmeasured confounders. CONCLUSIONS: PPTs in KOA pain are associated with functional outcomes such as the 10-Meter Walking Test and activity-related pain intensity; thus more disability is associated with smaller pain thresholds. Similarity between models may suggest central sensitization.

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Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (ß: -0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (ß: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (ß: -3.11) and central area (ß: -3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.

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Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.

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OBJECTIVE: To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammatory markers and clinical outcomes in patients with COVID-19. METHODS: A randomized blinded pilot study was carried out with 21 individuals hospitalized with COVID-19 who received 14 sessions of active (a-taVNS) or sham taVNS (s-taVNS). The level of interleukin-6 (IL-6), interleukin-10 (IL-10), cortisol, and C-reactive protein (CRP) in plasma and clinical evolution pre- and post-intervention were evaluated. The memory and attention levels were evaluated 14 days after the end of the treatment. RESULTS: After treatment, significant intragroup differences were found in the CRP (p = 0.01), IL-6 (p = 0.01), and cortisol (p = 0.01) levels; however, in the comparison between the groups, only the CRP level was statistically lower for the a-taVNS (p = 0.04). The impression of improvement in memory and attention was greater in the a-taVNS than in the s-taVNS (p = 0.01, p = 0.04, respectively). There was no difference between the other clinical outcomes. CONCLUSIONS: taVNS is a viable and safe intervention in the acute care of patients with COVID-19, which can modulate their inflammatory profile and improve cognitive symptoms. However, improvements in overall clinical outcomes were not detected. Larger sample sizes and longer follow-ups are needed to confirm the anti-inflammatory and clinical effects of taVNS in patients with COVID-19. TRIALS REGISTRY: The Brazilian Registry of Clinical Trials (RBR-399t4g5).

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OBJECTIVES: The pain related to spinal cord injury (SCI) is difficult to treat, and it is associated with significant morbidity. One aspect to improve therapeutics is to explore markers of pain and its correlates in SCI. METHODS: In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 39 patients with SCI were included. We analyzed conditioned pain modulation (CPM) efficiency as the index of the descending pain inhibitory system, EEG variables, and clinical pain levels as measured by the Visual Analogue Scale. Regression analyses were performed to assess the relationship among EEG variables, pain levels, and CPM. RESULTS: We included 39 SCI patients, 74% reported SCI-related pain. We found that (1) less alpha and beta power are related to pain presence, (2) less alpha and beta power are associated with higher pain levels among patients with pain, (3) patients with pain have decreased peak alpha-theta frequency compared to no-pain group, (4) more relative theta power are related to the presence of low CPM efficiency, (5) higher relative theta power is associated with lower CPM efficiency. CONCLUSIONS: Our results confirm and provide additional data on the relationship between decreased alpha and beta frequencies and higher pain levels. One important finding, though, was a specific and different EEG signature for the descending inhibitory pain system, as we showed that increased theta EEG power is related to decreased CPM efficiency; suggesting that, although low CPM efficiency plays a major role in pain in these participants, it does seem to be associated with a specific oscillatory brain rhythm different from clinical pain. These findings have significant implications for future research on EEG-based biomarkers of pain in post-SCI and new interventions as neurofeedback to manage pain in this population.

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Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

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The cyanobacterial genus Nostoc is an important contributor to carbon and nitrogen bioavailability in terrestrial ecosystems and a frequent partner in symbiotic relationships with non-diazotrophic organisms. However, since this currently is a polyphyletic genus, the diversity of Nostoc-like cyanobacteria is considerably underestimated at this moment. While reviewing the phylogenetic placement of previously isolated Nostoc-like cyanobacteria originating from Brazilian Amazon, Caatinga and Atlantic forest samples, we detected 17 strains isolated from soil, freshwater, rock and tree surfaces presenting patterns that diverged significantly from related strains when ecological, morphological, molecular and genomic traits were also considered. These observations led to the identification of the evaluated strains as representative of three novel nostocacean genera and species: Amazonocrinis nigriterrae gen. nov., sp. nov.; Atlanticothrix silvestris gen. nov., sp. nov.; and Dendronalium phyllosphericum gen. nov., sp. nov., which are herein described according to the rules of the International Code of Nomenclature for algae, fungi and plants. This finding highlights the great importance of tropical and equatorial South American ecosystems for harbouring an unknown microbial diversity in the face of the anthropogenic threats with which they increasingly struggle.

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The saline-alkaline lakes (soda lakes) are the habitat of the haloalkaliphilic cyanobacterium Anabaenopsis elenkinii, the type species of this genus. To obtain robust phylogeny of this type species, we have generated whole-genome sequencing of the bloom-forming Anabaenopsis elenkinii strain CCIBt3563 isolated from a Brazilian soda lake. This strain presents the typical morphology of A. elenkinii with short and curved trichomes with apical heterocytes established after separation of paired intercalary heterocytes and also regarding to cell dimensions. Its genome size is 4 495 068 bp, with a G+C content of 41.98 %, a total of 3932 potential protein coding genes and four 16S rRNA genes. Phylogenomic tree inferred by RAxML based on the alignment of 120 conserved proteins using GTDB-Tk grouped A. elenkinii CCIBt3563 together with other genera of the family Aphanizomenonaceae. However, the only previous available genome of Anabaenopsis circularis NIES-21 was distantly positioned within a clade of Desikacharya strains, a genus from the family Nostocaceae. Furthermore, average nucleotide identity values from 86-98 % were obtained among NIES-21 and Desikacharya genomes, while this value was 76.04 % between NIES-21 and the CCIBt3563 genome. These findings were also corroborated by the phylogenetic tree of 16S rRNA gene sequences, which also showed a strongly supported subcluster of A. elenkinii strains from Brazilian, Mexican and Kenyan soda lakes. This study presents the phylogenomics and genome-scale analyses of an Anabaenopsis elenkinii strain, improving molecular basis for demarcation of this species and framework for the classification of cyanobacteria based on the polyphasic approach.

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Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

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A new Phormidium-like genus was found during an investigation of Oscillatoriales diversity in Brazil. Eight aerophytic populations from south and southeastern regions were isolated in monospecific cultures and submitted to polyphasic evaluation. The populations presented homogeneous morphology with straight trichomes, not attenuated, and apical cell with thickened cell wall. Phylogenetic analyses based on 16S rRNA gene sequences showed that these populations, plus the Brazilian strain Phomidium sp. B-Tom from GenBank, formed a highly supported and distinctive clade, which corresponds to the new genus Pycnacronema, comprising six new species: P. brasiliensis (type species), P. arboriculum, P. conicum, P. marmoreum, P. rubrum, and P. savannensis. These results were confirmed and supported by rpoC1 and rbcL genes evaluated independently and by the concatenated analysis of 16S rRNA, rpoC1 and rbcL genes (for all species but P. savannensis). Secondary structures of the D1-D1', box-B, and V3 regions of the internal transcribed spacer were informative at specific level, being conserved in P. brasiliensis and variable among the other strains, also confirming the phylogenetic analyses. The generic name and specific epithets of the new taxa are proposed under the provisions of the International Code of Nomenclature of algae, fungi, and plants.

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The last decade was marked by efforts to define and identify the main cyanobacterial players in biological crusts around the world. However, not much is known about biocrusts in Brazil's tropical savanna (cerrado), despite the existence of environments favorable to their development and ecological relevance. We examined the community composition of cyanobacteria in biocrusts from six sites distributed in the Southeast of the country using high throughput sequencing of 16S rRNA and phylogenetic placement in the wider context of biocrusts from deserts. Sequences ascribable to 22 genera of cyanobacteria were identified. Although a significant proportion of sequences did not match those of known cyanobacteria, several clades of Leptolyngbya and Porphyrosiphon were found to be the most abundant. We identified significant differences in dominance and overall composition among the cerrado sites, much larger than within-site variability. The composition of cerrado cyanobacterial communities was distinct from those known in biocrusts from North American deserts. Among several environmental drivers considered, the opposing trend of annual precipitation and mean annual temperature best explained the variability in community composition within Brazilian biocrusts. Their compositional uniqueness speaks of the need for dedicated efforts to study the ecophysiology of tropical savanna biocrust and their roles in ecosystem function for management and preservation.

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Tropical ecosystems worldwide host very diverse microbial communities, but are increasingly threatened by deforestation and climate change. Thus, characterization of biodiversity in these environments, and especially of microbial communities that show unique adaptations to their habitats, is a very urgent matter. Information about representatives of the phylum Cyanobacteria in tropical environments is scarce, even though they are fundamental primary producers that help other microbes to thrive in nutrient-depleted habitats, including phyllospheres. In order to increase our knowledge of cyanobacterial diversity, a study was conducted to characterize isolates from Avicennia schaueriana and Merostachys neesii leaves collected at a mangrove and an Atlantic forest reserve located at the littoral of São Paulo state, south-east Brazil. The morphological, ultrastructural, phylogenetic, molecular and ecological features of the strains led to the recognition of the new genus Kryptousia, comprising two new species, Kryptousiamacronema gen. nov., sp. nov. and Kryptousiamicrolepis sp. nov., described here according to the International Code of Nomenclature for algae, fungi and plants. The new genus and species were classified in the nostocalean family Tolypotrichaceae. This finding advances knowledge on the microbial diversity of South American ecosystems and sheds further light on the systematics of cyanobacteria.

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Several new genera originally classified as the genus Phormidium, a polyphyletic and taxonomically complex genus within the Oscillatoriales, were recently described. The simple morphology of Phormidium does not reflect its genetic diversity and the delimitation of a natural group is not possible with traditional classification systems based on morphology alone. Therefore, this study used morphological, ecological, and molecular approaches to evaluate four populations morphologically similar to Ammassolinea, Kamptonema, and Ancylothrix (simple, curved, and gradually attenuated at the ends trichome), found in subtropical and tropical Brazilian regions. 16S rRNA gene sequences grouped all the strains in a highly supported clade with other two European strains isolated from thermal springs surrounding areas. The 16S-23S ITS secondary structure corroborated the phylogenetic analysis with all the strains having similar structures. Consequently, a genetically well-defined and cryptic new genus, Koinonema gen. nov., is proposed containing the aquatic, mesophilic, and morphologically homogeneous new species, Koinonema pervagatum sp. nov.

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Introduction: Iñapari is a town located in Peru, on the border of Brazil, between the Amazonian states of Acre and Amazonas. The local Peruvian children under five years of age present moderate anemia while the percentage of chronic child malnutrition is a major public health problem in the country as a whole. Goals: The purpose of this study was to identify the prevalence of major childhood morbidities caused by anemia, malnutrition, intestinal parasites, toxocariasis, and hepatitis A, and identify connections with the socioeconomic and environmental conditions found in Iñapari. Methods: Interviews with questionnaires; anthropometric measurements, collection of feces and venous blood samples. Results: A 20% prevalence of anemia and 8.5% prevalence of chronic malnutrition (height for age deficiency) was found. A pathogenic intestinal parasite was noted in 24.5% of the samples, where Giardia intestinalis (14.7%) was the most frequent. The seroprevalence of toxocariasis was 33.8% and hepatitis A was 21.2%. Conclusion: There is a connection between the results found and the poor living and sanitary conditions of the population. The low income noted is also linked to the malnutrition and anemia detected

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Phormidium Kützing ex Gomont, a common genus of the Cyanobacteria, is widely known as a problematic group. Its simple morphology is not congruent with its genetic heterogeneity and several new generic entities have been described based on 16S rRNA gene sequence analyses from populations with similar morphology. During a study of the diversity of Phormidioideae (Phormidiaceae, Oscillatoriales) in Brazil, ten Phormidium-like strains from south-eastern and mid-western regions were isolated in monospecific cultures and submitted to polyphasic evaluation (morphological, ecological and molecular studies). The populations studied presented homogeneous morphology (trichomes straight, not attenuated and apical cell rounded or obtuse), differing mainly in cell length from the type species of the genus Phormidium (Phormidium lucidum Agardh ex Gomont) and occurring as three morphotypes. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the populations studied, with European Phormidium aerugineo-caeruleum (Gomont) Anagnostidis & Komárek strains, were placed together in a very distinctive and highly supported clade. Thus, the set of characteristics of the strains resulted in the recognition of the new genus Potamolinea Martins et Branco with two species: Potamolinea magna as the type species (strains 47PC and 48PC) and Potamolinea aerugineo-caerulea (Gomont) Martins et Branco (strains 1PC, 2PC and 38PC). These two species plus one still undetermined lineage,Potamolinea sp., are morphologically and genetically distinguishable, whereas the secondary structures of the D1-D1', box-B and V3 regions were conserved within each one. The generic name and specific epithets of the new taxa are proposed under the provisions of the International Code of Nomenclature for algae, fungi and plants.

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During a study about the diversity of Phormidioideae (Phormidiaceae, Oscillatoriales) in Brazil, seven strains from southern and southeastern regions were isolated in monospecifc cultures and submitted to polyphasic evaluation (morphological, ecological, cytological and molecular studies). The populations studied were found to be morphologically similar to Kamptonema (filaments narrowed and bent at the end) and cytologically different (thylakoids' arrangement - radial distribution in Brazilian strains and parietal distribution in Kamptonema). The original habitats were very diverse among the Brazilian strains (freshwater, wet soil and barks of trees). Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strains were placed together in a very distinctive and highly supported clade. Thus, the set of characteristics of the strains resulted in the recognition of the new genus Ancylothrix Martins et Branco gen. nov. with two species [Ancylothrix rivularis gen. nov., sp. nov. (type species) and Ancylothrix terrestris sp. nov.], distinguishable by differences in genetic and ecological characteristics and described under the provisions of the International Code of Nomenclature for algae, fungi and plants. Secondary structures of D1-D1', box-B and V3 regions were conserved in A. rivularis gen. nov. sp. nov. and more variable in A. terrestris sp. nov.

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Two Cyanobacteria isolated from South Atlantic Ocean continental shelf deep water and from a marine green algae inhabiting the Admiralty Bay, King George Island, Antarctica were investigated based on morphological and ultrastructural traits, phylogeny of 16S rRNA gene sequences, secondary structure of the 16S-23S internal transcribed spacer regions and phylogenomic analyses. The majority of these evaluations demonstrated that both strains differ from the genera of cyanobacteria with validly published names and, therefore, supported the description of the novel genus as Aliterella gen. nov. The identity and phylogeny of 16S rRNA gene sequences, together with the secondary structure of D1D1' and BoxB intergenic regions, further supported the two strains representing distinct species: Aliterella atlantica gen. nov., sp. nov. (type SP469036, strain CENA595T) and Aliterella antarctica sp. nov. (type SP469035, strain CENA408T). The phylogenomic analysis of A. atlantica sp. nov. CENA595T, based on 21 protein sequences, revealed that this genus belongs to the cyanobacterial order Chroococcidiopsidales. The isolation and cultivation of two geographically distant unicellular members of a novel cyanobacterial genus and the sequenced genome of the type strain bring new insights into the current classification of the coccoid group, and into the reconstruction of their evolutionary history.

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Cyanobacteria dwelling on the salt-excreting leaves of the mangrove tree Avicennia schaueriana were isolated and characterized by ecological, morphological and genetic approaches. Leaves were collected in a mangrove with a history of oil contamination on the coastline of São Paulo state, Brazil, and isolation was achieved by smearing leaves on the surface of solid media or by submerging leaves in liquid media. Twenty-nine isolated strains were shown to belong to five cyanobacterial orders (thirteen to Synechococcales, seven to Nostocales, seven to Pleurocapsales, one to Chroococcales, and one to Oscillatoriales) according to morphological and 16S rRNA gene sequence evaluations. More detailed investigations pointed six Rivulariacean and four Xenococcacean strains as novel taxa. These strains were classified as Phyllonema gen. nov. (type species Phyllonema aviceniicola sp. nov. with type strain CENA341T) and Foliisarcina gen. nov. (type species Foliisarcina bertiogensis sp. nov. with type strain CENA333T), according to the International Code of Nomenclature for Algae, Fungi, and Plants. This investigation shows some of the unique cyanobacteria inhabiting the phyllosphere of Avicennia schaueriana can be retrieved by culturing techniques, improving current taxonomy and providing new insights into the evolution, ecology, and biogeography of this phylum.

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The novel chroococcalean cyanobacterium strain CENA595 was isolated from the deep chlorophyll maximum layer of the continental shelf of the South Atlantic Ocean. Here, we report the draft genome sequence for this strain, consisting of 60 contigs containing a total of 5,265,703 bp and 3,276 putative protein-coding genes.