Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration.

Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes. To understand how these mutations impact brain development, we generated H3.3G34R/V/W knock-in mice and identified strikingly distinct developmental defects for each mutation. H3.3G34R-mutants exhibited progressive microcephaly and neurodegeneration, with abnormal accumulation of disease-associated microglia and concurrent neuronal depletion. G34R severely decreased H3K36me2 on the mutant H3.3 tail, impairing recruitment of DNA methyltransferase DNMT3A and its redistribution on chromatin. These changes were concurrent with sustained expression of complement and other innate immune genes possibly through loss of non-CG (CH) methylation and silencing of neuronal gene promoters through aberrant CG methylation. Complement expression in G34R brains may lead to neuroinflammation possibly accounting for progressive neurodegeneration. Our study reveals that H3.3G34-substitutions have differential impact on the epigenome, which underlie the diverse phenotypes observed, and uncovers potential roles for H3K36me2 and DNMT3A-dependent CH-methylation in modulating synaptic pruning and neuroinflammation in post-natal brains.

Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals.

Acetate is a major nutrient that supports acetyl-coenzyme A (Ac-CoA) metabolism and thus lipogenesis and protein acetylation. However, its source is unclear. Here, we report that pyruvate, the end product of glycolysis and key node in central carbon metabolism, quantitatively generates acetate in mammals. This phenomenon becomes more pronounced in the context of nutritional excess, such as during hyperactive glucose metabolism. Conversion of pyruvate to acetate occurs through two mechanisms: (1) coupling to reactive oxygen species (ROS) and (2) neomorphic enzyme activity from keto acid dehydrogenases that enable function as pyruvate decarboxylases. Further, we demonstrate that de novo acetate production sustains Ac-CoA pools and cell proliferation in limited metabolic environments, such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. By virtue of de novo acetate production being coupled to mitochondrial metabolism, there are numerous possible regulatory mechanisms and links to pathophysiology.

Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus.

The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has antiproliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin-, nucleolus- and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription, rRNA expression and chromatin-remodeling proteins. The global transcriptional rate and nucleolus area increased along with nucleolar disorganization upon 24 h of FGF2 stimulation. FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing. RNA Pol I inhibition partially reversed the growth arrest induced by FGF2, indicating that changes in rRNA expression might be crucial for triggering the antiproliferative effect. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes and modulates the main cell transcription site, the nucleolus.

Spathaspora marinasilvae sp. nov., a xylose-fermenting yeast isolated from galleries of passalid beetles and rotting wood in the Amazonian rainforest biome.

Four yeast isolates were obtained from rotting wood and galleries of passalid beetles collected in different sites of the Brazilian Amazonian Rainforest in Brazil. This yeast produces unconjugated allantoid asci each with a single elongated ascospore with curved ends. Sequence analysis of the internal transcribed spacer-5.8 S region and the D1/D2 domains of the large subunit ribosomal RNA (rRNA) gene showed that the isolates represent a novel species of the genus Spathaspora. The novel species is phylogenetically related to a subclade containing Spathaspora arborariae and Spathaspora suhii. Phylogenomic analysis based on 1884 single-copy orthologs for a set of Spathaspora species whose whole genome sequences are available confirmed that the novel species represented by strain UFMG-CM-Y285 is phylogenetically close to Sp. arborariae. The name Spathaspora marinasilvae sp. nov. is proposed to accommodate the novel species. The holotype of Sp. marinasilvae is CBS 13467 T (MycoBank 852799). The novel species was able to accumulate xylitol and produce ethanol from d-xylose, a trait of biotechnological interest common to several species of the genus Spathaspora.

Spencermartinsiella nicolii sp. nov., a potential opportunistic pathogenic yeast species isolated from rotting wood in Brazil.

Nineteen isolates representing a candidate for a novel yeast species belonging to the genus Spencermartinsiella were recovered from rotting wood samples collected at different sites in Atlantic Rainforest and Amazonian Forest ecosystems in Brazil. Similarity search of the nucleotide sequence of the intergenic spacer (ITS)-5.8S and large subunit D1/D2 regions of the ribosomal gene cluster showed that this novel yeast is closely related to Spencermartinsiella cellulosicola. The isolates differ by four nucleotide substitutions in the D1/D2 domain and six substitutions and 31 indels in the ITS region from the holotype of S. cellulosicola. Phylogenomic analysis based on 1474 single-copy orthologues for a set of Spencermartinsiella species whose whole genome sequences are available confirmed that the novel species is phylogenetically close to S. cellulosicola. The low average nucleotide identity value of 83% observed between S. cellulosicola and the candidate species confirms that they are distinct. The novel species produced asci with hemispherical ascospores. The name Spencermartinsiella nicolii sp. nov. is proposed. The holotype is CBS 14238T. The MycoBank number is MB855027. Interestingly, the D1/D2 sequence of the S. nicolii was identical to that of an uncultured strain of Spencermartinsiella causing systemic infection in a male adult crocodile (Crocodylus niloticus). The characterization of some virulence factors and antifungal susceptibility of S. nicolii isolates suggest that this yeast may be an opportunistic pathogen for animals, including humans; the isolates grow at 37 °C.

Consumer food environments change over a 5-year period.

OBJECTIVE: Evaluate the 5-year changes in the consumers' food environment in the area of a health promotion service in Brazilian primary health care. Our hypothesis is that the consumers' food environment in the areas with primary healthcare services has changes that may favour healthy eating habits over time. DESIGN: Longitudinal study. SETTING: The territory around the primary healthcare services in Belo Horizonte, Minas Gerais, Brazil. PARTICIPANTS: All food stores and open-air food markets that sell fruits and vegetables around the primary healthcare services in 2013 (n 272) and in 2018 (n 265). RESULTS: Fruit diversity increased by 13·4 % (P < 0·001) and vegetables variety and quality by 16·1 % (P = 0·003) and 12·5 % (P < 0·001), respectively. Corn snacks showed an increase in availability (13·5 %; P = 0·002). The increase in advertising was observed for fruits and vegetables (34·6 %; P < 0·001) and ultra-processed foods (47·6 %; P < 0·001). Supermarkets showed an increase in the Healthy Food Store Index (three points; P < 0·001), while fruits and vegetables stores showed a decrease of one point in the index (P < 0·001). CONCLUSIONS: The unequal changes in the consumers' food environment according to the food stores types demonstrate the importance of food supply policies that promote a healthy environment and favour the maintenance of traditional healthy food retailers.

Protocol of Randomized Controlled Community Trial (RCCT) for obesity management in Brazilian primary health care.

BACKGROUND: Obesity is a chronic disease characterized by excess body fat and is a risk factor for other chronic non-communicable diseases. Its multifactorial and complex nature makes its management a challenge for health services. This manuscript presents an investigation protocol that aims to analyze the effectiveness of collective nutritional interventions for obesity management applicable to primary health care. METHODS: Randomized Controlled Community Trial (RCCT) in a representative sample of users of the Programa Academia de Saúde (PAS), in Belo Horizonte, Minas Gerais, Brazil, with obesity. The research consists of four phases: (1) Screening to identify the participants eligible for the nutritional interventions (individuals with obesity, readiness for change to lose body weight, and willingness and interest to participate in a group activity for six months or more); (2) Baseline to characterize the participants; (3) Implementation of collective nutritional interventions; (4) Reassessment of the participants. Participants in the control group (CG) will receive the usual health service care, and participants in the intervention group (IG) will participate in collective nutritional interventions based on Therapeutic Group 1 (TG1) or Therapeutic Group 2 (TG2) of the "Instructive of Collective Approach for the obesity management in SUS". DISCUSSION: The strengths of the study include its robust RCCT design, which allows for longitudinal analyses and is suitable for investigating causal hypotheses and applying strategies to improve adherence to interventions. Furthermore, the study included a representative sample of a public health service and aims to evaluate therapeutic proposals from the Brazilian Ministry of Health, which can contribute to implementation and extension in the national territory. TRIAL REGISTRATION: RBR-3vzsyqq and RBR-6pg682m.

Human Satellite 1A analysis provides evidence of pericentromeric transcription.

BACKGROUND: Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have historically posed a challenge for the assembly of the human reference genome where they are misrepresented due to their repetitive nature. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSat1A has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of functional knowledge. Here, we aim to characterize and provide an understanding on the biological relevance of HSat1A. RESULTS: The path followed herein trails with HSat1A isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSat1A was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSat1A transcripts and further characterize them by 3' RACE-Seq. Size-varying polyadenylated HSat1A transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation. CONCLUSION: As far as we know, this work pioneers HSat1A transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSat1A sequences and associated noncoding RNAs will most certainly prove significant in the future of HSat research.

Body Composition Assessment in Adult Females with Anorexia Nervosa and Bulimia Nervosa-A Cross-Sectional Study Comparing Dual-Energy X-Ray Absorptiometry Scan and Isotopic Dilution of Deuterium.

BACKGROUND: Eating disorders (EDs) compromise individuals' nutritional status, affecting, among other organs and systems, bone health. OBJECTIVES: This study aimed to assess and compare bone mineral density (BMD) from DXA scan and deuterium (D2O) dilution of adult females with anorexia nervosa (AN) and bulimia nervosa (BN). METHODS: This was a cross-sectional study with 53 female participants (18-49 y) with a diagnosis of AN (n = 25) or BN (n = 28). DXA scan was performed to assess BMD, FM, and FFM, and D2O dilution was used to assess total body water (TBW), FM, and FFM. Interviews/questionnaires were used to assess symptoms, illness trajectory, and physical activity. t-test, chi-square test, Pearson's linear correlation, linear regressions, and Bland-Altman analyses were performed, with a significance level of 5%. RESULTS: TBW below the recommended level for adult females (≥ 45%) was more frequent in BN (60%) compared with AN (21%; P = 0.013). FM index (FMI) (soft tissue only) (t-test P = 0.06), and FFM index (FFMI) (t-test P = 0.08) agreed between DXA scan and D2O dilution. Only FFMI did not show systematic bias of proportion (ß: -0.2, P = 0.177). The diagnosis of BN, binge-eating episodes, and physical activity in AN were associated with the differences in the methods' results. FMI was positively associated with BMD in AN, and both FMI and FFMI were positively associated with BMD in BN. CONCLUSIONS: In adult females with EDs, DXA scan and D2O dilution achieved agreement for FMI and FFMI. Changes in FM and FFM are important in understanding the mechanisms behind bone loss in EDs. Protocols for body composition assessment in EDs can help to minimize the effect of the ED diagnosis, ED behaviors (that is, excessive exercise and purging behaviors), and weight on the accuracy of measurements.

Spathaspora brunopereirae sp. nov. and Spathaspora domphillipsii sp. nov., two d-xylose-fermenting ascosporogenous yeasts from Amazonian Forest biomes.

Four isolates of Spathaspora species were recovered from rotting wood collected in two Brazilian Amazonian biomes. The isolates produced unconjugated allantoid asci with a single elongated ascospore with curved ends. Sequence analysis of the ITS-5.8S region and the D1/D2 domains of the large subunit rRNA gene showed that the isolates represent two different novel Spathaspora species, phylogenetically related to Sp. boniae. Two isolates were obtained from rotting wood collected in two different sites of the Amazonian forest in the state of Pará. The name Spathaspora brunopereirae sp. nov. is proposed to accommodate these isolates. The holotype of Spathaspora brunopereirae sp. nov. is CBS 16119T (MycoBank MB846672). The other two isolates were obtained from a region of transition between the Amazonian forest and the Cerrado ecosystem in the state of Tocantins. The name Spathaspora domphillipsii sp. nov. is proposed for this novel species. The holotype of Spathaspora domphillipsii sp. nov. is CBS 14229T (MycoBank MB846697). Both species are able to convert d-xylose into ethanol and xylitol, a trait with biotechnological applications.

Evolution of fruit and vegetable intake among health promotion service participants in a Brazilian metropolis: 48-month follow-up of a randomized controlled community trial.

OBJECTIVE: To assess longitudinal effects of a nutrition intervention on fruit and vegetable (F&V) intake among Primary Health Care (PHC) service participants in Belo Horizonte, Brazil. METHODS: Demographics and health data on 3414 PHC service participants were collected at baseline in 2013-2014. F&V intake was assessed at baseline, 12, 36, and 48 months until 2017-2018. Services were randomized to control (CG, usual care) or intervention (IG, usual care and a Transtheoretical Model-based intervention to increase F&V intake). We performed difference-in-differences (DiD) analysis to identify intervention effects on F&V intake, and sensitivity analyses of participants observed at all timepoints. RESULTS: Participants were mostly middle-aged, low-income women. Mean baseline intakes were 168.7 g of fruit, 202.0 g of vegetables, and 370.7 g of F&V, with lower fruit in the IG (164.1 g) than the CG (172.3 g). At 12 months, the intervention increased fruit intake in the IG and fruit and F&V intake among individuals with low baseline F&V intake. Fruit intake remained higher at 36 months in the IG. No effect on vegetable intake was identified. According to sensitivity analyses, effects on fruit intake among the complete sample did not remain significant at 36 months, and an effect on fruit intake at 36 months was identified among those with adequate baseline F&V intake. Reductions in F&V intake did not remain significant. CONCLUSIONS: At 12 months, a TTM-based intervention increased fruit intake in the overall sample, and fruit and F&V intake among individuals with low baseline intakes. Repeated interventions may be needed over time. TRIAL REGISTRATION NUMBER: RBR-9h7ckx.

A functional assay using human whole blood and flow cytometry analysis to evaluate cytotoxicity and immunomodulatory effect of anti-Trypanosoma cruzi drugs.

The discovery and development of new drugs for the treatment of Chagas disease is urgent due to the high toxicity and low cure efficacy, mainly during the chronic phase of this disease. Other chemotherapeutic approaches for Chagas disease treatment are being researched and require screening assays suitable for evaluating the effectivity of new biologically active compounds. This study aims to evaluate a functional assay using the internalization of epimastigotes forms of Trypanosoma cruzi by human peripheral blood leukocytes from healthy volunteers and analyses by flow cytometry of cytotoxicity, anti-T. cruzi activity, and immunomodulatory effect of benznidazole, ravuconazole, and posaconazole. The culture supernatant was used to measure cytokines (IL-1-ß, IL-6, INF-γ, TNF and IL-10) and chemokines (MCP-1/CCL2, CCL5/RANTES and CXCL8/IL-8). The data showed a reduction in the internalization of T. cruzi epimastigote forms treated with ravuconazole, demonstrating its potential anti-T. cruzi activity. In addition, an increased amount of IL-10 and TNF cytokines was observed in the supernatant of cultures upon the addition of the drug, mainly IL-10 in the presence of benznidazole, ravuconazole and posaconazole, and TNF in the presence of ravuconazole and posaconazole. Moreover, the results revealed a decrease in the MCP-1/CCL2 index in cultures in the presence of benznidazole, ravuconazole, and posaconazole. A decrease in the CCL5/RANTES and CXCL8/IL-8 index in cultures with BZ, when compared to the culture without drugs, was also observed. In conclusion, the innovative functional test proposed in this study may be a valuable tool as a confirmatory test for selecting promising compounds identified in prospecting programs for new drugs for Chagas disease treatment.

A longitudinal analysis of the fluctuation of food stores in Belo Horizonte, Minas Gerais, Brazil.

BACKGROUND: Changes in food environments have the potential to affect consumption, nutritional status, and health, and understanding these changes is of utmost importance. This study, therefore, aimed to examine the fluctuation of food stores that sell fruits and vegetables over five years in the health promotion service area of Primary Health Care (PHC) in Belo Horizonte, Minas Gerais, Brazil. METHODS: This was an ecological study that used data from a food environment audit conducted in the realm of Brazilian PHC. Buffers of 1 mile (equivalent to 1600 m) were created around health promotion services to define food environments. All food stores and open-air food markets that sold fruits and vegetables (FV) within this buffer area were considered eligible. The data collection was performed during two periods: the baseline, in 2013, and after five years, in 2018. This study compares the fluctuation by the type of stores and according to the health vulnerability index (HVI). RESULTS: After 5 years, 35.2% of the stores were stable; 154 stores were closed, and 155 were opened. The stability was greater in low-vulnerability areas, and the fluctuation differed by type of store only for areas with high vulnerability. The number of supermarket decreased in high HVI territories; and local stores, showed greater stability when compared to specialized FV markets. CONCLUSIONS: The differences in store fluctuations according to the vulnerability of areas demonstrate the importance of food supply policies considering the local characteristics to reduce inequities of access to healthy foods.

One minute analysis of 200 histone posttranslational modifications by direct injection mass spectrometry.

DNA and histone proteins define the structure and composition of chromatin. Histone posttranslational modifications (PTMs) are covalent chemical groups capable of modeling chromatin accessibility, mostly due to their ability in recruiting enzymes responsible for DNA readout and remodeling. Mass spectrometry (MS)-based proteomics is the methodology of choice for large-scale identification and quantification of protein PTMs, including histones. High sensitivity proteomics requires online MS coupling with relatively low throughput and poorly robust nano-liquid chromatography (nanoLC) and, for histone proteins, a 2-d sample preparation that includes histone purification, derivatization, and digestion. We present a new protocol that achieves quantitative data on about 200 histone PTMs from tissue or cell lines in 7 h from start to finish. This protocol includes 4 h of histone extraction, 3 h of derivatization and digestion, and only 1 min of MS analysis via direct injection (DI-MS). We demonstrate that this sample preparation can be parallelized for 384 samples by using multichannel pipettes and 96-well plates. We also engineered the sequence of a synthetic "histone-like" peptide to spike into the sample, of which derivatization and digestion benchmarks the quality of the sample preparation. We ensure that DI-MS does not introduce biases in histone peptide ionization as compared to nanoLC-MS/MS by producing and analyzing a library of synthetically modified histone peptides mixed in equal molarity. Finally, we introduce EpiProfileLite for comprehensive analysis of this new data type. Altogether, our workflow is suitable for high-throughput screening of >1000 samples per day using a single mass spectrometer.

Austropuccinia psidii uses tetrapolar mating and produces meiotic spores in older infections on Eucalyptus grandis.

Austropuccinia psidii is the causal agent of myrtle rust, a fungal disease that infects over 480 species in the Myrtaceae. A. psidii is a biotrophic pathogen that reproduces sexually and asexually. Sexual reproduction has been previously shown on Syzygium jambos and little is known about its reproductive biology on other hosts or whether populations that were formerly structured by host range can outcross on universally susceptible hosts. We investigated if mating genes in three genomes of A. psidii were under selection as a proxy for whether different strains can reproduce sexually on a shared host. We examined three homologs of the STE3.2 gene, sequences of which were near-identical in the three genomes, and the homeodomain locus, which contained two alleles of two homeodomain genes in each genome. A. psidii likely uses tetrapolar mating. Pheromone/receptor loci were distal to homeodomain loci, and based on haplotypes of a phased assembly, mate compatibility is regulated by multiallelic HD genes and biallelic STE3.2 genes; the third homolog of STE3.2 (STE3.2-1) was present in both haplotypes, and our study supports hypotheses this gene does not regulate mate recognition. Populations of A. psidii formerly structured by host range could potentially outcross on universal hosts based on their related mating genes, however this hypothesis should remain theoretical given the implications for biosecurity. Additionally, we searched for core meiotic genes in genomes of A. psidii, four species of Puccinia, and Sphaerophragmium acaciae through comparative genomics based on 136 meiosis-related orthologous genes modeled from Mycosarcoma maydis. Meiotic genes are conserved in rust fungi at family rank. We analyzed the expression of two meiotic and four mitotic genes of A. psidii on E. grandis over a 28-day time course to validate that identified meiotic genes were upregulated in teliospores. Three mitotic genes were significantly downregulated in samples collected 28 days after inoculation (DAI) compared to 14 DAI. Expression of meiotic genes was significantly up-regulated in samples collected 28 DAI compared to 14 DAI, indicating a temporal switch from production of uredinia (mitotic stage) to telia in the life cycle, which we hypothesize may be in response to leaf ageing.

Non-tuberculous mycobacteria: clinical and laboratory characterisation (2009 and 2019).

A cross-sectional and retrospective study of patients with Mycobacterium spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in isolations of nontuberculous mycobacteria (NTM). The number of patients with positive samples for Mycobacterium spp. grew from 56 in 2009 to 83 in 2019. The proportion of NTM rose from 39.3% to 49.4% (P = 0.240), with Mycobacterium avium complex being more frequent in 2009 and Mycobacterium gordonae in 2019, and Mycobacterium tuberculosis complex decreased from 60.7% to 50.6%. Higher age was associated with NTM in both years, and pulmonary disease and immunosuppression were associated with NTM in 2019 (P < 0.05), with weak to moderate correlation (V = 0.231-0.343). The overall rise of NTM, allied to their known capacity to resist antimicrobial therapy, alerts clinicians to the importance of recognising potential risk factors for infection and improving future prevention strategies.

Guillain-Barré syndrome as the first presentation of human immunodeficiency virus infection.

AIM: Antiretroviral therapy (ART) development has reduced the severity of neurological complications of the human immunodeficiency virus (HIV), but they remain prevalent and need prompt recognition. Acute inflammatory demyelinating polyneuropathy (AIDP) is a rare complication of human immunodeficiency virus (HIV) infection that may appear at any stage of the disease. In this case, AIDP represents a late presentation of HIV infection. METHODS: Descriptive study. Patient data were collected from their medical records and by health assessment interviews. RESULTS: We report a case of a 52-year-old male with acute lower limb weakness. Given the suggestive clinical presentation of AIDP and a positive HIV test, intravenous immunoglobulin (IVIG) was administered along with antiretroviral therapy. Progressive weakness to the upper limbs, autonomic dysfunction, and pain was observed. The second regimen of IVIG plus corticosteroids was administered. Muscle strength improved after three weeks. CONCLUSIONS: Screening for HIV in a patient with AIDP may provide a better outcome because of the early start of ART with good central nervous system penetration in HIV-infected patients.

Prevalence of SARS-CoV-2 antibodies among workers of the public higher education institutions of Porto, Portugal: a cross-sectional study.

OBJECTIVES: To assess the prevalence of SARS-CoV-2-specific IgM and IgG antibodies among workers of the three public higher education institutions of Porto, Portugal, up to July 2020. METHODS: A rapid point-of-care test for specific IgM and IgG antibodies of SARS-CoV-2 was offered to all workers (SD Biosensor STANDARD Q COVID-19 IgM/IgG Duo and STANDARD Q COVID-19 IgM/IgG Combo). Testing was performed and a questionnaire was completed by 4592 workers on a voluntary basis from 21 May to 31 July 2020. We computed the apparent IgM, IgG, and combined IgM or IgG prevalence, along with the true prevalence and 95% credible intervals (95% CrI) using Bayesian inference. RESULTS: We found an apparent prevalence of 3.1% for IgM, 1.0% for IgG and 3.9% for either. The estimated true prevalence was 2.0% (95% CrI 0.1% to 4.3%) for IgM, 0.6% (95% CrI 0.0% to 1.3%) for IgG, and 2.5% (95% CrI 0.1% to 5.3%) for IgM or IgG. A SARS-CoV-2 molecular diagnosis was reported by 21 (0.5%) workers; and of these, 90.5% had a reactive IgG result. Seroprevalence was higher among those reporting contacts with confirmed cases, having been quarantined, having a previous molecular negative test or having had symptoms. CONCLUSIONS: The seroprevalence among workers from the three public higher education institutions of Porto after the first wave of the SARS-CoV-2 infection was similar to national estimates for the same age working population. However, the estimated true seroprevalence was approximately five times higher than the reported SARS-CoV-2 infection based on a molecular test.

Challenges for obesity management in a unified health system: the view of health professionals.

BACKGROUND: Obesity is an increasingly prevalent chronic condition. Its multiple causes and the complexity of its treatment pose challenges for health professionals. OBJECTIVE: To explore and describe the challenges for obesity management in the Brazilian Unified Health System according to health professionals. METHODS: An exploratory quantitative web-based study, carried out in 2018 with health professionals, developed from the first stage of a national project that aims to examine the management of obesity in Brazil. The questionnaire was self-applied. Invitations to participate in the research were sent by the Ministry of Health, Health Department of Minas Gerais and members of the research group. We collected data on sex, age, professional category, region and level of care. The challenges were investigated using a Likert scale and categorized into structure and work process. RESULTS: We evaluated 1323 professionals, of which about 45% were dietitians, 90.2% were women, and 83.1% self-reported working in primary health care. The main barriers cited included a high demand for curative and individual assistance, the presence of comorbidities, and the absence or insufficient access to instructional materials, professional qualification and lack of support. CONCLUSION: Obesity management is a critical challenge for all professionals. Barriers were related to the work process and structural aspects and reinforce the need to empower health teams. We propose that permanent education activities should be established, as well as the development of instructional materials that are applicable to routine work. Finally, the results may be used to develop policies and strategies to improve obesity management.