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Introduction: Severe acute respiratory syndrome coronavirus infection is responsible for multisystemic disease and has high transmissibility. It culminated in a pandemic, challenging scientific knowledge and care capacity. Neurological symptoms are highly prevalent, and cases of encephalitis have been described, in both peri- and postinfectious periods. However, pathogenesis and prognosis are unclear. Thus, we aim to describe the clinical findings in cases of encephalitis in patients infected with severe acute respiratory syndrome coronavirus, together with a 1-year follow-up of self-perception of recovery and remaining neuropsychiatric symptoms., Methods: This is a retrospective observational study in which patients with cerebrospinal fluid collection and a recent diagnosis of severe acute respiratory syndrome coronavirus infection were screened for encephalitis through analysis of medical records. We describe their clinical and paraclinical findings using descriptive statistics, together with their long-term outcome, through a self-assessment questionnaire., Results: Among the 135 patients screened, 11 patients were included. Most of them were admitted for neurological symptoms (73%), and in 63% of cases, those symptoms occurred within the first 7 days of systemic symptoms. Most patients had minor pulmonary involvement assessed on chest computed tomography. On cerebrospinal fluid analysis, the most relevant finding was hyperproteinorrachia. Three patients (27%) had positive changes on magnetic resonance studies. In the outcome analysis, most patients (77%) reported gait difficulties and 66% reported memory and concentration problems., Conclusion: Encephalitis associated with severe acute respiratory syndrome coronavirus 2 infection is rare but responsible for chronic sequelae in cognitive and motor aspects. The pathophysiology seems to be associated with both the immune-mediated and inflammatory processes, and the low frequency of paraclinical findings demands a high clinical suspicion., Competing Interests: Declarations. Ethics approval and consent to participate: This study is part of a project entitled ISARIC/WHO Clinical Characterization Protocol for Severe Emerging Infections: Coronavirus. Approved by the National Ethics and Research Committee, by the Instituto D’Or de Pesquisa e Ensino (CONEP-CAAE 29496920.8.0000.5262, 19 March, 2020), with an individual patient consent waiver. All authors have read and consented to the publication of this manuscript. Consent for publication: Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal, and in the instance of the patient who passed away, written informed consent was obtained from the patient’s next-of-kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: None of the authors report relevant financial or nonfinancial competing interests., (© 2025. The Author(s).)

Background: Common variable immunodeficiency (CVID) is a rare disease that affects children and adults and is often difficult to diagnose. Despite being one of the most frequent causes of immunodeficiency, involving gastrointestinal (GI), respiratory, and hematological systems, the disease onset can have heterogeneous and intermittent symptoms, frequently leading to diagnostic delay. GI symptoms are common and can include diarrhea, but the asymptomatic periods lead to overlooking the recurrent pattern. The same can occur with respiratory infections, thus delaying CVID suspicion. The starting point for CVID diagnosis is the decreased gamma globulin levels in serum protein electrophoresis (SPE), also observed through direct immunoglobulin's dosage., Case Presentation: The patient is a 38 years-old man who had intermittent diarrhea and recurrent airway infections for 19 years, but the CVID diagnosis was achieved only after SPE was carried out. At that time, he was already malnourished, and developed other complications related to CVID in a short period., Conclusions: SPE is readily available and inexpensive, but is not part of the laboratory approach in diarrhea. According to the case presented herein, it can be useful for patients with recurrent infections or other clues of the disease., (© 2022. The Author(s).)

Background: Bradyrhizobium japonicum strain SEMIA 5079 (= CPAC 15) is a nitrogen-fixing symbiont of soybean broadly used in commercial inoculants in Brazil. Its genome has about 50% of hypothetical (HP) protein-coding genes, many in the symbiosis island, raising questions about their putative role on the biological nitrogen fixation (BNF) process. This study aimed to infer functional roles to 15 HP genes localized in the symbiosis island of SEMIA 5079, and to analyze their expression in the presence of a nod-gene inducer., Results: A workflow of bioinformatics tools/databases was established and allowed the functional annotation of the HP genes. Most were enzymes, including transferases in the biosynthetic pathways of cobalamin, amino acids and secondary metabolites that may help in saprophytic ability and stress tolerance, and hydrolases, that may be important for competitiveness, plant infection, and stress tolerance. Putative roles for other enzymes and transporters identified are discussed. Some HP proteins were specific to the genus Bradyrhizobium, others to specific host legumes, and the analysis of orthologues helped to predict roles in BNF., Conclusions: All 15 HP genes were induced by genistein and high induction was confirmed in five of them, suggesting major roles in the BNF process., (© 2022. The Author(s).)

Background: The multidrug therapy (MDT) for leprosy treatment adopted by Brazil in the 1990s was important for reducing leprosy in the country; however, recurrent cases remained problematic. Mechanisms involved in leprosy recurrence are heterogeneous and can be sorted into three groups: insufficient therapy, bacillary persistence and new infections. This study aimed to analyse the time interval of leprosy recurrence in relation to the therapeutic scheme in the state of Acre. The hypotheses were as follows: 1) treatments (a) rifampicin, ofloxacin and minocycline (ROM) and (b) dapsone (DDS) have a short leprosy recurrence time, 2) treatments based on MDT have a long leprosy recurrence time, 3) there is a dose-response relationship between MDT and the time interval between leprosy episodes., Methods: This retrospective cohort study included 201 patients with a second episode of clinical leprosy at the reference centers for leprosy control in the state of Acre. Exposure was the type of therapeutic scheme as follows: 1) ROM, 2) DDS, 3) MDT 0-9 doses , 4) MDT 10-19 doses , 5) MDT 20-29 doses , and 6) MDT 30+ doses . Outcome was the time interval between release from treatment and a diagnosis of a recurrent leprosy case. Incidence rate ratios and relative risk Poisson regressions adjusted by age and sex were calculated with 95% confidence intervals., Results: The 201 patients studied during this retrospective follow-up resulted in a total of 224 cases of recurrent leprosy. Incidence rate ratios within this therapeutic scheme were as follows: 3.3 (2.39, 4.2; ROM/MDT 30+ ), 1.12 (0.33, 1.92; DDS/MDT 30+ ), 2.17 (1.39, 2.94; MDT 0-9 /MDT 30+ ), 1.94 (1.13, 2.75; MDT 10-19 /MDT 30+ ) and 1.26 (0.47, 2.05; MDT 20-29 /MDT 30+ ). Relative risk Poisson regressions showed a protective effect of MDT 30+ in comparison with ROM (0.22; 0.07, 0.72), MDT 0-9 (0.42; 0.21, 0.85), and MDT 10-19 (0.44; 0.21, 0.92). No differences among MDT 30+ and DDS (0.71; 0.36, 1.41) and MDT 20-29 (0.76; 0.38, 1.49) were observed., Conclusions: New infection is an important-yet neglected-mechanism in leprosy recurrence in the state of Acre and can challenge the leprosy elimination plan in Brazil. MDT with few doses might be associated with leprosy recurrence due to insufficient therapy or bacillary persistence.

Background: GATA2 is a transcription factor that is a critical regulator of gene expression in hematopoietic cells. GATA2 deficiency presents with multi-lineage cytopenia, mycobacterial, fungal and viral infections. Patients with GATA2 mutation have a high risk of developing myelodysplastic syndrome or acute myeloid leukemia., Case Presentation: We described a 43 years-old white male with 20-year follow-up of autoimmune and thrombotic phenomena, hypothyroidism, disseminated refractory Mycobacterium kansasii infection and MonoMAC syndrome. GATA2 c.1061 C > T; p.T354 M mutation was identified after he progressed from myelodysplastic pancytopenia to refractory anemia with excess blasts type II. His relatives were also investigated and he underwent unsuccessful haematopoietic stem cell transplantation. We discuss the clinical features, genetic diagnosis and treatment of this immunodeficiency disorder., Conclusions: This case illustrates the challenge how a multidisciplinary disease should be handle. Once usual causes of immunodeficiency were excluded, clinicians should considerGATA2 deficiency in patients with myelodysplasia and long-standing Mycobacterium kansasii infection.

Background: Zika virus is an emerging arbovirus of the family Flaviviridae and genus Flavivirus that until 2007 was restricted to a few cases of mild illness in Africa and Asia., Case Presentation: We report a case of atrial fibrillation disclosed during an acute Zika virus infection in a 49-year-old man. Different biological samples were analyzed for the molecular diagnosis of Zika by real-time PCR, however only the saliva specimen was positive. The patient's wife tested positive in the serum sample, although she was an asymptomatic carrier. Moreover, a complete overview of patient's biomarkers, including cytokines, chemokines, and growth-factors levels, was analyzed and compared to gender and age matching non-infected controls, as well as other Zika infected patients, considering the 95%CI of the mean values. Elevated levels of CXCL8, CCL11, CCL2, CXCL10, IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-1Ra, IL-4, IL-9, FGF-basic, PDGF, G-CSF, and GM-CSF were observed in the Atrial fibrillation patient, in contrast to uninfected controls. Furthermore, increased levels of CCL5, IL-1β, TNF-α, IFN-γ, IL-9, G-CSF, and GM-CSF were observed only in the atrial fibrillation patient, when compared to other Zika patients., Conclusions: To our knowledge, this is the first description of this type of cardiac disorder in Zika patients which may be considered another atypical manifestation during Zika virus infection.

Background: Meningoencephalitis is one of the most common disorders of the central nervous system (CNS) worldwide. Viral meningoencephalitis differs from bacterial meningitis in several aspects. In some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. Virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. The knowledge of how mediators of inflammation can induce disease would contribute for the design of affordable therapeutic strategies, as well as to the diagnosis of virus not detected and viral meningoencephalitis. Cytokine-induced inflammation to CNS requires several factors that are not fully understood yet., Methods: Considering this, several cytokines were measured in the cerebrospinal fluid (CSF) of patients with undiagnosed and viral meningoencephalitis, and these were correlated with cellularity in the CSF., Results: The results demonstrate that an altered biochemical profile alongside increased cellularity in the cerebrospinal fluid is a feature of patients with meningoencephalitis that are not associated with the detection of virus in the CNS (P < 0.05). Moreover, HIV-positive patients (n = 10) that evolve with meningoencephalitis display a distinct biochemical/cytological profile (P < 0.05) in the cerebrospinal fluid. Meningoencephalitis brings about a prominent intrathecal cytokine storm regardless of the detection of virus as presumable etiological agent. In the case of Enterovirus infection (n = 13), meningoencephalitis elicits robust intrathecal pro-inflammatory cytokine pattern and elevated cellularity when compared to herpesvirus (n = 15) and Arbovirus (n = 5) viral infections (P < 0.05)., Conclusion: Differences in the cytokine profile of the CSF may be unique if distinct, viral or presumably non-viral pathways initially trigger the inflammatory response in the CNS.

Background: There is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls., Methods: Healthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated., Results: sVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR., Conclusion: Oxidized-LDL and sVCAM might be used as endothelial dysfunction biomarkers for elderly with normal cardiovascular risk factors.

Background: Hepatocellular carcinoma is a primary tumor of the liver and involves different treatment modalities according to the tumor stage. After local therapies, the tumor evaluation is based on the mRECIST criteria, which involves the measurement of the maximum diameter of the viable lesion. This paper describes a computed methodology to measure through the contrasted area of the lesions the maximum diameter of the tumor by a computational algorithm., Methods: 63 computed tomography (CT) slices from 23 patients were assessed. Non-contrasted liver and HCC typical nodules were evaluated, and a virtual phantom was developed for this purpose. Optimization of the algorithm detection and quantification was made using the virtual phantom. After that, we compared the algorithm findings of maximum diameter of the target lesions against radiologist measures., Results: Computed results of the maximum diameter are in good agreement with the results obtained by radiologist evaluation, indicating that the algorithm was able to detect properly the tumor limits. A comparison of the estimated maximum diameter by radiologist versus the algorithm revealed differences on the order of 0.25 cm for large-sized tumors (diameter > 5 cm), whereas agreement lesser than 1.0 cm was found for small-sized tumors., Conclusions: Differences between algorithm and radiologist measures were accurate for small-sized tumors with a trend to a small decrease for tumors greater than 5 cm. Therefore, traditional methods for measuring lesion diameter should be complemented non-subjective measurement methods, which would allow a more correct evaluation of the contrast-enhanced areas of HCC according to the mRECIST criteria.

Background: The soybean-Bradyrhizobium symbiosis can be highly efficient in fixing nitrogen, but few genomic sequences of elite inoculant strains are available. Here we contribute with information on the genomes of two commercial strains that are broadly applied to soybean crops in the tropics. B. japonicum CPAC 15 (=SEMIA 5079) is outstanding in its saprophytic capacity and competitiveness, whereas B. diazoefficiens CPAC 7 (=SEMIA 5080) is known for its high efficiency in fixing nitrogen. Both are well adapted to tropical soils. The genomes of CPAC 15 and CPAC 7 were compared to each other and also to those of B. japonicum USDA 6T and B. diazoefficiens USDA 110T., Results: Differences in genome size were found between species, with B. japonicum having larger genomes than B. diazoefficiens. Although most of the four genomes were syntenic, genome rearrangements within and between species were observed, including events in the symbiosis island. In addition to the symbiotic region, several genomic islands were identified. Altogether, these features must confer high genomic plasticity that might explain adaptation and differences in symbiotic performance. It was not possible to attribute known functions to half of the predicted genes. About 10% of the genomes was composed of exclusive genes of each strain, but up to 98% of them were of unknown function or coded for mobile genetic elements. In CPAC 15, more genes were associated with secondary metabolites, nutrient transport, iron-acquisition and IAA metabolism, potentially correlated with higher saprophytic capacity and competitiveness than seen with CPAC 7. In CPAC 7, more genes were related to the metabolism of amino acids and hydrogen uptake, potentially correlated with higher efficiency of nitrogen fixation than seen with CPAC 15., Conclusions: Several differences and similarities detected between the two elite soybean-inoculant strains and between the two species of Bradyrhizobium provide new insights into adaptation to tropical soils, efficiency of N2 fixation, nodulation and competitiveness.

Background: Deregulation of the MAPK genes signalling caused by somatic mutations have been implied in leukaemia pathogenesis, including RAS mutation (RASmut) in acute myeloid leukaemia (AML), which has been associated with intra-uterine chemical exposures. A case-case study was conducted in order to explore maternal and child exposures to tobacco smoking associations with early age leukaemia (EAL)., Methods: Covariables of reference were MLL rearrangements (MLL-r), RASmut and NQO1 rs1800566 (C609T). Samples from 150 acute lymphoblastic leukaemia (ALL) and 85 AML were included. Maternal exposures were assessed using a structured questionnaire with demographic, personal habits and residence history information. Restriction fragment length polymorphism and denaturing high performance liquid chromatography were used to screen FLT3, KRAS, and NRAS mutations; direct sequencing was performed to validate the results. NQO1 polymorphism was detected by real-time allelic discrimination technique., Results: Overall, RASmut were detected in 28.7% of EAL cases; BRAFmut was found only in one AML patient. Higher rate of KRASmut was found in ALL (30.3%) compared to AML (20.8%) with MLL-r; RASmut showed an association with second-hand tobacco smoking exposures (OR, 3.06, 95% CI, 1.03-9.07). A considerable increased risk for EAL with the combination of RASmut and NQO1 609CT (OR, 4.24, 95% CI, 1.24-14.50) was observed., Conclusions: Our data demonstrated the increased risk association between maternal smoking and EAL with MLL-r. Additionally, suggests that children second-hand tobacco exposures are associated with increased risk of EAL with RASmut modulated by NQO1 rs1800566 (C609T).

Introduction: Mediastinal masses in pediatric patients are very heterogeneous in origin and etiology. In the first decade of life, 70% of the mediastinal masses are benign whereas malignant tumors are more frequent in the second decade of life. Among the mediastinal masses, lymph nodes are the most common involved structures and could be enlarged due to a lymphoma, leukemia, metastatic disease, or due to infectious diseases as sarcoidosis, tuberculosis and others., Case Presentation: We report a case of a 13-year-old Caucasian girl who came to the emergency room with a history of intermittent fever, weight loss and night sweating for at least 1 month. A radiologic image work-up presented an anterior and posterior mediastinal mass. The 18F-fluorodeoxyglucose positron emission tomography presented a high maximum standard uptake value, which directed our decision for mediastinal biopsy for diagnostic elucidation. Histologic examination described the mass as granulomatous tuberculosis. The patient was treated with anti-tuberculosis therapy and developed a full clinical recovery., Conclusions: The present case report demonstrates that a bulky mediastinal lymphadenopathy detected on 18F-fluorodeoxyglucose positron emission tomography is not always a malignant lesion, and in countries where tuberculosis is endemic, this etiology should not be forgotten during clinical investigations. There is a need for more accurate cut-off values for this technology; meanwhile, the further investigation of patients with bulky mediastinal masses with procedures such as the open biopsy is indispensable.

Background: Hepatic encephalopathy (HE) is a severe complication in patients with hepatic cirrhosis, which causes numerous hospital admissions and deaths. Antibiotics are the best options in HE treatment, but head-to-head comparisons between these drugs are scarce. Erythromycin combines the antimicrobial effect and prokinetic properties in the same drug, but it has never been used in HE treatment. Our aim was to evaluate the efficacy of erythromycin as an HE treatment., Methods: We achieved a randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted in our hospital. After randomization, the subjects received either erythromycin 250 mg or neomycin 1 g orally QID until hospital discharge or prescription of another antibiotic. All subjects were blindly evaluated every day towards quantifying clinical, neuropsychometric, hepatic and renal exams. Statistical analysis was employed to compare the groups and correlate the variables with hospitalization duration., Results: 30 patients were evaluated (15 treated with each drug). At hospital admission, the groups were homogeneous, but the erythromycin group subjects achieved a shorter hospitalization stay (p = 0.032) and a more expressive reduction in alanine aminotranspherase levels (p = 0.026). Hospitalization duration was positively correlated with C reactive protein levels measured previous to (p = 0.015) and after treatment (p = 0.01)., Conclusions: In the sample evaluated erythromycin was associated with significant reductions in hospital stay and in alanine aminotranspherase values. Hospitalization time was positive correlated with C reactive protein levels measured before and after the treatments.

Background: Escherichia coli is believed to participate in the etiology of Crohn's disease (CD) and possibly of ulcerative colitis (UC), due at least in part to the observed rise in the number of these bacteria in the gut microbiota of CD and UC patients. Nevertheless, it is not fully understood whether this quantitative variation occurs equally throughout the mucosal and luminal spaces of the gut. To assess this question, stools and mucosa biopsies from distinct intestinal sites were cultured aiming at determining their E. coli concentration. The cultures were additionally screened for the presence of some virulence genes of pathogenic E. coli., Results: Analyses of clinical materials from 14 controls (38 biopsies and 14 stools samples), 11 CD (25 biopsies and 11 stools samples) and 7 UC patients (18 biopsies and 7 stools samples) indicated no significant variation in the number of E. coli present in stools, but a rise of at least one log10 CFU/mg in biopsies from the ileum of CD patients and the sigmoid and rectum of CD and UC patients. The cultures were screened for the presence of E. coli attaching and effacing (eae), invasion plasmid antigen H (ipaH), aggregative adherence transcriptional activator (aggR), Shiga cytotoxins (stx), and heat labile enterotoxin (elt) and the following serine proteases autotransporters of Enterobacteriaceae (SPATE) genes: plasmid encoded toxin (pet), secreted autotransporter toxin (sat), Shigella extracellular protein (sepA), protein involved in intestinal colonization (pic) and Shigella IgA-like protease homolog (sigA). Six of the 10 genes screened were detected in the total of samples investigated: aggR, eae, pet, sat, sepA and sigA. No difference in the prevalence of any of these markers was observed in cultures from different clinical materials or groups of patients., Methods: Bacterial quantitation was carried out following cultures of diluted samples suspensions in MacConkey agar, Wilkins Chalgren agar for anaerobes, E. coli/coliform chromocult agar, and blood agar. Screening for E. coli virulence genes was performed by multiplex PCR of DNA purified from total MacConkey undiluted broth cultures., Conclusion: In CD and UC patients only the mucosa associated population of E. coli is augmented and the proliferation is prominent in the ileum of CD and rectum and sigmoid of both UC and CD patients which are sites where the lesions usually are observed. The augmented E. coli population in these sites presented a low number of the virulence markers, possibly meaning that they are not relevant for the disease process.

Background: Here, we investigated the phylogenetic relationships of the HIV-1 subtype F1 circulating in Angola with subtype F1 strains sampled worldwide and reconstructed the evolutionary history of this subtype in Central Africa., Methods: Forty-six HIV-1-positive samples were collected in Angola in 2006 and subtyped at the env-gp41 region. Partial env-gp120 and pol-RT sequences and near full-length genomes from those env-gp41 subtype F1 samples were further generated. Phylogenetic analyses of partial and full-length subtype F1 strains isolated worldwide were carried out. The onset date of the subtype F1 epidemic in Central Africa was estimated using a Bayesian Markov chain Monte Carlo approach., Results: Nine Angolan samples were classified as subtype F1 based on the analysis of the env-gp41 region. All nine Angolan sequences were also classified as subtype F1 in both env-gp120 and pol-RT genomic regions, and near full-length genome analysis of four of these samples confirmed their classification as "pure" subtype F1. Phylogenetic analyses of subtype F1 strains isolated worldwide revealed that isolates from the Democratic Republic of Congo (DRC) were the earliest branching lineages within the subtype F1 phylogeny. Most strains from Angola segregated in a monophyletic group together with Romanian sequences; whereas South American F1 sequences emerged as an independent cluster. The origin of the subtype F1 epidemic in Central African was estimated at 1958 (1934-1971)., Conclusion: "Pure" subtype F1 strains are common in Angola and seem to be the result of a single founder event. Subtype F1 sequences from Angola are closely related to those described in Romania, and only distantly related to the subtype F1 lineage circulating in South America. Original diversification of subtype F1 probably occurred within the DRC around the late 1950s.