Scale-free dynamics of COVID-19 in a Brazilian city.

A common basis to address the dynamics of directly transmitted infectious diseases, such as COVID-19, are compartmental (or SIR) models. SIR models typically assume homogenous population mixing, a simplification that is convenient but unrealistic. Here we validate an existing model of a scale-free fractal infection process using high-resolution data on COVID-19 spread in São Caetano, Brazil. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2-5. This model parameter correlated tightly with physical distancing measured by mobile phone data, such that in periods of greater distancing the model recovered a lower average number of contacts, and vice versa. We show that the SIR model is a special case of our scale-free fractal process model in which the parameter that reflects population structure is set at unity, indicating homogeneous mixing. Our more general framework better explained the dynamics of COVID-19 in São Caetano, used fewer parameters than a standard SIR model and accounted for geographically localized clusters of disease. Our model requires further validation in other locations and with other directly transmitted infectious agents.

Natural infection by Culex flavivirus in Culex quinquefasciatus mosquitoes captured in Cuiabá, Mato Grosso Mid-Western Brazil.

New species of insect-specific viruses (ISV) have been reported worldwide. In the present study, the complete genome of Culex flavivirus (CxFV) and partial sequences of other ISVs in Culex quinquefasciatus Say 1823 females (n = 3425) sampled in 200 urban areas census tracts of Cuiaba, state of Mato Grosso, were identified via reverse transcriptase-polymerase chain reaction for a NS5 region of flaviviruses, nucleotide and high-throughput sequencing, and viral isolation in C6/36 cells. CxFV was detected in 16 of 403 mosquito pools; sequences found in the study presented a high similarity with isolates from São Paulo, Brazil and other countries in Latin American that belong to genotype II, supporting the geographical influence on CxFV evolution. The monthly maximum likelihood estimation for CxFV ranged from 1.81 to 9.94 per 1000 mosquitoes. In addition to the CxFV complete genome, one pool contained an ORF1 sequence (756 bp) that belongs to a novel Negevirus from the Sandewavirus supergroup most similar to the Santana virus (77.1%) and another pool presented an RNA-dependent RNA polymerase sequence (1081 bp) of a novel Rhabdovirus most similar to Wuhan mosquito virus 9 (44%). After three passages in C6/36 cells, only CxFV was isolated from these co-infected pools. The importance of ISVs relies on their possible ability to interfere with arbovirus replication in competent vectors.

Mutational analysis of the genes encoding RFamide-related peptide-3, the human orthologue of gonadotrophin-inhibitory hormone, and its receptor (GPR147) in patients with gonadotrophin-releasing hormone-dependent pubertal disorders.

RFamide-related peptide-3 (RFRP-3), the orthologue of avian gonadotrophin-inhibitory hormone, and its receptor GPR147 have been recently identified in the human hypothalamus, and their roles in the regulation of reproductive axis has been studied. The present study aimed to investigate whether the presence of variants in the genes encoding human RFRP-3 (NPVF gene) and its receptor, GPR147 (NPFFR1 gene), is associated with the occurrence of gonadotrophin-releasing hormone-dependent pubertal disorders. Seventy-eight patients with idiopathic central precocious puberty (CPP) and 51 with normosmic isolated hypogonadotrophic hypogonadism (nIHH) were investigated. Fifty healthy subjects comprised the control group. The coding sequences of the NPVF and NPFFR1 genes were amplified and sequenced. Odds ratios (OR) were used to estimate the likelihood of CPP or nIHH in the presence of the described polymorphisms. All such polymorphisms have already been registered in the National Center for Biotechnology Information database. A three-nucleotide in frame deletion was identified in the NPVF gene (p.I71_K72), with a smaller proportion in the CPP (5%) compared to the nIHH (15%) group (P = 0.06). This results in the deletion of the isoleucine at position 71, adjacent to lysine at an endoproteolytic cleavage site of the precursor peptide. This polymorphism was associated with a lower risk of CPP (OR = 0.33; 95% confidence interval = 0.08-0.88); interestingly, only two men with nIHH were homozygotes for this variant. A total of five missense polymorphisms were found in the NPFFR1 gene, which encodes GPR147, with similar frequencies among groups and no association with pubertal timing. Our data suggest that RFRP-3/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out and deserves further investigation.

Levels of matrix metalloproteinase-2 and metalloproteinase-9 in the cerebrospinal fluid of dogs with visceral leishmaniasis.

Inflammation causes increases in the level of matrix metalloproteinases (MMPs), which, in central nervous system (CNS), are associated with neuroinflammation and disruption of blood-brain barrier. Analysis of cerebrospinal fluid (CSF) is pivotal for detecting diseases in CNS and, although a specific diagnosis may not be achieved, this analysis is helpful to confirm the diagnosis or to rule out relevant differential diagnoses. This study examined the levels of MMP-2 and MMP-9 in the CSF of dogs using gelatin zymography to verify possible alterations in these enzymes during natural systemic infection with Leishmania chagasi. Latent and active forms of MMP-2 were detected in some dogs of both groups, with high levels in the control group. In contrast, latent and active forms of MMP-9 were detected only in some animals with leishmaniasis. These results clearly demonstrate that MMP-9 is elevated in CSF of dogs with visceral leishmaniasis (VL). Although these results are preliminary, they suggest that MMP-9 might play a role in disruption of blood-brain barrier and/or blood-CSF barrier. While the presence of MMPs in CSF is not a condition exclusive to VL, their presence and persistence in CSF supports the hypothesis of an inflammatory state within CNS of dogs with VL.

Synthesis and cytotoxicity screening of substituted isobenzofuranones designed from anacardic acids.

This work is part of a large program, which seeks to discover new antitumor isobenfuranones designed from anacardic acids. The synthetic strategy for the construction of the title compounds takes into consideration the use of inexpensive anacardic acids (2), the major natural cashew (Anacardium occidentale) nut-shell phenolic lipid, and features one-pot construction of fused-ring aromatic gamma-lactones, phthalides. The cytotoxicity screening in different human cancer cell lines (HL-60 leukemia, SF295 glioblastoma and MDA-MB435 melanoma) by the MTT assay showed that acyclic precursor (6), and isobenfuranones (1a and 1b) are active compounds. Interestingly, 1a exhibits significant antiproliferative effect against HL-60 cells and moderate activity against SF295 and MDA-MB435 cell lines. Analysis of mechanisms involved in the cytotoxic activity showed that active compounds were leading to DNA damage, triggering apoptosis or necrosis induction.

Prognostic factors and treatment of penetrating gunshot wounds to the head.

BACKGROUND: In an attempt to evaluate the predictive factors of morbidity and mortality in patients who suffered from civilian gunshot wounds to the head, we reviewed a series of 319 patients admitted to the Hospital Santa Marcelina, São Paulo, Brazil, between 1994 and 2000. METHODS: Clinical and cranial computed tomography (CT) results are described. The initial Glasgow Coma Scale (GCS), the presence of an unilateral dilated pupil or medium fixed pupils, and five different findings in the CT scan were considered as variables. The Qui-Square Fisher test was utilized to verify the correlation between the presence of the variables and the occurrence of an increased mortality rate and of an unfavorable outcome (Glasgow Outcome Scale = 2 and 3). RESULTS: In 265 cases the missile penetrated the dura (83%). In our study there was a significant correlation between the low GCS scores on admission and a higher mortality (p < 0.001). This kind of correlation was also noted with patients admitted with unilateral dilated pupil and medium fixed pupil. There were 187 patients (70.5%) evaluated by CT scan. There was a significant correlation between the presence of transventricular or bihemispheric central type trajectory and high mortality. The patients admitted with unilobar supratentorial wounds resulted in better outcome when compared to those with bilobar or multilobar wounds (p < 0.001). A group of 156 patients was submitted to an aggressive surgical protocol. The best results were seen in patients admitted with initial GCS score higher than 8. CONCLUSIONS: We conclude that low GCS scores at admission, unilateral dilated pupil or medium fixed pupil, transventricular or bihemispheric central type trajectory, and bilobar or multilobar wounds noted through CT scan are predictive factors of high morbidity and mortality in patients with gunshot wounds to the head, in our clinical experience. We also conclude that surgical treatment is not recommended for patients with penetrating wounds and GCS score of 3 to 5 in the absence of hematoma causing a mass effect.

Naso-ethmoid schwannoma with intracranial extension: case report.

Intranasal schwannomas are rare lesions, specially when they present with an intracranial extension. The fifth case in the medical literature of a naso-ethmoid schwannoma with extension into the anterior cranial fossa is presented. The magnetic resonance findings and the details of the combined intracranial / transfacial operative approach used are described. The possible origin and the clinical characteristics of this rare lesion are reviewed.

[Intraspinal dermoid tumor associated with diastematomyelia: case report]. / Tumor dermóide intramedular associado a diastematomielia: relato de caso.

Intraspinal dermoid tumor and diastematomyelia is a rare combination of pathologies and only eight cases were priorly published. We report a new case in an adult with clinical presentation of progressive paresis and sensitive deficit in the lower limbs, associated with a thoraco-lombar kyphoscoliosis. The diagnosis based on the CT scan and MR images was confirmed at surgery. Pathophysiologic and clinical aspects as well as the radiological characteristics of these pathologies are dicussed and the importance of the early diagnosis is emphasized.