Exposure to air pollution and hospitalization due to COVID-19 in São José dos Campos, Brazil

The association between exposure to air pollutants and respiratory diseases is well known. This study aimed to identify the association between this exposure and hospitalizations for COVID-19 in São José dos Campos, SP, a medium-sized city, between April 2020 and April 2021. Hospitalization data, concerning code B34.2, was supplied by DATASUS, and data concerning pollutants and climate variables were supplied by CETESB. Cases were quantified by sex, age, length of hospital stay in days, and type of discharge, whether hospital discharge or death. The negative binomial regression model was chosen. Estimates were produced for the relative risk (RR) of significant exposure to pollutants (P≤0.05) with a 10 µg/m3 increase of pollutant, as well as for excess hospitalizations. There were 1873 hospitalizations, with a daily average of 4.7 (±3.8), ranging from zero to 21: 716 deaths (38.2%) were recorded, 1065 admissions were men, and women were less susceptible (OR=0.82). The average age of women was higher than that of men; in cases of death, men were older than women; discharged patients were younger. All the above variables were significant. The risk of ozone exposure was higher and more significant in Lag 2, and the risk of nitrogen dioxide exposure was high in Lag 3, which was the period of the highest increase in hospitalizations, at 11.3%. The findings of this study, the first conducted in Brazil, corroborate the results of studies conducted in other centers.

Cellular consequences of small supernumerary marker chromosome derived from chromosome 12: mosaicism in daughter and father

Constitutional genomic imbalances are known to cause malformations, disabilities, neurodevelopmental delay, and dysmorphia and can lead to dysfunctions in the cell cycle. In extremely rare genetic conditions such as small supernumerary marker chromosomes (sSMC), it is important to understand the cellular consequences of this extra marker, as well the factors that contribute to their maintenance or elimination through successive cell cycles and phenotypic impact. The study of chromosomal mosaicism provides a natural model to characterize the effect of aneuploidy on genome stability and compare cells with the same genetic background and environment exposure, but differing in the presence of sSMC. Here, we report the functional characterization of different cell lines from two familial patients with mosaic sSMC derived from chromosome 12. We performed studies of proliferation dynamics, stability, and variability of these cells using fluorescent in situ hybridization (FISH), sister chromatid exchanges (SCE), and conventional staining. We also quantified the telomere-related genomic instability of sSMC cells using 3D telomeric profile analysis by quantitative-FISH. sSMC cells exhibited differences in the cell cycle dynamics compared to normal cells. First, the sSMC cells exhibited lower proliferation index and higher frequency of SCE than normal cells, associated with a higher level of chromosomal instability. Second, sSMC cells exhibited more telomeric-related genomic instability. Lastly, the differences of sSMC cells distribution among tissues could explain different phenotypic repercussions observed in patients. These results will help in our understanding of the sSMC stability, maintenance during cell cycle, and the cell cycle variables involved in the different phenotypic manifestations.

In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

Small cell lung cancer (SCLC) is an aggressive disease, representing 15 percent of all cases of lung cancer, has high metastatic potential and low prognosis that urgently demands the development of novel therapeutic approaches. One of the proposed approaches has been the down-regulation of BCL2, with poorly clarified and controversial therapeutic value regarding SCLC. The use of anti-BCL2 small interfering RNA (siRNA) in SCLC has never been reported. The aim of the present study was to select and test the in vitro efficacy of anti-BCL2 siRNA sequences against the protein and mRNA levels of SCLC cells, and their effects on cytotoxicity and chemosensitization. Two anti-BCL2 siRNAs and the anti-BCL2 G3139 oligodeoxynucleotide (ODN) were evaluated in SCLC cells by the simultaneous determination of Bcl-2 and viability using a flow cytometry method recently developed by us in addition to Western blot, real-time reverse-transcription PCR, and cell growth after single and combined treatment with cisplatin. In contrast to previous reports about the use of ODN, a heterogeneous and up to 80 percent sequence-specific Bcl-2 protein knockdown was observed in the SW2, H2171 and H69 SCLC cell lines, although without significant sequence-specific reduction of cell viability, cell growth, or sensitization to cisplatin. Our results question previous data generated with antisense ODN and supporting the present concept of the therapeutic interest in BCL2 silencing per se in SCLC, and support the growing notion of the necessity of a multitargeting molecular approach for the treatment of cancer.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Evaluation of Gilles de la Tourette syndrome with [99mTc] HMPAO Brain SPECT

Gilles de la Tourette syndrome (GLTS) is a disorder characterized by tics and several behavioral disturbances. Although GLTS is a relatively common disorder, little is known about its pathophysiology. Previous studies with SPECT and PET were performed in a small number of patients and have shown some discordant data. The aim of this study is to evaluate brain perfusion abnormalities in patients with GLTS and to correlate them with the clinical manifestations of the syndrome. Twenty-eight patients were submitted to brain [99mTc]-HMPAO SPECT. 82 percent of the patients had abnormal studies. The most frequent finding was perfusion abnormalities in the thalami in 16 patients (57 percent) and 85 percent of patients with hyperperfusion of one or both thalami had complex motor tics. This investigation has demonstrated that brain perfusion SPECT is able to identify cortical perfusion abnormalities, associated with clinical symptoms in patients with GLTS. These abnormalities involve the pre-frontal-striatal-thalamic-cortical pathways

Valor prognóstico da cintilografia na avaliaçäo da formaçäo do regenerado ósseo no tratamento por alongamento do fêmur curto congênito / Prognostic value of scintigraphy in the evaluation of calus formation in the treatment by congenital short femur lengthening

O fêmur curto congênito é a deficiência longitudinal mais comum do fêmur. O membro acometido é aproximadamente 10 por cento menor do que o normal. O tratamento geralmente é feito por alongamento ósseo e as técnicas mais empregadas utilizam as corticotomias e a colocaçäo de fixador externo com alongamento progressivo. A avaliaçäo da resposta ao tratamento é difícil, baseando-se na análise radiográfica do calo ósseo em formaçäo. O objetivo deste estudo foi avaliar se a cintilografia óssea trifásica seria capaz de prever a formaçäo de calo ósseo adequado ou näo nos pacientes com fêmur curto congênito submetidos ao alongamento com fixador externo. Cinco pacientes, submetidos ao alongamento ósseo com fixador externo, foram investigados com radiografias e cintilografia óssea trifásica. Em três pacientes que apresentaram boa evoluçäo clínica a cintilografia óssea trifásica mostrou captaçäo moderada ou acentuada do radiofármaco no calo ósseo. Nos dois pacientes que apresentaram má evoluçäo clínica, a captaçäo do radiofármaco no calo ósseo foi normal ou apenas discretamente aumentada. Portanto, a captaçäo do radiofármaco na fase tardia da cintilografia óssea correlacionou-se com a evoluçäo clínica. A cintilografia óssea parece ser um método capaz de prever o prognóstico dos pacientes com fêmur curto congênito submetidos a alongamento por fixador externo

Cintilografia óssea trifásica para guiar a retirada de implantes metálicos em fraturas: estudo preliminar / Three-phase bone scintigraphy as a guide to metallic implant removal

O objetivo deste estudo foi avaliar o papel da cintilografia óssea trifásica na indicação da retirada do material de síntese de pacientes com fratura diafisária do fêmur, submetidos à fixação com haste intramedular bloqueada (HIB) ou com placa em ponte (PP), já que, atualmente, a indicação da retirada é feita por critérios não totalmente confiáveis. Foram estudados 13 pacientes, seis com colocação de HIB e sete com PP. Todos os pacientes foram submetidos a cintilografia óssea trifásica com 740MBq de MDP-99mTc em uma câmara de cintilação computadorizada. Em quatro pacientes (dois com HIB e dois com PP) houve retirada do material de síntese, em média, 42,2 meses após a fratura. Os pacientes com HIB apresentaram alterações discretas na fase tardia da cintilografia óssea e formação discreta do calo ósseo, enquanto os com PP mostraram alterações cintilográficas moderadas e formação anormal do calo ósseo. As discretas alterações descritas na cintilografia óssea nos pacientes com HlB indicam que este tipo de fixação leva a menor exigência mecânica do calo ósseo com remodelação mais fisiológica, comprovada pelo estudo tomográfico em dois pacientes, mostrando sua anatomia semelhante à do fêmur contralateral. Isto não ocorreu nos pacientes com PP, talvez devido a uma maior movimentação dos fragmentos ósseos permitida por este material. Esta movimentação sugere que este tipo de fixação talvez não seja o mais fisiológico, não proporcionando à fratura condições adequadas para se consolidar.