Simulation-based evaluation of school reopening strategies during COVID-19: A case study of São Paulo, Brazil.

During the coronavirus disease 2019 (COVID-19) pandemic, many countries opted for strict public health measures, including closing schools. After some time, they have started relaxing some of those restrictions. To avoid overwhelming health systems, predictions for the number of new COVID-19 cases need to be considered when choosing a school reopening strategy. Using a computer simulation based on a stochastic compartmental model that includes a heterogeneous and dynamic network, we analyse different strategies to reopen schools in the São Paulo Metropolitan Area, including one similar to the official reopening plan. Our model allows us to describe different types of relations between people, each type with a different infectiousness. Based on our simulations and model assumptions, our results indicate that reopening schools with all students at once has a big impact on the number of new COVID-19 cases, which could cause a collapse of the health system. On the other hand, our results also show that a controlled school reopening could possibly avoid the collapse of the health system, depending on how people follow sanitary measures. We estimate that postponing the schools' return date for after a vaccine becomes available may save tens of thousands of lives just in the São Paulo Metropolitan Area compared to a controlled reopening considering a worst-case scenario. We also discuss our model constraints and the uncertainty of its parameters.

Periodontitis as a risk factor for head and neck cancer.

BACKGROUND: Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them. MATERIAL AND METHODS: Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed. RESULTS: A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases. CONCLUSIONS: Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association.

Incidence and profile of benign epithelial tumors of salivary glands from a single center in Northeast of Brazil.

BACKGROUND: Benign tumors of the salivary glands are a group of lesions with varied histopathological and clinical spectrum. The aim was to determine the incidence and clinicopathological characteristics of benign salivary gland neoplasms diagnosed between 2007 and 2016 in a single center located in northeastern Brazil. MATERIAL AND METHODS: Records regarding sex, age, anatomical location, histopathological subtype and treatment were retrieved, and data were analyzed using the Stata/IC software (version 12.0). RESULTS: There were above 7,100 cases of neoplasms in the head and neck region, of which 403 corresponded to salivary gland neoplasms. Of these, 238 (59%) were benign, being pleomorphic adenoma (PA) the most frequent neoplasm (n=178; 74.8%), followed by Warthin's tumor (WT) (n=23; 9.7%). Overall, most cases occurred in females (n=136; 57.1%) and age ranged from 11 to 83 years. The parotid gland (n=188; 79%) was the most common anatomical site, and all patients were treated by surgical excision. Of the cases diagnosed as PA, malignant transformation to carcinoma ex-pleomorphic adenoma (CAEXPA) occurred in 7 (3.9%) cases. CONCLUSIONS: The present study confirmed the clinical and demographic profile of benign salivary gland neoplasms, which contributes to the continuous knowledge of current data about these lesions.

Association study of functional polymorphisms of dopaminergic pathway in epilepsy-related factors of temporal lobe epilepsy in Brazilian population.

BACKGROUND AND PURPOSE: There are few data about the role of neurotransmission modulated by dopamine in epilepsy, especially temporal lobe epilepsy (TLE). This is the first study that aimed to analyze the dopaminergic polymorphisms in an etiologically homogeneous group of patients with TLE with hippocampal sclerosis. Selected polymorphisms were: (i) the most expressed D2-like receptors in the limbic system (DRD2/ANKK1 TAQ-1A, D4_VNTR and D4_rs1800955); (ii) the dopamine transporter (DAT) 3'-untranslated region and intron 8; and (iii) two degrading enzymes regulating the synaptic activity, i.e. the main metabolizer of dopamine, catechol-O-methyltransferase, and monoamine oxidase A. METHODS: We assessed 119 patients with unequivocal TLE with hippocampal sclerosis and 112 healthy volunteers. Individuals were genotyped for the polymorphisms of the gene encoding dopaminergic pathway transporter DAT haplotype, dopaminergic receptors, catechol-O-methyltransferase and monoamine oxidase A. We also evaluated epilepsy-related factors (e.g. seizure frequency, age of onset, duration and status epilepticus). RESULTS: There was no difference between the groups for the studied polymorphisms. The polymorphism DRD4_VNTR was associated with family history of epilepsy (P = 0.003), DRD2_rs1800497 was related to status epilepticus (P = 0.022), and intron 8 VNTR DAT was related to higher seizure frequency (P = 0.019) and family history of epilepsy (P = 0.011). CONCLUSIONS: Our findings demonstrated that polymorphisms of the dopaminergic pathway are associated with significant clinical features of this form of epilepsy, such as seizure frequency, family history of epilepsy and status epilepticus.

State-dependent microstructural white matter changes in drug-naïve patients with first-episode psychosis.

BACKGROUND: Diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) microstructural abnormalities in schizophrenia. Whether or not such alterations could vary depending on clinical status (i.e. acute psychosis v. remission) remains to be investigated. METHODS: Twenty-five treatment-naïve first-episode psychosis (FEP) patients and 51 healthy-controls (HC) underwent MRI scanning at baseline. Twenty-one patients were re-scanned as soon as they achieved sustained remission of symptoms; 36 HC were also scanned twice. Rate-of-change maps of longitudinal DTI changes were calculated for in order to examine WM alterations associated with changes in clinical status. We conducted voxelwise analyses of fractional anisotropy (FA) and trace (TR) maps. RESULTS: At baseline, FEP presented reductions of FA in comparison with HC [p < 0.05, false-discovery rate (FDR)-corrected] affecting fronto-limbic WM and associative, projective and commissural fasciculi. After symptom remission, patients showed FA increase over time (p < 0.001, uncorrected) in some of the above WM tracts, namely the right anterior thalamic radiation, right uncinate fasciculus/inferior fronto-occipital fasciculus, and left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. We also found significant correlations between reductions in PANSS scores and FA increases over time (p < 0.05, FDR-corrected). CONCLUSIONS: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities in brain tracts are a key neurobiological feature of acute psychotic disorders, and recovery from such WM pathology can lead to amelioration of symptoms.

Neurobiological support to the diagnosis of ADHD in stimulant-naïve adults: pattern recognition analyses of MRI data.

OBJECTIVE: In adulthood, the diagnosis of attention-deficit/hyperactivity disorder (ADHD) has been subject of recent controversy. We searched for a neuroanatomical signature associated with ADHD spectrum symptoms in adults by applying, for the first time, machine learning-based pattern classification methods to structural MRI and diffusion tensor imaging (DTI) data obtained from stimulant-naïve adults with childhood-onset ADHD and healthy controls (HC). METHOD: Sixty-seven ADHD patients and 66 HC underwent high-resolution T1-weighted and DTI acquisitions. A support vector machine (SVM) classifier with a non-linear kernel was applied on multimodal image features extracted on regions of interest placed across the whole brain. RESULTS: The discrimination between a mixed-gender ADHD subgroup and individually matched HC (n = 58 each) yielded area-under-the-curve (AUC) and diagnostic accuracy (DA) values of up to 0.71% and 66% (P = 0.003) respectively. AUC and DA values increased to 0.74% and 74% (P = 0.0001) when analyses were restricted to males (52 ADHD vs. 44 HC). CONCLUSION: Although not at the level of clinically definitive DA, the neuroanatomical signature identified herein may provide additional, objective information that could influence treatment decisions in adults with ADHD spectrum symptoms.

Retrospective study of 289 odontogenic tumors in a Brazilian population.

BACKGROUND: Odontogenic tumors (OTs) are considered important among oral lesions because of their clinicopathological heterogeneity, and variable biological behavior. This paper aims to determine the frequency and distribution of OTs, over a period of 10 years, at a public university in Northeastern Brazil and compare this data with previous reports. MATERIAL AND METHODS: We reviewed all cases of OTs from oral pathology laboratory of University of Pernambuco (UPE), from 2004 to 2014. Diagnoses were re-evaluated and the tumors were classified according to the latest (2005) World Health Organization Classification of Tumors. In addition, we searched in the English-language literature retrospective studies on OTs that used the same classification. RESULTS: Within the total of 6028 oral biopsies, 289 (4.79%) were OTs. Of these, 287 (99.3%) were benign and 2 (0.7%) were malignant. The overall incidence was 31.1/million. Mandible-maxilla ratio was 2.5:1 and mean age 35 years. Keratocystic odontogenic tumor (KCOT) (34.6%) was the most frequent lesion, followed by ameloblastoma (AMB) (32.9%) and odontoma (ODO) (11.4%). CONCLUSIONS: OTs are uncommon neoplasms with geographic variation. Our clinicopathological features are according to literature. In the present study, KCOT was the most frequent one, showing that the new classification of OTs altered the distribution of these lesions and possibly made KCOT the most common OT observed in diagnostic services worldwide.

Dose calculation and verification of the Vero gimbal tracking treatment delivery.

The Vero linear accelerator delivers dynamic tumor tracking (DTT) treatment using a gimbal motion. However, the availability of treatment planning systems (TPS) to simulate DTT is limited. This study aims to implement and verify the gimbal tracking beam geometry in the dose calculation. Gimbal tracking was implemented by rotating the reference CT outside the TPS according to the ring, gantry, and gimbal tracking position obtained from the tracking log file. The dose was calculated using these rotated CTs. The geometric accuracy was verified by comparing calculated and measured film response using a ball bearing phantom. The dose was verified by comparing calculated 2D dose distributions and film measurements in a ball bearing and a homogeneous phantom using a gamma criterion of 2%/2 mm. The effect of implementing the gimbal tracking beam geometry in a 3D patient data dose calculation was evaluated using dose volume histograms (DVH). Geometrically, the gimbal tracking implementation accuracy was <0.94 mm. The isodose lines agreed with the film measurement. The largest dose difference of 9.4% was observed at maximum tilt positions with an isocenter and target separation of 17.51 mm. Dosimetrically, gamma passing rates were >98.4%. The introduction of the gimbal tracking beam geometry in the dose calculation shifted the DVH curves by 0.05%-1.26% for the phantom geometry and by 5.59% for the patient CT dataset. This study successfully demonstrates a method to incorporate the gimbal tracking beam geometry into dose calculations. By combining CT rotation and MU distribution according to the log file, the TPS was able to simulate the Vero tracking treatment dose delivery. The DVH analysis from the gimbal tracking dose calculation revealed changes in the dose distribution during gimbal DTT that are not visible with static dose calculations.

GH response to hypoglycemia and clonidine in the GH-releasing hormone resistance syndrome.

GH secretion by the pituitary is the result of the balance between the stimulatory effect of GHRH and the inhibitory effect of SS. Patients with mutations in GHRH receptor (GHRH-R) gene (GHRH-R) offer a unique model to study the mechanism of action of different GH secretion stimuli. In the past, we have demonstrated a small but significant GH response to a GH secretagogue (GHRP-2) in a homogenous cohort of patients with severe GH deficiency (GHD) due to a homozygous null mutation in GHRH-R (IVS1+1G-->A). Now, we sought to determine if we could detect a GH response to hypoglycemia (ITT: insulin tolerance test) or clonidine (CL) in these patients. Nine young GHD subjects underwent both ITT and CL tests, and 2 additional subjects underwent only CL test. There was a small but significant GH increase during ITT, but not during CL test. These results indicate that a minimal albeit significant GH response to ITT can occur despite complete lack of GHRH-R function.

Incidence of retroviruses in some Brazilian groups.

The prevalence of human T lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) antibodies was evaluated in Brazil among 116 aboriginal Indians living in a pre-Amazonian region, and in 44 patients with haematological malignant disorders being treated in Rio de Janeiro. Screening for the presence of antibodies to HIV was performed routinely for 17,224 blood donors at the National Cancer Institute, Rio de Janeiro, from January 1986 to May 1987. The results demonstrated that HIV infection was not endemic among Brazilian Indians, as none of them had antibodies to HIV, in contrast with the population of Rio de Janeiro, which showed a high prevalence (0.34%) of positivity among normal individuals. In a small group of patients with haematological disease only one with acute lymphoblastic leukaemia proved to be HIV-positive, the infection having been acquired through previous blood transfusion. None of the serum samples reacted with HTLV-I, including those of 17 non-Hodgkin's lymphoma patients. HTLV-I infection does not seem to be endemic in this country, but further large scale studies are necessary, especially in patients with haematological disorders, homosexual individuals and drug users.

A sulphated fucan from the Laminaria abyssalis inhibits the human T cell lymphotropic virus type 1-induced syncytium formation in HeLa cells.

This work evaluated the effect of a sulphated fucan extracted from the Laminaria abyssalis marine algae on the human T cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation. The experiments were carried out in HeLa cells cocultured with a HTLV-1-infected T cell line (C91/PL cells) in the presence of the sulphated polysaccharide at concentration below that corresponding to the ED50. The sulphated fucan inhibited almost 100% of the syncytium formation at concentration of 100 microg/mI and was still active (>95%) at a concentration of 25 microg/ml. It was also observed that the best inhibition occurred when the compound was added in the first 2 h of the cell-to-cell contact. This is the first report showing that a purified sulphated polysaccharide, extracted from marine algae, is able to inhibit the cell-to-cell contact essential for the spreading of the HTLV-1.

Spastic paraparesis of obscure origin. A case-control study of HTLV-I positive and negative patients from Rio de Janeiro, Brazil.

In order to find clinical findings that could significantly discriminate between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-I negative spastic paraparesis of obscure origin (SPOneg) prior to serological testing, and to find risk factors significantly associated with HAM/TSP we devised a case-control study. Sixty consecutive SPO patients were studied without previous knowledge of their HTLV-I serological status. Thirty-four (56.7%) turned out to be HTLV-I positive and 26 (43.3%) HTLV-I negative. HTLV-I infected patients tended to have more commonly motor and bladder disturbances at the beginning of their illness and a disease that was still in progression at the time of the examination. Bladder dysfunction, constipation and penile impotence, and more widespread pyramidal signs, were also more frequent during the whole course of their illness. Likewise, an increased intrathecal synthesis of IgG was found more often in the HTLV-I positive group. The only risk factor for HTLV-I infection significantly associated to HAM/TSP was a prior history of sexually transmitted diseases. These results suggest that, at least in RJ, HAM/TSP might be mainly sexually acquired.

Progression of neurological disability in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is apparently a disease with a chronic evolution without spontaneous remissions. The real profile of its natural history and of the progression of the neurological disability, however, awaits confirmation. We devised the present study to evaluate the progression profile of the neurological disability of HAM/TSP in a series of 43 patients who have never received any kind of previous immune therapy. Patients were divided into different groups according to the duration of their disease. Age, gender and the Kurtzke's disability status scale (DSS) at the time of the first examination were compared. There were no statistically significant differences among groups with different disease duration. The present study suggests that the evolution of the neurological disability in HAM/TSP occurs mainly during the first year of the disease and becomes relatively stable after that. Therefore we speculate that the variable therapeutic success rates observed in many series of the literature could be due to the timing in the beginning of the pharmacological immunosuppression. Probably the therapeutic window in HAM/TSP lies within the first year of the disease. Thus it might be of utmost importance that future therapeutical trials take into consideration the duration of the disease since this factor can play an important role in the results of the trial.

Immunological features of HTLV-I myelopathy in Rio de Janeiro, Brazil, and in vitro effects of cyclosporin A.

Brazilian patients with HTLV-1 myelopathy present a significant spontaneous lymphocyte proliferation (SLP), and an increased response to IL-2 exogenous stimulation, in both peripheral blood lymphocytes and in whole blood proliferative assays, when compared to the control group. High antibody titers against HTLV-I antigens were also observed in comparison to healthy seropositive individuals. IL-6 was detected in cerebrospinal fluid (CSF) of 50% of the patients (10 out of 20) and TNF-alpha in four out of nineteen individuals. No correlation was found between the presence of levels of cytokines IL-6 and TNF-alpha and duration or severity of disease. The addition of cyclosporin A (CsA) significantly inhibited SLP suggesting that this therapeutic agent should be studied in HTLV-1 myelopathy. Brazilian patients with HTLV-I myelopathy present the same immunological abnormalities described in other endemic regions. The whole blood assay reflects the same results of separated blood cells and, due to its rapid execution may be used as an assay to follow clinical trials.

Detection and isolation of human T-cell leukemia/lymphoma virus type I (HTLV-I) from cultured lymphocytes of a Brazilian TSP/HAM patient.

Some Brazilian regions are considered to be endemic for human T-cell leukemia/lymphoma virus type I (HTLV-I) infection. Several studies have shown a high prevalence of HTLV-I infection among different groups such as blood donors, hemophiliacs and patients suffering from hematological and neurological diseases. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) have already been described in Brazil. We report the isolation of an HTLV-I strain from cultured lymphocytes of a TSP/HAM patient. An IL-2-dependent HTLV-I-infected T-cell line (ROB) expressing viral antigens was established and reverse transcriptase activity could be detected in the culture supernatant. Ultrastructural analysis showed immature and mature HTLV retrovirus particles. Finally, HTLV-I provirus type I was demonstrated by the polymerase chain reaction. This is the first isolation completely carried out in Latin America. The molecular analysis of viral strains, now in progress, should clarify the molecular epidemiology of HTLV-I in Brazil.

Detection and analysis of apoptosis in peripheral blood cells from breast cancer patients.

Apoptosis is a well-known specific process of cell death that normally occurs in physiological situations such as tissue or organ development and involution. During tumor growth there is a balance between proliferation and cell death which involves apoptotic mechanisms. In the present study genomic DNAs from 120 breast tumor biopsies were analyzed by agarose gel electrophoresis and none of them presented the fragmentation pattern characteristic of the apoptosis process. However, 33% of the 105 breast cancer patients clearly showed the apoptotic pattern when DNA from blood cells was analyzed. None of the DNAs from healthy volunteer blood cells showed any trace of apoptosis. Since the breast cancer patients were not receiving chemo- or hormone therapy, the possible relationship between blood cortisol levels and the apoptotic pattern found in patient blood cells was investigated. Using a chemoluminescence immunodetection assay, similar cortisol levels were observed in breast cancer patient sera presenting or not apoptotic blood cells and in healthy volunteer sera. Analysis of the clinical data obtained from 60 of these patients showed that patients bearing tumors of smaller size (under 20 mm) were more susceptible to the apoptotic effect in blood cells. According to the Elston grade, it was observed that 7 of 12 patients with grade III tumors (58%) presented apoptotic peripheral blood cells, in contrast to 10 of 48 patients with grade I and grade II tumors. These observations may reflect the immunosuppression characteristic of some breast cancer patients, which may contribute to tumor growth. Therefore, further studies are necessary to elucidate the factor(s) involved in such massive blood cell death.

Electron microscopic observation of a Brazilian HTLV-I isolated.

Several studies carried out in Brazil have shown a high incidence of HTLV-I infection among the general population and in different groups, such as blood donors, hemophiliacs, hematological and neurological patients. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I associated myelopathy have already been described. Therefore, it is important to characterize Brazilian HTLV strains using different technical approaches. The purpose of this paper is to characterize and recognize HTLV particles employing routine and immunoelectron microscopy in lymphocyte cocultures. Ultrastructural analysis showed typical large and small virus particles in close relation with the lymphocyte membrane. Immunoelectron microscopy, carried out with HTLV positive sera, allowed the identification of the virus as a type C oncovirus, group HTLV-BLV. The first interaction events between virus and lymphocyte membrane have also been analysed and structures related to the endocytic route for HTLV entrance were pointed out.

Image quality improvements of electronic portal imaging devices by multi-level gain calibration and temperature correction.

Amorphous silicon (aSi:H) flat panel detectors are prevalent in radiotherapy for megavoltage imaging tasks. Any clinical and dosimetrical application requires a well-defined dose response of the system to achieve meaningful results. Due to radiation damages, panels deteriorate and the linearity of pixel response to dose as well as the stability with regard to changing operating temperatures get worse with time. Using a single level gain correction can lead to an error of about 23% when irradiating a flood field image with 100 MU min(-1) on an old detector. A multi-level gain (MLG) correction is introduced, emending the nonlinearities and subpanel-related artifacts caused by insufficient radiation hardness of amplifiers in the read-out electronics. With rising temperature, offset values typically increase (up to 300 gray values) while the response at higher dose values per frame remain constant for a majority of pixels. To account for temperature-related image artifacts, two additional temperature correction methods have been developed. MLG in combination with temperature corrections can re-establish the aSi:H image quality to the performance required by reliable medical verification tools. Furthermore, the life span and recalibration intervals of these costly devices can be prolonged decisively.