Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma.

PURPOSE: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity. METHODS AND MATERIALS: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint. RESULTS: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003). CONCLUSIONS: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications.

Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis.

BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.

Loss of Caveolin-1 Expression in Tumor Cells is Associated with Increased Aggressiveness and Cell Invasion in Oral Squamous Cell Carcinoma.

BACKGROUND: Changes in Caveolin-1 (CAV-1) expression are related to tumorigenesis. The aim of this study was to evaluate the role of CAV-1 in tumor progression in oral squamous cell carcinoma (SCC) tissue samples and the effect of CAV-1 silencing on two oral tongue SCC (OTSCC) cell lines (SCC-25, from a primary tumor, and HSC-3 from lymph node metastases). METHODS: Mycroarray hybridization, mRNA expression, and immunohistochemistry were performed on OSCC tissue samples and corresponding non-tumoral margin tissues. The effects of CAV-1 silencing (siCAV-1) on cell viability, membrane fluidity, on the expression of epithelial to mesenchymal transition (EMT) markers and on cell migration and invasion capacity of OTSCC cell lines were evaluated. RESULTS: Microarray showed a greater CAV-1 expression (1.77-fold) in OSCC tumors than in non-tumoral tissues and 2.0-fold more in less aggressive OSCCs. However, significant differences in CAV-1 gene expression were not seen between tumors and non-tumoral margins nor CAV-1 with any clinicopathological parameters. CAV-1 protein was localized both in carcinoma and in spindle cells of the tumor microenvironment (TME), and CAV-1 positive TME cells were associated with smaller/more aggressive tumors, independent of the carcinoma cells' expression. Silencing of CAV-1 increased cell viability only in SCC-25 cells. It also stimulated the invasion of HSC-3 cells and increased ECAD and BCAT mRNA in these cells; however, the protein levels of the EMT markers were not affected. CONCLUSION: Decreased expression of CAV-1 by tumor cells in OSCC and an increase in the TME were associated with increased cell invasiveness and tumor aggressiveness.

Plasma metabolomics of oral squamous cell carcinomas based on NMR and MS approaches provides biomarker identification and survival prediction.

Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views-differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.

Association of Systemic Inflammatory and Immune Indices With Survival in Canine Patients With Oral Melanoma, Treated With Experimental Immunotherapy Alone or Experimental Immunotherapy Plus Metronomic Chemotherapy.

Analysis of the expression of inflammatory markers before starting treatment in human patients with cancer helps to predict outcomes and prognosis; however, there have been few studies on this topic in veterinary medicine. The present study aimed to evaluate inflammatory indices before treatment with autologous antitumor vaccine alone or this vaccine plus metronomic chemotherapy (MC) to predict response and prognosis. The indices included the neutrophil-lymphocyte ratio (NRL), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), C-reactive-protein-albumin ratio (CRP/ALB), lactate dehydrogenase level (LDH), frequency of blood lymphocyte subsets (CD4+, CD8+, Treg, and CD4/CD8 ratio) and frequency of blood myeloid-derived suppressor cells (MDSCs: monocytic [M]- MDSCs, and granulocytic [PMN]-MDSCs). Blood samples were collected from 25 dogs with oral melanoma treated with the autologous antitumor vaccine and from nine dogs that received MC plus vaccine before surgery. There were no statistically significant differences in the progression-free survival (PFS) or overall survival (OS) between the groups. In addition to the clinical stage, the CRP/ALB ratio and blood circulating Tregs in the univariate analysis showed an association with PFS and OS, and thus were selected for multivariable analysis. The CRP/ALB ratio was associated with PFS [hazard ratio (HR), 1.1; 95% confidence interval (CI), 1.0-1.1; p = 0.017] and OS [HR, 1; 95%CI, 1.0-1.1; p = 0.023]. Similarly, Treg was associated with PFS (HR, 1.6; 95% CI, 1.2-2.1; p = 0.001) and OS (HR, 1.6; 95% CI, 1.2-2.1; p = 0.001). Furthermore, canine patients with a CRP/ALB ratio above the cut-off point of 1.9 (established by receiver operating characteristic curve analysis) had worse PFS and OS, indicating the impact of the preoperative CRP/ALB ratio on the PFS and OS of dogs with oral melanoma. The CRP/ALB ratio and frequency of circulating Tregs are potential prognostic markers in dogs with oral melanoma.

Effect of age on resting energy expenditure in patients with cancer.

OBJECTIVE: Because older patients with cancer are at high risk for developing malnutrition, it is critical to understand their energy needs and to feed them appropriately. The aim of this study was to determine whether there are differences in resting energy expenditure between younger and older adults with cancer and in various age groups of older patients. METHODS: This retrospective, observational, and descriptive study from a single center included adult (≥18 to <60 y) and older (≥60 y) outpatients with gastrointestinal tract and head and neck cancers. According to the World Health Organization classification for adults and Pan American Health Organization for older individuals, nutritional status was estimated using body mass index. Nutritional risk screening was used to assess the nutritional risk and Patient-Generated Subjective Global Assessment for those at risk. Resting energy expenditure (REE) was measured by indirect calorimetry coupled to a gas exchange canopy. Bodystat and Quadscan 4000 multifrequency electrical bioimpedance devices were used to assess body composition at four frequencies (5, 50, 100, and 200 kHz). RESULTS: The study included 326 patients of whom 197 were older (60.4%), 244 were men (74.8%), 197 had gastric cancer (60.4%), and 129 had head and neck cancer (39.6%). Most patients had advanced cancer (stages III and IV) and had not undergone cancer treatment in the previous 3 mo. Compared with the younger adults, patients ≥60 y had a higher rate of malnutrition (88.4 versus 54.3%; P < 0.001), a higher percentage of fat-free mass deficit (88.3 versus 74.4%; P < 0.001), and higher percentage of fat mass (91.4 versus 58.9% adult; P < 0.001). The REE of older patients (1263.3 [234.1] kcal/d) was lower than that of patients ≥18 to <60 y (1382.5 [210.5] kcal/d; P < 0.001), for women (1055.2 kcal/d for the older adults versus 1214.3 kcal/d for younger adults), and men (1337.9 versus 1433 kcal/d; P = 0.001). The REE comparison categorized by decades has shown that for patients <60 y, an REE greater than those for individuals 60 to 69 y, 70 to 79 y, and ≥80 y (P < 0.001). REE in patients 60 to 69 y was greater than for those ≥80 y (P < 0.001). When compared with the Harris-Benedict formula, the REE intraclass correlation coefficient for all older patients was 0.514 (95% confidence interval [CI], 0.064-0.736); for ages 60 to 69 y it was 0.527 (95% CI, 0.126-0.733), and for ages >70 y, it was 0.466 (95% CI, -0.080 to -0.756). CONCLUSION: Measured REE in patients with cancer decreases with age. This finding is critical for appropriate caloric provision for older patients with cancer.

Prognostic value of integrin αV expression and localization pattern in invasive breast carcinomas.

Invasion of surrounding stroma is an early event in breast cancer metastatic progression, and involves loss of cell polarity, loss of myoepithelial layer, epithelial-mesenchymal transition (EMT) and remodeling of the extracellular matrix (ECM). Integrins are transmembrane receptors responsible for cell-ECM binding, which triggers signals that regulate many aspects of cell behavior and fate. Changes in the expression, localization and pairing of integrins contribute for abnormal responses found in transformed epithelia. We analyzed 345 human breast cancer samples in tissue microarrays (TMA) from cases diagnosed with invasive breast carcinoma to assess the expression and localization pattern of integrin αV and correlation with clinical parameters. Patients with lower levels of integrin αV staining showed reduced cancer specific survival. A subset of cases presented a peripheral staining of integrin αV surrounding tumor cell clusters, possibly matching the remaining myoepithelial layer. Indeed, the majority of ductal carcinoma in situ (DCIS) components found in the TMA presented integrin αV at their periphery, whereas this pattern was mostly lost in invasive components, even in the same sample. The lack of peripheral integrin αV correlated with decreased cancer specific survival. In addition, we observed that the presence of integrin αV in the stroma was an indicative of poor survival and metastatic disease. Consistently, by interrogating publicly available datasets we found that, although patients with higher mRNA levels of integrin αV had increased risk of developing metastasis, high co-expression of integrin αV and a myoepithelial cell marker (MYH11) mRNA levels correlated with better clinical outcomes. Finally, a 3D cell culture model of non-malignant and malignant cells reproduced the integrin αV pattern seen in patient samples. Taken together, our data indicate that both the expression levels of integrin αV and its tissue localization in primary tumors have prognostic value, and thus, could be used to help predict patients at higher risk of developing metastasis.

Risk factors associated with head and neck cancer in former smokers: A Brazilian multicentric study.

BACKGROUND: Reduced tobacco consumption in the population has not been associated with reduced incidence rates of head and neck cancer in several countries. OBJECTIVE: To explore the associations between HNC and sociodemographic characteristics and lifestyle of former smokers from three Brazilian cancer centers. METHODS: A multicenter case-control study was conducted with 229 former smokers diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, larynx, and 318 controls (former smokers without head and neck cancer). Bivariate and multiple logistic regression analyses were conducted to estimate odds ratios (ORs) with a 95% confidence interval (CI). RESULTS: 11-20 years after smoking cessation showed significant impact on HNC reduction (OR 0.22, 95% CI, 0.12-0.39), which reached 82% (95% CI, 0.09-0.35) among 20 + former smokers when compared to individuals who had stopped smoking for up to 5 years. A history of high-intensity smoking (>40 pack-years) increased HNC risk by 2.09 times (95% CI 1.13-3.89) when compared to subjects who smoked up to 20 pack-years. Past alcohol consumption (OR 1.99, 95% CI, 1.06-3.82) was also associated with head and neck cancer risk in former smokers when compared to no alcohol consumption. There was a decreased head and neck cancer risk in former smokers who had high school level of education (OR 0.38, 95% CI, 0.16-0.91) compared to illiterate former smokers; and former smokers with moderate intake of vegetables (OR 0.49, 95% CI, 0.28-0.85) and fruits (OR 0.43, 95% CI, 0.25-0.73) compared to those with low intake. CONCLUSION: Head and neck cancer risk in former smokers decreases after 11 years after smoking cessation, former smokers with past alcohol consumption showed an increased risk of HNC. High school level of education and moderate intake of vegetables and fruits reduced HNC risk among former smokers.

Prevalence and persistence of HPV-16 molecular variants in the anal canal of men: The HIM study.

BACKGROUND: HPV-16 causes approximately 90% of anal canal (AC) cancers worldwide. This study aimed to evaluate the prevalence and persistence of HPV-16 genetic variants in the AC of men from three different countries (Brazil, Mexico and United States) and to further identify sociodemographic and behavioral factors associated with these infections. METHODS: Participants from the multinational prospective HPV Infection in Men (HIM) Study who had at least one HPV-16 positive AC swab were included. Characterization into HPV-16 genetic variants was successfully performed by PCR-sequencing in 95.6% (217/227) samples and these were classified into HPV-16 lineages and sublineages. RESULTS: We observed higher prevalence of lineage A variants, mainly from A1 sublineage, in all countries. Non-A lineage variants were mostly detected in men from Brazil, where higher diversity of sublineage variants was detected during follow-up. Compare to men detected with Non-A HPV-16 lineage variants, men infected with lineage A reported a higher lifetime number of female sexual partners. Finally, a significantly higher prevalence of Non-A lineage variants was observed among men who have sex with men (MSM) with a transient HPV-16 AC infection (p = 0.033), but no significant differences regarding variants lineages and persistence status were observed when stratified by country, self-reported ethnicity or age. CONCLUSIONS: Our data extend previous reports which indicate that globally HPV-16 variants are unevenly distributed, and contribute further to studies of the natural history of AC HPV infections in men.

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Genetic diversity of germline variants in breast cancer (BC) predisposition genes is unexplored in miscegenated populations, such those living in Latin America. We evaluated 1663 Brazilian BC patients, who underwent hereditary multigene panel testing (20-38 cancer susceptibility genes), to determine the spectrum and prevalence of pathogenic/likely pathogenic (P/LP) variants and variants of uncertain significance (VUS). Associations between P/LP variants and BC risk were estimated in a case-control analysis of BC patients and 18,919 Brazilian reference controls (RC). In total, 335 (20.1%) participants carried germline P/LP variants: 167 (10.0%) in BRCA1/2, 122 (7.3%) in BC actionable non-BRCA genes and 47 (2.8%) in candidate genes or other cancer predisposition genes. Overall, 354 distinctive P/LP variants were identified in 23 genes. The most commonly mutated genes were: BRCA1 (27.4%), BRCA2 (20.3%), TP53 (10.5%), monoallelic MUTYH (9.9%), ATM (8.8%), CHEK2 (6.2%) and PALB2 (5.1%). The Brazilian variant TP53 R337H (c.1010G>A, p.Arg337His), detected in 1.6% of BC patients and 0.1% of RC, was strongly associated with risk of BC, OR = 17.4 (95% CI: 9.4-32.1; p < 0.0001); monoallelic MUTYH variants c.1187G>A and c.536A>G, detected in 1.2% (0.9% RC) and 0.8% (0.4% RC) of the patients, respectively, were not associated with the odds of BC, the former with OR = 1.4 (95% CI: 0.8-2.4; p = 0.29) and the latter with OR = 1.9 (95% CI: 0.9-3.9; p = 0.09). The overall VUS rate was 46.1% for the entire patient population. Concluding, the use of multigene panel testing almost doubled the identification of germline P/LP variants in clinically actionable predisposition genes in BC patients. In Brazil, special attention should be given to TP53 P/LP variants.

Oncological Surgery During the COVID-19 Pandemic: Effectiveness of Preoperative Screening and Factors Associated with Postoperative SARS-CoV-2 Infection.

BACKGROUND: Routine preoperative screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with reverse transcriptase-polymerase chain reaction (RT-PCR) may reduce in-hospital SARS-CoV-2 transmission. METHODS: This was a prospective, observational, cohort study. The endpoints were the incidence of asymptomatic patients with positive preoperative RT-PCR results and the incidence and factors associated with postoperative SARS-CoV-2 infection in patients with cancer referred for elective surgery. Patients with elective surgery between May and October 2020 were included. RT-PCR of nasopharyngeal swabs was performed preoperatively for all patients. Postoperative SARS-CoV-2 infection was assessed within 30 postoperative days. RESULTS: A total of 1636 preoperative screening RT-PCR tests were performed. Of these, 102 (6.2%) cases were positive, and 1,298 surgical procedures were analyzed. The postoperative SARS-CoV-2 infection rate was 0.9%. The length of stay (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.04-1.11; p < 0.001), surgical time (OR 1.004; 95% CI 1.001-1.008; p = 0.023), intensive care unit admission (OR 7.7; 95% CI 2.03-29.28; p = 0.003), and hospital readmissions (OR 9.56; 95% CI 2.50-36.56; p = 0.001) were associated with postoperative coronavirus disease (COVID-19). Using unadjusted and adjusted logistic regression, length of stay (OR 1.08; 95% CI 1.04-1.11; p < 0.001), and readmission (OR 9.02; 95% CI 2.30-35.48; p = 0.002) were independent factors of postoperative COVID-19. CONCLUSIONS: Screening patients preoperatively may reduce in-hospital SARS-CoV-2 transmission. Length of stay and readmission were independently correlated with postoperative COVID-19.

Survival analysis of young adults from a Brazilian cohort of non-small cell lung cancer patients.

BACKGROUND: The influence of age at diagnosis in non-small cell lung cancer (NSCLC) prognosis is unclear. OBJECTIVES: To compare in a Brazilian cohort of NSCLC patients of different age groups: 1) The overall survival; 2) Clinical features and treatment options. METHODS: This is a retrospective cohort study using a hospital-based registry, for NSCLC patients registered in years 2000-2009. Patients were grouped into three age groups: Young adults (YA: < 40 years), middle-aged (MA: 40-64 years) and elderly (E: ≥ 65 years). Kaplan-Meier was used to estimate overall survival and Cox regression for hazard ratios (HRs) and 95% confidence intervals. RESULTS: 17,422 NSCLC patients were included: 370 YA (2.1%), 8,697 MA (49.9%) and 8,355 E (48.0%). Compared with older age groups, the YA group had a higher proportion of females, patients diagnosed with adenocarcinoma and metastatic disease (63.2%). Overall survival was longer in YA in the entire cohort and in all clinical stages (CSs) (p < 0.001). For YA, higher education level was a good prognosis factor (compared with illiterate and incomplete elementary); advanced or metastatic disease (compared with early-stage disease) and treatment based in radiotherapy or chemotherapy (CT) (without surgery), compared with treatment combinations with surgery, were poor prognostic factors. Young men (but not women) had lower HR of death compared with older groups; YA had lower HR of death in all CSs compared with patients from older groups. A higher percentage of YA were treated with surgery or CT in early-stage disease compared with older groups. Besides that, YA and MA patients treated with surgery or CT had a better prognosis than elderlies. Conclusions: In this Brazilian cohort of NSCLC patients, most young individuals were diagnosed with metastatic disease. YA presented longer survival than older age groups in all CSs, but mainly in CS I/II and III, where some patients may achieve long remissions or cure.

Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs.

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients' plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development.

To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p < 0.001), PLK1 (p = 0.001), and p63 (p < 0.001) in parallel to reduced immunostaining of p40 (p < 0.001) and BCL2 (p = 0.029) was observed among the tissue segments analyzed. Our study revealed that survivin, PLK1, p63, p40 and BCL2 play a role in oral tumorigenesis and represent promising biomarkers able to recognize mesenchymal phenotype induction in the transition from nonmalignant cells to tumor cells. These results reveals critical interaction between survivin, PLK1, p63, p40 promising proteins during invasive carcinoma development.

COVID-19 outbreak in Brazil: adherence to national preventive measures and impact on people's lives, an online survey.

BACKGROUND: The first case of COVID-19 infection was diagnosed in Brazil 26th February 2020. By March 16th, physical distancing and confinement measures were implemented by the Brazilian government. Little is known about how these measures were followed up by the Brazilian people and their impact on daily routine. METHODS: In early April 2020, using an online platform, we organized an online survey among adults living in Brazil about their COVID-19 preventive behavior and impact on their daily routine. RESULTS: Data from 23,896 respondents were analyzed (mean age: 47.4 years). Due to COVID-19 restrictions, half (51.1%) of the professionals reported working from home. Regular handwashing was practiced by 98.7% of participants; 92.6% reported adhering to the 1.5-2 m physical distancing rule, but only 45.5% wore a face mask when going outside. While 29.3% of respondents found it relatively easy to stay at home, indoor confinement was extremely difficult for 7.9% of participants. Moreover, 11% of participants were extremely worried about their health during the COVID-19 epidemic. Younger people, male, persons living in a rural area/village or popular neighbourhoods, students and workers reported less preventive behaviour. CONCLUSION: Restrictive measures markedly affected the daily and professional routines of Brazilians. Participants showed a satisfactory level of adherence to national COVID-19 prevention guidelines. Qualitative and follow-up studies are needed to monitor the impact of COVID-19 in the Brazilian society.

Host feeding patterns of Nyssorhynchus darlingi (Diptera: Culicidae) in the Brazilian Amazon.

Nyssorhynchus darlingi (Root) is the dominant malaria vector in the Brazilian Amazon River basin, with additional Anophelinae Grassi species involved in local and regional transmission. Mosquito blood-feeding behavior is an essential component to define the mosquito-human contact rate and shape the transmission cycle of vector-borne diseases. However, there is little information on the host preferences and blood-feeding behavior of Anophelinae vectors in rural Amazonian landscapes. The barrier screen sampling (BSS) method was employed to sample females from 34 peridomestic habitats in 27 rural communities from 11 municipalities in the Brazilian Amazon states of Acre, Amazonas, Pará and Rondônia, from August 2015 to November 2017. Nyssorhynchus darlingi comprised 97.94% of the females collected resting on barrier screens, and DNA sequence comparison detected 9 vertebrate hosts species. The HBI index ranged from 0.03-1.00. Results revealed the plasticity of Ny. darlingi in blood-feeding on a wide range of mainly mammalian hosts. In addition, the identification of blood meal sources using silica-dried females is appropriate for studies of human malaria vectors in remote locations.

Association Between Early Admission at School and Oral Health and Nutritional Status of Children in the City of São Paulo, Brazil

ABSTRACT Objective: To investigate the possible relationship between early admission to the school of children in early childhood and oral health conditions (OH) and nutritional status (NS). Material and Methods: Cross-sectional study conducted with 140 children aged 3-4 years, selected for convenience, in 4 public schools in the city of São Paulo, Brazil, during 2016, divided into children with early (IE) and late (IL) admission at school. Comparisons between groups were performed for the presence of overweight / obesity (OW / OB), caries lesions (CL), malocclusion (MO) and dental biofilm (DB), in addition to socioeconomic and dietary data. Multiple regression analysis was applied to determine the association between age of admission at school and OH and NS. Results: Children with IE had CL = 28.1%; DB = 46.9%; MO = 54.7% and OW / OB = 25.9%. Children with IE had IL = 29.8%; DB = 35.1%; MO = 61.4% and OW / OB = 30.8%. No significant association was found between age of admission at school and CL: 1.40 (0.53-3.73) 0.490; DB: 0.51 (0.22-1.16) 0.112; MO: 1.77 (0.77-4.05) 0.173 and OW / OB: 1.27 (0.55-2.92) 0.568, [OR (95% CI) p]. Conclusion: The age of admission at school of children in early childhood did not show a significant association with OH and NS.

Ultrasonography Echotexture as a surrogate for Sialadenitis secondary to 131I Radioiodine Therapy for differentiated Thyroid Cancer: a review and metaanalysis.

To systematically review and analyze the medical literature to assess ultrasonography echotexture changes in thyroid cancer patients for the detection of chronic sialadenitis caused by radioiodine therapy. METHODS: Sources were retrieved from PubMed, Scopus, EMBASE and LILACS through November 2018. All studies that assessed ultrasonographic features before 131I administration and at 12 months after 131I administration were selected. After data extraction, statistical analysis was performed by using Stata software. RESULTS: From a total of 435 studies, 4 studies involving 665 patients were considered eligible, and echotexture heterogeneity was found with a significant difference. CONCLUSIONS: Ultrasound echotexture may detect chronic sialadenitis secondary to salivary radioiodine therapy.

Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review. / Exposição ocupacional a agrotóxicos organofosforados e neoplasias hematológicas: uma revisão sistemática.

OBJECTIVE: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. METHODOLOGY: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). CONCLUSION: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.