Increase in suicide rates in the elderly population of the state of São Paulo, Brazil: Could Alzheimer's disease be a risk factor?

OBJECTIVES: In recent years, there has been an increase in suicide rates in Brazil. From 2015 to 2019, a 34% increase in self-inflicted deaths was observed. The aim of this study was to analyse population data to determine whether some subgroups of the population, specifically the elderly population with Alzheimer's disease, are at a greater risk of suicide. STUDY DESIGN: An analysis of population data was carried out. METHODS: Population data from the state of São Paulo, Brazil, were obtained from two platforms: the Brazilian Institute of Geography and Statistics (IBGE); and the Brazilian Ministry of Health (DataSUS). Data were measured and compared in 2010 and 2022 using the two most recent censuses. RESULTS: Between 2010 and 2022, the number of registered deaths of patients with Alzheimer's increased by 21.93%. In addition, there was a 100.37% increase in suicides among the elderly population compared to a 37.78% increase in the general population. CONCLUSIONS: In recent years, there has been a notable increase in both suicides among the elderly and mortality rates attributed to Alzheimer's disease within São Paulo state, Brazil. However, it is not possible to conclude that the increase in suicide among the elderly is directly linked to Alzheimer's disease. To determine a correlation between suicide and Alzheimer's disease, further studies are required.

CO2 laser irradiation combined with fluoridated dentifrice improved its protective effect on caries lesion progression regardless of the acidulated phosphate fluoride gel application: An in situ study.

OBJECTIVE: This in situ study aimed to investigate the efficacy of CO2 laser at a 10.6-µm wavelength combined with 1.23% acidulated phosphate fluoride (APF) and fluoridated dentifrice with 1100 µg F/g (FD) to control enamel caries progression. MATERIALS AND METHODS: Sixteen volunteers wore palatal appliances containing eight demineralized enamel specimens for four 14-day phases under sucrose exposure. These specimens were submitted to CO2 laser irradiation and APF alone or combined with FD. Treatment groups were non-fluoridated dentifrice-NFD, NFD + CO2 laser, NFD + APF, NFD + CO2 laser + APF, FD, FD + CO2 laser, FD + APF, and FD + CO2 laser + APF. Mineral loss, calcium fluoride (CaF2), fluorapatite (FAp), and fluoride in the biofilm were analyzed by analysis of variance followed by the Student-Newman-Keuls test, p < 0.05. RESULTS: The highest mineral loss inhibition was noted when FD and CO2 laser irradiation were combined, which did not significantly differ from the FD + CO2 laser + APF group. The CaF2, FAp, and F in the biofilm were more pronounced when the FD and APF were combined. The CO2 laser irradiation promoted a slightly higher concentration of CaF2 in the enamel and F in the biofilm. CONCLUSION: Although APF promotes the high formation of CaF2 and FAp, the combined use of FD with CO2 laser overcomes the APF effect in inhibiting the progression of artificial caries-like lesions in situ. CLINICAL SIGNIFICANCE: Under the in situ design of this study, remineralization of white spot lesions was achieved through CO2 laser irradiation and daily use of fluoridated dentifrice. Future clinical trials are encouraged to substantiate this finding.

A benchmark for hypothalamus segmentation on T1-weighted MR images.

The hypothalamus is a small brain structure that plays essential roles in sleep regulation, body temperature control, and metabolic homeostasis. Hypothalamic structural abnormalities have been reported in neuropsychiatric disorders, such as schizophrenia, amyotrophic lateral sclerosis, and Alzheimer's disease. Although mag- netic resonance (MR) imaging is the standard examination method for evaluating this region, hypothalamic morphological landmarks are unclear, leading to subjec- tivity and high variability during manual segmentation. Due to these limitations, it is common to find contradicting results in the literature regarding hypothalamic volumetry. To the best of our knowledge, only two automated methods are available in the literature for hypothalamus segmentation, the first of which is our previous method based on U-Net. However, both methods present performance losses when predicting images from different datasets than those used in training. Therefore, this project presents a benchmark consisting of a diverse T1-weighted MR image dataset comprising 1381 subjects from IXI, CC359, OASIS, and MiLI (the latter created specifically for this benchmark). All data were provided using automatically generated hypothalamic masks and a subset containing manually annotated masks. As a baseline, a method for fully automated segmentation of the hypothalamus on T1-weighted MR images with a greater generalization ability is presented. The pro- posed method is a teacher-student-based model with two blocks: segmentation and correction, where the second corrects the imperfections of the first block. After using three datasets for training (MiLI, IXI, and CC359), the prediction performance of the model was measured on two test sets: the first was composed of data from IXI, CC359, and MiLI, achieving a Dice coefficient of 0.83; the second was from OASIS, a dataset not used for training, achieving a Dice coefficient of 0.74. The dataset, the baseline model, and all necessary codes to reproduce the experiments are available at https://github.com/MICLab-Unicamp/HypAST and https://sites.google.com/ view/calgary-campinas-dataset/hypothalamus-benchmarking. In addition, a leaderboard will be maintained with predictions for the test set submitted by anyone working on the same task.

Digital workflow to produce esthetic space maintainers for growing patients.

Digital workflows have been used to enhance the predictability of oral rehabilitations. However, techniques to digitally design and manufacture esthetic space maintainers by following a prosthetically driven treatment plan for young patients are lacking. This technique report describes a full digital workflow to produce computer-aided design and computer-aided manufacturing (CAD-CAM) esthetic space maintainers by using intraoral scans, a dental CAD software program, and a milling machine. CAD-CAM space maintainers can be provided for young patients with satisfactory patient compliance and with minimal chairside adjustment.

Effects of JL13, a pyridobenzoxazepine compound, in dopaminergic and glutamatergic models of antipsychotic activity.

The pyridobenzoxazepine compound, 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13), has been developed as a potential antipsychotic drug. We tested the hypothesis that JL13 is efficacious in both dopaminergic and glutamatergic animal models of schizophrenia. We investigated JL13 for its efficacy to prevent cocaine- and ketamine-induced hyperlocomotion and MK-801-induced deficits in prepulse inhibition (PPI) of the startle reflex. Male Swiss mice received injections of JL13 (0.1-10 mg/kg) and were tested in the open field for basal locomotion. In separate experiments, the animals received injections of JL13 (0.1-3 mg/kg) followed by cocaine (10 mg/kg), ketamine (60 mg/kg), or MK-801 (0.5 mg/kg) and were tested in the open field for hyperlocomotion. In addition, it was also tested if JL13 prevented MK-801-induced disruption of PPI. Only the highest dose of JL13 impaired spontaneous locomotion, suggesting its favorable profile regarding motor side effects. At doses that did not impair basal motor activity, JL13 prevented cocaine-, ketamine-, and MK-801-induced hyperlocomotion. Moreover, JL13 prevented MK-801-induced disruption of PPI. Extending previous findings, this study shows that JL13 exerts antipsychotic-like activity in both dopaminergic and glutamatergic models. This compound has a favorable pharmacological profile, similar to second-generation antipsychotics.

Mapping carbon and nitrogen isotopic composition of fingernails to demonstrate a rural-urban nutrition transition in the Center-West, Northeast, and Amazon regions of Brazil.

OBJECTIVE: The main objective of this study is to investigate diet patterns among rural and urban populations of the Center-West, Northeast, and Amazon regions of Brazil through the carbon and nitrogen isotopic composition of fingernails, recognizing that the extent of market integration is a key driver of food consumption. MATERIALS AND METHODS: In the Center-West, Northeast, and Amazon regions of Brazil, fingernails were sampled in clusters encompassing a major city, town, and rural village. A total of 2,133 fingernails were analyzed. Fingernails were clipped by donors using fingernail clippers. In the laboratory, samples were cleaned then weighed in small tin capsules before being isotopically analyzed for carbon and nitrogen. RESULTS: The overall mean δ13 C and δ15 N were -19.7 ± 2.8‰ and 10.6 ± 1.1‰, respectively. In the more remote villages, where access to food markets is more challenging, lower δ13 C prevails, suggesting that Brazilian staple foods (rice, beans, and farinha) still dominate. In areas with easier access to food markets, δ13 C values were higher, suggesting a change to a diet based on C4 plants, typical of a Brazilian supermarket diet. The variability among inhabitants in the same location expressed by a significant inverse correlation between δ13 C and δ15 N fingernail values suggested that "market integration" does not affect everyone equally in each community. DISCUSSION AND CONCLUSION: The nutrition transition has not yet reached some remote villages in these regions of Brazil or that the nutrition transition has not yet reached all residents of these remote villages. On the other hand, in several villages there is a considerable adherence to the supermarket diet or that some residents of these villages are already favoring processed food.

Relationship among α amylase and carbonic anhydrase VI in saliva, visible biofilm, and early childhood caries: a longitudinal study.

AIM: This longitudinal study investigated the relationship among early childhood caries (ECC), α amylase, carbonic anhydrase VI (CA VI), and the presence of visible biofilm, besides detecting if these variables could predict risk for ECC. DESIGN: One hundred children were divided into two groups: caries group (n = 45) and caries-free group (n = 55). Visible biofilm on maxillary incisors was recorded, followed by caries diagnosis in preschoolers at baseline and at follow-up. Saliva samples were collected, and activities of CA VI and α amylase were determined. Data normality was assessed by Shapiro-Wilk test and then Mann-Whitney, Spearman correlation, and chi-square tests followed by multiple logistic regression analysis (α = 0.05, 95% confidence interval). RESULTS: CA VI activity was significantly higher in saliva of children with caries (P ≤ 0.05), and α amylase activity was significantly higher in saliva of caries-free children (P < 0.0001). Children with α amylase activity in saliva lower than 122.8 U/mL (OR = 3.33 P = 0.042) and visible biofilm on maxillary incisors (OR = 3.6 P = 0.009) were more likely to develop ECC than caries-free children. A negative correlation between caries and α amylase activity was found (P = 0.0008). CONCLUSIONS: The presence of visible biofilm and low salivary activity of α amylase may be considered risk predictors for ECC.

Influence of salivary parameters in the caries development in orthodontic patients-an observational clinical study.

BACKGROUND: Previous studies have shown during the orthodontic treatment, the prevalence of active caries lesions (ACL) in 30 to 70% of patients. AIM: To evaluate the effect of orthodontic treatment on salivary properties considering caries development. DESIGN: Twenty two individuals (11-22 years) were assessed regarding caries, oral hygiene, sugar exposure, salivary flow rate (SFR), buffering capacity, pH, carbonic anhydrase VI (CA VI) and amylase activity, at baseline, 1, 3 and 6 months after the orthodontic appliances placement. Caries index was determined by Nyvad criteria. CA VI and amylase activities were performed by zymography and ELISA, respectively. RESULTS: Buffering capacity decreased after 3 months (P < 0.0001) and showed positive correlation with pH at baseline and after 1 month in individuals who did not develop active caries lesions. Amylase activity decreased after 1 and 6 months (P = 0.0003) and presented positive correlation with CA VI in patients who developed ACL. SFR increased after 1 month (P = 0.0283) and showed positive correlation with CA VI activity after 3 months in individuals who did not develop ACL. Salivary pH showed negative correlation with CA VI after 1 month in patients who did not develop ACL. ACL were firstly diagnosed after 3 months. CONCLUSIONS: The present study demonstrated that saliva of individuals under orthodontic treatment is subjected to changes in properties that have implications on the onset of ACL.

CO2 laser irradiation enhances CaF2 formation and inhibits lesion progression on demineralized dental enamel-in vitro study.

This study evaluated if Carbon dioxide (CO2) (λ 10.6 µm) laser irradiation combined with acidulated phosphate fluoride gel application (APF gel) enhances "CaF2" uptake by demineralized enamel specimens (DES) and inhibits enamel lesion progression. Thus, two studies were conducted and DES were subjected to APF gel combined or not with CO2 laser irradiation (11.3 or 20.0 J/cm(2), 0.4 or 0.7 W) performed before, during, or after APF gel application. In study 1, 165 DES were allocated to 11 groups. Fluoride as "CaF2 like material" formed on enamel was determined in 100 DES (n = 10/group), and the surface morphologies of 50 specimens were evaluated by scanning electron microscopy (SEM) before and after "CaF2" extraction. In study 2, 165 DES (11 groups, n = 15), subjected to the same treatments as in study 1, were further subjected to a pH-cycling model to simulate a high cariogenic challenge. The progression of demineralization in DES was evaluated by cross-sectional microhardness and polarized light microscopy analyses. Laser at 11.3 J/cm(2) applied during APF gel application increased "CaF2" uptake on enamel surface. Laser irradiation and APF gel alone arrested the lesion progression compared with the control (p < 0.05). Areas of melting, fusion, and cracks were observed. CO2 laser irradiation, combined with a single APF application enhanced "CaF2" uptake on enamel surface and a synergistic effect was found. However, regarding the inhibition of caries lesion progression, no synergistic effect could be demonstrated. In conclusion, the results have shown that irradiation with specific laser parameters significantly enhanced CaF2 uptake by demineralized enamel and inhibited lesion progression.

Food Insecurity in Urban and Rural Areas in Central Brazil: Transition from Locally Produced Foods to Processed Items.

Aiming to investigate the effect of diet and food consumption with regard to health, environment, and economy in light of nutrition ecology, we studied the dimensions of nutrition and food security in urban and rural settings in the region of Chapada dos Veadeiros, Central Brazil. We tracked diet and food consumption through carbon and nitrogen stable isotope ratios in fingernails of these inhabitants together with food intake data as a proxy for their diet patterns. We estimated household food insecurity by using the Brazilian Food Insecurity Scale. Nutrition and food insecurity was observed in both urban and rural areas, but was accentuated in rural settings. The diet pattern had high δ(13)C values in fingernails and low δ(15)N. Both urban and rural areas have diets with low diversity and relying on low-quality processed food staples at the same time that nutrition and food insecurity is quite high in the region.

Neuroinflammation as a possible link between cannabinoids and addiction.

OBJECTIVE: Substance dependence disorder is a chronically relapsing condition characterised by neurobiological changes leading to loss of control in restricting a substance intake, compulsion and withdrawal syndrome. In the past few years, (endo)cannabinoids have been raised as a possible target in the aetiology of drug addiction. On the other hand, although the exact mechanisms of the genesis of addiction remain poorly understood, it is possible that neuroinflammation might also play a role in the pathophysiology of this condition. Studies demonstrated that (endo)cannabinoids act as immunomodulators by inhibiting cytokines production and microglial cell activation. Thus, in the present review, we explore the possible role of neuroinflammation on the therapeutic effects of cannabinoids on drug addiction. METHODS: We conducted an evidence-based review of the literature in order to assess the role of cannabinoids on the neuroinflammatory hypothesis of addiction (terms: addiction, cannabinoids and inflammation). We searched PubMed and BioMedCentral databases up to April 2014 with no date restrictions. RESULTS: In all, 165 eligible articles were included in the present review. Existing evidence suggests that disruption in cannabinoid signalling during the drug addiction process leads to microglial activation and neuroinflammation. CONCLUSION: The literature showed that inflammation and changes in endocannabinod signalling occur in drug abuse; however, it remains uncertain whether these changes are causally or coincidentally associated with addiction. Additional studies, therefore, are needed to elucidate the contribution of neuroinflammation on the behavioural and neuroprotective effects of cannabinoids on drug addiction.

Alzheimer's Disease and Suicide: An Integrative Literature Review.

INTRODUCTION: Suicide has been described in patients with Alzheimer's disease. Some promising medications for treating Alzheimer's disease have had their studies suspended because they increase the risk of suicide. Understanding the correlations between suicide and Alzheimer's disease is essential in an aging world. METHODS: A search was carried out on electronic websites (PubMed and Scielo) using the MeSH Terms "suicide" and "Alzheimer" (1986-2023). Of a total of 115 articles, 26 were included in this review. RESULTS: Depression and the allele ε4 of Apolipoprotein (APOE4) were demonstrated to be the main risk factors for suicide in patients with Alzheimer's disease. CONCLUSION: Adequately delineating which elderly people are vulnerable to suicide is important so that new treatments for Alzheimer's disease can be successful. This review showed a need for new studies to investigate the interface between Alzheimer's disease and suicide.

Association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from the 2010/2011 BRISA birth cohort.

OBJECTIVE: To study the association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from a birth cohort. METHOD: This was a secondary cross-sectional analysis of data obtained in a cohort study (Brazilian RibeirãoPreto and São Luís Birth Cohort Studies - BRISA), whose deliveries were performed between 2010 and 2011. Standardized questionnaires were applied to mothers, and placentas and newborns were evaluated shortly after delivery. Placental efficiency was assessed using the ratio between birth weight and placental weight (BW/PW ratio); values below the lower quartile (25th percentile for gestational age) were considered to have low placental efficiency. Newborn phenotypes were small and large for gestational age, stunted and wasted, evaluated using the INTERGROWTH-21 growth standard. To identify the confounding variables theoretical model was constructed using Directed Acyclic Graphs, and unadjusted and adjusted logistic regression were performed. Placental measurements were obtained blindly from pregnancy and delivery data. RESULTS: 723 mother-placenta-child triads were studied. 3.2 % of newborns were small-for-gestational-age (SGA), 6.5 %large-for-gestational-age (LGA), 5.7 %had stunting, and 0.27 % wasting. A significantly higher risk was found between low placental efficiency and SGA (OR 2.82;95 % CI 1.05-7.57), stunting (OR 2.23; 95 % CI 1.07-4.65), and wasting (OR 8.22; 95 % CI 1.96-34.37). No relationship was found between LGA and placental efficiency. CONCLUSIONS: Low placental efficiency was associated with increased risk for small-for-gestational-age, stunting, and wasting. Placental morphometry can provide valuable information on intrauterine conditions and neonatal health, helping to identify newborns at higher risk of future comorbidities.

High-resolution segmentations of the hypothalamus and its subregions for training of segmentation models.

Segmentation of brain structures on magnetic resonance imaging (MRI) is a highly relevant neuroimaging topic, as it is a prerequisite for different analyses such as volumetry or shape analysis. Automated segmentation facilitates the study of brain structures in larger cohorts when compared with manual segmentation, which is time-consuming. However, the development of most automated methods relies on large and manually annotated datasets, which limits the generalizability of these methods. Recently, new techniques using synthetic images have emerged, reducing the need for manual annotation. Here we provide a dataset composed of label maps built from publicly available ultra-high resolution ex vivo MRI from 10 whole hemispheres, which can be used to develop segmentation methods using synthetic data. The label maps are obtained with a combination of manual labels for the hypothalamic regions and automated segmentations for the rest of the brain, and mirrored to simulate entire brains. We also provide the pre-processed ex vivo scans, as this dataset can support future projects to include other structures after these are manually segmented.

Injury prevention in Brazilian women's football: Perceptions of physiotherapists and practices within elite clubs.

OBJECTIVES: To describe the perceptions of physiotherapists and the injury prevention practices implemented within elite women's football clubs in Brazil. DESIGN: Cross-sectional study. SETTING: Online survey. PARTICIPANTS: Head physiotherapists from 32 Brazilian elite clubs. MAIN OUTCOME MEASURES: Structured questionnaire. RESULTS: Physiotherapists identified ACL rupture as the primary target for prevention. The top-five perceived injury risk factors included 'early return to sport after injury', 'workload too high', 'previous injury', 'poor sleep/rest', and 'muscle strength/power deficit'. 'Adoption of return to sport criteria' was almost unanimously recognized as a very important preventive strategy. 'Poor infrastructure' was elected as the main barrier to implementing prevention programs. From a practical standpoint, at least two-third of clubs implemented multi-component exercise interventions for injury prevention. These interventions typically encompassed flexibility/mobility, balance/proprioception, lumbo-pelvic stability, and agility exercises, alongside exposure to sprinting. Strength training routines typically included traditional, functional, and eccentric exercises. Most teams also employed other prevention strategies, including adoption of return to sport criteria, internal workload monitoring, post-exercise recovery modalities, preseason risk factor screening, and application of rigid strapping tapes. CONCLUSIONS: This study provided unprecedented insights into the physiotherapists' perceptions and injury prevention practices implemented within elite women's football clubs.

A novel weight-drop closed head focal traumatic brain injury: A candidate to translational studies?

Traumatic brain injury (TBI) is a neurotrauma with a complex pathophysiology caused by an external mechanical force. This global public health problem is a leading cause of death and disability in young adults. In this scenario, many models were developed to try to simulate human TBI. The weight drop model allows the investigation of the pathophysiological cascades of TBI without surgical interference. In this protocol, a new closed-head weight-drop rat model consisting of a 48.5g weight projectile that free falls from 1.10m high onto the skull of the animals was built. We classify the present TBI model performed as moderately severe due to its mortality rate. Animals from TBI and Control (Sham) groups underwent weight for 7 days and temperature assessments within 1 hour after TBI and for 7 days. Results demonstrated that the TBI group showed less body weight gain in the days after the injury. Temperature oscillations within the first-hour post-injury and on the 3rd day after injury were observed. As the results of this study demonstrated similarity to human TBI vital parameters, this new adaptation of the Weight-drop model injury can be a suitable candidate for translational studies.•We developed a novel closed head focal traumatic brain injury using a projectile.•This TBI model does not require surgical intervention.•The validation of this method demonstrates that the vital parameters of the injured rats exhibit similarities with those of TBI patients.

Cardiovascular and kidney diseases are positively associated with neuroinflammation and reduced brain-derived neurotrophic factor in patients with severe COVID-19.

Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms are described in many patients. However, the connection between the neuroimmune profile and the lung's inflammatory condition during COVID-19 and its association with the neurological symptoms reported by COVID-19 patients still needs further exploration. The present study characterizes the SARS-CoV-2 infectivity profile in postmortem nervous and lung tissue samples of patients who died due to severe COVID-19, and the pro-inflammatory factors present in both nervous and lung tissue samples, via a proteomic profiling array. Additionally, Brain-Derived Neurotrophic Factor (BDNF) levels and intracellular pathways related to neuroplasticity/neuroprotection were assessed in the samples. Out of the 16 samples analyzed, all samples but 1 were positive for the viral genome (genes E or N2, but only 3.9% presented E and N2) in the olfactory brain pathway. The E or N2 gene were also detected in all lung samples, with 43.7% of the samples being positive for the E and N2 genes. In the E/N2 positive brain samples, the Spike protein of SARS-CoV-2 co-localized with TUJ-1+ (neuron-specific class III beta-tubulin) and GFAP+ (glial fibrillary acidic protein) astrocytes. IL-6, but not IL-10, expression was markedly higher in most nervous tissue samples compared to the lung specimens. While intracellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF), and plasminogen activator inhibitor 1 (PAI-1) were increased in lung samples from SARS-Cov-2 patients, only MIF and IL-18 were detected in nervous tissue samples. Correlation analysis suggested that high levels of IL-6 are followed by increased levels of IL-10 in the brain, but not in lung samples. Our analysis also demonstrated that the presence of comorbidities, such as cardiovascular disease, hypertension, and hypothyroidism, is associated with neuroinflammation, while chronic kidney conditions predict the presence of neurological symptoms, which correlate with lower levels of BDNF in the brain samples. Our results corroborate the hypothesis that a pro-inflammatory state might further impair neural homeostasis and induce brain abnormalities found in COVID-19 patients.

Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.

About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were unresponsive to the antidepressant-like effects induced by the tricyclic antidepressant imipramine and the selective serotonin reuptake inhibitor fluoxetine. However, acute pharmacological inhibition of PI3Kγ did not block the antidepressant-like effect of ketamine, showing that a chronic deficiency of the PI3Kγ-mediated pathway is necessary for the effects of classic doses of ketamine and antidepressants. Therefore, we propose that PI3Kγ participates in the antidepressant activity and is likely implicated in the neurobiology and phenotype observed in patients with MDD who demonstrate treatment resistance.

Prevalence of germline variants in Brazilian pancreatic carcinoma patients.

We evaluated the prevalence of pathogenic/likely pathogenic germline variants (PGV) in Brazilian pancreatic adenocarcinoma (PC) patients, that represent a multiethnic population, in a cross-sectional study. We included 192 PC patients unselected for family history of cancer. We evaluated a panel of 113 cancer genes, through genomic DNA sequencing and 46 ancestry-informative markers, through multiplex PCR. The median age was 61 years; 63.5% of the patients presented disease clinical stages III or IV; 8.3% reported personal history of cancer; 4.7% and 16.1% reported first-degree relatives with PC or breast and/or prostate cancer, respectively. Although the main ancestry was European, there was considerable genetic composition admixture. Twelve patients (6.25%) were PGV carriers in PC predisposition genes (ATM, BRCA1, BRCA2, CDKN2A, MSH2, PALB2) and another 25 (13.0%) were PGV carriers in genes with a limited association or not previously associated with PC (ACD, BLM, BRIP1, CHEK2, ERCC4, FANCA, FANCE, FANCM, GALNT12, MITF, MRE11, MUTYH, POLE, RAD51B, RAD51C, RECQL4, SDHA, TERF2IP). The most frequently affected genes were CHEK2, ATM and FANC. In tumor samples from PGV carriers in ACD, BRIP1, MRE11, POLE, SDHA, TERF2IP, which were examined through exome sequencing, the main single base substitutions (SBS) mutational signature was SBS1+5+18, probably associated with age, tobacco smoking and reactive oxygen species. SBS3 associated with homologous repair deficiency was also represented, but on a lower scale. There was no difference in the frequency of PGV carriers between: (a) patients with or without first-degree relatives with cancer; and (b) patients with admixed ancestry versus those with predominantly European ancestry. Furthermore, there was no difference in overall survival between PGV carriers and non-carriers. Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.

Development and validation of a questionnaire to measure association factors with suicide: An instrument for a populational survey.

Background and Aims: Our goal was to develop an online questionnaire to survey the prevalence of suicidal behavior. Methods: We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test-rest. Results: The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got Kaiser-Meyer-Olkin = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates root mean square error of approximation = 0.000 and comparative fit index = 1.000. The test-retest had an intraclass correlated coefficient of 0.98. Conclusion: The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors during the pandemic time. Patient or Public Contribution: The general population of Marília voluntarily responded to the questionnaire, as well as patients from the principal investigator's office.