Coping with the experience of frustration throughout life: Sex- and age-specific effects of early life stress on the susceptibility to reward devaluation.

Early life stress may lead to lifelong impairments in psychophysiological functions, including emotional and reward systems. Unpredicted decrease in reward magnitude generates a negative emotional state (frustration) that may be involved with susceptibility to psychiatric disorders. We evaluated in adolescents and adult rats of both sexes whether maternal separation (MS) alters the ability to cope with an unexpected reduction of reward later in life. Litters of Wistar rats were divided into controls (non handled - NH) or subjected to MS. Animals were trained to find sugary cereal pellets; later the amount was reduced. Increased latency to reach the reward-associated area indicates higher inability to regulate frustration. The dorsal hippocampus (dHC) and basolateral amygdala (BLA) were evaluated for protein levels of NMDA receptor subunits (GluN2A/GluN2B), synaptophysin, PSD95, SNAP-25 and CRF1. We found that adult MS males had greater vulnerability to reward reduction, together with decreased GluN2A and increased GluN2B immunocontent in the dHC. MS females and adolescents did not differ from controls. We concluded that MS enhances the response to frustration in males. The change in the ratio of GluN2A and GluN2B subunits in dHC could be related to a stronger, more difficult to update, memory of the aversive experience.

Cytokine levels in the gingival crevicular fluid and their association with periodontal status of down syndrome patients: a cross-sectional study.

OBJECTIVE: To evaluate cytokine levels of interleukin (IL)-1ß, IL-4, IL-6, IL-17a, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the gingival crevicular fluid (GCF) of periodontal sites in individuals with Down syndrome (DS) and analyze their relationship with clinical periodontal parameters. MATERIALS AND METHODS: A cross-sectional study was conducted with 49 DS patients and 32 individuals without DS (non-DS group). Periodontal probing depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and visible plaque index (VPI) were evaluated. The periodontal sites were classified as shallow, moderate, and deep. GCF was collected in all shallow sites and, when present, in moderate and deep sites for the analysis of cytokine levels. The cytokines, IL-1ß, IL-4, IL-6, IL-17a, TNF-α, and IFN-γ, were quantified using the Luminex® automatic analyzer system. RESULTS: The DS group presented greater severity of periodontitis compared to the non-DS group (P = 0.005). The DS group showed a significant direct correlation of IL-1ß and an inverse correlation of IFN-γ and IL-14 with all periodontal variables. In the analysis stratified by periodontal pocket depth, we observed a higher level of IFN-γ, IL-17a, IL-1ß, and IL-6 in the shallow sites, and IL-17a, IL-1ß, and IL-6 in deep pockets of DS group individuals. Multivariate models showed that higher levels of IL-1ß, IL-4, IL-6, and IL-17a were associated with Down syndrome even after adjusting for periodontal status, sex, and age. CONCLUSION: The findings suggest that people with DS have greater periodontal impairment and higher levels of cytokines in GCF, even in sites having clinical periodontal parameters similar to those of individuals without DS. These data reiterate the concept of an altered and less effective immune response in the population with DS in the face of a periodontal microbial challenge. CLINICAL RELEVANCE: Elevated periodontal inflammation burden can be observed with higher cytokine levels in the gingival crevicular fluid of people with Down syndrome, especially IL-1, IL-4, IL-6, and IL-17, regardless of the stage of periodontitis.

Translation and Cross-Cultural Adaptation of the LYMPH-ICF Instrument for Lymphedema into Portuguese/Brazil.

OBJECTIVE: The aim of this study is to cross-culturally adapt the Lymphoedema Functioning, Disability and Health Questionnaire Lymphoedema (LYMPH-ICF) instrument into Brazilian Portuguese and conduct a pilot application (n = 10), without psychometric pretensions. METHOD: Methodological research was conducted, following the steps of translation, synthesis, back-translation, and evaluation by the expert committee. Two translators, two back-translators, and twelve professionals participated in the expert committee. A pretest was carried out with 10 patients with secondary lymphedema due to breast cancer. The degree of agreement was determined by the content validity coefficient. RESULTS: It was necessary to modify 8 out of the 29 questions comprising the questionnaire, which exhibited idiomatic disagreement. However, despite these changes, there were no indications of impairments, as content reliability was achieved through a validity coefficient of 0.90. FINAL CONSIDERATIONS: The instrument was successfully translated and cross-culturally adapted for Brazil with a high level of agreement.

Adenosine A2A and dopamine D2 receptor interaction controls fatigue resistance.

Introduction: Caffeine and the selective A2A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A2A receptors and dopamine D2 receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. Methods: We employed DPCPX and SCH58261 to antagonize A1 and A2A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D2 receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. Results and discussion: The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A2A receptors in the control of central fatigue but suggest that the D2 receptor-mediated control of the ergogenic effects of caffeine and of A2A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.

Carcinogenic Risk from Lead and Cadmium Contaminating Cow Milk and Soya Beverage Brands Available in the Portuguese Market.

Our previous work demonstrated the presence of lead (Pb) and cadmium (Cd) contamination in cow milk (CM) and soy beverages (SBs) in Portugal. These metals share carcinogenic mechanisms, suggesting at least additive effects. Our goals were to assess carcinogenic risks from Pb and Cd intake detected in various CM and SB brands on the Portuguese market and to determine the relative contributions of Pb and Cd. Furthermore, we modeled different consumption scenarios for various age/body weight groups to estimate cumulative Excess Lifetime Carcinogenic Risk (ELCR). ELCR was computed by multiplying chronic daily intake by a cancer slope factor for each metal, with an ELCR > 1 × 10-4 indicating carcinogenic risk. Five CM and three SB brands posed cancer risks in children, with the highest values at 1.75 × 10-4 and 9.12 × 10-5, respectively; Pb had mean relative contributions of 87.8 ± 3.1% in CM and 54.9 ± 12.1% in SB. Carcinogenic risks were observed for children, adolescents, and adults in several CM or SB consumption scenarios, albeit at levels above typical Portuguese intakes. Strict monitoring of metal levels, such as Pb and Cd, is advised because CM is a component of many foods, including baby food.

Too Much Dentistry.

This Viewpoint explores whether all dental procedures are clinically necessary given their expense and the disparate access to treatment among some socioeconomic and racial and ethnic groups.

Prophylactic use of standardized extract of propolis of Apis mellifera (EPP-AF®) reduces lung inflammation and improves survival in experimental lethal sepsis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

High certainty evidence is stable and trustworthy, whereas evidence of moderate or lower certainty may be equally prone to being unstable.

OBJECTIVES: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available. METHODS: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSION: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

Biochemical profile and oocyte quality of primiparous Bos indicus cows submitted to a timed artificial insemination protocol.

The objective of this study was to verify the causes of the lower response of primiparous Bos indicus cows to the ovulation synchronization protocol. Two experiments were performed to evaluate the biochemical profile, oocyte and follicular cell quality (Experiment 1) and pregnancy (Experiment 2). In Experiment 1, suckled primiparous (n = 24) and multiparous cows (n = 24) were submitted to ovum pick up (OPU). On Day 0 (D0), all cows received 2 mg of estradiol benzoate (EB) and an intravaginal progesterone insert (P4). Five days (D5) after the first hormonal administration (EB + P4), all follicles larger than 3 mm were counted on each ovary, and ovum pick-up (OPU) was performed. On day 12 (D12), the intravaginal progesterone insert was removed, and measurement and aspiration of the largest follicle were performed. Blood samples were collected on D5 and D12 to evaluate the concentrations of glucose, cholesterol, NEFA, IGF-1 and insulin. In Experiment 2, suckled primiparous (n = 50) and multiparous (n = 50) cows were subjected to an ovulation synchronization protocol based on E2/P4 (D0: 2 mg EB plus P4 intravaginal insert; D8: 500 µg of cloprostenol, 1 mg cypionate estradiol and 300UI of eCG; D10: artificial insemination). In addition, blood samples were collected on D10 for evaluation of the same hormones and metabolites described in Experiment 1. In all studies, calves remained with the cows during the experimental period. In experiment 1, the number of oocytes grade 1 (P = 0.83), grade 2 (P = 0.23) and grade 3 (P = 0.51), total number of retrieved oocytes (P = 0.14), oocyte quality index (P = 0.93) and total viable oocytes (P = 0.38) did not differ between primiparous and multiparous cows. The number of follicles at the time of follicular aspiration (20.7 ± 1.5 vs. 18.0 ± 1.9; P = 0.05) and the diameter of the largest follicle on D12 (13.5 ± 0.6 vs. 11.4 ± 0.6; P = 0.04) were greater in multiparous cows, and the number of degenerated oocytes was greater in primiparous cows (1.9 ± 0.7 vs. 1.2 ± 0.3; P = 0.05). On D5, the concentrations of IGF-1 (P = 0.47), insulin (P = 0.08), total cholesterol (P = 0.47), NEFA (P = 0.77) and glucose (P = 0.55) in the blood and IGF-1 (P = 0.97) and insulin (P = 0.11) in the follicular fluid did not differ between parity groups. On D12, there was no difference in the concentrations of IGF-1 (P = 0.26), total cholesterol (P = 0.32), NEFAs (P = 0.31) and glucose (P = 0.93) in the blood between primiparous and multiparous cows, however, the serum insulin concentration (P = 0.04) was higher in primiparous cows. There was no correlation between serum and follicular fluid insulin concentrations (r = 0.17; P = 0.31), however, there was a low correlation between serum and follicular fluid IGF-1 concentrations (r = 0.47; P = 0.002). Quantification of transcripts did not differ between parity groups. In experiment 2, concentrations of NEFA (P = 0.12) and insulin (P = 0.16) in the blood and P/AI (P = 0.93) did not differ between parity [60 % (30/50) primiparous vs. 60 % (30/50) multiparous]. In contrast, blood concentrations of IGF-1 (P = 0.0001), total cholesterol (P = 0.005) and glucose (P = 0.01) were greater in primiparous cows. It was concluded that the oocyte quality and expression of the genes evaluated in the granulosa cells were not different between primiparous and multiparous cows. Unexpectedly, the pregnancy rate did not differ between parity. Nevertheless, the blood concentrations of IGF-1, total cholesterol and glucose were greater in primiparous cows.

Water Resistance Therapy in Individuals with Parkinson's Disease: A Session-by-Session Analysis of the Vocal Quality.

OBJECTIVES: Verify session-by-session effects of the water resistance therapy (WRT) on the vocal quality of individuals with Parkinson's disease (PD). METHODS: This is a retrospective analytical study. Then, the samples were acquired from a database composed of 10 men aged between 50 and 90 years old diagnosed with PD. The participants underwent WRT with a resonance tube; then, they were guided to perform the following phonatory tasks: comfortable pitch and loudness, high pitch, low pitch, ascending and descending glissandos, and sentence uttering. Furthermore, tube depth ranged from 2 cm to 9 cm. Finally, WRT was implemented twice per week, totaling eight sessions, each lasting 45 minutes. Participants were assessed before and after each therapy session. Hence, the data were assessed with spectrographic analysis, vocal intensity, cepstral peak prominence-smoothed, alpha ratio, L1-L0, oscillatory frequency, and auditory-perceptual assessment of overall degree, roughness, breathiness, and instability. One-way repeated measures analysis of variance and Friedman tests were applied (P < 0.05). Furthermore, Holm-Sidak and Tukey tests were used as posthoc tests. RESULTS: After the sixth session, the spectrographic analysis revealed that the tracing color intensity of medium frequencies darkened, whereas a better result could be observed after the eighth session. Regarding vocal intensity, the improvement could be observed from the third session. Additionally, L1-L0 followed the same results. The overall degree auditory-perceptual assessment revealed the best results only after the second, third, and fourth sessions; however, after the eighth session, the instability increased. CONCLUSIONS: WRT allowed better results from the third session, with some improvements in the sixth session. However, the instability increased after the eighth session; thus, it is important to review the phonatory tasks and session numbers to avoid an overload in the phonatory system.

Risk of bias and methodological critical appraisal in systematic reviews of non- and micro-invasive caries management for primary and permanent teeth.

INTRODUCTION: Paediatric dentistry should rely on evidence-based clinical decisions supported by high-quality, unbiased systematic reviews (SRs). Therefore, the purpose of this study was to systematically evaluate the methodological quality and risk of bias of SRs focused on non- and micro-invasive treatment for caries lesions in primary and permanent teeth. METHODS: A comprehensive search was conducted in multiple databases, including MEDLINE/PubMed, Scopus, Web of Science, EMBASE, Epistemonikos, and ProQuest, up to March 2023 to identify relevant systematic reviews (SRs) focused on non- and micro-invasive caries treatment. Two independent reviewers extracted data from the included SRs and assessed the methodological quality and risk of bias using the AMSTAR 2 and ROBIS tools, respectively. RESULTS: A total of 39 SRs were included in the analysis. Among these, 27 SRs (69.2%) were assessed as having critically low methodological quality, 11 SRs (28.2%) were considered to have low methodological quality and only one SR was rated as high-quality. The primary concern identified was the absence of protocol registration before the commencing the study, observed in 33 SR when using the AMSTAR 2 tool. According to the ROBIS tool, 21 studies (53.8%) were categorised as low risk of bias, 10 (25.6%) as high risk and eight (20.5%) as unclear risk of bias. CONCLUSION: Our analysis revealed that SRs focused on non- and micro-invasive treatment for caries in children and adolescents had critically low methodological quality according to the AMSTAR 2 tool but demonstrated a low risk of bias based on the ROBIS tool. These findings highlight the importance of emphasizing prospective protocol registration, clear reporting of statistical analyses, and addressing potential bias implications within this topic. By addressing these issues, we can enhance the quality of SRs and ensure that clinical decisions rely on unbiased and trustworthy evidence. Registry DOI: 10.17605/OSF.IO/AR4MS.

How different attributes are weighted in professionals' decision-making in Pediatric Dentistry-a protocol for guiding discrete choice experiment focused on shortening the evidence-based practice implementation for dental care.

BACKGROUND: Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that. METHODS: This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals' perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice. DISCUSSION: Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals' decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals. TRIAL REGISTRATION: https://osf.io/bhncv .

Hospitalizations for coronavirus disease 2019: an analysis of the occurrence waves.

The pandemic has been characterized by several waves defined by viral strains responsible for the predominance of infections. We aimed to analyze the mean length of hospital stay for patients with COVID-19 during the first three waves of the pandemic and its distribution according to sociodemographic and clinical variables. This retrospective study used the notifications of patients hospitalized for COVID-19 in a Brazilian state during the period of the three waves of the disease as the data source. There were 13,910 hospitalizations for confirmed COVID-19 cases. The first wave was the longest, with 4101 (29.5%) hospitalizations, while the third, although shorter, had a higher number of hospitalized patients (N = 6960). The average length of stay in the hospital in all waves was associated with age groups up to 60 years old., elementary, high school and higher education, residents of the periurban area Regarding the presence of comorbidities, there was a statistically significant difference in the mean number of days of hospitalization among patients with chronic cardiovascular disease and obesity (P < 0.001). In conclusion, the COVID-19 pandemic has been distinctly revealed among the waves.

Association of Alcohol Consumption with Cognition and Functionality in Older Adults Aged 75+ Years: The Pietà Study.

The relationship between alcohol consumption and cognition is still controversial. This is a cross-sectional population-based study conducted in Caeté (MG), Brazil, where 602 individuals aged 75+ years, 63.6% female, and with a mean education of 2.68 years, were submitted to thorough clinical assessments and categorized according to the number of alcoholic beverages consumed weekly. The prevalence rates of previous and current alcohol consumption were 34.6% and 12.3%, respectively. No association emerged between cognitive diagnoses and current/previous alcohol consumption categories. Considering current alcohol intake as a dichotomous variable, the absence of alcohol consumption was associated with dementia (OR = 2.34; 95%CI: 1.39-3.90) and worse functionality (p = 0.001). Previous consumption of cachaça (sugar cane liquor) increased the risk of dementia by 2.52 (95%CI: 1.25-5.04). The association between the consumption of cachaça and dementia diagnosis has not been described before.

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease.

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

X-linked congenital adrenal hypoplasia: Report of long clinical follow-up and description of a new complex variant in the NR0B1 gene.

Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.

Prevalence, incidence, risk factors and residual risk associated with viral infections among eligible Brazilian blood donors.

Knowledge regarding the profile of eligible blood donors presenting positive results in laboratory screening is essential for reducing transfusion-transmitted human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Our study aimed to evaluate the prevalence, incidence, predictor variables and residual risk (RR) of HIV/HBV/HCV in blood bags donated in Minas Gerais, Brazil. This study analysed data retrieved from the records of a large blood bank relating to donations collected at multiple centres within the period 2012-2018, during which 1 991 120 blood bags were screened using immunoassays and nucleic acid tests (NATs). Multilevel modelling was used to investigate the association between sex, civil status and age group with HIV/HBV/HCV. RR was estimated from the incidence values (restricted to negative and positive tests within the study period) and window periods for infections. The prevalence in first time donors, incidence and RR of HCV (223.73 cases per 100 000; 54.84 per 100 000 persons-year and 1.6527 per 100 000, respectively) were higher than those of HIV (172.65 cases per 100 000; 28.25 per 100 000 persons-year and 0.8514 per 100 000) and HBV (168.17 cases per 100 000; 18.54 per 100 000 persons-year and 0.5588 per 100 000). The odds of acquiring infection were greater in male, single and older donors. Sixteen donors were identified as seronegative and NATs+ during the 7-year span of the study. Our study has clarified some spatiotemporal trends regarding HIV/HBV/HCV infections in donated blood in Brazil. The results will contribute to the formulation of directives addressed to high-risk donors.

Microbiome reveals inflammatory-related bacteria and putative functional pathways involved in human papillomavirus-associated penile squamous cell carcinoma.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare disease that is more prevalent in developing countries, such as Brazil, and is linked to poor genital hygiene, which promotes the proliferation of microorganisms. Dysbiosis has an effect on the local immune response, increases the risk of viral infection, and can generate inflammatory processes. Current knowledge of the microbiota found in penile tissues is limited, and the bacterial diversity of the PSCC remains unknown. In this investigation, the microbiota associated with penile cancer and its potential role in tumor development and progression were identified. METHODS: The 16S rRNA gene was analyzed by next-generation sequencing in 19 tumors and their respective non-tumor adjacent tissues to perform taxonomic classification, analysis of core microbiome, abundance, and diversity of amplicon sequence variants (ASVs) (QIIME2 v.2020.2), and in silico functional prediction (PICRUST2, p < 0.05). RESULTS: In both tissues, the phyla Proteobacteria and Firmicutes, and genera Alcaligenes and Fusobaterium, were the most prevalent. Tumors presented a greater relative abundance of Fusobacteriota, Campilobacteria, and Fusobacterium (p = 0.04, p = 0.04, and p = 0.039, respectively). In addition, the beta diversity analysis revealed a tendency for the formation of two distinct groups when only advanced tumors (pT2 and pT3) were considered. Further, the functional analysis identified the top 35 pathways, and 79.5% of PSCC samples contained pro-inflammatory microorganisms. CONCLUSION: We describe the first microbiome of penile carcinoma, which revealed an abundant and diverse microbiota as well as inflammatory-related taxa (the phyla Proteobacteria and Firmicutes, the genera Fusobacterium and Prevotella, and the species Finegoldia magma and Pseudomonas geniculata) and molecular pathways (chitin derivates degradation, the protocatechuic acid pathway, inositol metabolism, and the sucrose pathway), which have also been linked to inflammation and carcinogenesis. Moreover, we found specific and abundant ASVs in both tumor and non-tumor tissues. Our data encourage further study to better understand the role of these microorganisms in penile carcinogenesis, offering an opportunity for advances in diagnosis, prognosis, and early therapy.

Health professionals' recommendations on the use of fluoride varnish for caries prevention in preschool children.

BACKGROUND: Fluoride varnish (FV) is widely recommended for caries prevention in preschool children, despite its anticaries benefits being uncertain and modest. Dentists often report using clinical practice guidelines (CPGs) as a source of scientific information. AIM: To identify and analyze recommendations for clinical practice on the use of FV for caries prevention in preschool children and to assess the methodological quality of the CPG on this topic. DESIGN: Two researchers independently used 12 search strategies and searched the first five pages of Google Search™ and three guideline databases for recommendations freely available to health professionals on the use of FV for caries prevention in preschoolers. Then, they retrieved and recorded recommendations that met the eligibility criteria and extracted the data. A third researcher resolved disagreements. Each included CPG was appraised using the AGREE II instrument. RESULTS: Twenty-nine documents were included. Recommendations varied according to age, patients' caries risk, and application frequency. Of the six CPGs, only one scored above 70% in the AGREE II overall assessment. CONCLUSION: Recommendations on the use of FV lacked scientific evidence, and CPGs were of poor quality. Application of FV is widely recommended despite recent evidence showing an uncertain, modest, and possibly not clinically relevant anticaries benefit. Dentists should be aware that it is necessary to critically appraise CPGs since they may be of poor quality.

Translation and Cross-Cultural Adaptation of the LYMPH-ICF Instrument for Lymphedema into Portuguese/Brazil / Traducción y adaptación transcultural al portugués/Brasil del instrumento LYMPH-ICF para linfedema / Tradução e adaptação transcultural para o português/Brasil do instrumento LYMPH-ICF para linfedema

ABSTRACT Objective: The aim of this study is to cross-culturally adapt the Lymphoedema Functioning, Disability and Health Questionnaire Lymphoedema (LYMPH-ICF) instrument into Brazilian Portuguese and conduct a pilot application (n = 10), without psychometric pretensions. Method: Methodological research was conducted, following the steps of translation, synthesis, back-translation, and evaluation by the expert committee. Two translators, two back-translators, and twelve professionals participated in the expert committee. A pretest was carried out with 10 patients with secondary lymphedema due to breast cancer. The degree of agreement was determined by the content validity coefficient. Results: It was necessary to modify 8 out of the 29 questions comprising the questionnaire, which exhibited idiomatic disagreement. However, despite these changes, there were no indications of impairments, as content reliability was achieved through a validity coefficient of 0.90. Final Considerations: The instrument was successfully translated and cross-culturally adapted for Brazil with a high level of agreement.

RESUMEN Objetivo: Realizar la adaptación transcultural del instrumento Cuestionario de Funcionamiento, Discapacidad y Salud del Linfedema (LYMPH-ICF) al portugués de Brasil y una aplicación piloto (n = 10), sin pretensiones psicométricas. Método: Investigación metodológica, siguiendo los pasos de traducción, síntesis, retrotraducción y evaluación por parte del comité de expertos. Participaron dos traductores, dos retrotraductores y doce profesionales para el comité de expertos. Se realizó una prueba piloto con 10 pacientes con linfedema secundario al cáncer de mama. Y el grado de concordancia se obtuvo mediante el coeficiente de validez de contenido. Resultados: Hubo necesidad de modificar 8 de las 29 preguntas que componen el cuestionario, las cuales mostraron discordancia idiomática. Sin embargo, a pesar de que se realizaron dichas modificaciones, no hubo indicación de perjuicios, ya que se alcanzó la confiabilidad del contenido mediante la obtención de 0,90 en el coeficiente de validez. Conclusiones: El instrumento fue traducido y adaptado transculturalmente para Brasil con un alto grado de concordancia.

RESUMO Objetivo: realizar a adaptação transcultural do instrumento Lymphoedema Functioning, Disability and Health Questionnaire Lymphoedema (LYMPH-ICF) para o português do Brasil e uma aplicação piloto (n = 10), sem pretensão psicométrica. Método: pesquisa metodológica, seguindo os passos de tradução, síntese, retrotradução e avaliação pelo comitê de especialistas. Participaram dois tradutores, dois retrotradutores e doze profissionais para o comitê de especialistas. Realizou-se o pré-teste com 10 pacientes com linfedema secundário ao câncer de mama. E o grau de concordância foi obtido pelo coeficiente de validade de conteúdo. Resultados: houve a necessidade de modificar 8 das 29 questões que compõem o questionário, as quais demonstraram discordância idiomática. Contudo, mesmo que tais alterações tenham sido realizadas, não houve indicação de prejuízos, já que foi alcançada a confiabilidade do conteúdo através da obtenção de 0,90 pelo coeficiente de validade. Considerações finais: o instrumento foi traduzido e adaptado transculturalmente para o Brasil com alto grau de concordância.