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A Doença Meningocócica tem sido um sério problema de saúde pública no município do Rio de Janeiro nos últimos 10 anos, com altas taxas de incidência em crianças de baixa idade, elevada letalidade e predomínio do sorogrupo B. Em dezembro de 1994 foi realizada a segunda campanha de vacinação anti-meningocócica contra os sorogrupos B e C, visando à imunização de crianças de 6 meses a 13 anos de idade. Foram vacinadas com duas doses cerca de 950 mil crianças. A vacina utilizada foi a produzida pelo Instituto Finlay de Cuba. Em 1995 foi observada uma modificação no comportamento da doença, quando passou a predominar o sorogrupo C e aumentou a incidência global da doença, particularmente entre os menores de 1 ano, adolescentes e adultos jovens. Nos grupos etários vacinados, a incidência foi menor que no ano de 1994, em função da diminuição do sorogrupo B. Não foram observadas modificações importantes no comportamento da letalidade.

Objective  To evaluate the effects of the botulinum toxin (BTX-A) on muscle tone and joint mobility in children with congenital Zika syndrome (CZS). Methods  This was a longitudinal case series carried out in a Support Center for Children with Microcephaly, located in Northeastern Brazil. We collected data from the institution's medical records, containing information about muscle tone and passive joint mobility measured at least 3 months before and 4 weeks after BTX-A application. Results  We evaluated 13 children (9 boys) with a mean age of 77 ± 7.1 months. After BTX-A application, a bilateral reduction in the hypertonia level was observed in the elbow flexor ( p  < 0.01) and hip abductor ( p  < 0.05) muscles. Conclusion  No changes were observed in joint mobility and no adverse effects were reported by caregivers after application. The use of BTX-A can reduce hypertonia in CZS children, with no impact on joint mobility., Competing Interests: Conflitos de Interesse Os autores não têm conflito de interesses a declarar., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Split hand-foot malformation (SHFM) is a congenital limb malformation affecting primarily the central rays of the hands and/or feet, with variable expressivity, incomplete penetrance and syndromic forms. It is genetically heterogeneous, including point mutations and structural variants in different loci. Five individuals with SHFM were clinically evaluated in a Tertiary Center in Brazil: four of them presented additional, nonskeletal findings, including one individual with split foot, hand syndactyly, and ectodermal findings. Structural variants and point mutations in genes associated with SHFM were identified in all individuals. Our results highlight genetic heterogeneity observed in this group of skeletal disorders, alongside incomplete penetrance, a challenging task imposed on genetic counseling. Of note, an individual harboring a recurrent heterozygous variant in MAP3K20 presented a phenotype reminiscent of TP63-related disorders, contrary to the one recently reported in the literature with prominent facial dysmorphisms, expanding the phenotypic spectrum of this newly recognized syndromic form of SHFM., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aimed to assess the immediate effects of transcutaneous spinal direct current stimulation (tsDCS) on pain outcomes, measured using the visual analog scale (VAS) and pressure pain thresholds in a cohort of 55 participants experiencing chronic pain using a controlled, randomized trial with 55 participants allocated into 2 groups: 2 mA and 0.5 mA of tsDCS for 20 min. Anodal stimulation was applied on the 12th thoracic vertebra, with the cathode positioned on the 7th cervical vertebra. Pain outcomes were assessed before and post intervention using the VAS and pressure algometry. Between- and within-group differences, along with chi-square tests, were used to determine the differences and responsiveness. Significance was established at p < 0.05. Findings showed significant temporal effects for both VAS ( p < 0.001) and pressure algometry ( p = 0.04). However, no between-group differences were noted for the time × group factor for VAS ( p = 0.46) and pressure algometry ( p = 0.78). No significant between-group differences were observed for the responsiveness analysis. The results indicate that a single 20-min session of 2 and 0.5 mA tsDCS improves pain scores for both intensities equally. However, there were no statistically significant between-group differences in pain perception or pressure pain threshold.

Salicylic acid (SA) is a bioregulator well-known for mitigating salinity damage in plants. However, no studies have examined the interaction between SA and salinity in Dizygostemon riparius , a species rich in bioactive molecules. Therefore, we aimed to evaluate the effect of SA application on Dizygostemon riparius under different salinity levels. A completely randomized experiment was conducted in a 2 × 3 factorial design (two SA concentrations of 0 and 100 µM and three salinity concentrations of 0, 200, and 400 mM NaCl) with five replicates. At 400 mM NaCl, leaf temperature increased by 11%, while relative water content and total soluble carbohydrates decreased by 30% and 35%, respectively, leading to reduced biomass accumulation. Notably, the SA application mitigated these effects by restoring relative water content under 400 mM NaCl and improving carboxylation efficiency and intrinsic water-use efficiency under 200 mM NaCl. Additionally, dry biomass was maintained under both 200 and 400 mM NaCl with SA treatment. These findings suggest that SA has a promising potential to alleviate salt stress in Dizygostemon riparius . Our results could inform cultivation practices, opening new perspectives on the use of SA as an attenuator of salinity stress.

Transcranial direct current stimulation (tDCS) is often reported to have positive effects on brain hemodynamics as well as cognitive performance. Binaural beats (BBs) have also shown the potential to improve cognitive performance. However, we could not find any studies assessing prefrontal hemodynamics using a combination of these techniques or assessing the effects on hemodynamic response at different intensity levels of tDCS (two and three mA). This study aimed to compare the immediate hemodynamic responses to tDCS at different intensities (two and three mA) with and without 40 Hz BBs. Sixty-eight healthy young individuals of both sexes were split into four groups: the tDCS 2 mA group; tDCS 3 mA group; tDCS 2 mA + BB group; and tDCS 3 mA + BB group. All groups received 20 min tDCS (F3-Fp2) alone or combined with BBs. The hemodynamic effect was assessed using a functional near-infrared intracranial spectroscope (fNIRS) positioned on the left supraorbital region (Fp1). The mean values of rates of oxygen saturation (SatO 2 ) were recorded at baseline, during the intervention period, and post-stimulation. The oxygenated hemoglobin rates (HbO) were also extracted. No between-group differences were observed. The within-group analysis did not show significant differences in terms of the time×groups factor. However, the time factor showed significant within-group differences. No differences were found for the HbO rates. The present findings showed that two and three mA tDCS had effects on pre-frontal cortex SatO 2 ; however, the use of additional BBs did not change the SatO 2 levels compared to the use of tDCS alone.

Health disparities present a barrier to successful oncology treatment. The potential for precision oncology to reduce health disparities has not previously been analyzed. We performed a retrospective analysis of 12,627 patients from six major cancer centers whose tumors underwent molecular testing at Caris Life Sciences between 2010 and 2020. Kaplan-Meier and Cox regression were used to describe and analyze overall survival. The molecular and demographic features of the cohort were analyzed by χ2 and ANOVA tests. Black patients composed 25% of the cohort and White patients 63%. Among this molecularly-tested cohort, there were minimal outcome differences based on race, geographic location, or poverty level. When analyzing the interaction of age, race, and sex, racial-based disparities were noted primarily for young non-White women in the study cohort but were more pronounced for men and women of all ages in the broader patient population within the Surveillance, Epidemiology, and End Results database. Mutations in five genes-APC, EGFR, STK11, TP53, and KRAS-were found to affect overall survival among our cohort, and their prevalence varied by race in specific tumor types. Real-world outcomes data in mutation-defined cohorts also provided additional context to previously reported therapeutic response trends. Our study shows that patients who undergo molecular testing display reduced racial health disparities compared with the general population, whereas persistent racial disparities are influenced by age and sex. Genomic-driven racial disparities should be examined at a tumor lineage-specific level. Increased access to molecular testing for all eligible patients may play a role in improving health equity. Significance: This study is the largest of its kind to analyze health disparities and genomic features among a diverse multiinstitutional cohort of patients who underwent molecular testing. Continuing to increase awareness of and access to molecular testing approaches may help to reduce cancer health disparities and improve outcomes for all patients., (©2024 The Authors; Published by the American Association for Cancer Research.)

Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson's disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Excessive weight (overweight and obesity) is a common disorder involving genetic and environmental factors, associated with cardiovascular diseases, type-2 diabetes, and others. NOTCH1 is critical for the maintenance of stem cells and adult tissues, being reported as a key player in metabolism and adipogenesis in animals. Thus, we test the hypothesis that NOTCH1 Single Nucleotide Polymorphisms (SNPs) are associated with excessive weight. Participants from the census-based cohort SABE (Saúde, Bem Estar e Envelhecimento-Health, Well-Being, and Aging), carried out in the city of São Paulo-Brazil, were stratified into cases and controls according to BMI. We filter the SNPs located at the start and end positions of NOTCH1 and 50 Kb on both sides. We selected SNPs with minor allelic frequency (MAF) greater than or equal to 0.01 and Hardy-Weinberg equilibrium (p > 0.05) and r 2  ≥ 0.8. We performed an association study with genotypes and haplotypes, as well as in silico functional analysis of the identified SNPs. We observed an association of the SNP rs9411207 with the risk of excessive weight, under log-additive model, and the genotype distribution showed an increased frequency of homozygous TT (OR 1.50, CI 1.20-1.88; p = 0.0002). The haplotype GAT constructed from this and other SNPs in high Linkage Disequilibrium was more frequent in excessive-weight individuals (p = 0.003). In silico analyses suggested that these SNPs are likely to affect the transcription of NOTCH1 and other genes involved in adipogenesis and metabolism. This is the first study reporting association between NOTCH1 SNPs and the risk of excessive weight. Considering the possibility of NOTCH1 modulation, additional population studies are important to replicate these data and confirm the usefulness of risk genotypes for management strategies of excessive weight., (© 2024. The Author(s).)

The fungus Phyllosticta citricarpa is a quarantine phytopathogen responsible for causing citrus black spot (CBS) disease. To export fruits to CBS-free countries, they must undergo a sanitation process to ensure disease control. In this study, neem essential oil (NEO) was tested against P. citricarpa for the first time as an alternative sanitizer. In vitro experiments were conducted to determine the inhibition concentration of NEO for P. citricarpa , and the mode of action of the essential oil was evaluated. In vivo assays were performed to simulate the sanitization process used in packinghouses. NEO was characterized by GC-MS/MS. The results revealed that NEO at 100  μ L·mL -1 exhibited a similar inhibitory effect as copper oxychloride, suppressing 89.68 ± 1.14% of fungal mycelium growth. Fluorescence microscopy experiments demonstrated that NEO functions by disrupting the cytoplasmic membrane of fungal hyphae, leading to their death within 30 minutes of contact with NEO. GC-MS/MS characterization revealed a high presence of phenolic compounds, which serve as the primary antifungal agents responsible for the action against fungal hyphae. In vivo assays showed that NEO at 100  μ L·mL -1 also reduced microorganisms (CFU mL -1 ) by 93.00 ± 3.88% compared to the negative control. Overall, the results demonstrate that NEO can effectively serve as an alternative sanitizer against P. citricarpa in citrus packinghouses. Our findings allow future studies to explore the use of NEO for sanitizing other fruits and combating different phytopathogens to broaden its potential application in fruit sanitation for export., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Joyce Maria Schuch et al.)

Introduction: Solid pseudopapillary tumor is a low-grade malignancy of the pancreas and predominantly affects young women. This neoplasm is a rare pancreatic entity with vague clinical presentation. Diagnosis is often incidental through imaging or even during surgical approach for another condition., Case Presentation: A 22-year-old Brazilian female with gastrointestinal symptoms was diagnosed with achalasia and underwent Heller myotomy. Intraoperatory findings included an enlarging mass in the distal pancreas. During follow-up for the surgical approach of achalasia, a hypothesis of Frantz's tumor was stated, and spleen-preserving distal pancreatectomy was performed., Discussion: The pathological pathways of Frantz's tumor is still unclear, and its connection with chromosomal abnormalities is under investigation. Although the tumor has been reclassified over the years to solid pseudopapillary tumor, surgical resection remains the standard treatment., Conclusion: Despite a surgical challenge, surgery presents a great prognosis in these patients and long-term survival. High suspicion and proper investigation are fundamental to diagnosis and early treatment., Competing Interests: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women's perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development. We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women's experiences of Zika virus (ZIKV) test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews. Participants in Brazil and Colombia reported that the healthcare system's lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy. Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families' preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Montoya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aimed to compare the insertion torque (IT), flexural strength (FS) and surface alterations between stainless steel (SS-MIs) and titanium alloy (Ti-MIs) orthodontic mini-implants., Methods: Twenty-four MIs (2 x 10 mm; SS-MIs, n = 12; Ti-MIs, n = 12) were inserted on artificial bone blocks of 20 lb/ft3 (20 PCF) and 40 lb/ft3 (40 PCF) density. The maximum IT was recorded using a digital torque meter. FS was evaluated at 2, 3 and 4 mm-deflection. Surface topography and chemical composition of MIs were assessed by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). General linear and mixed models were used to assess the effect of the MI type, bone density and deflection on the evaluated outcomes., Results: The IT of Ti-MIs was 1.1 Ncm greater than that obtained for the SS-MIs (p= 0.018). The IT for MIs inserted in 40 PCF test blocks was 5.4 Ncm greater than that for those inserted in 20 PCF test blocks (p < 0.001). SS-MIs inserted in higher density bone (40 PCF) had significantly higher flexural strength than the other groups, at 2 mm (98.7 ± 5.1 Ncm), 3 mm (112.0 ± 3.9 Ncm) and 4 mm (120.0 ± 3.4 Ncm) of deflection (p< 0.001). SEM evidenced fractures in the Ti-MIs. EDS revealed incorporation of 18% of C and 2.06% of O in the loaded SS-MIs, and 3.91% of C in the loaded Ti-MIs., Conclusions: Based on the findings of this in vitro study, it seems that SS-MIs offer sufficient stability and exhibit greater mechanical strength, compared to Ti-MIs when inserted into higher density bone.

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: There are no conflicts of interest.

Objective: This study evaluated the independent and combined environmental impacts of the consumption of beef and ultra-processed foods in Brazil., Design: Cross-sectional study., Setting: Brazil., Participants: We used food purchases data from a national household budget survey conducted between July 2017 and July 2018, representing all Brazilian households. Food purchases were converted into energy, carbon footprints and water footprints. Multiple linear regression models were used to assess the association between quintiles of beef and ultra-processed foods in total energy purchases and the environmental footprints, controlling for sociodemographic variables., Results: Both beef and ultra-processed foods had a significant linear association with carbon and water footprints ( P < 0·01) in crude and adjusted models. In the crude upper quintile of beef purchases, carbon and water footprints were 47·7 % and 30·8 % higher, respectively, compared to the lower quintile. The upper quintile of ultra-processed food purchases showed carbon and water footprints 14·4 % and 22·8 % higher, respectively, than the lower quintile. The greatest reduction in environmental footprints would occur when both beef and ultra-processed food purchases are decreased, resulting in a 21·1 % reduction in carbon footprint and a 20·0 % reduction in water footprint., Conclusions: Although the environmental footprints associated with beef consumption are higher, dietary patterns with lower consumption of beef and ultra-processed foods combined showed the greatest reduction in carbon and water footprints in Brazil. The high consumption of beef and ultra-processed foods is harmful to human health, as well as to the environment; thus, their reduction is beneficial to both.

Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I, with biallelic variants in ANAPC1 and juvenile cataracts, and type II, with biallelic variants in RECQL4 , increased cancer risk and no cataracts. We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in DNA2 , with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in DNA2 were previously associated with microcephalic osteodysplastic primordial dwarfism. Although the individuals reported here present a similar growth pattern, the presence of poikiloderma and ocular anomalies is unique. Thus, we have broadened the phenotypical spectrum of DNA2 mutations, incorporating clinical characteristics of RTS. Although a clear genotype-phenotype correlation cannot be definitively established at this moment, we speculate that the residual activity of the splicing variant allele could be responsible for the distinct manifestations of DNA2 -related syndromes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients' treatment options and has been progressively incorporated into diagnostic laboratories. Here, we assessed the performance of an in-house HRD testing system deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDM TM HRD Solution and AmoyDx ® (HRD Focus Panel)) with the reference assay from Myriad MyChoice ® (CDx). A total of 85 ovarian cancer samples were subject to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R = 0.87, p -value = 3.39 × 10 -19 ). The comparison of the assigned HRD status to the reference Myriad's test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA's test, while AmoyDx's test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data shows that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, making it an ideal alternative to offer to a broader number of patients while maintaining high-quality standards at more accessible price tiers.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations., Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity., Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status., Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients., Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication., Clinical Trial Number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701., Competing Interests: GN, SV, AK, TS, NK, DA, JA, JA, ZB, NB, TB, BB, SB, MB, PB, SB, BB, HB, CC, HC, JD, AD, NE, LF, DF, CF, MG, CG, PG, SG, MH, HH, DH, CH, CJ, SJ, MJ, VK, EK, NK, VK, AK, DK, CL, PL, KL, ML, XL, GL, GL, DM, AM, MM, SM, RM, IM, VM, RN, SN, RN, TN, TO, OP, KP, JP, KP, JP, HP, MP, YR, PR, SR, JR, DR, MR, SR, AR, LS, PS, MS, LS, MS, DS, MS, LT, MT, ST, LW, GW, MW, EW, SM, BF, JW, ML, MA, DS No competing interests declared

Background: During the aging process, cognitive functions and performance of the muscular and neural system show signs of decline, thus making the elderly more susceptible to disease and death. These alterations, which occur with advanced age, affect functional performance in both the lower and upper members, and consequently human motor functions. Objective measurements are important tools to help understand and characterize the dysfunctions and limitations that occur due to neuromuscular changes related to advancing age. Therefore, the objective of this study is to attest to the difference between groups of young and old individuals through manual movements and whether the combination of features can produce a linear correlation concerning the different age groups., Methods: This study counted on 99 participants, these were divided into 8 groups, which were grouped by age. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Firstly, the participants were divided into groups of young and elderly to verify if the groups could be distinguished through the features alone. Following this, the features were combined using the linear discriminant analysis (LDA), which gave rise to a singular feature called the LDA-value that aided in verifying the correlation between the different age ranges and the LDA-value., Results: The results demonstrated that 125 features are able to distinguish the difference between the groups of young and elderly individuals. The use of the LDA-value allows for the obtaining of a linear model of the changes that occur with aging in the performance of tasks in line with advancing age, the correlation obtained, using Pearson's coefficient, was 0.86., Conclusion: When we compare only the young and elderly groups, the results indicate that there is a difference in the way tasks are performed between young and elderly individuals. When the 8 groups were analyzed, the linear correlation obtained was strong, with the LDA-value being effective in obtaining a linear correlation of the eight groups, demonstrating that although the features alone do not demonstrate gradual changes as a function of age, their combination established these changes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Benign fibro-osseous lesions with cystic degenerations have been scarcely reported in craniofacial bones and its unusual characteristics pose a diagnostic challenge. Here, we report a case of craniofacial fibrous dysplasia presenting a large cystic degeneration. A 55-year-old woman had a history of pain, slight asymmetry on the zygomatic region and ocular pressure. Computed tomography revealed on the right side, multiple craniofacial bones showing a ground glass aspect, associated with an extensive hypodense, unilocular, well circumscribed lesion in the maxilla, and smaller lesions in the sphenoid bone. After a surgical procedure performed in another service, there was a complete improvement in symptoms, and after 1 year, the patient remains stable, with no changes. In the literature review, thirty-three reported cases of the same association in the craniofacial region were found. The main symptoms were sudden increase in the lesion and pain, and the indication of intervention in cystic lesions was only indicated in symptomatic cases or functional deficit. The knowledge of the possibility of the association of benign fibro-osseous lesions and cystic degenerations in craniofacial bones is essential to perform a correct diagnosis and treatment for these patients, consequently avoiding unnecessary procedures. Key words: Craniofacial fibrous dysplasia, Fibrous dysplasia, Benign fibro-osseous lesions, Cystic degeneration., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright: © 2023 Medicina Oral S.L.)

Background: Pembrolizumab is FDA approved for tumors with tumor mutational burden (TMB) of ≥10 mutations/megabase (mut/Mb). However, the response to immune checkpoint inhibitors (ICI) varies significantly among cancer histologies. We describe the landscape of frameshift mutations (FSs) and evaluated their role as a predictive biomarker to ICI in a clinical cohort of patients., Methods: Comprehensive genomic profiling was performed on a cohort of solid tumor samples examining at least 324 genes. The clinical cohort included patients with metastatic solid malignancies who received ICI monotherapy and had tumor sequencing. Progression-free survival (PFS), overall survival, and objective response rates (ORR) were compared between the groups., Results: We analyzed 246,252 microsatellite stable (MSS) and 4561 samples with microsatellite instability across solid tumors. Histologies were divided into groups according to TMB and FS. MSS distribution: TMB-L (<10 mut/Mb)/FS-A (absent FS) (N=111,065, 45%), TMB-H (≥10 mut/Mb)/FS-A (N=15,313, 6%), TMB-L/FS-P (present ≥1 FS) (N=98,389, 40%) and TMB-H/FS-P (N=21,485, 9%). FSs were predominantly identified in the p53 pathway. In the clinical cohort, 212 patients were included. Groups: TMB-L/FS-A (N=80, 38%), TMB-H/FS-A (N=36, 17%), TMB-L/FS-P (N=57, 27%), TMB-H/FS-P (N=39, 18%). FSs were associated with a higher ORR to ICI, 23.8% vs 12.8% (p=0.02). TMB-L/FS-P had superior median PFS (5.1 months) vs TMB-L/FS-A (3.6 months, p<0.01). The 12-month PFS probability was 34% for TMB-L/FS-P vs 17.1% for TMB-L/FS-A., Conclusions: FSs are found in 47% of patients with MSS/TMB-L solid tumors in a pan-cancer cohort. FS may complement TMB in predicting immunotherapy responses, particularly for tumors with low TMB., Competing Interests: Competing interests: VF consultant or advisory role Deciphera, Incyte. AM has patent applications related to the use of cytokines to enhance macrophage immunotherapy. ESS and GF are employees of Foundation Medicine and Shareholders in Roche. HPS consultant or advisory role Ipsen, AstraZeneca, ITM, Novartis, TerSera. SP consultant or advisory role IntegrityCE, Dava Oncology. US consultant or advisory role Astellas, Exelixis, Seattle Genetics, Imvax, Sanofi, and AstraZeneca. WP consultant or advisory role Astellas. IG-L consultant or advisory role SOTIO, Kanaph, Jazz, OncXer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify the novel subgroups of ALL in 144 B-other and 40 "classical" ALL samples. The classical TCF3-PBX1, ETV6-RUNX1, KMT2A-rearranged, and BCR-ABL1, and novel P2RY8-CRLF2, ABL-, JAK2-, ZNF384-, MEF2D-, and NUTM1-fusions were easily identified by fusion transcript analysis. IGH-CRLF2 and IGH-EPOR were found by abnormally high levels of expression of CRLF2 or EPOR. DUX4-rearranged was identified by the unusual expression of DUX4 genes and an alternative exon of ERG, or by clustering analysis of gene expression. PAX5-driven ALL, including fusions, intragenic amplifications, and mutations were identified by single-nucleotide variant analysis and manual inspection using the IGV software. Exon junction analysis allowed detection of some intragenic ERG and IKZF1 deletions. CRLF2-high associated with initial white blood cell (WBC) counts of ≥50 × 103/μL and GATA3 risk alleles (rs3781093 and rs3824662), whereas ABL/JAK2/EPOR-fusions associated with high WBC counts, National Cancer Institute's high-risk classification, and IKZF1del. ZNF384-fusions associated with CALLA-negativity and NUTM1-fusions in infants. In conclusion, targeted RNA sequencing further classified 66.7% (96 of 144) B-other ALL cases. All BCP-ALL subgroups, except for iAMP21, hyperdiploid and hypodiploid cases, were identified. Curiously, we observed higher frequencies of females within B-rest ALLs and males in PAX5-driven cases., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Bauhinia forficata Link. is a native South American plant, which possesses volatile compounds with pharmaceutical and medicinal properties such as antidiabetic and anti-inflammatory effects. However, the conservation and propagation of this plant are complicated by its recalcitrant seeds and delayed flowering transition. Hence, tissue culture is employed for the safe and efficient propagation of B. forficata . However, the optimal conditions for the in vitro cultivation of B. forficata remain unknown. Thus, this study aimed to characterize the volatile profile of adult B. forficata field plants and evaluate the effects of different light intensities (43 and 70 μmol m -2  s -1 ), gas exchange rates (14 and 25 µL L -1  s -1 ), and exogenous sucrose concentrations (0, 20, and 30 g L -1 ) on their in vitro development. The results showed that β-caryophyllene is the major volatile compound produced by B. forficata . Moreover, culturing in a medium containing 30 g L -1 of sucrose and flasks with membranes that allow CO 2 exchange at the rate of 25 µL L -1  s -1 produced vigorous and hardened plants with high survival rates independent of irradiance. This study is the first to report the optimal in vitro culture conditions for B. forficata as a reference for future studies on micropropagation and secondary metabolite production using this species., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03634-8., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Ureteral duplication is a common congenital anomaly, although multiple ureters is a rare disorder. Bifid ureter or multiple ureters are diagnosed incidentally and generally associated with obstruction by lithiasis., Case Presentation: We present a case of ureteral quintuplication converging into a sacculation obstructed by a 7 cm calculus., Conclusion: Two or more ureters are more common in women and it is mostly associated with asymptomatic presentation, excepting when related to complications of urinary tract infection or lithiasis. More than four ureters are extremely rare and our case is the first of incomplete quintuplication found so far in the literature., Competing Interests: Declaration of competing interest Each named author has no conflict of interest, financial or otherwise, (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis., Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed., Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003)., Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples., Competing Interests: The authors report no conflicts of interest.

Introduction: Diverticular disease most common site in digestive tract is large intestine, but can also appears in small intestine and esophagus. Esophageal diverticula are divided according to injured portion (pharyngeal, middle or epiphrenic)., Case Presentation: We present a case of large epiphrenic diverticulum in a 71-year-old woman with mild gastrointestinal symptoms managed laparoscopically with diverticulectomy and fundoplication., Discussion: Epiphrenic esophageal diverticulum is rare, originated from unknown increase of intraesophageal pressure. Diagnosis usually occurs with imaging and endoscopic investigation and surgical treatment is indicated for symptomatic patients., Conclusion: High suspicion and proper analysis are fundamental for diagnosis and treatment definition, which may include outpatient follow-up or surgery., Competing Interests: Conflict of interest statement Each named author has no conflict of interest, financial or otherwise., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Oral myiasis is a rare parasitic disease that requires immediate treatment once diagnosed. However, no standard treatment protocol can be found in the literature. Through a clinical-surgical report, we present the case of an 82-year-old man with lesions extending through the vestibule and alveolar ridge of the maxilla on both sides, in addition to occupying a large part of the palate, with a considerable number of larvae. The patient was initially treated with a single dose of systemic ivermectin (6 mg orally) and topical application of a tampon soaked in ether. The larvae were then surgically removed and debridement of the wound was performed. A crushed tablet of ivermectin 6 mg was applied topically for 2 days, the remaining larvae were again mechanically removed, and the patient received intravenous antimicrobial therapy. Treatment with systemic and topical ivermectin combined with antibiotic therapy and debridement proved to be effective in treating oral myiasis.

Background: Congenital syphilis (CS) is a major and avoidable cause of neonatal death worldwide. In this study, we aimed to estimate excess all-cause mortality in children under 5 years with CS compared to those without CS., Methods and Findings: In this population-based cohort study, we used linked, routinely collected data from Brazil from January 2011 to December 2017. Cox survival models were adjusted for maternal region of residence, maternal age, education, material status, self-declared race and newborn sex, and year of birth and stratified according to maternal treatment status, non-treponemal titers and presence of signs and symptoms at birth. Over 7 years, a total of 20 057 013 live-born children followed up (through linkage) to 5 years of age, 93 525 were registered with CS, and 2 476 died. The all-cause mortality rate in the CS group was 7·84/1 000 person-years compared with 2·92/1 000 person-years in children without CS, crude hazard ratio (HR) = 2·41 (95% CI 2·31 to 2·50). In the fully adjusted model, the highest under-five mortality risk was observed among children with CS from untreated mothers HR = 2·82 (95% CI 2·63 to 3·02), infants with non-treponemal titer higher than 1:64 HR = 8·87 (95% CI 7·70 to 10·22), and children with signs and symptoms at birth HR = 7·10 (95% CI 6·60 to 7·63). Among children registered with CS, CS was recorded as the underlying cause of death in 33% (495/1 496) of neonatal, 11% (85/770) of postneonatal, and 2·9% (6/210) of children 1 year of age. The main limitations of this study were the use of a secondary database without additional clinical information and the potential misclassification of exposure status., Conclusions: This study showed an increased mortality risk among children with CS that goes beyond the first year of life. It also reinforces the importance of maternal treatment that infant non-treponemal titers and the presence of signs and symptoms of CS at birth are strongly associated with subsequent mortality., Trial Registration: Observational study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Paixao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Current first-line standard therapy for metastatic non-small cell lung cancer without driver mutations involves chemotherapy and immunotherapy combination. Prior to the advent of immune checkpoint inhibition, REVEL, a randomized phase III trial demonstrated improved progression-free and overall survival with ramucirumab and docetaxel (ram+doc) in patients who failed platinum-based first-line therapy. Long-term outcomes related to second-line ramucirumab and docetaxel after first-line immunotherapy exposure remain unknown. We analyzed outcomes for 35 patients from our center whom received ramucirumab and docetaxel following disease progression on chemotherapy and immunotherapy combination. Median progression-free survival among patients who received ram+doc after exposure to immunotherapy was 6.6 months (95% CI = 5.5 to 14.9 months; p <0.0001), and median overall survival was 20.9 months (95% CI = 13.4 months to infinity; p <0.0001). These outcomes suggest that there may a synergistic benefit to combining chemotherapy with anti-angiogenic therapy after immunotherapy exposure. Future analyses should be evaluated prospectively and among a larger patient subset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kareff, Gawri, Khan, Kwon, Rodriguez, Lopes and Dawar.)

Background: Peripheral nerve disease may lead to physical disability because of decreased muscle strength and/or loss of sensitivity in the dermatomes of affected peripheral nerves. Both human immunodeficiency virus (HIV)- and leprosy-affected patients can develop neurological damage; therefore, the coinfection of these diseases presents new challenges to the health care of these patients., Aims and Objective: This study aimed to investigate the motor alterations of patients coinfected with HIV and leprosy and their relationship with clinical and anthropometric characteristics, compared with individuals with isolated diseases., Materials and Methods: In this cross-sectional study, 90 individuals were divided equally into three groups: HIV/acquired immunodeficiency syndrome (AIDS) group, leprosy group and HIV/leprosy group. All individuals underwent an evaluation of muscle strength and upper limb endurance adjusted for the Brazilian standards, a palm print pressure test using a digital dynamometer and anthropometric measurements (weight, height and skin folds)., Results: The HIV/leprosy group had the highest mean body mass index, followed by the leprosy group and the HIV/AIDS group. Skinfolds were similar between the groups. Multiple linear regression, adjusted for sex and age, revealed the coinfection of HIV and leprosy as possible contributor to a worse prognosis of muscle function, highlighting the bilateral reduction in the levels of palm print compression strengths compared with isolated diseases (HIV and leprosy). High CD4 count and shorter antiretroviral therapy duration were associated with worse indices of muscle strength, such as gripping and resistance, in coinfected patients., Conclusion: Patients coinfected with HIV and leprosy exhibited greater motor damage than those with isolated diseases. Thus, motor damage may be related to the sum of the neurological manifestations of the two morbidities., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

The objective of this study was to evaluate the influence of the extraction socket (distal or lingual root) and the type of region of interest (ROI) definition (manual or predefined) on the assessment of alveolar repair following tooth extraction using micro-computed tomography (micro-CT). The software package used for scanning, reconstruction, reorientation, and analysis of images (NRecon ® , DataViewer ® , CT-Analyzer ® ) was acquired through Bruker <  https://www.bruker.com  > . The sample comprised the micro-CT volumes of seven Wistar rat mandibles, in which the right first molar was extracted. The reconstructed images were analyzed using the extraction sockets, i.e., the distal and intermediate lingual root and the method of ROI definition: manual (MA), central round (CR), and peripheral round (PR). The bone volume fraction (BV/TV) values obtained were analyzed by two-way ANOVA with Tukey's post hoc test (α = 5%). The distal extraction socket resulted in significantly lower BV/TV values than the intermediate lingual socket for MA (P = 0.001), CR (P < 0.001), and PR (P < 0.001). Regarding the ROI, when evaluating the distal extraction socket, the BV/TV was significantly higher (P < 0.001) for MA than for CR and PR, with a lower BV/TV for CR. However, no significant difference was observed for MA (P = 0.855), CR (P = 0.769), or PR (P = 0.453) in the intermediate lingual extraction socket. The bone neoformation outcome (BV/TV) for alveolar bone repair after tooth extraction is significantly influenced by the ROI and the extraction socket. Using the predefined method with a standardized ROI in the central region of the distal extraction socket resulted in the assessment of bone volume, demonstrating the most critical region of the bone neoformation process., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Purpose: To analyze the influence of occlusive dressing on the healing of excisional skin wounds in mice., Methods: Pre-clinical, comparative, and translational study. Mice were divided into three experimental groups: wounds occluded with hydrocolloid (HD) dressings, transparent polyurethane film (TF) dressings, and without occlusion (WO), monitored at three, six and 14 days, with eight animals each. Closure rate, infiltration of neutrophils and macrophages, measurement of tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) and, histologically, angiogenesis were evaluated., Results: Wound closure was accelerated in the occlusive groups. There was a decrease in TNF-α levels in the HD group when compared to the WO and TF groups. Neutrophils accumulation decreased in the HD group. Increased dosages of macrophages were evidenced in the HD group, compared to the WO and TF groups. Levels of VEGF were increased in the TF and HD groups., Conclusions: It is suggested that the occlusion of wounds modulates the inflammatory response.

Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Santos, Rodrigues, Alecrim-Zeza, de Araújo Ferreira, Trettel, Gimenes, Silva, Sousa-Filho, Serdan, Levada-Pires, Hatanaka, Borges, de Barros, Cury-Boaventura, Bertolini, Cassolla, Marzuca-Nassr, Vitzel, Pithon-Curi, Masi, Curi, Gorjao and Hirabara.)

Background: Agile, accessible and cheap diagnosis of hepatitis C virus (HCV) infection is essential to achieve the elimination of this infection, worldwide, as mandated by the World Health Organzation as part of its strategy for 2030. Dried blood spots (DBS) can be an attractive alternative for sample collection among people living in remote areas and vulnerable populations due to the less invasive collection, its biosafety, and storage & transportation of samples at room temperature., Design: This study aims to estimate the usefulness of dried blood spot samples for the diagnosis and the assessment of HCV infection rates in three different settings in Brazil. Cross-sectional analysis of a sample collection from different populations, aiming to assess the performance of the testing algorithms and respective procedures among different populations with diverse background infection rates., Methods: We reported the evaluation of DBS as alternative samples for detecting anti-HCV in different groups in real life conditions: (I) Vulnerable subjects living in remote areas of Southeast, North and Northeast Brazil (n = 1464); (II) Beauticians (n = 288); (III) People who use non-injectable drugs (n = 201); (IV) patients referred to outpatient care (n = 275)., Results: General assay accuracy was 99%, with a weighted kappa value of 0.9, showing an excellent performance. Sensitivities ranged from 87.5% to 100.0% between groups and specificities were above 99.2%. A total of 194 individuals had HCV RNA in serum and concordance of anti-HCV detection in DBS was 98.4%., Conclusions: DBS samples could be used for anti-HCV detection in different populations recruited in real life conditions and ambulatory settings, with a high overall sensitivity and specificity., (© 2022. The Author(s).)

This study investigated the anti-caries and anti-inflammatory effects of mouthwash formulations containing Punica granatum (pomegranate) peel extract (PPE), sodium-trimetaphosphate, and low concentrations of fluoride. PPE was characterized using high-performance liquid chromatography (ellagic acid and punicalagin). Total phenolics were quantified among formulations, and their stability was analyzed for 28 days. The formulation effects were evaluated as follows: (1) inorganic component concentration and reduced demineralization on bovine enamel blocks subjected to pH cycling; (2) anti-biofilm effect on dual-biofilms of Streptococcus mutans ATCC 25175 and Candida albicans ATCC 10231 treated for 1 and 10 min, respectively; and (3) cytotoxicity and production of inflammatory mediators (interleukin-6 and tumor necrosis factor-alpha). The formulation containing 3% PPE, 0.3% sodium-trimetaphosphate, and 225 ppm of fluoride resulted in a 34.5% surface hardness loss; a 13% (treated for 1 min) and 36% (treated for 10 min) biofilm reduction in S. mutans ; a 26% (1 min) and 36% (10 min) biofilm reduction in C. albicans ; absence of cytotoxicity; and anti-inflammatory activity confirmed by decreased interleukin-6 production in mouse macrophages. Thus, our results provide a promising prospect for the development of an alcohol-free commercial dental product with the health benefits of P. granatum that have been recognized for a millennium., Competing Interests: The authors (G.L.F; A.P.M.V.; A.A.B.; A.C.B.D. and D.B.B.) have a patent for the mouthwash formulations used in the study, by the National Institute of Industrial Property &minus; INPI/SP, on 19 December 2019 under number BR 10 2019 027251 1.

Schinus terebinthifolia Raddi is a species with several potential uses; selecting the proper substrate and fertilizer rate can be vital for seedling production in a nursery environment. This study aims to evaluate two substrates, namely: (i) sewage sludge (SS) from Ilha WWTP; (ii) a commercial substrate (CS) made of organic materials (mainly sphagnum peat). Increasing rates of controlled-release fertilizer - CRF (0, 3, 6, and 12 kg m -3 ) were applied. The experiment was completely randomized with a factorial 2 × 4 scheme (substrates × rates). The seedlings' growth, biomass, and quality were evaluated. The treatments were compared by Tukey test and regression analysis, where linear, quadratic, and cubic models were considered. Principal components analysis (PCA) and cluster analysis were performed. The CRF rates showed non-significant effects for most of the investigated variables in the SS substrate. In the CS, a 7.8 kg m -3 rate of CRF showed the best growth performance. The multivariate analysis of the morphological parameters proved suitable as a complementary approach to evaluate the seedlings' quality. Seedlings reached recommended values for height, diameter, and quality in the 100% SS substrate without chemical fertilizers; thus, Schinus terebinthifolia production in the SS from Ilha is recommended. Besides the growth advantage, the SS can promote nursery cost savings with commercial substrates and chemical fertilizers., (© 2022. The Author(s).)

The fruits from the Arecaceae family, although being rich in bioactive compounds with potential benefits to health, have been underexplored. Studies on their composition, bioactive compounds, and effects of their consumption on health are also scarce. This review presents the composition of macro- and micronutrients, and bioactive compounds of fruits of the Arecaceae family such as bacaba, patawa, juçara, açaí, buriti, buritirana, and butiá. The potential use and reported effects of its consumption on health are also presented. The knowledge of these underutilized fruits is important to encourage production, commercialization, processing, and consumption. It can also stimulate their full use and improve the economy and social condition of the population where these fruits are found. Furthermore, it may help in future research on the composition, health effects, and new product development. Arecaceae fruits presented in this review are currently used as raw materials for producing beverages, candies, jams, popsicles, ice creams, energy drinks, and edible oils. The reported studies show that they are rich in phenolic compounds, carotenoids, anthocyanins, tocopherols, minerals, vitamins, amino acids, and fatty acids. Moreover, the consumption of these compounds has been associated with anti-inflammatory, antiproliferative, antiobesity, and cardioprotective effects. These fruits have potential to be used in food, pharmaceutical, and cosmetic industries. Despite their potential, some of them, such as buritirana and butiá, have been little explored and limited research has been conducted on their composition, biological effects, and applications. Therefore, more detailed investigations on the composition and mechanism of action based on in vitro and/or in vivo studies are needed for fruits from the Arecaceae family.

Introduction Neuropathic pain is a common and disabling late complication of leprosy. We investigated the clinical and electrophysiological characteristics of neuropathic pain in leprosy patients by evaluating nerve conduction, sympathetic skin response (SSR) and A-waves. Methods Twenty one leprosy patients with neuropathic pain validated by the Douleur Neuropathique en 4 (DN4)Questionnaire were selected for study. Pain intensity was measured by the visual analog scale. Demographic and clinical data were collected for all patients. Clinical data included appraisal of the median, ulnar, radial, tibial and common peroneal nerves, assessment of the sympathetic skin response and conventional electrophysiological recordings. Results Among all electroneuromyographic presentations, multifocal mononeuropathy was still the most prevalent. Sensory loss was observed more frequently than motor deficits. As most patients presented advanced clinical forms of leprosy and were under treatment, this high mean was found and the ulnar nerve was most frequently affected. The sympathetic skin response was absent in 16 patients. Higher DN4 Questionnaire scores were observed in women and in those receiving corticosteroid therapy. These inferences are possible to be made, but our study's limitations don't allow us to be certain about it. The statistical significance found only permits us to evidence what we related on the textual part of the study. Limitations The small number of patients studied, the lack of sophisticated diagnostic methods for leprosy, as well as the difficulties in assessing nerve conduction were the main limitations of this study. Conclusion The neurophysiological and clinical findings in leprous neuropathy were modest despite the conspicuous neuropathic pain. Although electrophysiological studies are a vital tool to verify nerve damage, variations in the clinical presentation of leprosy neuropathic pain render the diagnosis challenging. Further studies are needed to describe the neurophysiological evolution of this disease.

Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long-term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process., Competing Interests: Conflict of interest: None., (Copyright © 2022 The Authors.)

Background: This study aimed to determine the prevalence, beliefs, attitudes, and perceptions of hookah use in a population of undergraduate students at a large public university in Brazil., Methods: The sample consisted of 1348 undergraduate students aged over 18-year-old. They completed structured questionnaires on demographic information and close-ended questions on the past and current experiences of smoking hookah. The data underwent descriptive analysis and binary logistic regression., Findings: Finally, 1298 valid survey forms were obtained from printed and digital questionnaires. More than half (53.9%) of participants reported having tried hookah at least once, however, only 10.8% reported they had experienced it within the last 30 days. The majority of the studied population presented acceptable beliefs about the harmfulness and addictive capacity of hookah smoking. However, when comparing the perceptions of those who had smoked and those who had never smoked hookah, and also, the perceptions of users and non-users, significant differences were observed. Students who were users or had already tried hookah showed a tendency to underestimate the deleterious effects of this type of smoking., Conclusion: It could be concluded that hookah smoking was common among Brazilian university students. In addition, preoccupying misperceptions of hookah's harmfulness and addictive capacity were found. The results showed that the epidemic of hookah smoking, especially among young people, has spread far beyond the Arab world and the Persians. Accordingly, preventive measures must be taken if this population is to be protected from addiction and other serious health problems., Competing Interests: Conflict of Interests None declared., (© 2022 Kerman University of Medical Sciences.)

Arecaceae palm tree fruits (APTFs) with pulp or kernel rich in oil are widely distributed in six Brazilian biomes. APTFs represent a great potential for the sustainable exploitation of products with high added value, but few literature studies have reported their properties and industrial applications. The lack of information leads to underutilization, low consumption, commercialization, and processing of these fruit species. This review presents and discusses the occurrence of 13 APTFs and the composition, physicochemical properties, bioactive compounds, and potential applications of their 25 oils and fats. The reported studies showed that the species present different lipid profiles. Multivariate analysis based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) indicated a correlation between the composition of pulp and kernel oils. Myristic, caprylic, capric, and lauric acids are the main saturated fatty acids, while oleic acid is the main unsaturated. Carotenoids and phenolic compounds are the main bioactive compounds in APTFs, contributing to their high oxidative stability. The APTFs oils have a potential for use as foods and ingredients in the cosmetic, pharmaceutical, and biofuel industries. However, more studies are still necessary to better understand and exploit these species.

Purpose: To evaluate a biofilm model of Pseudomonas aeruginosa in excisional cutaneous wound in mice., Methods: Preclinical, translational study conducted with 64 C57BL/6 mice randomly assigned to control and intervention groups. Evaluation was on days D0, D3, D5, D7 and D10 of wound making. The profile of biofilm formation and induction was evaluated using wound closure kinetics, quantitative culture, and evaluation of wounds using transmission electron microscopy (TEM). Clinical evaluation was performed by liver tissue culture, weight variation, and quantification of leukocytes in peripheral blood. Analyses were performed with GraphPad Prism software., Results: Bacterial load for induction of infection with P. aeruginosa and survival of animals was 104 UFC·mL-1. In D5 (p < 0.0001) and D7 (p < 0.01), animals in the intervention group showed a delay in the healing process and had their wounds covered by necrotic tissue until D10. Statistical differences were observed in wound cultures and weight at D5 and D7 (p < 0.01). Liver cultures and leukocyte quantification showed no statistical differences. No bacteria in planktonic or biofilm form were identified by TEM., Conclusions: The findings raise questions about the understanding of the ease of formation and high occurrence of biofilm in chronic wounds.

Objective: To describe the urological outcomes in children with congenital Zika syndrome (CZS) and investigate the relationship between clinical and urological findings in this population., Methods: This cross-sectional study involved children with CZS followed up by a referral centre for children with microcephaly in the state of Paraiba in northeast Brazil. The urological evaluation included clinical history, urine culture results, ultrasonography of the urinary tract, and urodynamic evaluation, following the protocol proposed by Costa Monteiro et al. (2017). Descriptive statistical analysis was performed in addition to association and correlation tests, considering clinical and urodynamic variables., Results: Among the 88 children with CZS (35.5 ± 5.5 months), 97.7% had microcephaly, and 51% presented urinary tract infection (UTI) confirmed with clinical history and lab tests. The number of confirmed UTI episodes varied from one to 14 per child. The urodynamic evaluation confirmed the presence of an overactive bladder in 78 children and incomplete voiding in 50. Urodynamic findings were associated with the number of confirmed UTI episodes, child's sex, and actual weight, in addition to the use of anticonvulsant and myorelaxant drugs., Conclusions: UTIs were confirmed in most children. Other urological outcomes observed were overactive bladder and low bladder capacity, which were associated with the number of confirmed UTI episodes, use of anticonvulsants and myorelaxants, and the child's sex and weight. These are treatable conditions, and it is paramount that paediatricians, neonatologists, and infectious disease specialists are aware of them to make clinical decisions and help reduce the risk of renal damage and other morbidities., (© 2022 John Wiley & Sons Ltd.)

Abstract: The aqueous (AF) and solid (SF) fractions obtained as co-products in the aqueous extraction of pecan nut oil assisted by Alcalase ® were evaluated. In the AF, the degree of protein hydrolysis (DH) and the electrophoretic profile of protein hydrolysates, phenolic compounds, and antioxidant capacity (reducing potential of the hydrophilic compounds, RPHC, 2,2-diphenyl-1-picrylhydrazyl, DPPH; and inhibition of lipid peroxidation) were determined. The proximate composition and microstructure were evaluated in SF. The results indicated a DH of 3.9%. The sample treated with the enzyme (ET) showed a molecular weight of proteins lower than 15 kDa. The ET showed higher content of phenolics (726.3 mg GAE/100 g) and antioxidant capacity higher than the sample without enzymatic treatment. The SF showed a residual lipid content rich in oleic and linoleic acids. Furthermore, changes in the proximate composition and the microstructure were observed. The results indicate the potentiality of hydrolyzed fractions for application in food., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2021.)

Objective: Human epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancer cases. Ado-trastuzumab emtansine (T-DM1) is approved to treat residual HER2-positive breast cancer after neoadjuvant therapy. The aim of this study was to determine the quality-adjusted time with symptoms or toxicity and without symptoms or toxicity (Q-TWiST) of T-DM1 compared to trastuzumab for residual invasive HER2-positive breast cancer., Methods: The authors developed an analytical model extracting individual patient data and estimated invasive disease-free survival and overall survival over a 30-year time horizon. Only direct costs from adjuvant treatment were considered as well as relapse treatment from Brazilian and American payer perspectives. Heart events were considered for utility and cost analysis., Results: The 30-year projection utilizing the Weibull method estimated a mean invasive disease-free survival of 16.4 years for T-DM1 and 10.4 for Trastuzumab, in addition to a mean overall survival of 18.1 and 15.4 years, respectively. We determined a Q-TWiST gain of 3,812 years for the T-DM1 arm when compared to trastuzumab and an Incremental cost-effectiveness ratio per Q-TWiST of US$ 11,467.65 in the United States and US$ 3,332.73 in Brazil., Conclusion: Ado-trastuzumab emtansine is cost-effective from both Brazilian and American perspectives.

The aim of this study was to investigate volatile organic compounds (VOCs) in exhaled breath as possible non-invasive markers to monitor the inflammatory response in inflammatory bowel disease (IBD) patients as a result of repeated and prolonged moderate-intensity exercise. We included 18 IBD patients and 19 non-IBD individuals who each completed a 30, 40, or 50 km walking exercise over three consecutive days. Breath and blood samples were taken before the start of the exercise event and every day post-exercise to assess changes in the VOC profiles and cytokine concentrations. Proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) was used to measure exhaled breath VOCs. Multivariate analysis, particularly ANOVA-simultaneous component analysis (ASCA), was employed to extract relevant ions related to exercise and IBD. Prolonged exercise induces a similar response in breath butanoic acid and plasma cytokines for participants with or without IBD. Butanoic acid showed a significant correlation with the cytokine IL-6, indicating that butanoic acid could be a potential non-invasive marker for exercise-induced inflammation. The findings are relevant in monitoring personalized IBD management.