Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

Systemic and oral abnormalities in Kabuki syndrome: a case series.

OBJECTIVE: This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health. STUDY DESIGN: Clinical examination was conducted on 15 individuals to investigate orodental alterations such as tooth abnormalities and cleft lip and/or palate, and the patient records were also reviewed to investigate systemic diseases such as cardiopathies, infectious and immunologic diseases, nephropathies, and delayed neuropsychomotor development. RESULTS: All individuals with KS presented cleft lip and/or palate, 11 (73.34%) tooth abnormalities, 5 (33.34%) congenital cardiopathies, 12 (80%) infectious or immunologic diseases, 1 (6.67%) nephropathy, and 14 (93.34%) had an intellectual disability. CONCLUSION: Individuals with KS often have dental anomalies such as hypodontia, cleft or palate, and systemic disorders such as congenital heart disease and infectious diseases. Intellectual disability is present in most cases. These alterations should be investigated as early as possible to prevent the increase in morbidity in these individuals.

Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Efficacy of acellular xenogeneic dermal matrix graft in the treatment of multiple gingival recessions: systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare the efficacy of acellular xenogeneic dermal matrix graft (AXDM) compared to connective tissue graft (CTG) in treating multiple gingival recessions. MATERIALS AND METHODS: A systematic search of electronic databases was conducted to identify randomized clinical trials (RCTs) that compared AXDM and CTG. The selected studies were subjected to bias risk assessment, data extraction, and meta-analyses. Parameters such as gingival recession height, width, mean percentage of root coverage, and complete root coverage were analyzed. RESULTS: Seven RCTs involving 146 patients were included. The meta-analyses indicated that CTG was statistically superior to AXDM in reducing gingival recession height at the final follow-up (mean difference: -0.104 mm, 95% confidence interval [CI]: -0.180-0.028, p = 0.008) and width at the final follow-up (mean difference: -0.285 mm, 95% CI: -0.541-0.030, p = 0.029). CTG also demonstrated a significantly higher mean percentage of root coverage at the 6-month follow-up (difference in means: -2.761 mm, 95% CI: -4.932-0.590, p = 0.013) and a higher percentage of complete root coverage at the 6-month follow-up (odds Ratio [OR]: 0.598, 95% CI: 0.4-0.892, p = 0.012) compared to AXDM. However, there was no significant difference in the number of teeth with complete root coverage between CTG and AXDM (OR: 1.610, 95% CI: 0.983-2.636, p = 0.058) and aesthetic outcomes (mean difference: 0.148, 95% CI: -0.277-0.573, p = 0.494). CONCLUSIONS: CTG is more effective than AXDM in treating multiple gingival recessions. This is evidenced by significant reductions in gingival recession height and width, a higher mean percentage of root coverage, and a greater percentage of complete root coverage at the 6-month follow-up. CLINICAL RELEVANCE: In some clinical situations an alternative to CTG is required for the treatment of multiple gingival recessions. AXDM, despite presenting clinical outcomes that are not as satisfactory as CTG, can be used for this purpose.

Renal biomarkers, clinical parameters, and renal Doppler velocimetry in bitches with cystic endometrial hyperplasia-pyometra complex.

Cystic endometrial hyperplasia (CEH)-pyometra complex is the most common uterine infection in adult and elderly bitches and can cause renal dysfunction. The aim of this study was to measure and compare urinary creatinine, urea, symmetric dimethylarginine (SDMA), urinary protein-creatinine ratio (UPC), measurement of systolic blood pressure (SBP), and Doppler velocimetry of renal arteries in patients with CEH-pyometra complex before and after an average of 6 months of treatment, evaluating the possibility of the changes persisting. The evaluation was conducted at two moments: M1 (at the diagnosis of CEH-pyometra, n = 36) and M2 (after an average of six months of treatment, n = 16). For the control group, eight bitches with no changes in blood tests or history of conditions underwent Doppler ultrasound evaluation of the renal arteries. At both M1 and M2, we measured creatinine, urea, and serum SDMA, UPC, SBP, and Doppler ultrasound of the renal arteries. Patients were evaluated according to the following groups: azotemic (AZO) and non-azotemic (NAZO), and open and closed cervix pyometra. The parameters were compared between animals present in both moments presented as M1R (bitches that were in M1 and M2) and M2. Statistical significance was considered when p < .05. The medians found for creatinine in M1 were as follows: 1.15 mg/dL, being 1.8 mg/dL for AZO (12/36) and 0.95 mg/dL for NAZO (24/36); and in M2: 0.85 mg/dL (16/16), being 1.15 mg/dL for AZO (4/16) and 0.8 mg/dL for NAZO (12/36). For urea, in M1 it was 36 mg/dL (32/36), with AZO being 103 mg/dL (11/32) and 33 mg/dL in NAZO (21/32); and in M2 32 mg/dL (16/ 16), being 29 mg/dL for AZO (4/36), and 31 mg/dL for NAZO (3/15). The median SDMA measured in M1R was 17 µg/dL (15/16), with AZO being 31 µg/dL (3/15), and NAZO being 16.5 µg/dL (12/15); and in M2, SDMA was 12 µg/dL (16/16), with AZO being 12.5 µg/dL (4/16), and NAZO being 12 µg/dL (12/16). The median UPC measured in M1 was 1.15 (10/36), with AZO being 0.25 (1/10), and NAZO being 1.38 (9/10); and in M2, it was 0.2 (13/16), being 0.1 in AZO (4/13), and 0.2 (9/16) in NAZO. For SBP, in M1, it was 118 mmHg (30/36), with AZO being 102 mmHg (10/30) and 133 mmHg in NAZO (20/30); and in M2 142.5 mmHg (12/16), being 155 mmHg for AZO (4/12), and 140 mg/dL for NAZO (8/12). When comparing animals with open and closed cervixes, a difference was found between SDMA measurements (p = .001). There was a distinction between PI and RI of the left and right kidneys consecutively (p = .007; p = .033; p = .019; p = .041). Correlations found in M1: SDMA × PI RIM DIR (r = 0.873; p = .002), SDMA × PSV RIM ESQ (r = 0.840; p = .004), SDMA × EDV RIM ESQ (r = 0.675; p = .046). With this study, we conclude a return to normality of renal biomarkers and clinical parameters after six months. Yet, there is a persistence of Doppler velocimetric measurements between the two moments. Thus, this parameter is not suitable for identifying and classifying chronic kidney injury in bitches with pyometra.

Comparative analysis of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Zeta (P.2) and Delta (B.1.617.2) in Vero-E6 cells: ultrastructural characterization of cytopathology and replication kinetics.

This study compares the effects of virus-cell interactions among SARS-CoV-2 variants of concern (VOCs) isolated in Brazil in 2021, hypothesizing a correlation between cellular alterations and mortality and between viral load and transmissibility. For this purpose, reference isolates of Alpha, Gamma, Zeta, and Delta variants were inoculated into monolayers of Vero-E6 cells. Viral RNA was quantified in cell supernatants by RT‒PCR, and infected cells were analyzed by Transmission Electron Microscopy (TEM) for qualitative and quantitative evaluation of cellular changes 24, 48, and 72 hours postinfection (hpi). Ultrastructural analyses showed that all variants of SARS-CoV-2 altered the structure and function of mitochondria, nucleus, and rough endoplasmic reticulum of cells. Monolayers infected with the Delta variant showed the highest number of modified cells and the greatest statistically significant differences compared to those of other variants. Viral particles were observed in the cytosol and the cell membrane in 100 % of the cells at 48 hpi. Alpha showed the highest mean particle diameter (79 nm), and Gamma and Delta were the smallest (75 nm). Alpha and Gamma had the highest particle frequency per field at 48 hpi, while the same was observed for Zeta and Delta at 72 hpi and 24 hpi, respectively. The cycle threshold of viral RNA varied among the target protein, VOC, and time of infection. The findings presented here demonstrate that all four VOCs evaluated caused ultrastructural changes in Vero-E6 cells, which were more prominent when infection occured with the Delta variant.

Healthy lifestyle and genomic ancestry related to good glycemic control in type 1 diabetes patients from Northeastern Brazil: a hierarchical analysis.

Introduction: This study aimed to investigate the sociodemographic factors, dietary adherence, regular physical activity, and genomic ancestry percentage associated with good glycemic control in Brazilian patients with type 1 diabetes (T1D) using a hierarchical approach. Methods: A cross-sectional study was conducted in 152 T1D patients. Glycated hemoglobin (HbA1C) levels were measured to evaluate the glycemic control status (good, moderate, or poor). Independent factors included sex, age, self-reported skin color, educational level, family income, dietary patterns, and physical activity. The percentage of genomic ancestry (Native American, European, and African) was influenced by a panel of 46 autosomal insertion/deletion ancestry markers. Statistical analyses included receiver operating characteristic curves, and hierarchical logistic regression analysis. Results: The hierarchical analysis, patients who had high dietary adherence showed a positive association with good glycemic control (adjustedOR = 2.56, 95% CI:1.18-5.59, P = 0.016). Thus, age greater than 40 years was associated with good glycemic control compared to the children and adolescents group (adjustedOR = 4.55, 95% CI:1.14-18.1, P = 0.031). Males were associated with good glycemic control (adjustedOR = 2.00, 95% CI:1.01-4.00, P =0.047). Conclusion: The study findings suggest that consistent adherence to dietary regimens is associated with good glycemic control after adjusting for sociodemographic and genomic ancestry factors in an admixed population of T1D patients from Northeast Brazil.

Challenges of a two-phase orthodontic treatment of a mandibular lateral incisor-canine transposition and a maxillary palatally displaced canine: A case report.

INTRODUCTION: The management of eruption disturbances in orthodontics may be challenging and requires a careful diagnosis and treatment planning. This case report discusses the challenges of a two-phase orthodontic treatment of a patient presenting with a dental eruption pattern anomaly. PATIENT CONCERNS: A 10-year-old boy was presented with no complaints for a routine orthodontic evaluation during mixed dentition. PRIMARY DIAGNOSES: The patient was diagnosed with a skeletal Class I malocclusion with unilateral posterior crossbite, incomplete mandibular lateral incisor-canine transposition and a unilateral maxillary ectopic canine. INTERVENTIONS: Phase 1 started with rapid maxillary expansion to correct maxillary constriction and the ectopic eruption of the right maxillary canine. In the mandibular arch, phase 1 included the extraction of the left primary lateral incisor and canine, alignment of the left permanent lateral incisor and orthodontic traction of the left permanent canine. The duration of phase 1 was 14 months. Phase 2 involved a comprehensive course of orthodontic treatment and started when the patient was aged 13 years. This phase lasted 18 months. RESULTS: An adequate dental occlusion was obtained, and the treatment results were stable after an 18-month follow-up. CONCLUSION: In this case, the early diagnosis of the dental anomalies was valuable as it allowed an early intervention to be undertaken, which resulted in overall treatment simplification and potentially minimised the adverse effects. This case report reinforces the importance of a careful follow-up during mixed dentition.

Survival Rate of Dental Implants in the Cleft Area: A Cross-Sectional Retrospective Study.

This study aimed to evaluate the survival rate of osseointegrated implants installed in the cleft area. An extensive data survey was conducted using the medical records of individuals who had implants installed in the cleft area between 1999 and 2020. The variables assessed were age, sex, implant follow-up time, implantation procedures, and rehabilitation with implant-supported prostheses. Data were analyzed in terms of implant survival time, correlating with the factors: age, sex, execution, or no-execution of bone regrafting, the time interval between secondary alveolar bone grafting and regrafting, the time interval between regrafting and implant installation, and the time interval between implant installation and provisional and definitive prosthesis. Data were analyzed with respect to implant survival. χ 2 and Student t tests were used with a 5% significance level. A total of 1295 medical records were analyzed, of which 688 reported implants in cleft areas (56.1% in females, 43.9% in males) with a success rate of 92.73% and a mean follow-up time of 53.2 (±45.0) months. There were no statistically significant differences in the correlation between the survival rate and sex ( P = 0.895, χ 2 test), between the implant survival rate and regrafted area ( P = 0.904, χ 2 test), or between the survival rate and patient age ( P = 0.246, Student t test). The survival rate of implants in the cleft area was 92.73%. Age, sex, and the need for regrafting did not influence the survival rate of implants installed in the cleft area. Clinical studies that evaluate the survival rate of implants installed in patients with cleft maxilla are of great relevance to the dental field.

Perinatal depression and mental health uptake referral rate in an obstetric service.

Perinatal depression is an important indicator of mothers' mental health. Studies have been carried out to identify and characterize women at risk of such affective disorder. The aim of this study is to assess mothers' adherence to our perinatal depression screening and eventual follow-up by a multidisciplinary team, including mental health and obstetrics professionals. Ultimately, a risk profile for the uptake rate of referral was described to psychological support. Pregnant women from a maternity of a tertiary center with on-site assessment and treatment (n = 2163) were included in this study. The identification of women at risk for depression was based on a two-question screening and the EPDS scale. Demographic and obstetric data were obtained from medical records. The number of screening evaluations, the uptake referral rate and the compliance to treatment were analyzed. Logistic regression was used to predict a risk profile for adherence. Among 2163 enrolled in the protocol, 10.2% screened positive for depression. Of these, 51.8% accepted referral for mental health assistance. 74.9% were compliant to Psychology appointments and 74.1% to Psychiatry appointments. Women who had a previous history of depression were more likely to accept referral for mental health support. With this study, we were able to understand the behaviour of this population towards the screening protocol we offer. Women with a previous history of depression are more likely to accept mental health assistance.

Energetic responses of head-out water immersion at different temperatures during post-exercise recovery and its consequence on anaerobic mechanical power.

PURPOSE: While exercise recovery may be beneficial from a physiological point of view, it may be detrimental to subsequent anaerobic performance. To investigate the energetic responses of water immersion at different temperatures during post-exercise recovery and its consequences on subsequent anaerobic performance, a randomized and controlled crossover experimental design was performed with 21 trained cyclists. METHOD: Participants were assigned to receive three passive recovery strategies during 10 min after a Wingate Anaerobic Test (WAnT): control (CON: non-immersed condition), cold water immersion (CWI: 20 â„ƒ), and hot water immersion (HWI: 40 â„ƒ). Blood lactate, cardiorespiratory, and mechanical outcomes were measured during the WAnT and its recovery. Time constant (τ), asymptotic value, and area under the curve (AUC) were quantified for each physiologic parameter during recovery. After that, a second WAnT test and 10-min recovery were realized in the same session. RESULTS: Regardless the water immersion temperature, water immersion increased [Formula: see text] (+ 18%), asymptote ([Formula: see text]+ 16%, [Formula: see text] + 13%, [Formula: see text] + 17%, HR + 16%) and AUC ([Formula: see text]+ 27%, [Formula: see text] + 18%, [Formula: see text] + 20%, HR + 25%), while decreased [Formula: see text] (- 33%). There was no influence of water immersion on blood lactate parameters. HWI improved the mean power output during the second WAnT (2.2%), while the CWI decreased 2.4% (P < 0.01). CONCLUSION: Independent of temperature, water immersion enhanced aerobic energy recovery without modifying blood lactate recovery. However, subsequent anaerobic performance was increased only during HWI and decreased during CWI. Despite higher than in other studies, 20 °C effectively triggered physiological and performance responses. Water immersion-induced physiological changes did not predict subsequent anaerobic performance.

Comparison of two pharmacological semen collection times with α2-adrenergic agonist in domestic cats.

The use of α2-adrenergic agonists in association with urethral catheterization has been used as a technique for pharmacological semen collection in cats. The mechanism of action of this drug is the stimulation of adrenoreceptors in the vas deferens, which results in ejaculation. While medetomidine is the α2-agonist most commonly used in studies, ejaculation with the use of dexmedetomidine associated with ketamine has been effective, but with variable results. Therefore, further studies regarding the methodology of use are required to obtain better seminal quality. This study aimed to compare two pharmacological semen collection times after the association of dexmedetomidine (30 µg/kg, IM; Dormitor®, Zoetis), ketamine (5 mg/kg, IM; ketamine, Vetnil) and urethral catheterization using a tomcat probe (0.8 mm × 1.00 mm × 11 cm). The collections were divided into two experimental groups: G10 (N = 8; urethral catheterization after 10 min of anaesthesia) and G15 (N = 8; urethral catheterization after 15 min of anaesthesia). The ejaculates were evaluated for ejaculate volume, sperm concentration, morphology and kinetics using the CASA system. To compare the groups, the t-test and the Mann-Whitney U-test were used with a significance level of 5%. It was identified that ejaculate volume (G10: 22.62 ± 2.13 vs. G15: 26.81 ± 1.55; p < .001) and sperm concentration (G10: 48.10 × 106 ± 17.84 vs. G15: 90.18 × 106 ± 19.35; p < .001) was higher in G15 than in G10 and had a lower percentage of minor defects than G10 (G10: 3.12 ± 2.41 vs. G15: 1.00 ± 1.19; p = .043). Regarding the kinetic parameters, the results of G15 were better for total motility-TM (G10: 67.00 ± 10.33 vs. G15: 81.87 ± 7.99; p = .006) and faster cells-RAPID: (G10: 55.00 ± 16.63 vs. G15: 74.25 ± 11.94; p = .019); whereas a higher proportion of cells with slow speed-SLOW were seen in G10 (G10: 31.00 ± 12.07 vs. 17.12 ± 7.53; p = .015). Based on these findings, we suggest that collection via urethral catheterization should be performed 15 min after the application of ketamine-associated dexmedetomidine to obtain a better-quality ejaculate.

Estimated costs for Duchenne muscular dystrophy care in Brazil.

BACKGROUND: The economic burden of rare diseases on health systems is still not widely measured, with the generation of accurate information about the costs with medical care for subjects with rare diseases being crucial when defining health policies. Duchenne Muscular Dystrophy (DMD) is the most common form of muscular dystrophy, with new technologies recently being studied for its management. Information about the costs related to the disease in Latin America is scarce, and the objective of this study is to evaluate the annual hospital, home care and transportation costs per patient with DMD treatment in Brazil. RESULTS: Data from 27 patients were included, the median annual cost per patient was R$ 17,121 (IQR R$ 6,786; 25,621). Home care expenditures accounted for 92% of the total costs, followed by hospital costs (6%) and transportation costs (2%). Medications and loss of family, and patient's productivity are among the most representative consumption items. When disease worsening due to loss of the ability to walk was incorporated to the analysis, it was shown that wheelchair users account for an incremental cost of 23% compared with non-wheelchair users. CONCLUSIONS: This is an original study in Latin America to measure DMD costs using the micro-costing technique. Generating accurate information about costs is crucial to provide health managers with information that could help establish more sustainable policies when deciding upon rare diseases in emerging countries.

Meanings of social isolation for young Brazilians during the covid-19 pandemic

Introduction: The covid-19 pandemic has left a high number of infected and dead in the world, where several social measures have been imposed on the population, especially social isolation. Objective: Given this scenario, based on Vygotsky's socio-historical theory, this original article aimed to identify the meanings of social isolation in the covid-19 pandemic for Brazilian youth. Method: A survey was carried out, with the participation of 571 young Brazilians, women and men aged between 18 and 25, who answered a sociodemographic questionnaire and the Free Word Association Method (FWAM), analyzed with the help of IRaMuTeQ. Results: The results showed that virtualized socialization is insufficient for the social demand of young people, as evidenced by the most evoked words in category 1, "Homesickness" (χ² = 55,41); "Boredom" (χ² = 50,06); "Anxiety" (χ² = 42,67); "Loneliness" (χ² = 37,15); "Sadness" (χ² = 32,78). It was also identified that their routine was transformed with the insertion of obligations and leisure primarily in the home environment, demonstrated by the prevalence of words like "House" (χ² = 116,18); "Home Office" (χ² = 26,06); "Movie" (χ² = 26,06); "Mask" (χ² = 24,96); "Alcohol" (χ² = 21,67); "Lockdown" (χ² = 21,67), in category 2. Still, young people brought their resignifications in this period, in the face of collective responsibility, indicated by the choice of words in category 3, such as "Care" (χ² = 84,05); "Responsibility" (χ² = 59,21); "Respect" (χ² = 55,03); "Prevention" (χ² = 52,68); "Empathy" (χ² = 34,06); "Protection" (χ² = 21,99). Conclusions: It is concluded that isolation brought negative consequences on relationships and mental health of young people, but also a greater social awareness.

Introducción: La pandemia del covid-19 ha dejado un alto número de contagiados y muertos en el mundo, donde se han impuesto varias medidas sociales a la población, en especial el aislamiento social. Objetivo: Ante ese escenario, con base en la teoría sociohistórica de Vygotsky, este artículo original tuvo como objetivo identificar los significados del aislamiento social en la pandemia de covid-19 para la juventud brasileña. Método: Se realizó una encuesta, con la participación de 571 jóvenes brasileños, mujeres y hombres de 18 a 25 años, que respondieron un cuestionario sociodemográfico y la Técnica de Asociación Libre de Palabras (TALP), analizados con la ayuda de IRaMuTeQ. Resultados: Los resultados mostraron que la socialización virtualizada es insuficiente para la demanda social de los jóvenes, como lo demuestran las palabras más evocadas en la clase 1, "Nostalgia" (χ² = 55,41) "Aburrimiento" (χ² = 50,06); "Ansiedad" (χ² = 42,67); "Soledad" (χ² = 37,15); "Tristeza" (χ² = 32,78). También identificaron que su rutina se transformó con la inserción de obligaciones y ocio principalmente en el ámbito del hogar demostrado por la prevalencia de palabras como "Casa" (χ² = 116,18); "Teletrabajo" (χ² = 26,06); "Película" (χ² = 26,06); "Mascarilla" (χ² = 24,96); "Alcohol" (χ² = 21,67); "Confinamiento" (χ² = 21,67), en la clase 2. Aún así, los jóvenes trajeron sus resignificaciones en este período, frente a la responsabilidad colectiva, indicado por la elección de palabras en la clase 3, como "Cuidado" (χ² = 84,05); "Responsabilidad" (χ² = 59,21); "Respeto" (χ² = 55,03); "Prevención" (χ² = 52,68); "Empatía" (χ² = 34,06); "Protección" (χ² = 21,99). Conclusiones: Se concluye que el aislamiento trajo consecuencias negativas en las relaciones y la salud mental de los jóvenes, pero también una mayor conciencia social.

Introdução: A pandemia de covid-19 tem deixado um elevado número de infectados e mortos no mundo, onde diversas medidas sociais foram impostas à população, especialmente de isolamento social. Objetivo: Diante desse cenário, com base na teoria sócio-histórica de Vygotsky, este artigo original objetivou identificar quais os significados do isolamento social na pandemia de covid-19 para a juventude brasileira. Método: Realizou-se uma pesquisa de levantamento, com a participação de 571 jovens brasileiros, mulheres e homens de 18 a 25 anos, que responderam um questionário sociodemográfico e à Técnica de Associação Livre de Palavras (TALP), analisados com auxílio do IRaMuTeQ. Resultados: Os resultados mostraram que a socialização virtualizada é insuficiente para a demanda social dos jovens, como evidenciado através das palavras mais evocadas na classe 1, "Saudade" (χ² = 55,41) "Tédio" (χ² = 50,06); "Ansiedade" (χ² = 42,67); "Solidão" (χ² = 37,15); "Tristeza" (χ² = 32,78). Também identificaram que a rotina destes foi transformada com a inserção das obrigações e lazer prioritariamente no ambiente de casa, demonstrado pela prevalência de palavras como "Casa" (χ² = 116,18); "Home Office" (χ² = 26,06); "Filme" (χ² = 26,06); "Máscara" (χ² = 24,96); "Álcool" (χ² = 21,67); "Lockdown" (χ² = 21,67), na classe 2. Ainda, os jovens trouxeram suas ressignificações nesse período, diante da responsabilidade coletiva, apontado pela escolha de palavras na classe 3, como "Cuidado" (χ² = 84,05); "Responsabilidade" (χ² = 59,21); "Respeito" (χ² = 55,03); "Prevenção" (χ² = 52,68); "Empatia" (χ² = 34,06); "Proteção" (χ² = 21,99). Conclusão: Conclui-se que o isolamento trouxe consequências negativas nas relações e saúde mental dos jovens, mas também uma maior conscientização social.

Primary infection of BALB/c mice with a dengue virus type 4 strain leads to kidney injury.

BACKGROUND: Dengue is a disease caused by dengue virus (DENV-1 through -4). Among the four serotypes, DENV-4 remains the least studied. Acute kidney injury is a potential complication of dengue generally associated with severe dengue infection. OBJECTIVES: The goal of this study was to investigate the alterations caused by experimental dengue infection in the kidney of adult BALB/c mice. METHODS: In this study, BALB/c mice were infected through the intravenous route with a DENV-4 strain, isolated from a human patient. The kidneys of the mice were procured and subject to histopathological and ultrastructural analysis. FINDINGS: The presence of the viral antigen was confirmed through immunohistochemistry. Analysis of tissue sections revealed the presence of inflammatory cell infiltrate throughout the parenchyma. Glomerular enlargement was a common find. Necrosis of tubular cells and haemorrhage were also observed. Analysis of the kidney on a transmission electron microscope allowed a closer look into the necrotic tubular cells, which presented nuclei with condensed chromatin, and loss of cytoplasm. MAIN CONCLUSIONS: Even though the kidney is probably not a primary target of dengue infection in mice, the inoculation of the virus in the blood appears to damage the renal tissue through local inflammation.

Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression.

Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs' therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion. Here, we evaluated strategies for arming Seneca Valley virus (SVV) with relevant immunomodulatory transgenes. Specificially in the contex of arming SVV, we evaluated transgene maximum size and stabiltity, transgene secretion, and the impact of transgene inclusion on viral fitness. We find that SVV is not capable of expressing secreted payloads and has a transgene packaging capacity of ∼10% of viral genome size. To enable transgene expression, we developed SVV replicons with greater transgene size capacity and secretion capabilities. SVV replicons can be packaged in trans by virus in co-infected cells to express immunomodulatory transgenes in surrounding cells, thus providing a means to enhance the potential of this therapeutic to augment the anti-tumor immune response.

DC-SIGN receptor is expressed by cells from cutaneous leishmaniasis lesions and differentially binds to Leishmania (Viannia) braziliensis and L. (Leishmania) amazonensis promastigotes.

BACKGROUND: Dendritic cells (DCs) specific intercellular adhesion molecule (ICAM)-3-grabbing non integrin receptor (DC-SIGN) binds to subgenera Leishmania promastigotes mediating its interaction with DC and neutrophils, potentially influencing the infection outcome. OBJECTIVES: In this work, we investigated whether DC-SIGN receptor is expressed in cells from cutaneous leishmaniasis (CL) lesions as well as the in vitro binding pattern of Leishmania (Viannia) braziliensis (Lb) and L. (L.) amazonensis (La) promastigotes. METHODS: DC-SIGN receptor was labeled by immunohistochemistry in cryopreserved CL tissue fragments. In vitro binding assay with CFSE-labeled Lb or La promastigotes and RAJI-transfecting cells expressing DC-SIGN (DC-SIGNPOS) or mock-transfected (DC-SIGNNEG) were monitored by flow cytometry at 2 h, 24 h and 48 h in co-culture. RESULTS: In CL lesion infiltrate, DC-SIGNPOS cells were present in the dermis and near the epidermis. Both Lb and La bind to DC-SIGNPOS cells, while binding to DC-SIGNNEG was low. La showed precocious and higher affinity to DC-SIGNhi population than to DC-SIGNlow, while Lb binding was similar in these populations. CONCLUSION: Our results demonstrate that DC-SIGN receptor is present in L. braziliensis CL lesions and interact with Lb promastigotes. Moreover, the differences in the binding pattern to Lb and La suggest DC-SIGN can influence in a difference way the intake of the parasites at the first hours after Leishmania infection. These results raise the hypothesis that DC-SIGN receptor could participate in the immunopathogenesis of American tegumentary leishmaniasis accounting for the differences in the outcome of the Leishmania spp. infection.

Diachronic profile of startup companies through social media.

Social media platforms have become powerful tools for startups, helping them find customers and raise funding. In this study, we applied a social media intelligence-based methodology to analyze startups' content and to understand how their communication strategies may differ during their scaling process. To understand if a startup's social media content reflects its current business maturation position, we first defined an adequate life cycle model for startups based on funding rounds and product maturity. Using Twitter as the source of information and selecting a sample of known Portuguese IT startups at different phases of their life cycle, we analyzed their Twitter data. After preprocessing the data, using latent Dirichlet allocation, topic modeling techniques enabled the categorization of the data according to the topics arising in the published contents of the startups, making it possible to discover that contents can be grouped into five specific topics: "Fintech and ML," "IT," "Business Operations," "Product/Service R&D," and "Bank and Funding." By comparing those profiles against the startup's life cycle, we were able to understand how contents change over time. This provided a diachronic profile for each company, showing that while certain topics remain prevalent in the startup's scaling, others depend on a particular phase of the startup's cycle. Our analysis revealed that startups' social media content differs along their life cycle, highlighting the importance of understanding how startups use social media at different stages of their development.

Bone Substitutes Graft for Regeneration of the Anterior Maxillary Alveolar Process: A Systematic Review.

The objective of this systematic review was to identify the available scientific evidence on bone substitutes (BSs) compared with autogenous bone grafts (ABGs) for regeneration of horizontal bone resorption in the anterior maxillary alveolar process, aiming at rehabilitation with endosseous implants. This review was performed according to the PRISMA guidelines (2020) and registered in the database PROSPERO (CRD: 42017070574). The databases searched were PUBMED/MEDLINE, EMBASE, SCOPUS, SCIENCE DIRECT, WEB OF SCIENCE, and CENTRAL COCHRANE, in the English language. The Australian National Health and Medical Research Council (NHMRC) and Cochrane Risk of Bias Tool were used to assess the study's quality and risk of bias. A total of 524 papers were found. After the selection process, 6 studies were selected for review. A total of 182 patients were followed for a period of 6 to 48 months. The mean age of patients was 46.46 years, and 152 implants were installed in the anterior region. Two studies achieved a reduced graft and implant failure rate, whereas the remaining 4 studies had no losses. It may be concluded that the use of ABGs and some BSs is a viable alternative for the rehabilitation with implants in individuals with anterior horizontal bone loss. However, additional randomized controlled trials are warranted due to the limited number of papers.