Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population.

INTRODUCTION: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. METHODS: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. RESULTS: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. CONCLUSION: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. GOV REGISTRATION: NCT03892655.

Rediscovering Portuguese White Crowberries (Corema album): Cultural Insights and Nutritional Significance.

White crowberries (Corema album) are a fruit from an endemic shrub found in Southern European Atlantic costal dunes. Although this shrub and its fruits never became a formal commercial crop for a number of reasons, it has a long-lasting relevance and tradition, much associated with summer, beach and holidays. The main goal of this study was to conduct a thematic analysis of the words and small expressions people associate with white crowberries. For that, a questionnaire was used, and the participants were asked to indicate in an open-ended question which top-of-mind words/small expressions they associate with white crowberries. A total of 501 people participated in this study, of which only 394 knew about white crowberries, and from those, only 229 answered the open-ended question of interest to this purpose. The results showed that the words/small expressions given by the participants were distributed between five categories (1-Memories of places, people and times, 2-Emotions and experiences, 3-Sensorial perception, 4-Properties and uses, and 5-Natural resources' valuation). Additionally, 18 subcategories were also identified. The most representative of the categories was sensorial perception and the most relevant of the subcategories was habitats (a subcategory from category 1). The most frequent words mentioned by the participants were beach, berry and summer. In addition, the effect of sociodemographic groups was investigated and some variations were observed in the categories of the words mentioned by the participants according to sex, living environment or region. This work allowed for the identification of a high variability in the words or expressions that account for a rich patrimony of tacit knowledge, memories, emotions and perceptions of the population towards white crowberries, thus confirming their social as well as nutritional relevance.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

Anti-Acanthamoeba metallopharmaceuticals: Amoebicidal activity and synergistic effect of copper(II) coordination compound.

Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492). The cytotoxicity on rabbit corneal cell line (ATCC-CCL 60) was performed. The compounds showed high amoebicidal potential, with inhibition of trophozoite viability above 80%. The Cp12 and Cp13 compounds showed Minimal Inhibitory Amoebicidal Concentration (MIAC) at 200 µM and mean inhibitory concentration (IC50) values lower than 10 µM. Against the cysts, Cp12 showed a reduction in viability (48%) in the longest incubation period. A synergistic effect for Cp12 with chlorhexidine was observed. The compounds have a dose-dependent effect against rabbit corneal cells. Compound Cp12 has potential for future application in developing ophthalmic formulations against Acanthamoeba keratitis and its use in multipurpose solutions is highlighted.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Early Intensive Neurorehabilitation in Traumatic Peripheral Nerve Injury-State of the Art.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.

Fertilization with follicular fluid reduces HSP70 and BAX expression on bovine in vitro embryos.

The in vivo fertilization process occurs in the presence of follicular fluid (FF). The aim of this study was to evaluate the effect of in vitro fertilization medium supplementation with 5% or 10% bovine follicular fluid (BFF) on the production of in vitro bovine embryos. FF was collected from ovarian follicles with a diameter of 8-10 mm, and cumulus-oocyte complexes (COCs) were co-incubated with sperm for 24 h in the commercial medium BotuFIV® (BotuPharma©), being distributed among the experimental groups: oocytes fertilized in a control medium; oocytes fertilized in a medium supplemented with 5% BFF; and oocytes fertilized in a medium supplemented with 10% BFF. After fertilization, the zygotes were cultured in vitro for 8 days. Embryo development was assessed through cleavage rates (day 2) and blastocyst formation rates (day 8). The relative expression of the genes OCT4, IFNT2, BAX, HSP70 and SOD2 was measured using the real-time polymerase chain reaction method. There was no difference (p > .05) among the different experimental groups in terms of cleavage rates and blastocyst formation rates. Regarding the gene expression results, only the blastocysts from oocytes fertilized with 10% BFF showed significantly lower expression of IFNT2 (p = .003) and SOD2 (p = .01) genes compared to blastocysts from oocytes fertilized in control medium alone, while there was no difference between blastocyst from oocytes fertilized in control medium and the ones from oocytes fertilized with 5% BFF. In addition to this, the blastocysts from oocytes fertilized with 5% BFF showed significantly reduced levels of expression of the heat shock protein HSP70 (p < .001) and the pro-apoptotic protein BAX (p = .015) compared to blastocysts from oocytes fertilized with control medium. This may indicate that lower supplementation of BFF to the IVF medium creates a more suitable environment for fertilization and is less stressful for the zygote.

Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study.

Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).

Chronic arsenic exposure suppresses proteasomal and autophagic protein degradation.

Ubiquitin Proteasomal System (UPS) and autophagy dysregulation initiate cancer. These pathways are regulated by zinc finger proteins. Trivalent inorganic arsenic (iAs) displaces zinc from zinc finger proteins disrupting functions of important cellular proteins. The effect of chronic environmental iAs exposure (100 nM) on UPS has not been studied. We tested the hypothesis that environmental iAs exposure suppresses UPS, activating autophagy as a compensatory mechanism. We exposed skin (HaCaT and Ker-CT; independent quadruplicates) and lung (BEAS-2B; independent triplicates) cell cultures to 0 or 100 nM iAs for 7 or 8 weeks. We quantified ER stress (XBP1 splicing employing Reverse Transcriptase -Polymerase Chain Reaction), proteasomal degradation (immunoblots), and initiation and completion of autophagy (immunoblots). We demonstrate that chronic iAs exposure suppresses UPS, initiates autophagy, but suppresses autophagic protein degradation in skin and lung cell lines. Our data suggest that chronic iAs exposure inhibits autophagy which subsequently suppresses UPS.

Psoriasis and steatotic liver disease: Are PNPLA3 and TM6SF2 polymorphisms suitable for the hepato-dermal axis hypothesis?

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.

Distinct ontogenetic lineages dictate cDC2 heterogeneity.

Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet+ cDC2As and T-bet- cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues. Here, we identified distinct mouse pre-cDC2 subsets biased to give rise to cDC2As or cDC2Bs. We showed that a Siglec-H+ pre-cDC2A population in the bone marrow preferentially gave rise to Siglec-H- CD8α+ pre-cDC2As in tissues, which differentiated into T-bet+ cDC2As. In contrast, a Siglec-H- fraction of pre-cDCs in the bone marrow and periphery mostly generated T-bet- cDC2Bs, a lineage marked by the expression of LysM. Our results showed that cDC2A versus cDC2B fate specification starts in the bone marrow and suggest that cDC2 subsets are ontogenetically determined lineages, rather than cell states imposed by the peripheral tissue environment.

The Role of Early Rehabilitation and Functional Electrical Stimulation in Rehabilitation for Cats with Partial Traumatic Brachial Plexus Injury: A Pilot Study on Domestic Cats in Portugal.

This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore responses to an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal approach were based on the potential structural and protective role of proteins and the release of neurotrophic factors. Furthermore, FES was parametrized according to the presence or absence of deep pain. Following treatment, 72.6% of the cats achieved ambulation: 9 cats within 15 days, 2 cats within 30 days and 5 cats within 60 days. During the four-year follow-up, there was evidence of improvement in both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats showed improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES applied in the first weeks after injury and accurate parametrization according to the presence or absence of deep pain, may help in functional recovery and ambulation, reducing the probability of amputation.

Religiosidade/espiritualidade entre a população brasileira diante da pandemia Covid-19 e a correlação com a qualidade de vida / Religiosity/spirituality among the brazilian population in the face of the Covid-19 pandemic and the correlation with quality of life / Religiosidad/espiritualidad en la población brasileña frente a la pandemia de Covid-19 y la correlación con la calidad de vida

A pandemia causada pelo SARS-CoV-2 (COVID-19) trouxe inúmeros impactos na vida cotidiana, tanto nos aspectos econômicos, como nos emocionais, psicológicos e sociais. Em situações difíceis, as pessoas, muitas vezes, recorrem à espiritualidade ou à religiosidade. O objetivo deste estudo foi investigar a presença da religiosidade/espiritualidade entre a população brasileira diante da pandemia da COVID- 19, correlacionado com a qualidade de vida. É um estudo quantitativo, descritivo e transversal, realizado nos últimos meses de 2020. Os dados foram coletados por meio de respostas aos instrumentos WHOQOL-Bref e o WHOQOL-SRPB, de forma online, por meio do Google Forms®. Utilizou-se o método de amostragem não probabilístico do tipo snowball sampling, totalizando 948 respostas. Os dados foram tabulados por meio do software Microsoft Excel (2019) e analisados estatisticamente, considerando significativo p<0,05. Os dados apresentados mostram de forma enfática como os participantes que pertencem a alguma religião, apresentaram melhor relação nos domínios saúde psicológica, independência, meio ambiente e espiritualidade/religião/crenças pessoais em comparação àqueles que declaram não pertencer a uma religião. No entanto, não houve diferença estatisticamente significativa para os domínios saúde física e relações sociais. Conclui-se que o pertencimento a uma religião pode contribuir para a melhoria da qualidade de vida e auxiliar o enfrentamento das situações desfavoráveis durante a pandemia COVID-19. Diante disso, destaca-se a importância do desenvolvimento de novos estudos sobre o tema, para compreender com mais veemência e detalhamento, a relação dessas variáveis em contextos de crise que possam alterar a rotina de vida das pessoas.

The pandemic caused by SARS-CoV-2 (COVID-19) has brought numerous impacts on daily life, both in economic, emotional, psychological, and social aspects. In difficult situations, people often turn to spirituality or religiosity. The objective of this study was to investigate the presence of religiosity/spirituality among the Brazilian population facing the pandemic of COVID-19, correlated with quality of life. Quantitative, descriptive, cross-sectional study conducted in the last months of 2020. Data were collected by means of responses to the WHOQOL-Bref and the WHOQOL-SRPB instruments, online, through Google Forms®. The non-probabilistic snowball sampling method was used, totaling 948 answers. Data were tabulated using Microsoft Excel software (2019) and statistically analyzed, considering p<0.05 significant. The data presented emphatically show how the participants, who belong to some religion, presented a better relationship in the domains psychological health, independence, and environment and spirituality/religion/personal beliefs compared to those who do not have a religion. However, there was no statistically significant difference for the physical health and social relationships domains. It is concluded that belonging to a religion can contribute to improved quality of life and assist in coping with unfavorable situations during the COVID-19 pandemic. Therefore, the importance of developing new studies on the subject is highlighted, in order to understand more vehemently the relationship of these variables in crisis contexts that can change the routine of people's lives.

La pandemia causada por el SARS-CoV-2 (COVID-19) ha traído numerosos impactos en la vida cotidiana, tanto en los aspectos económicos, emocionales, psicológicos y sociales. En situaciones difíciles, las personas suelen recurrir a la espiritualidad o la religiosidad. El objetivo de este estudio fue investigar la presencia de religiosidad/espiritualidad en la población brasileña que enfrenta la pandemia de COVID- 19, correlacionada con la calidad de vida. Estudio cuantitativo, descriptivo, transversal, realizado en los últimos meses de 2020. Los datos fueron recolectados por medio de respuestas a los instrumentos WHOQOL-Bref y WHOQOL-SRPB, en línea, a través de Google Forms®. Se utilizó el método de muestreo no probabilístico de bola de nieve, totalizando 948 respuestas. Los datos fueron tabulados utilizando el software Microsoft Excel (2019) y analizados estadísticamente, considerando p<0,05 significativa. Los datos presentados muestran enfáticamente cómo los participantes, que pertenecen a alguna religión, presentaron una mejor relación en los dominios salud psicológica, independencia y entorno y espiritualidad/religión/creencias personales en comparación con aquellos que no tienen religión. Sin embargo, no hubo diferencias estadísticamente significativas para los dominios salud física y relaciones sociales. Se concluye que la pertenencia a una religión puede contribuir a mejorar la calidad de vida y ayudar a afrontar situaciones desfavorables durante la pandemia de COVID-19. Por lo tanto, se destaca la importancia de desarrollar nuevos estudios sobre el tema, para comprender con más vehemencia la relación de estas variables en contextos de crisis que pueden cambiar la rutina de vida de las personas.

Assessing Mode-Switching Strategies for Assistive Robotic Manipulators Using a Preliminary Version of the Novel Non-invasive Tongue-Computer Interface.

The inductive tongue-computer interface allows individuals with tetraplegia to control assistive devices. However, controlling assistive robotic arms often requires more than 14 different commands, which cannot always fit into a single control layout. Previous studies have separated the commands into modes, but few have investigated strategies to switch between them. In this feasibility study, we compare the efficiency of switching modes using buttons, swipe gestures and double taps using a preliminary version of a new non-invasive mouthpiece unit (nMPU), which includes an integrated activation unit and a single sensor board. Three participants controlled a JACO assistive robot to pick up a bottle using different mode-switching strategies. Compared with switching modes with buttons, switching modes with swipes and double taps increased the task completion time by 21% and 58% respectively. Therefore, we recommend that configurations with multiple modes for the non-invasive tongue-computer interface include buttons for mode-switching.Clinical relevance- Cumbersome mode-switching strategies can lower a control interface's responsiveness and contribute to end-user abandonment of assistive technologies. This study showed that using buttons to switch modes is more reliable. Moreover, this study will inform the development of future control layouts with improved usability.

Using workspace restrictiveness for adaptive velocity adjustment of assistive robots and upper limb exoskeletons.

Individuals with severe disabilities can benefit from assistive robotic systems (ARS) for performing activities of daily living. However, limited control interfaces are available for individuals who cannot use their hands for the control, and most of these interfaces require high effort to perform simple tasks. Therefore, autonomous and intelligent control strategies were proposed for assisting with the control in complex tasks. In this paper, we presented an autonomous and adaptive method for adjusting an assistive robot's velocity in different regions of its workspace and reducing the robot velocity where fine control is required. Two participants controlled a JACO assistive robot to grasp and lift a bottle with and without the velocity adjustment method. The task was performed 9.1% faster with velocity adjustment. Furthermore, analyzing the robot trajectory showed that the method recognized highly restrictive regions and reduced the robot end-effector velocity accordingly.Clinical relevance- The autonomous velocity adjustment method can ease the control of ARSs and improve their usability, leading to a higher quality of life for individuals with severe disabilities who can benefit from ARSs.

The Effect of Upper Eyelid Blepharoplasty on Corneal Tomography and Epithelial Profile.

Introduction: Upper tarsal mechanical forces influence corneal epithelial thickness profile, which could modulate corneal astigmatism. Upper eyelid blepharoplasty reduces upper tarsal strength and may have an impact on ocular surface. The aim of this study is to evaluate the effect of upper eyelid blepharoplasty on corneal epithelial thickness profile, astigmatism and aberrations. Methods: Patients with dermatochalasis underwent bilateral upper eyelid blepharoplasty. Anterior segment optical coherence tomography (AS-OCT) (Zeiss Cirrus 5000 HD-OCT) and Pentacam (Oculus, Wetzlar Germany) were performed before surgery and in the 8th postoperative week. Corneal epithelial thickness, keratometry, aberrations and asphericity were considered for statistical purposes. Only right eyes were considered. A p-value lower than 0.05 was considered significant. Results: Thirty eyes of 30 patients were included. The degree of astigmatism did not change after surgery (0.95D vs 0.83D, p=0.23). The difference between preoperative and postoperative steepest axis was 3.1° (p=0.04) with a tendency to change toward the vertical meridian. Mean epithelial thickness was higher in the inferior region both pre- and postoperatively and did not change. ET in the superior octant was lower (42 µm vs 45 µm, p<0.01) and the difference between inferior and superior octants (I-S) was higher (7 µm vs 3 µm, p<0.001) before surgery. There were no statistically significant changes in corneal aberrations (p=0.52) and asphericity (p=0.41) after surgery. Conclusion: Our results support that upper tarsus pressure influences epithelial thickness profile and, consequently, the corneal steepest keratometry. These results lead us to postulate that upper eyelid blepharoplasty may influence biometric and keratometric measurements.

IL-4 shapes microglia-dependent pruning of the cerebellum during postnatal development.

Interleukin-4 (IL-4) is a type 2 cytokine with pleiotropic functions in adaptive immunity, allergies, and cognitive processes. Here, we show that low levels of IL-4 in the early postnatal stage delineate a critical period in which microglia extensively prune cerebellar neurons. Elevating the levels of this cytokine via peripheral injection, or using a mouse model of allergic asthma, leads to defective pruning, permanent increase in cerebellar granule cells, and circuit alterations. These animals also show a hyperkinetic and impulsive-like phenotype, reminiscent of attention-deficit hyperactivity disorder (ADHD). These alterations are blocked in Il4rαfl/fl::Cx3cr1-CreER mice, which are deficient in IL-4 receptor signaling in microglia. These findings demonstrate a previously unknown role for IL-4 during a neuroimmune critical period of cerebellar maturation and provide a first putative mechanism for the comorbidity between allergic disease and ADHD observed in humans.