Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety. date disease reallife real life attacks vasoocclusive vaso occlusive events syndrome transfusion which part physicians physician s report safety

Resumo Introdução: a toxicidade financeira pode elevar os custos com cuidados em saude, alem de impactar negativamente a adesao terapéutica e a qualidade de vida relacionada a saude dos pacientes com cancer no ambito do sistema publico de saude. Objetivo: correlacionar a toxicidade financeira com a qualidade de vida relacionada a saude de adultos com cancer durante a pandemia da covid-19. Materiais e método: estudo observacional, transversal, correlacional com 179 pacientes atendidos pelo Sistema Unico de Saude, em uma capital do sul do Brasil. A coleta de dados ocorreu de setembro de 2021 a dezembro de 2022, utilizando questionarios com dados sociodemograficos e clinicos, e o COmprehensive Score for Financial Toxicity e o Functional Assessment of Cancer Therapy-General. A correlacao entre toxicidade financeira e qualidade de vida relacionada a saude foi avaliada com o coeficiente de correlacao de Spearman a um nivel de significancia de 5 %. Resultados: a correlacao entre a toxicidade financeira e a qualidade de vida relacionada a saude foi de 0,41 (p-valor < 0,001). O escore de toxicidade financeira e de qualidade de vida relacionada a saude foi de 20,1/44 e 73,3/108, respectivamente. Conclusão: este estudo revelou que, quanto menor a toxicidade financeira, melhor a qualidade de vida relacionada a saude dos pacientes. Nesse sentido, reconhecer a presenca da toxicidade financeira no itinerario terapeutico podera contribuir para melhorar a adesao ao tratamento e a qualidade de vida relacionada a saude.

Resumen Introducción: la toxicidad financiera puede aumentar los costes en salud, así como impactar negativamente en la adherencia terapéutica y en la calidad de vida relacionada con la salud de los pacientes con cáncer en el sistema público de salud. Objetivo: correlacionar la toxicidad financiera con la calidad de vida relacionada con la salud de adultos con cáncer durante la pandemia covid-19. Materiales y método: estudio observacional, transversal y correlacional con 179 pacientes atendidos por el Sistema Único de Salud en una capital del sur de Brasil. La recolección de datos se realizó de septiembre de 2021 a diciembre de 2022, utilizando cuestionarios con datos sociodemográficos y clínicos, y el COmprehensive Score for Financial Toxicity y la Functional Assessment of Cancer Therapy-General. La correlación entre la toxicidad financiera y la calidad de vida relacionada con la salud se evaluó mediante el coeficiente de correlación de Spearman a un nivel de significación del 5 %. Resultados: la correlación entre la toxicidad financiera y la calidad de vida relacionada con la salud fue de 0,41 (valor p < 0,001). Las puntuaciones de toxicidad económica y calidad de vida relacionada con la salud fueron 20,1/44 y 73,3/108, respectivamente. Conclusión: este estudio revelo que cuanto menor era la toxicidad financiera, mejor era la calidad de vida relacionada con la salud de los pacientes. En este sentido, reconocer la presencia de toxicidad financiera en el itinerario terapéutico podría ayudar a mejorar la adherencia al tratamiento y la calidad de vida relacionada con la salud.

Abstract Introduction: Financial toxicity can increase healthcare costs, in addition to negatively impacting the therapeutic adherence and healthrelated quality of life of cancer patients within the public healthcare system. Objective: To correlate financial toxicity with the adults living with cancer health-related quality of life during the COVID-19 pandemic. Materials and Methods: This is an observational, cross-sectional, correlational study conducted with 179 patients receiving care from the Unified Health System in a capital city in southern Brazil. Data collection was performed from September 2021 to December 2022, using questionnaires containing sociodemographic and clinical data, and the Comprehensive Score for Financial Toxicity and the Functional Assessment of Cancer Therapy-General. The correlation between financial toxicity and health-related quality of life was assessed using Spearman’s correlation coefficient at a 5 % significance level. Results: The correlation between financial toxicity and health-related quality of life was 0.41 (p-value < 0.001). The financial toxicity and health-related quality of life scores were 20.1/44 and 73.3/108, respectively. Conclusion: This study has found that the lower the financial toxicity, the better the patients’ health-related quality of life. In this sense, recognizing the presence of financial toxicity in the treatment course could help improve adherence to treatment and health-related quality of life.

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. Background (MTX moderatesevere moderate severe AD. . (AD) Objective 2 weeks Methods singleinstitution single institution 1 15 (1 mgwk mg wk wks nonatopic non controls nonlesional pre IL31, IL31 IL 31, 31 IL31RA, IL31RA ILRA 31RA, 31RA RA OSMR TSLP Ki67 Ki IL4 4 IL- mRNA IL6, IL6 6, 6 IL-6 IL10, IL10 10, IL-10 TNFα, TNFα TNF α, α TNF-α IFNγ, IFNγ IFN γ, γ IFN-γ TARC CCL22. CCL22 CCL 22. 22 CCL-22 Results p 0.021, 0021 0.021 , 0 021 0.021) immunohistochemistry (immunohistochemistry 0.016 0016 016 IL-3 0.019 0019 019 postMTX identified limitations followup. followup follow up. up follow-up Conclusions pruritus IL31RA. 31RA. (AD ( IL3 3 Ki6 IL1 IL-1 CCL2 CCL-2 002 0.02 02 0.01 001 01 CCL- 00 0.0 0.

ABSTRACT Objective: To analyze the compliance with the commercialization of children's products included in the Brazilian Code of Marketing of Infant and Toddlers Food and Childcare-Related Products (NBCAL) in drugstores in Uberlândia/MG. Methods: A cross-sectional study was carried out in 143 drugstores that sold infant products: infant formula (IF), follow-up IF, nipples, teats, pacifiers and nipple shields; FI for young children, transition foods and cereal-based foods, fluid or powdered milk, modified/similar milks of plant origin and dairy compounds. The location of drugstores in the five geographic sectors was performed by geoprocessing. The data collected were: types of promotion and types of drugstore administration (drugstore chains/drugstores with independent administration). Irregular commercial promotion was expressed as absolute and relative frequencies. Results: Irregular commercial promotion was found in 11.7% of nipples, pacifiers and bottles, in 10.0% of IF and follow-up formula, in 9.5% of IF for young children, in 11.1% fluid or powdered milk, in 25.0% of transition foods and cereal-based foods and in 59.1% of dairy compounds. In commercial drugstore chains, the presence of promotion for dairy (81.8 vs. 28.6%, respectively) was higher than in drugstores with independent administration. The opposite ocurred for fluid or powdered milk, modified and similar milks of plant origin. The downtown and eastern sectors had the highest percentages of promotions (26%). Conclusions: NBCAL violations still occur in drugstores, mainly in the sale of young children's foods and in the commercial network drugstores. Objective childrens children s ChildcareRelated Childcare Related (NBCAL UberlândiaMG Uberlândia MG Uberlândia/MG Methods crosssectional cross sectional 14 , (IF) followup follow up nipples teats shields cerealbased cereal based milk modifiedsimilar compounds geoprocessing were chainsdrugstores chains . administration) frequencies Results 117 11 7 11.7 bottles 100 10 0 10.0 95 9 5 9.5 111 1 11.1 250 25 25.0 591 59 59.1 81.8 818 81 8 (81. vs 286 28 6 28.6% respectively 26%. 26 26% (26%) Conclusions (IF 11. 10. 9. 2 25. 59. 81. (81 28.6 (26% (8 28. (26 ( (2

RESUMO Objetivo: Analisar a conformidade da comercialização dos produtos infantis incluídos na Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância, Bicos, Chupetas e Mamadeira (NBCAL) e de compostos lácteos em drogarias de Uberlândia/MG. Métodos: Estudo transversal realizado em 143 drogarias que vendiam produtos infantis: fórmulas infantis (FI) para lactentes, FI de seguimento para lactentes, mamadeiras, bicos, chupetas e protetores de mamilo; FI para crianças de primeira infância, alimentos de transição e alimentos à base de cereais, leites fluidos/em pó, leites modificados/similares de origem vegetal e composto lácteo. A localização das drogarias nos cinco setores geográficos foi realizada por geoprocessamento. Os dados coletados foram: tipos de promoção comercial irregular e tipo de administração da drogaria (rede/independente). As promoções comerciais irregulares foram expressas em frequências absoluta e relativa. Resultados: Verificamos a presença de promoção comercial irregular em 11,7% dos bicos, chupetas e mamadeiras, em 10,0% das FI lactentes/seguimento de lactentes, em 9,5% das FI para crianças de primeira infância, em 11,1% dos leites, em 25,0% de alimentos de transição e em 59,1% dos compostos lácteos. Nas drogarias de rede, a presença de promoção comercial irregular foi maior para compostos lácteos (81,8 vs. 28,6%, respectivamente) e, para leites, foi maior nas drogarias independentes (30,8 vs. 6,0%). Os setores central e leste apresentaram os maiores percentuais de promoção comercial irregular (26%). Conclusões: As violações à NBCAL ainda ocorrem nas drogarias, principalmente para os produtos destinados às crianças de primeira infância, e nas drogarias de rede. Objetivo Infância Bicos (NBCAL UberlândiaMG Uberlândia MG Uberlândia/MG Métodos 14 (FI lactentes mamadeiras bicos mamilo infância cereais fluidosem fluidos pó modificadossimilares modificados similares lácteo geoprocessamento rede/independente. redeindependente rede/independente . rede independente (rede/independente) relativa Resultados 117 11 7 11,7 100 10 0 10,0 lactentesseguimento 95 9 5 9,5 111 1 11,1 250 25 25,0 591 59 59,1 81,8 818 81 8 (81, vs 286 28 6 28,6% respectivamente 30,8 308 30 (30, 6,0%. 60 6,0% 6,0%) 26%. 26 26% (26%) Conclusões (rede/independente 11, 10, 9, 2 25, 59, 81, (81 28,6 30, 3 (30 6,0 (26% (8 28, (3 6, (26 ( (2

ABSTRACT Objective: To investigate the impact of tenofovir disoproxil fumarate on bone mineral density and bone mineral content in children and adolescents infected with the human immunodeficiency virus. Data source: The search procedure was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. The search was carried out until April 2022 in Medical Literature Analysis and Retrieval System Online (Medline), Embase, Cochrane Central, Latin American and Caribbean Health Sciences Literature, Web of Science, Scopus, and MedRxiv. The combination of terms used was: (Children OR Youth OR Teenagers) AND HIV AND (Tenofovir OR “Antiretroviral therapy”) AND (“Bone density” OR Osteoporosis OR Osteopenia). The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022312851) Data synthesis: The initial searches resulted in 1156 papers. After the exclusion of duplicate studies, three blinded reviewers analyzed the title and abstract of 563 papers, of which 57 remained to be read in full. Only nine papers met the eligibility criteria and were included in descriptive and risk-of-bias analyses. Regarding study design, four were cross-sectional, three were longitudinal before-after studies without a control group, and two were prospective cohorts. Among these nine papers, seven showed no significant association between tenofovir disoproxil fumarate use and reduced bone mass in young people. However, these papers did not have high methodological quality. Conclusions: Although most of the selected papers found no harmful effect of tenofovir disoproxil fumarate on bone mass, further primary research with higher methodological quality is needed so robust scientific evidences can be obtained. Objective virus source MetaAnalyses Meta Analyses Statement 202 Medline, Medline , (Medline) Embase Central Science Scopus MedRxiv Children Teenagers Tenofovir Antiretroviral therapy therapy” Bone Osteopenia. Osteopenia . Osteopenia) PROSPERO, PROSPERO (PROSPERO CRD42022312851 CRD synthesis 115 56 5 full riskofbias risk bias analyses design crosssectional, crosssectional cross sectional, sectional cross-sectional beforeafter before after group cohorts people However Conclusions obtained 20 (Medline CRD4202231285 11 2 CRD420223128 1 CRD42022312 CRD4202231 CRD420223 CRD42022 CRD4202 CRD420 CRD42 CRD4

RESUMO Objetivo: Investigar o impacto do tenofovir disoproxil fumarato sobre a densidade mineral óssea e o conteúdo mineral ósseo em crianças e adolescentes infectados pelo vírus da imunodeficiência humana. Fontes de dados: O procedimento de busca foi executado de acordo com o Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. A busca foi realizada até abril de 2022 nas seguintes bases de dados: Medical Literature Analysis and Retrieval System Online (Medline), Embase, Cochrane Central, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Web of Science, Scopus, and MedRxiv. A combinação de termos utilizada foi: (Children OR Youth OR Teenagers) AND HIV AND (Tenofovir OR “Antiretroviral therapy”) AND (“Bone density” OR Osteoporosis OR Osteopenia). O protocolo foi registrado na base International Prospective Register of Systematic Reviews — PROSPERO (CRD42022312851). Síntese dos dados: As pesquisas iniciais resultaram em 1.156 artigos. Após a exclusão dos estudos duplicados, três revisores cegos analisaram título e resumo de 563 estudos, dos quais 57 permaneceram para leitura na íntegra. Somente nove artigos atenderam aos critérios de elegibilidade e foram incluídos para análises descritivas e de risco de viés. Com relação ao desenho dos estudos, quatro foram transversais, três foram estudos longitudinais antes-depois sem grupo controle e dois foram coortes prospectivas. Dos nove artigos, sete não mostraram associação significativa entre uso de TDF e redução de massa óssea em pessoas jovens. Entretanto, esses estudos não tiveram alta qualidade metodológica. Conclusões: Embora a maioria dos estudos selecionados não tenha encontrado efeito prejudicial do TDF sobre massa óssea, novas pesquisas primárias com maior qualidade metodológica são necessárias para que sejam obtidas evidências científicas robustas. Objetivo humana dados MetaAnalyses Meta Analyses PRISMA (PRISMA Statement 202 Medline, Medline , (Medline) Embase Central LatinoAmericana Latino Americana Lilacs, Lilacs (Lilacs) Science Scopus MedRxiv Children Teenagers Tenofovir Antiretroviral therapy therapy” Bone density Osteopenia. Osteopenia . Osteopenia) CRD42022312851. CRD42022312851 CRD (CRD42022312851) 1156 1 156 1.15 duplicados 56 5 íntegra viés transversais antesdepois antes depois prospectivas jovens Entretanto Conclusões robustas 20 (Medline (Lilacs CRD4202231285 (CRD42022312851 115 15 1.1 2 CRD420223128 (CRD4202231285 11 1. CRD42022312 (CRD420223128 CRD4202231 (CRD42022312 CRD420223 (CRD4202231 CRD42022 (CRD420223 CRD4202 (CRD42022 CRD420 (CRD4202 CRD42 (CRD420 CRD4 (CRD42 (CRD4 (CRD

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min–max) SLEDAI-2 K scores were 9 (0–38), median (min–max) SLICC/ACR-DI (SDI) score were 1 (1–5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series. adultsystemic systemic SLE, , (SLE) childhoodonset childhood onset (cSLE series characteristics casenotes notes review centres biopsyproven biopsy proven activitydamage accrual centre protocol 175 07 0 7 (0.7% 91 females malignancies singlesite, singlesite site, site single-site sites 0.22% 022 22 (0.22% 0.45%. 045 0.45% . 45 (0.45%) min–max minmax min max (min–max SLEDAI2 SLEDAI SLEDAI- 0–38, 038 0–38 38 (0–38) SLICC/ACRDI SLICCACRDI SLICC/ACR DI SLICC ACR SDI (SDI 1–5 15 5 (1–5 Hodgkins Hodgkin s lymphoma nonHodgkins non leukaemia carcinoid carcinomas oligodendroglioma teratoma 0.7 diagnoses high (SLE 17 (0.7 0.22 02 (0.22 04 0.45 (0.45% 03 0–3 (0–38 ACRDI SLICCACR 1– (1– 0. (0. 0.2 (0.2 0.4 (0.45 0– (0–3 (1 (0 (0.4 (0– (

Abstract The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs. COVID19 19 COVID-1 worldwide SARSCoV2, SARSCoV2 SARSCoV SARS CoV 2, 2 nonstructural non structural 1 NSP (NSP12 RNAdependent dependent complex NSP1 evolution SARS-CoV- 202 Manaus Amazonas Brazil PL P L G671S GS G S efficiency location addition E796D ED E D R914K RK R K MV M V N911K NK N enzyme COVID1 COVID- (NSP1 SARS-CoV 20 (NSP

Abstract We investigated the vasodilatory effects of Hymenaea rubriflora Ducke stem bark extract (HR- HAc). Vascular reactivity of the aortic rings of Wistar rats was tested by in vitro cumulative doses (0.1 - 729 μg/mL). Rats (n=5) were treated with 25 (G25), 50 (G50) and 100 (G100) mg/ kg of HR-HAc or saline (control group - CG) for four weeks. An in vitro assay resulted in dose-dependent relaxation of the aortic rings with functional endothelium, which was inhibited in the presence of L-NAME. Rings of the treated animals increased acetylcholine relaxing potency at all doses, with a greater effect on G50 (pD2 = 7.8±0.1, Emax = 95.6±1.1) and a decreased contractile potency to phenylephrine in G25 (pD2 = 6.9±0.06, Emax = 61.5±6.0%) and G50 (pD2= 6.6±0.06, Emax = 71.0±8.5%) when compared to the CG in the presence and absence of endothelium (pD2= 6.4± 0.1, 6.4±0.1 and 6.9±0.1, respectively). Cumulative doses of nitroprusside resulted in increased relaxing potency in all treated groups and maintained Emax at 100%. It is concluded that HR-HAc has vasorelaxant capacity and inhibitory vascular contraction activity applied either directly to aortic rings or after treatment with in vivo supplementation, which places this extract as a potential nutraceutical or pharmacological agent for treating diseases associated with vascular dysfunction. HR (HR HAc. HAc . HAc) 0.1 01 0 1 (0. 72 μg/mL. μgmL μg/mL μg mL μg/mL) n=5 n5 n 5 (n=5 2 G25, G , (G25) (G50 10 G100 (G100 mg HRHAc control weeks dosedependent dose dependent LNAME. LNAME L NAME. NAME L-NAME G5 pD2 pD (pD 7801 7 8 7.8±0.1 95.6±1.1 95611 95 6 G2 69006 9 06 6.9±0.06 61.5±6.0% 61560 61 pD2= 66006 6.6±0.06 71.0±8.5% 71085 71 64 4 6.4 6401 6.4±0. 6901 6.9±0.1 respectively. respectively respectively) 100% supplementation dysfunction 0. (0 n= (n= (G25 (G5 G10 (G10 780 7.8±0. 95.6±1. 9561 6900 6.9±0.0 61.5±6.0 6156 6600 6.6±0.0 71.0±8.5 7108 6. 640 6.4±0 690 6.9±0. ( (n (G2 (G G1 (G1 78 7.8±0 95.6±1 956 61.5±6. 615 660 6.6±0. 71.0±8. 710 69 6.9±0 7.8± 95.6± 61.5±6 66 6.6±0 71.0±8 6.9± 7.8 95.6 61.5± 6.6± 71.0± 6.9 7. 95. 61.5 6.6 71.0 61. 71.

ABSTRACT Objective: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 – after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. Methods: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). Results: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. Conclusion: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2. Objective COVID19 COVID 19 COVID-1 D (D1 D7, , (D7) impairment Methods noninvasive non highflow high flow sumscore, sumscore sum score, sum-score tests NonInvasive Non NonIMV . Results n 31 33. 33 33) range 12 61 6 1 6. 43 4 3 4. 73 7 7. 38 8 3.8 13 1. 25 2 5 2. 26 37 3.7 unitacquired acquired 72 weak i.e., ie i e (i.e. 80 value sex Conclusion ventilated However recovery SARSCoV2. SARSCoV2 SARSCoV SARS CoV SARS-CoV-2 COVID1 COVID- (D (D7 3. i.e. (i.e SARS-CoV- i.e SARS-CoV

RESUMO Objetivo: Examinar a função física e a força muscular respiratória de pacientes que se recuperaram da COVID-19 grave após a alta da unidade de terapia intensiva para a enfermaria nos Dias 1 e 7 e investigar as variáveis associadas ao comprometimento funcional. Métodos: Trata-se de estudo de coorte prospectivo de pacientes adultos com COVID-19 que necessitaram de ventilação mecânica invasiva, ventilação mecânica não invasiva ou cânula nasal de alto fluxo e tiveram alta da unidade de terapia intensiva para a enfermaria. Os participantes foram submetidos aos testes Medical Research Council sum-score, força de preensão manual, pressão inspiratória máxima, pressão expiratória máxima e short physical performance battery. Os participantes foram agrupados em dois grupos conforme a necessidade de ventilação mecânica invasiva: o Grupo Ventilação Mecânica Invasiva (Grupo VMI) e o Grupo Não Ventilação Mecânica Invasiva (Grupo Não VMI). Resultados: Os pacientes do Grupo VMI (n = 31) eram mais jovens e tinham pontuações do Sequential Organ Failure Assessment mais altas do que os do Grupo VMI (n = 33). As pontuações do short physical performance battery (intervalo de zero a 12) nos Dias 1 e 7 foram 6,1 ± 4,3 e 7,3 ± 3,8, respectivamente para o Grupo Não VMI, e 1,3 ± 2,5 e 2,6 ± 3,7, respectivamente para o Grupo VMI. A prevalência de fraqueza adquirida na unidade de terapia intensiva no Dia 7 foi de 13% para o Grupo Não VMI e de 72% para o Grupo VMI. A pressão inspiratória máxima, a pressão expiratória máxima e a força de preensão manual aumentaram no Dia 7 em ambos os grupos, porém a pressão expiratória máxima e a força de preensão manual ainda eram fracas. Apenas a pressão inspiratória máxima foi recuperada (ou seja, > 80% do valor previsto) no Grupo Não VMI. As variáveis sexo feminino, e necessidade e duração da ventilação mecânica invasiva foram associadas de forma independente e negativa à pontuação do short physical performance battery e à força de preensão manual. Conclusão: Os pacientes que se recuperaram da COVID-19 grave e receberam ventilação mecânica invasiva apresentaram maior incapacidade do que aqueles que não foram ventilados invasivamente. No entanto, os dois grupos de pacientes apresentaram melhora funcional marginal durante a fase inicial de recuperação, independentemente da necessidade de ventilação mecânica invasiva. Esse resultado pode evidenciar a gravidade da incapacidade causada pelo SARS-CoV-2. Objetivo COVID19 COVID 19 COVID-1 Métodos Tratase Trata sumscore, sumscore sum score, score sum-score . Resultados n 31 33. 33 33) intervalo 12 61 6 6, 43 4 3 4, 73 7, 38 8 3,8 13 1, 25 2 5 2, 26 37 3,7 72 fracas seja 80 previsto feminino Conclusão invasivamente entanto recuperação SARSCoV2. SARSCoV2 SARSCoV SARS CoV 2. SARS-CoV-2 COVID1 COVID- 3, SARS-CoV- SARS-CoV

RESUMEN Objetivo: Comprender el significado atribuido por mujeres con discapacidad física a la asistencia de salud recibida y esperada durante el trabajo de parto y parto. Métodos: Estudio cualitativo, fundamentado en la Teoría de Redes Sociales, llevado a cabo mediante un taller en línea en abril de 2022, con la participación de seis mujeres con discapacidad física. Los datos, recopilados mediante la técnica de grupo focal, fueron sometidos a análisis de contenido temático con la ayuda de la herramienta IRaMuTeQ. Resultados: Emergieron tres categorías temáticas: Problemas experimentados durante el embarazo; La experiencia dentro de la maternidad; y La importancia de las redes sociales. La asistencia proporcionada por los profesionales de la salud, en ocasiones, difirió entre lo esperado y lo recibido por las mujeres con discapacidad física durante el trabajo de parto y parto. Consideraciones finales: Las experiencias fueron predominantemente negativas, resultado de conductas profesionales inadecuadas debido a actitudes capacitistas. El apoyo de los miembros de las redes sociales es fundamental para la prevención de factores estresores. Objetivo Métodos cualitativo Sociales 2022 datos focal IRaMuTeQ Resultados temáticas embarazo maternidad ocasiones finales negativas capacitistas estresores 202 20 2

ABSTRACT Objective: To understand the meaning attributed by women with physical disabilities to the health care received and expected during labor and delivery. Methods: Qualitative study, based on Social Network Theory, conducted through an online workshop in April 2022, with the participation of six women with physical disabilities. Data, collected through the focus group technique, underwent thematic content analysis with the assistance of the IRaMuTeQ tool. Results: Three thematic categories emerged: Challenges experienced during pregnancy; The experience within the maternity ward; and, The importance of social networks. The assistance provided by healthcare professionals sometimes differed between what was expected and what was received by women with physical disabilities during labor and delivery. Final Considerations: Experiences were predominantly negative, resulting from inappropriate professional conduct due to ableist attitudes. Support from members of social networks is crucial for preventing stressors. Objective delivery Methods study Theory 2022 Data technique tool Results emerged pregnancy ward Considerations negative attitudes stressors 202 20 2

RESUMO Objetivo: Compreender o significado atribuído por mulheres com deficiência física à assistência de saúde recebida e esperada durante o trabalho de parto e parto. Métodos: Estudo qualitativo, fundamentado na Teoria de Rede Social, realizado por meio de uma oficina online em abril de 2022, com a participação de seis mulheres com deficiência física. Os dados, coletados por meio da técnica de grupo focal, foram submetidos à análise de conteúdo temático com o auxílio da ferramenta IRaMuTeQ. Resultados: Três categorias temáticas emergiram: Problemas vivenciados na gravidez; A experiência dentro da maternidade; e A importância das redes sociais. A assistência prestada pelos profissionais de saúde, por vezes, diferiu entre o esperado e o recebido pelas mulheres com deficiência física durante o trabalho de parto e parto. Considerações Finais: As vivências foram predominantemente negativas, resultantes de condutas profissionais inadequadas devido a atitudes capacitistas. O apoio dos membros das redes sociais é fundamental para a prevenção de fatores estressores. Objetivo Métodos qualitativo Social 2022 dados focal IRaMuTeQ Resultados emergiram gravidez maternidade vezes Finais negativas capacitistas estressores 202 20 2

RESUMEN Objetivo: desarrollar y validar el serious game para la enseñanza-aprendizaje sobre la prevención de infecciones del sitio quirúrgico. Método: estudio metodológico realizado por etapas: desarrollo y validación del contenido del juego, basado en simulación virtual (preparación, participación y debriefing) y desafíos; desarrollo de juegos, siguiendo las etapas de concepto, preproducción, prototipo, producción y postproducción; y validación de usabilidad mediante el instrumento Heuristic Evaluation for Digital Educational Games. Para evaluar el contenido y usabilidad del juego participaron 12 enfermeros y 08 expertos en juegos digitales. Resultados: el guión del serious game contenía tres períodos pre, intra y postoperatorios secuenciales, centrándose en intervenciones de enfermería destinadas a prevenir infecciones del sitio quirúrgico. Se obtuvo un Coeficiente de Validez de Contenido superior a 0,80 para el contenido del juego. En cuanto a la evaluación de la jugabilidad mediante las heurísticas evaluadas, todas las afirmaciones presentes en el guión del juego fueron consideradas adecuadas y se implementaron ajustes en cuanto a retroalimentación, acceso al marco teórico sobre prevención de infecciones del sitio quirúrgico, inclusión de imágenes en el material de estudio y orientación del jugador en la sesión de debriefing. Conclusión: el serious game desarrollado se consideró válido y potencial herramienta pedagógica en el área de enfermería para aprender a prevenir infecciones del sitio quirúrgico. Objetivo enseñanzaaprendizaje enseñanza aprendizaje quirúrgico Método preparación, preparación (preparación debriefing desafíos concepto preproducción prototipo postproducción Games 1 0 digitales Resultados pre secuenciales 080 80 0,8 evaluadas retroalimentación Conclusión 8 0,

ABSTRACT Objective: To develop and validate serious game for teaching-learning regarding surgical site infection prevention. Method: This is a methodological study conducted in stages: game content development and validity based on virtual simulation (preparation, participation and debriefing) and challenges; game development, following the concept, pre-production, prototype, production and post-production stages; and usability validity, using an instrument called Heuristic Evaluation for Digital Educational Games. To assess the game content and usability, 12 nurses and 08 experts in digital games were involved. Results: The serious game script contained three sequential pre-, intra- and post-operative periods, focusing on nursing interventions aimed at preventing surgical site infections. A Content Validity Coefficient above 0.80 was obtained for game content. Regarding gameplay assessment using the assessed heuristics, all statements present in game script were considered adequate, and adjustments were implemented regarding feedback, access to the theoretical framework on preventing surgical site infections, the inclusion of images in the study material and directing players to the debriefing session. Conclusion: The serious game developed was considered valid and a potential pedagogical tool in nursing for learning how to prevent surgical site infections. Objective teachinglearning teaching prevention Method stages preparation, preparation (preparation challenges concept preproduction, preproduction pre production, pre-production prototype postproduction post Games 1 0 involved Results pre, , pre- intra postoperative operative periods infections 080 80 0.8 heuristics adequate feedback session Conclusion 8 0.

RESUMO Objetivo: desenvolver e validar serious game para o ensino-aprendizagem referente à prevenção de infecção de sítio cirúrgico. Método: estudo metodológico conduzido por etapas: desenvolvimento e validação do conteúdo do jogo, baseados na simulação virtual (preparação, participação e debriefing) e desafios; desenvolvimento do jogo, seguindo as etapas de conceito, pré-produção, protótipo, produção e pós-produção; e, validação da usabilidade, por meio do instrumento Heuristic Evaluation for Digital Educational Games. Para avaliação do conteúdo e usabilidade do jogo, contou-se com 12 enfermeiros e 08 especialistas em jogos digitais. Resultados: o script do serious game conteve três períodos sequenciais pré, intra e pós-operatório, com enfoque em intervenções de enfermagem voltadas para prevenção de infecção de sítio cirúrgico. Obteve-se um Coeficiente de Validade de Conteúdo acima de 0,80 para o conteúdo do jogo. Referente à avaliação da jogabilidade pelas heurísticas avaliadas, todas as afirmativas presentes no script do jogo foram consideradas adequadas e houve a implementação de ajustes no que se refere ao feedback, ao acesso ao referencial teórico sobre prevenção de infecção de sítio cirúrgico, à inclusão de imagens no material de estudo e ao direcionamento do jogador à sessão de debriefing. Conclusão: o serious game desenvolvido foi considerado válido e potencial ferramenta pedagógica na área de enfermagem para aprendizagem da prevenção de infecção de sítio cirúrgico. Objetivo ensinoaprendizagem ensino cirúrgico Método preparação, preparação (preparação debriefing desafios conceito préprodução, préprodução pré produção, pré-produção protótipo pósprodução pós pós-produção Games contouse contou 1 0 digitais Resultados pósoperatório, pósoperatório operatório, operatório pós-operatório Obtevese Obteve 080 80 0,8 avaliadas feedback Conclusão 8 0,

Abstract: Eugenia klotzschiana, commonly known as pêra-do-cerrado, belongs to the Myrtaceae family. It is an unconventional food plant that is exploited in an extractive manner. The purpose of this study was to investigate the germination behavior of E. klotzschiana O. Berg seeds and their sensitivity to desiccation. The seeds were manually pulped from the fruits and stored in plastic containers. The initial water content was subsequently determined using the oven method at 105°C for 24 hours, yielding a value of 46.6%. Sub-samples were then separated to obtain the desired water contents of 40%, 32%, 22%, and 15% for treatments 2, 3, 4, and 5. The data underwent analysis of variance (ANOVA) and, if significant by the F test (p<0.05), the means were compared using the T test. Graphs with 95% confidence intervals were generated to illustrate the comparisons. The seedling development data was arranged in a box plot. The R software was used for these analyses. The data analysis revealed that E. klotzschiana O. Berg seeds do not have the potential to germinate with a water content lower than 22.50% moisture. Furthermore, the water content with the highest percentage, 46.6%, resulted in 100% germination. Abstract pêradocerrado, pêradocerrado pêra cerrado, cerrado pêra-do-cerrado family manner E O desiccation containers 105C C 105 2 hours 466 46 6 46.6% Subsamples Sub samples 40 40% 32 32% 22 22% 15 3 4 5 ANOVA (ANOVA p<0.05, p005 p p<0.05 , 0 05 (p<0.05) 95 comparisons plot analyses 2250 50 22.50 moisture Furthermore percentage 100 10 46.6 1 p00 p<0.0 (p<0.05 9 225 22.5 46. p0 p<0. (p<0.0 22. p<0 (p<0. p< (p<0 (p< (p

Resumo Eugenia klotzschiana (pêra-do-cerrado) pertence à família Myrtaceae. É caracterizada como planta alimentícia não convencional, sendo explorada de forma extrativista. Este trabalho foi desenvolvido para conhecer o comportamento germinativo das sementes de E. klotzschiana e ainda a sua sensibilidade à dessecação. Após a despolpa dos frutos, realizada manualmente, as sementes foram armazena das em embalagens plásticas. O teor de água inicial foi determinado pelo método da estufa a 105°C por 24 horas, com valor de 46,6%. Separaram-se, em seguida,subamostras para obtenção dos demais teores de água desejados: 40%, 32%, 22% e 15%, sendo,respectivamente,os tratamentos 2, 3, 4 e 5. Os dados foram submetidos à análise de variância(ANOVA) e, quando significativas pelo teste F (p<0,05), as médias foram comparadas pelo teste T. Para ilustrar as comparações, foram gerados gráficos com intervalos de confiança de95%. Foi realizada também a disposição dos dados do desenvolvimento das plântulas em Boxplot. Essas análises foram desenvolvidas utilizando-se o software R. A partir da análise dos dados,foi possível constatar que as sementes de E. klotzschiana O. Berg nãoapresentam potencial germinativo com teor de água inferior a 22,5% de umidade. Além disso, o maiorteor de água de 46,6% proporcionou 100% de germinação. pêradocerrado pêra cerrado (pêra-do-cerrado Myrtaceae convencional extrativista E dessecação frutos manualmente plásticas 105C C 105 2 horas 466 46 6 Separaramse, Separaramse Separaram se, se Separaram-se seguidasubamostras seguida subamostras desejados 40 40% 32 32% 22 15 15% sendorespectivamenteos respectivamente os 3 5 variânciaANOVA variância ANOVA variância(ANOVA p<0,05, p005 p p<0,05 , 0 05 (p<0,05) T comparações de95 de95% Boxplot utilizandose utilizando R dadosfoi 225 22,5 umidade disso 46,6 100 germinação 10 1 p00 p<0,0 (p<0,05 de9 22, 46, p0 p<0, (p<0,0 p<0 (p<0, p< (p<0 (p< (p

Abstract This cross-sectional study investigated the association of SNPs rs670 (C>T) and rs693 (G>A) with parameters of lipid metabolism and endothelial activation in 167 subjects, including 86 COVID-19 outpatients and 81 healthy subjects (control group) matched for sex and age. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), triglycerides (TG), apolipoproteins (Apo A-I and B), and vascular cell adhesion molecule-1 (VCAM-1) were determined. The SNPs were genotyped by quantitative polymerase chain reaction (qPCR). A p -value<0.05 was assumed. COVID-19 outpatients showed increases in TC (187.0±48.3 vs . 160.8±32.0 mg/dL), LDL-c (110.3±41.5 vs . 98.8±28.2 mg/dL), non-HDL-c (138.3±45.8 vs . 115.6±31.6 mg/dL), TG (139.7±80.3 vs . 84.9±35.1 mg/dL), and Apo A-I (149.5±40.0 vs . 133.3±20.9 mg/dL), along with a high frequency of hypercholesterolemia and hypertriglyceridemia. VCAM-1 levels were double those of the control (682.7±231.8 vs. 299.3±102.9 ng/mL) and a strong predictor of COVID-19 (AUC=0.946). Moreover, VCAM-1 correlated with TC (r = -0.223) and HDL-c (r = -0.225). The decrease in TG and VCAM-1 is predicted by the dominance of the T allele (rs670) and its codominance with the A (rs693) allele in COVID-19 outpatients. COVID-19 has been shown to be associated with dyslipidemias and endothelial activation, and apolipoprotein polymorphisms may influence this. crosssectional cross sectional rs rs67 C>T CT C (C>T rs69 G>A GA G (G>A 16 8 COVID19 COVID 19 COVID-1 group age TC, , (TC) highdensity density HDLc, HDLc HDL c (HDL-c) lowdensity low LDLc, LDLc LDL (LDL-c) nonhighdensity non nonHDLc, nonHDLc (non-HDL-c) TG, (TG) AI I B, B B) molecule1 molecule 1 molecule- VCAM1 VCAM (VCAM-1 determined qPCR. qPCR (qPCR) value<0.05 value005 value 0 05 -value<0.0 assumed 187.0±48.3 1870483 187 48 3 (187.0±48. 1608320 160 32 160.8±32. mg/dL, mgdL mg/dL mg dL mg/dL) 110.3±41.5 1103415 110 41 5 (110.3±41. 988282 98 28 2 98.8±28. 138.3±45.8 1383458 138 45 (138.3±45. 1156316 115 6 31 115.6±31. 139.7±80.3 1397803 139 7 80 (139.7±80. 849351 84 9 35 84.9±35. 149.5±40.0 1495400 149 40 (149.5±40. 1333209 133 20 133.3±20. hypertriglyceridemia VCAM- 682.7±231.8 68272318 682 231 (682.7±231. 29931029 299 102 299.3±102. ng/mL ngmL ng mL AUC=0.946. AUC0946 AUC AUC=0.946 946 (AUC=0.946) Moreover r 0.223 0223 223 -0.223 0.225. 0225 0.225 225 -0.225) (rs670 (rs693 this rs6 COVID1 COVID- (TC (HDL-c (LDL-c (non-HDL-c (TG (VCAM- (qPCR value<0.0 value00 -value<0. 187.0±48. 187048 18 4 (187.0±48 160832 160.8±32 110.3±41. 110341 11 (110.3±41 98828 98.8±28 138.3±45. 138345 13 (138.3±45 115631 115.6±31 139.7±80. 139780 (139.7±80 84935 84.9±35 149.5±40. 149540 14 (149.5±40 133320 133.3±20 682.7±231. 6827231 68 23 (682.7±231 2993102 29 10 299.3±102 AUC094 AUC=0.94 94 (AUC=0.946 0.22 022 22 -0.22 -0.225 (rs67 (rs69 (VCAM value<0. value0 -value<0 187.0±48 18704 (187.0±4 16083 160.8±3 110.3±41 11034 (110.3±4 9882 98.8±2 138.3±45 13834 (138.3±4 11563 115.6±3 139.7±80 13978 (139.7±8 8493 84.9±3 149.5±40 14954 (149.5±4 13332 133.3±2 682.7±231 682723 (682.7±23 299310 299.3±10 AUC09 AUC=0.9 (AUC=0.94 0.2 02 -0.2 (rs6 value<0 -value< 187.0±4 1870 (187.0± 1608 160.8± 110.3±4 1103 (110.3± 988 98.8± 138.3±4 1383 (138.3± 1156 115.6± 139.7±8 1397 (139.7± 849 84.9± 149.5±4 1495 (149.5± 1333 133.3± 682.7±23 68272 (682.7±2 29931 299.3±1 AUC0 AUC=0. (AUC=0.9 0. -0. (rs value< -value 187.0± (187.0 160.8 110.3± (110.3 98.8 138.3± (138.3 115.6 139.7± (139.7 84.9 149.5± (149.5 133.3 682.7±2 6827 (682.7± 2993 299.3± AUC=0 (AUC=0. -0 187.0 (187. 160. 110.3 (110. 98. 138.3 (138. 115. 139.7 (139. 84. 149.5 (149. 133. 682.7± (682.7 299.3 AUC= (AUC=0 - 187. (187 110. (110 138. (138 139. (139 149. (149 682.7 (682. 299. (AUC= (18 (11 (13 (14 682. (682 (AUC (1 (68 ( (6

Abstract The disruption of cell cycle phases is one of the characteristics acquired by tumor cells during the process of carcinogenesis. In this study, we investigated the differences in cell cycle phases among human cell lines derived from triple-negative (BT-549), colorectal (RKO-AS45-1), and ovarian (TOV-21G) cancers treated with everolimus, recombinant TGF-alpha, and Methotrexate (MTX). Our data showed that MTX induced the transition from G1 to S phase in TOV-21G, while TGF-alpha decreased the percentage of cells in G1. For the triple-negative breast cancer (TNBC) cell line, TGF-alpha reduced the number of cells in G1. In the case of the RKO-AS45-1 cell line, no treatment affected the dynamics of the cell cycle in these cells, indicating intrinsic resistance to the treatments used. carcinogenesis study triplenegative triple negative BT549, BT549 BT 549 , (BT-549) RKOAS451, RKOAS451 RKOAS RKO AS45 1 AS (RKO-AS45-1) TOV21G TOVG TOV 21G G (TOV-21G everolimus TGFalpha, TGFalpha TGF alpha, alpha MTX. . (MTX) TOV21G, 21G, TOV-21G TNBC (TNBC line RKO-AS45- used BT54 54 (BT-549 RKOAS45 AS4 (RKO-AS45-1 (MTX RKO-AS45 BT5 5 (BT-54 RKOAS4 (RKO-AS45- RKO-AS4 (BT-5 (RKO-AS45 RKO-AS (BT- (RKO-AS4 (BT (RKO-AS