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Gaik Tian Ong, Sarimah Abdullah, Norsa’adah binti Bachok Biostatistics and Research Methodology Unit, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, MalaysiaCorrespondence: Sarimah Abdullah, Biostatistics and Research Methodology Unit, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab 2, Kubang Kerian, Kota Bharu, Kelantan, 16150, Malaysia, Tel +60199569759, Email sarimah@usm.myPurpose: The bilingual Malaysia Medication Adherence Assessment Tool (MyMAAT) was developed using the Exploratory Factor Analysis (EFA) and the current study intended to confirm the measurement model, dimensionality and ensure the factor structure by the Confirmatory Factor Analysis (CFA). The objective of this study was to validate the Malay version of the MyMAAT in measuring medication adherence among participants with chronic medications.Patients and Methods: A cross-sectional study was conducted using a self-report questionnaire at five health clinics and a hospital in Kuala Lumpur and Putrajaya region between May to November 2023. The participants were selected using quota sampling and written informed consent was obtained from each participant prior to data collection. There are two constructs in the MyMAAT, namely the Specific Medication-Taking Behaviour (Factor 1) and the Social-Cognitive Theory of Self-Efficacy and Social Support (Factor 2).Results: Four hundred and seventy participants participated in the CFA study. The final model for the Malay version of the MyMAAT retained the two constructs and 12 items with good fit: CFI = 0.978, TLI = 0.973, RMSEA = 0.036 (90% CI 0.001,0.067) and with good composite reliability CR 0.790 for Factor 1 and 0.787 for Factor 2. The factor loadings ranged from 0.413 to 0.832 with p-value < 0.001. The AVE for Factor 1 was 0.664 and for Factor 2 was 0.491. There was a strong correlation (ρ = 0.507, p < 0.001) between the Malay version of the MyMAAT and the Malay version of the MMAS-8 by adherence category from the data of 191 participants. Twenty-six participants completed the test–retest after five to ten days from the first administration. The Malay version of the MyMAAT showed moderate to excellent with ICC 0.932 (95% CI: 0.661,0.986) for Factor 1 and poor to excellent for with ICC 0.956 (95% CI:0.325,0.997) for Factor 2 by using the Two-Way Mixed Model and Consistency type.Conclusion: It is concluded that the Malay version of the MyMAAT is valid and reliable in measuring medication adherence among patients with chronic medications.Keywords: validation, questionnaire, medication-taking behaviour, social-cognitive theory, self-efficacy, social support

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long-Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space.

Anwar E Ahmed,1 Callista B Martin,2 Bassam Dahman,3 Gregory T Chesnut,4,5 Sean Q Kern4,5 1Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; 2School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; 3Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA, USA; 4Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; 5Center for Prostate Disease Research, Murtha Cancer Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USACorrespondence: Anwar E Ahmed, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road A-1039D, Bethesda, MD, 20814, USA, Tel +1 301-295-9756, Email anwar.ahmed@usuhs.eduBackground: Research suggests inconsistent evidence regarding the association between general obesity and prostate cancer among men in the United States. This study aimed to examine whether the association between general obesity and prostate cancer is influenced by abdominal obesity and ethnic groups.Methods: The study utilized data from the National Health and Nutrition Examination Survey (NHANES). The analysis was restricted to non-Hispanic men (10,683 White and 6,020 Black). Obesity was defined as body mass index (BMI) ≥ 30 and abdominal obesity as waist circumference (WC) ≥ 102 cm.Results: No significant difference was identified in the overall prevalence of prostate cancer between obese and non-obese (2.14% vs 2.25%, P = 0.678). When both obesity measures were combined, the general and abdominal obesity category was associated with a significant increase in the odds of prostate cancer in Black men [odds ratio (OR) = 1.49, 95% confidence interval (CI) (1.09, 2.04)], but not in White men [OR = 1.29, 95% CI (0.91, 1.82)]. In both Black [OR = 2.46, 95% CI (1.48, 4.06)] and White men [OR = 1.60, 95% CI (1.16, 2.21)], abdominal obesity was associated with significant increase in the odds of prostate cancer.Conclusion: The association between general obesity and prevalence of prostate cancer depends on abdominal obesity and ethnic groups. Our study utilized a nationally representative survey and emphasized the potential of combined effect of general and abdominal obesity as a modifiable factor to decrease racial disparity in prostate cancer screening and poor outcomes.Keywords: prostate cancer, waist circumference, obesity, Black men, racial disparity

The purpose of this research is to make an Android-based educational game to introduce endemic animals to the island of Borneo using Construct 2, the results of which can be useful for the community to increase knowledge about endemic animals on the island of Borneo. This educational game has a game of arranging animal name letters and multiple choice questions which are expected to hone the user's memory of endemic animals on the island of Borneo. The method used in this research is the Multimedia Development Life Cycle (MDLC) method are concept, design, material collecting, assembly, testing, and distribution. In this study, Black Box Testing was carried out and the result was that the game system ran well and its functionality could work smoothly. Based on the results of the questionnaire which was filled in by 30 respondents, the Endemic Animals of Kalimantan game was in the interval of strongly agreeing with the questionnaire and application category with a percentage of 85.42%, which means that the Endemic Animals of Kalimantan game is in demand by the public.

Background: The important issues of vaccination need to be integrated between medical science, the Islamic religion and the religious-social-cultural values of the community. The integration is important to build public trust in the vaccination program. Objective: to integrate the important issues of vaccination into the religious and socio-cultural values of the Banjar community. Methods: The research was designed qualitatively based on a phenomenological paradigm through field observations and in-depth interviews with Banjar community participants who did not vaccinate and participants who were experts in medicine-immunology-Islamic law-social-cultural in the Banjar community. Results: The research showed that some Banjar people still did not understand the principles of vaccination, the concept of istihalah and herd immunity. The Banjar community was a religious society, that liked to work together and care about their fellow citizens. Conclusion: The principles of vaccination, istihalah, and herd immunity can be integrated with the Banjar community who are religious, like working together, and care about their fellow citizens to build public trust in the vaccination program.

The Society of Cardiovascular Anesthesiologists (SCA) is committed to improving the quality, safety, and value that cardiothoracic anesthesiologists bring to patient care. To fulfill this mission, the SCA supports the creation of peer-reviewed manuscripts that establish standards, produce guidelines, critically analyze the literature, interpret preexisting guidelines, and allow experts to engage in consensus opinion. The aim of this report, commissioned by the SCA President, is to summarize the distinctions among these publications and describe a novel SCA-supported framework that provides guidance to SCA members for the creation of these publications. The ultimate goal is that through a standardized and transparent process, the SCA will facilitate up-to-date education and implementation of best practices by cardiovascular and thoracic anesthesiologists to improve patient safety, quality of care, and outcomes.

AbstractChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Currently, the environmental crisis is one of the key issues that need to be addressed. Cellulose is one such material which can be used as it is abundant and eco-friendly. The production and use of cellulose-based materials generally have a lower environmental footprint compared to synthetic polymers. Cellulose is biocompatible, making it safe for medical and pharmaceutical uses. These materials are lightweight with fibrous structures that are well suited for use in paper and textile industries. Other advantages of these materials are availability from renewable plant sources, possible use of recycled materials, and lower production costs. In packaging, it is used for its eco-friendly and biodegradable nature. Such materials are also used in health care electronics, construction, and in printing industries. The food industry uses cellulose nanocomposites to enhance food quality and shelf life. These applications highlight cellulosic materials role in creating innovative and sustainable products across multiple industries. Chemical modifications of cellulose are an essential requirement to achieve optimal properties for specific applications. Furthermore, cellulosic nanomaterials are developing into newer areas with larger scope and greater economic value. This review covers the isolation of cellulose from various sources and the different modifications performed along with their applications.

Girma Tenkolu Bune1,2 1School of Public Health, College of Medicine and Health Science, Dilla University, Dilla Town, SNNPR, Ethiopia; 2Departiment of Public Health, Rift Valley University, Hawassa Town, Sidama Regional State, EthiopiaCorrespondence: Girma Tenkolu Bune, Email girmatbune@gmail.com; girmatenkolu1973@gmail.comBackground: Gestational diabetes mellitus (GDM), a chronic condition leading to glucose intolerance during pregnancy, is common in low- and middle-income countries, posing health risks to both the mother and fetus. Limited studies have been done in Ethiopia, especially using WHO’s 2013 universal screening criteria. Therefore, this study aimed to evaluate the risk factors linked to GDM in women attending antenatal (ANC) clinics in Hawassa town public health institutions, located in the Sidama regional state of Ethiopia.Methods: An Unmatched case-control study was carried out in Ethiopia’s Sidama Region from April 1st to June 10th, 2023, involving 510 pregnant women. The Oral Glucose Tolerance Test (OGTT) was utilized for universal screening and diagnosing GDM based on the updated 2013 WHO diagnostic criteria. Data analysis included descriptive and analytical statistics, with variables having p-values below 0.1 deemed suitable for bivariate analysis. Statistical significance was assessed using the adjusted odds ratio (AOR) with a 95% confidence interval and a p-value < 0.05.Results: The study involved 633 participants (255 cases and 378 controls), resulting in a 100% response rate, with women having an average age of 29.03 years.Variables such as: age at first conception (AOR=0.97, P=0.01, 95% CI (0.95,0.99)), urban residency (AOR=1.66, P< 0.01, 95% CI(01.14,2.40)), widowed marital status (AOR=0.30, P=0.02, 95% CI (0.30,0.90)), parity (AOR=1.10, P< 0.01, 95% CI (1.03,1.17)), history of stillbirth (AOR=1.15, P=0.03, 95% CI(1.04,2.30)), and previous cesarean section (AOR=1.86, P=0.01, 95% CI (1.13,2.66)) were identified as independent factors associated with GDM.Conclusion: The study concluded that factors like age at first conception, place of residence, marital status, parity, history of Caesarian section, and stillbirth were independently associated with GDM. Surprisingly, upper arm circumference (MUAC), a proxy for pre-gestational BMI, was not identified as a risk factor for GDM. It is recommended that healthcare providers conduct comprehensive GDM risk assessments in pregnant women to identify and address risk factors, and propose specific screening and intervention strategies.Keywords: women, WHO, pregnancy, diabetes, DM, factors, screening, OGTT, glucose, SSA, Sub-Saharan Africa, SSA, Ethiopia, Sidama, Hawassa

Objetivos: Descrever o perfil epidemiológico da mortalidade hospitalar por transtornos falciformes (TF) no estado do Rio de Janeiro entre 2013 e 2022. Material e métodos: Estudo ecológico, realizado em maio de 2024, utilizando dados públicos referentes à mortalidade hospitalar por TF no estado do Rio de Janeiro, entre os anos de 2013 a 2022. Os dados públicos foram obtidos do Sistema de Informação sobre Mortalidade do Sistema Único de Saúde (SIM/SUS) as variáveis selecionadas foram: sexo e faixa etária. Não foi necessária a submissão ao Comite de Ética e Pesquisa. O programa Microsoft Excel foi utilizado para tabulação dos dados. Resultados: Ao todo foram 584 óbitos por TF no Estado do Rio de Janeiro de 2013 a 2022, sendo 261 (44,7%) no sexo masculino e 323 (55,3%) no sexo feminino. A faixa etária com maior número de óbitos no sexo masculino foi a de 20 a 29 anos (24,9%), seguida de 30 a 39 anos (16,85%), e no sexo feminino similar ao anterior a faixa etária foi entre 20 a 29 anos (21,7%), seguida da faixa etária entre 40 a 49 anos (20,12%). De 2013 a 2022, foram registrados respectivamente: 69 (11,81%), 70 (12,0%), 59 (10,1%), 69 (11,81%), 56 (9,6%), 47 (8,04%), 62 (10,61%), 47 (8,04%), 53 (9,07%), 52 (8,90%) óbitos no Rio de Janeiro, com 2014 representando o ano com maior número de óbitos registrados, sendo observado uma diminuição dos registros de óbitos a partir desse ano. Discussão: Os dados revelam padrões significativos que fornecem uma visão detalhada sobre o impacto desses transtornos na população. A mortalidade por TF é uma preocupação significativa para a saúde pública na região. A distribuição dos óbitos entre os sexos mostra uma prevalência ligeiramente maior em mulheres. A faixa etária com maior número de óbitos foi, para ambos os sexos, a de 20 a 29 anos, indicando que a mortalidade por TF é particularmente alta na faixa etária jovem adulta. Para os homens, a segunda faixa etária mais afetada foi de 30 a 39 anos, enquanto para as mulheres foi de 40 a 49 anos. Esta diferença pode refletir variações na progressão da doença ou na eficácia dos cuidados de saúde entre os sexos e diferentes faixas etárias. A variação anual dos óbitos mostra um pico em 2014, seguido por uma tendência de diminuição nos anos subsequentes, podendo ser atribuída a melhorias nos cuidados de saúde, avanços no tratamento e manejo dos TF, ou melhorias na detecção e intervenção precoce. É importante investigar mais a fundo os fatores que contribuíram para essa redução, que pode fornecer resultados valiosos para futuras estratégias de saúde pública. Conclusão: O estudo do perfil epidemiológico da mortalidade hospitalar por TF no Estado do Rio de Janeiro revela uma carga significativa da doença, com uma predominância de óbitos em jovens adultos e uma leve predominância no sexo feminino. A tendência de diminuição dos óbitos a partir de 2014 sugere que intervenções e melhorias nos cuidados de saúde possam estar contribuindo positivamente para a redução da mortalidade. Estes resultados sublinham a importância de continuar a monitorar a eficácia dos tratamentos e estratégias de gestão, bem como a necessidade de aprimorar a prevenção e o tratamento, sendo fundamental investir em políticas de saúde pública que priorizem a educação, o acesso a cuidados médicos de qualidade e a pesquisa contínua para melhorar os resultados para os pacientes afetados.

Objetivos: O objetivo deste trabalho é descrever o perfil epidemiológico dos pacientes diagnosticados com Doença de Hodgkin (DH), no estado do Rio de Janeiro nos últimos 10 anos. Dados de base populacional são relevantes para entendimento do perfil epidemiológico dessas doenças, para elaboração de intervenções de saúde direcionadas. Material e métodos: Estudo ecológico, realizado em maio de 2024, utilizando dados públicos referentes aos diagnósticos de DH no estado do Rio de Janeiro, por local de residência, entre os anos de 2014 a 2023. Os dados públicos foram obtidos do Painel de Oncologia Brasil do Sistema Único de Saúde (SUS), e as variáveis selecionadas foram: sexo, faixa etária, ano do diagnóstico, residência no estado do Rio de Janeiro, e casos. Não foi necessária a submissão ao Comite de Ética e Pesquisa pois são dados de acesso público. O programa Microsoft Excel foi utilizado para tabulação dos dados e cálculos realizados. Resultados: : Ao todo foram 1367 casos diagnosticados de DH no estado do Rio de Janeiro entre os anos de 2014 a 2023. De 2014 a 2023, foram registrados, respectivamente: 112 (8,2%), 124 (9,1%), 138 (10,1%), 160 (11,7%), 140 (10,2%), 145 (10,6%), 137 (10,0%), 159 (11,6%), 129 (9,4%), 123 (9,0%), casos no estado do Rio de Janeiro, sendo 2017 e 2021 os anos com maior número de casos registrados. Quanto ao sexo, 721 (52,7%) dos casos foram no sexo masculino, e 646 (47,3%) no sexo feminino. Quanto a faixa etária, a com maior número de casos foi a de 0 a 19 anos, e a com menor número foi a de 80 anos ou mais. A faixa etária com mais casos no sexo masculino foi a de 0 a 19 anos (18,2%), e no sexo feminino foi entre 25 a 29 anos (16,9%). Discussão: A DH é um tipo de linfoma maligno que se origina nas células do sistema linfático, caracterizada pela presença de células anormais chamadas células de Reed-Sternberg, e representa aproximadamente 0,5% de todos os casos de câncer. Segundo a literatura, sua incidência é ligeiramente maior em homens do que em mulheres, corroborando com os resultados encontrados neste trabalho. Quanto à faixa etária, a literatura descreve dois picos de incidência: o primeiro na adolescência e no início da idade adulta (entre 15 e 35 anos), e o segundo em pessoas com mais de 55 anos. Os dados deste estudo corroboram com o descrito, com 51,2% dos diagnósticos em pessoas entre 15 e 35 anos, com queda no número de casos com o avançar da faixa etária, com um novo aumento entre 50 a 54 anos, e nova queda até 80 anos ou mais. Cabe ressaltar que o Painel de Oncologia Brasil do SUS não dispõe nos registros dados referentes ao tipo de DH, estadiamento, e às comorbidades e outros dados referentes aos pacientes. Conclusão: Observou-se que a maioria dos casos diagnosticados de DH foram no sexo masculino, e na faixa etária de 15 a 35 anos, com um novo aumento entre 50 a 54 anos. Os dados encontrados corroboram com a literatura, e reforçam a necessidade de estratégias de saúde pública direcionadas para perfil epidemiológico mais acometido pela DH no estado do Rio de Janeiro. Trabalhos com outros desenhos de estudo são necessários para uma avaliação mais detalhada acerca do perfil epidemiológico da DH, levando em conta o tipo de DH, visto que cada tipo possui características distintas.

Objetivos: O objetivo deste trabalho é descrever o intervalo de tempo, entre a data do exame diagnostico e a data do primeiro tratamento do paciente com linfoma não Hodgkin difuso de grandes células B (LNHDGB), no estado do Rio de Janeiro nos últimos 10 anos, visto que o tempo entre as duas situações influencia no estadiamento do paciente, no prognóstico e na mortalidade, principalmente em usuários do Sistema Único de Saúde (SUS). Material e métodos: Estudo ecológico, realizado em maio de 2024, utilizando dados públicos referentes ao tempo entre o exame diagnóstico e o tratamento dos pacientes com LNHDGB no estado do Rio de Janeiro, por local de residência, entre os anos de 2014 a 2023. Os dados públicos foram obtidos do Painel de Oncologia Brasil do SUS, e as variáveis selecionadas foram: tempo de tratamento (detalhado), residência no estado do Rio de Janeiro, e casos. Não foi necessária a submissão ao Comite de Ética e Pesquisa pois são dados de acesso público. O programa Microsoft Excel foi utilizado para tabulação dos dados e cálculos realizados . Resultados: Ao todo foram 2.716 casos diagnosticados de LNHDGB entre 2014 e 2023 no estado do Rio de Janeiro, em que 3 casos (0,1%) foram registrados com o início do tratamento antes de 30 dias da data do exame diagnóstico, 206 (7,6%) iniciaram o tratamento na mesma data do exame diagnóstico, 420 (15,5%) de 1 a 10 dias após a data do exame diagnóstico, 620 (22,8%) entre 11 a 30 dias, 542 (20,0%) entre 31 a 60 dias, 274 (10,1%) entre 61 a 90 dias, 141 (5,2%) entre 91 dias a 120 dias, 246 (9,1%) entre 4 a 10 meses, 31 (1,1%) entre 10 meses a 1 ano, 74 (2,7%) entre 1 a 2 anos, 45 (1,7%) mais de 2 anos e em 114 casos (4,2%) não foram registrados essa informação. Discussão: Os linfomas representam um grupo de neoplasias que se desenvolvem a partir de clones linfoides podendo ser derivados de células B, T e natural killer. São classificados como linfomas de Hodgkin e não-Hodgkin, o qual apresenta como um dos seus subtipos o LNHDGB, que é o tipo mais comum. O prognóstico do LNHDGB depende da extensão da doença no momento do diagnóstico, do tempo entre o diagnóstico e o tratamento, e da resposta ao tratamento, que costuma ser a quimioterapia com o protocolo CHOP (ciclofosfamida, doxorrubicina, vincristina e prednisona) combinado com o anticorpo monoclonal anti-CD20, rituximabe. Quanto ao tempo entre o diagnóstico e o início do tratamento, observa-se que a maioria dos casos apresenta um intervalo de até 10 dias. Cabe ressaltar que o Painel de Oncologia Brasil do SUS não dispõe nos registros dados referentes às características do linfoma e sua extensão, e às comorbidades e outros dados referentes aos pacientes, que podem influenciar no início do tratamento. Conclusão: Observou-se que, o intervalo de tempo, entre a data do exame diagnostico e a data do primeiro tratamento dos pacientes com LNHDGB, no estado do Rio de Janeiro nos últimos 10 anos, foi em até 10 dias em 23,2% dos casos, porém, em 52,9% esse tempo foi de 10 a 90 dias. Esses dados reforçam a necessidade de estratégias de saúde pública direcionadas para reduzir o tempo do início do tratamento, que é uma variável fundamental no prognóstico desses pacientes. Trabalhos com outros desenhos de estudo são necessários para esclarecer melhor as causas que levaram aos intervalos de tempo observados para o início do tratamento dos pacientes com LNHDGB no estado do Rio de Janeiro.

Objetivos: Descrever o perfil epidemiológico dos pacientes diagnosticados com linfomas de células T cutâneas e periféricas no Brasil nos últimos 10 anos. Relevância: Dados de base populacional são relevantes para entendimento do perfil epidemiológico dessas doenças, para elaboração de intervenções de saúde direcionadas. Material e métodos: Estudo ecológico realizado em maio de 2024 utilizando dados públicos referentes aos diagnósticos de linfomas de células T cutâneas e periféricas no Brasil entre os anos de 2014 a 2023. Os dados públicos foram obtidos do Painel de Oncologia Brasil e as variáveis selecionadas foram: sexo, faixa etária e casos. Não foi necessária a submissão ao Comite de Ética e Pesquisa pois são dados de acesso público. O programa Microsoft Excel foi utilizado para tabulação dos dados e cálculos realizados. Resultados: Foram diagnosticados 5145 casos de linfomas de células T cutâneas e periférica de 2014 a 2023 no Brasil, sendo 2840 (55.2%) do sexo masculino e 2305 (44.8%) do sexo feminino. Em relação à faixa etária, o maior número de casos foi registrado entre 55 e 64 anos, representando 21.8% (1124 casos), e o menor foi de 0 a 24 anos com 8.7% (450 casos). Entre os pacientes do sexo masculinos e feminino, observou-se o mesmo padrão nessas faixas etárias. Discussão: Os linfomas de células T cutâneas e periféricas são tipos de cânceres que afetam o sistema linfático e são originados das células T, um tipo de célula do sistema imunológico, sendo classificados com base em sua localização primária e características celulares. O padrão de predominância do sexo masculino em relação ao feminino observado no estudo é consistente com estudos internacionais, que frequentemente mostram uma maior incidência de linfomas de células T em homens. Os dados também sugerem que linfomas de células T cutâneas e periféricas têm uma prevalência mais elevada em indivíduos de meia-idade a idosos. Isso pode estar relacionado ao fato de que parte considerável de neoplasias malignas tende a se manifestar em adultos, possivelmente devido a fatores cumulativos de exposição a carcinógenos, alterações genéticas e processos de envelhecimento imunológico. É interessante observar que o padrão de prevalência por faixa etária é consistente entre os sexos, o que pode indicar que os fatores de risco para essas condições não variam significativamente entre homens e mulheres. No entanto, a diferença observada na distribuição por sexo sugere que pode haver fatores biológicos ou ambientais específicos que contribuem para uma maior incidência em homens. Conclusão: O perfil epidemiológico dos linfomas de células T cutâneas e periféricas no Brasil entre 2014 e 2023 revela uma prevalência maior em homens e em faixas etárias mais avançadas, com um pico de casos na faixa etária de 55 a 64 anos. Esses achados são coerentes com a literatura existente e fornecem dados valiosos para a formulação de políticas de saúde pública e estratégias de intervenção direcionadas. A identificação de padrões de prevalência pode auxiliar na alocação de recursos e no desenvolvimento de programas de conscientização e triagem específicos para grupos de risco. No entanto, estudos adicionais são necessários para compreender melhor os fatores subjacentes ao aumento da incidência e para explorar possíveis diferenças regionais e temporais na prevalência desses linfomas.

Objetivos: Descrever o perfil epidemiológico dos pacientes diagnosticados com síndromes mielodisplásicas (SMD) na região Sudeste do Brasil nos últimos 10 anos. Material e métodos: Estudo ecológico realizado em maio de 2024 utilizando dados públicos referentes aos diagnósticos de SMD na região Sudeste do Brasil, por local de residência, entre os anos de 2014 a 2023. Os dados públicos foram obtidos do Painel de Oncologia Brasil e as variáveis selecionadas foram: sexo, faixa etária, ano do diagnóstico, e residência na região Sudeste. Não foi necessária a submissão ao Comite de Ética e Pesquisa pois são dados de acesso público, relevantes para entendimento do perfil epidemiológico de doenças e elaboração de intervenções de saúde direcionadas. O programa Microsoft Excel foi utilizado para tabulação dos dados e cálculos realizados. Resultados: Foram diagnosticados 4.095 casos de SMD entre 2014 e 2023 na região Sudeste do Brasil, com aumento importante no número de casos diagnosticados a partir de 2019 em relação aos anos anteriores. De 2014 a 2023 foram registrados, respectivamente: 237 (5,8%), 208 (5,1%), 226 (5,5%), 242 (5,9%), 354 (8,6%), 612 (14,9%), 496 (12,1%), 491 (12,0%), 574 (14,0%), 655 (16,0%) casos na região Sudeste, sendo 2023 os ano com maior número. Quanto ao sexo, 48,9% dos casos foram no sexo masculino e 51,1% no feminino. A faixa etária com mais casos em ambos os sexos foi a de 80 anos ou mais (15,6%). Discussão: As SMD são um grupo heterogêneo de neoplasias hematológicas caracterizadas por uma displasia das células hematopoiéticas na medula óssea, levando a uma produção inadequada e disfuncional das células sanguíneas. Segundo a literatura, as SMD são ligeiramente mais comuns em homens do que em mulheres, diferentemente dos resultados encontrados neste estudo, no qual o predomínio entre os sexos variou ao longo dos anos, porém, no total dos anos estudados, a maioria dos casos foi no sexo feminino. Também é descrito que a taxa de incidência tende a aumentar com a idade, sendo significativamente mais alta em populações acima de 60 anos, corroborando os dados encontrados neste trabalho, no qual as faixas etárias com maior número de casos foi de 80 anos ou mais, seguida de 70 a 74 anos. Cabe ressaltar que o Painel de Oncologia Brasil não dispõe nos registros dados referentes à classificação das SMD e às comorbidades e outros dados referentes aos pacientes. Conclusão: Observou-se um aumento importante nos diagnósticos de SMD no Brasil nos últimos anos, principalmente a partir de 2019. Uma hipótese para esse aumento é a melhora das técnicas diagnósticas nesta área, sendo possível diagnosticar casos que anteriormente ficavam sem diagnóstico claro, associada ao aumento da expectativa de vida da população – já que é uma doença que acomete indivíduos mais velhos. Em relação ao sexo, a maioria dos casos foram no sexo feminino, diferente do descrito pela literatura. Já quanto à faixa etária, foi predominante em pacientes com 80 anos ou mais, o que corrobora com os dados da literatura. Esses dados reforçam a necessidade de estratégias de saúde pública direcionadas para perfil epidemiológico mais acometido pelas SMD no Brasil. Trabalhos com outros desenhos de estudo são necessários para uma avaliação mais detalhada acerca do perfil epidemiológico das SMD levando em conta sua classificação, visto que cada tipo possui características distintas.

Introduction: Chronic Myeloid Leukemia (CML) represents a paradigm in oncology, characterized by the hallmark Philadelphia chromosome resulting from the t(9;22) reciprocal translocation. This abnormal chromosome gives rise to the BCR::ABL1 fusion gene, which encodes a constitutively active tyrosine kinase protein driving leukemogenesis. The use of tyrosine kinase inhibitors (TKI) have revolutionized CML treatment, demonstrating remarkable efficacy. However, TKI resistance, primarily attributed to point mutations within the BCR::ABL1 kinase domain (KD) remains a significant clinical challenge, affecting approximately 20-30% of patients. The gold standard technique for monitoring mensurable residual disease in CML is the quantitative PCR (qPCR), while Sanger sequencing is utilized to identify KD mutations upon relapse. Objective: This study aims to address the specific challenges posed by two BCR::ABL1 splicing variants — the deletion of exon 7 (Δ7) and the insertion of 35 base pairs between exons 8 and 9 (INS35) — in the molecular monitoring of CML patients. These splicing events occur frequently in CML, observed in approximately 20-25% of cases. Concurrent occurrence of alternative splicing variants with point mutations complicates the detection of low-frequency mutations, potentially leading to mislead or misinterpret results. Additionally, splicing variants are detected by qPCR and incorporated into the Molecular Response (MR) calculation, which may result in poorer MR outcomes, as literature suggests these variants exhibit reduced sensitivity to TKIs. Methods: To address these challenges in CML management, we developed a PCR-based technique coupled with fragment analysis to accurately identify these variants prior to sequencing. We validated this test with 30 samples with Δ7 and/or INS35, prior identified by the Sanger sequence. Moreover, we designed a specific qPCR assay to quantify splicing variants exclusively. Results and conclusion: We performed in silico modeling of the wild-type versus Δ7 and INS35 BCR::ABL1 isoforms, showing the KD disruption caused by the early stop codon resulting from the frameshift caused by Δ7 and INS35. Additionally, our findings indicate that this molecular approach enables highly accurate and sensitive identification of splicing variants, even at very low levels. We observed that these events are independent of CML status, also occurring in healthy donor samples. Furthermore, Δ7 and INS35 are present throughout the longitudinal patient follow-up and are not associated with TKI failure. However, Δ7 with a variant allele frequency (VAF) greater than 0.15 is more prevalent in samples with higher BCR::ABL1 transcript counts, whether at diagnosis, failure, or relapse. This study highlights how Δ7 and INS35 can confound mutational testing results and demonstrates how to overcome these challenges for a more precise analysis of point mutations in CML patients carrying splicing variants.

Objetivos: O objetivo deste trabalho é descrever o perfil epidemiológico dos pacientes diagnosticados com mieloma múltiplo (MM) ou outras neoplasias malignas de plasmócitos, na região Sudeste do Brasil nos últimos 10 anos. Dados de base populacional são relevantes para entendimento do perfil epidemiológico dessas doenças, para elaboração de intervenções de saúde direcionadas. Material e métodos: Estudo ecológico, realizado em maio de 2024, utilizando dados públicos referentes aos diagnósticos de MM e outras neoplasias malignas de plasmócitos na região Sudeste do Brasil, por local de residência, entre os anos de 2014 a 2023. Os dados públicos foram obtidos do Painel de Oncologia Brasil do Sistema Único de Saúde (SUS), e as variáveis selecionadas foram: sexo, faixa etária, diagnóstico detalhado, e residência na região Sudeste. Não foi necessária a submissão ao Comite de Ética e Pesquisa pois são dados de acesso publico. O programa Microsoft Excel foi utilizado para tabulação dos dados e cálculos realizados. Resultados: Ao todo foram 15614 casos diagnosticados de MM ou outras neoplasias malignas de plasmócitos entre 2014 e 2023 na região Sudeste do Brasil, sendo 8158 (52,3%) no sexo masculino, e 7456 (47,7%) no sexo feminino. A faixa etária com mais casos no sexo masculino foi a de 60 a 64 anos (16,4%), e no sexo feminino foi entre 65 a 69 anos (17,6%). De 2014 a 2023, foram registrados, respectivamente: 1133 (7,1%), 1161 (7,4%), 1144 (7,3%), 1195 (7,7%), 1391 (8,9%), 1655 (10,6%), 1606 (10,3%), 1847 (11,8%), 2480 (15,9%), 2002 (12,8%), casos na região Sudeste, sendo 2022 o ano com maior número de casos registrados em ambos os sexos. De 2014 a 2017, a faixa etária com maior número de casos foi de 60 a 64 anos, porém, exceto por 2020, nos anos seguintes a faixa etária com maior número de casos foi a de 65 a 69 anos. Exceto em 2016, 2020 e 2021, foi observado aumento no número de casos em todos os anos estudados. Discussão: As neoplasias malignas de plasmócitos são doenças hematológicas caracterizadas pela proliferação descontrolada e malignização das células plasmáticas. Além do MM, outras neoplasias malignas de plasmócitos incluem o linfoma de células plasmáticas e a Doença de Waldenström. O MM é responsável por cerca de 10% das malignidades hematológicas. Segundo a literatura, homens são mais afetados do que mulheres, o que corrobora com os dados encontrados neste trabalho. Quanto à idade do diagnóstico, dados do ano de 2022 do Observatório de Oncologia apontaram uma mediana de 63 anos no Brasil, já neste trabalho, a mediana foi entre 65 a 69 anos. Cabe ressaltar que o Painel de Oncologia Brasil do SUS não separa o MM de outras neoplasias malignas de plasmócitos, o que pode ter influenciado nesses resultados. Conclusão: Observou-se aumento no número de casos diagnosticados de MM ou outras neoplasias malignas de plasmócitos na região Sudeste do Brasil na maioria dos anos estudados, sendo o ano de 2022 com maior número de casos diagnosticados, predominantemente no sexo masculino. Quanto à faixa etária, a com maior número de casos foi em pacientes de 60 a 64 anos até 2017, com uma tendência a mudança para 65 a 69 anos nos anos seguintes. Os dados encontrados corroboram com a literatura, e reforçam a necessidade de estratégias de saúde pública direcionadas para perfil epidemiológico mais acometido pelo MM e outras neoplasias malignas de plasmócitos na região Sudeste do Brasil.

Objectives: Valoctocogene roxaparvovec (AAV5-hFVIII-SQ), a gene transfer therapy for severe hemophilia A, enables endogenous factor VIII (FVIII) production to prevent bleeding. We present efficacy and safety outcomes 4-years post-valoctocogene roxaparvovec treatment in the GENEr8-1 trial. Material and methods: In the open-label, multicenter, phase 3 GENEr8-1 trial (NCT03370913), 134 adult men with severe hemophilia A (FVIII ≤1 IU/dL) without FVIII inhibitors received 6E13 vg/kg valoctocogene roxaparvovec (Intention-To-Treat [ITT] population). Bleeds and FVIII use were self-reported after regular prophylaxis cessation (scheduled Week [W]4). The rollover population, which included 112 HIV-negative participants who enrolled from a non-interventional study, was used for comparisons with baseline FVIII use and bleeding rate. Chromogenic (CSA) and One-Stage Assay (OSA) FVIII activity were assessed in 132 HIV-negative participants (modified ITT [mITT] population). Safety was assessed in the ITT population. Results: In the ITT population, 118/134 participants completed W208; 24/134 participants resumed prophylaxis. In the rollover population, mean annualized treated bleeding rate was 0.8 bleeds/y, mean annualized bleeding rate for all bleeds was 1.3 bleeds/y, and mean annualized FVIII infusion rate was 6.1 infusions/y over 4-years. During year 4, 81/110 (73.6%) participants had 0 treated bleeds and 68/110 (61.8%) participants had 0 bleeds regardless of treatment. At W208, mean CSA and OSA FVIII activity were 16.1 and 27.1 IU/dL in the mITT population respectively. At W260, mean CSA and OSA FVIII activity were 18.0 and 25.5 IU/dL for the mITT subgroup dosed ≥ 5-years prior. FVIII activity (CSA) ≥ 40, ≥ 5 to < 40, ≥ 3 to < 5, and < 3 IU/dL was verified in 10/130 (7.7%), 68/130 (52.3%), 18/130 (13.8%), and 34/130 (26.2%) of participants, respectively. During year 4, the most common adverse event was alanine aminotransferase (ALT) elevation (56/131 participants; ALT > upper limit of normal or ≥ 1.5× baseline); no participants initiated immunosuppressants for ALT elevation. Conclusions: At four years post valoctocogene roxaparvovec therapy, bleed control and FVIII expression were maintained in the majority of patients. No new safety signals emerged.

Objetivo: : Compreender o impacto da realização de esplenectomia em crianças portadores de Esferocitose hereditária (EH) com indicação cirúrgica. Materiais e métodos: Foi realizada uma revisão de literatura na base de dados pubmed, com uma identificação inicial de 109 artigos, dos últimos 10 anos, sendo filtrados 8. A pesquisa foi realizada com os termos “hereditary spherocitosis”, “children”, “treatment”e ”splenectomy”. Resultados: Atualmente, para tratamento da anemia grave decorrente da esferocitose hereditária, é indicada a esplenectomia. Porém, o comprometimento imunológico secundário à remoção do baço aumenta a suscetibilidade a infecções bacterianas. Conforme os oitos artigos analisados, existem duas principais abordagens para a esplenectomia: total (ET), que envolve a remoção completa do baço, e parcial (EP), que preserva parte do tecido esplênico, geralmente o lobo inferior. Estudos comparativos mostram que, embora a ET inicialmente proporcione melhores resultados laboratoriais, como níveis de hemoglobina mais altos, a longo prazo, os benefícios entre ET e EP são semelhantes em termos de independência da transfusão e melhoria dos parâmetros hematológicos. No entanto, é necessário analisar os riscos associados à susceptibilidade a infecções graves. Em relação à septicemia pós esplenectomia, alguns autores falam a favor da EP em substituição à ET como forma de reduzir a propensão a infecções. Relacionado a prevenção das complicações, alguns consideram que mesmo com as imunizações adequadas existem preocupações, principalmente em crianças com menos de 5 anos, com risco de sepse pós-esplenectomia aumentado em 60 vezes. Discussão: : Com seguimento ambulatorial adequado, diretrizes de vacinação e antibióticos profiláticos, a sepse pós esplenectomia não é comum. Ensaios clínicos tiveram bons resultados em sua avaliação de 13 crianças esplenectomizadas, das quais todas receberam profilaxia antibiótica e vacinação e nenhuma apresentou infecção grave ou necessidade de transfusão sanguínea nos 33 meses em que foram acompanhadas após a operação. Conclusão: Estudos sustentam a ideia de que, com o seguimento adequado das diretrizes de vacinação e antibióticos profiláticos, a sepse pós esplenectomia não é comum. Para pacientes com EH grave, a esplenectomia é seguramente indicada e para EH moderada com apresentação clínica significativa, a esplenectomia é habitualmente indicada para melhorar a qualidade de vida. Ainda assim, a decisão cirúrgica deve ser avaliada, levando sempre em consideração a gravidade do caso, a condição socioeconômica e entendimento da família, assim como a idade dos pacientes pediátricos, sendo de maior risco crianças abaixo de 5 anos.

Objetivos: Avaliar o perfil epidemiológico e os resultados dos testes de triagem sorológico e molecular (NAT) para o Vírus da Imunodeficiência Humana (HIV) em doadores de sangue. Material e métodos: : Foram analisados os perfis de doadores de sangue com sorologia reagente e NAT detectável para HIV no período de julho/2013 a junho/2024, no Serviço de Hemoterapia do Hospital São Vicente de Paulo, Passo Fundo/RS. A triagem sorológica foi realiza na metodologia de Quimioluminescência e o NAT foi realizado pelo SIT NAT localizado no Centro de Hematologia e Hemoterapia de Santa Catarina (HEMOSC), com o KIT NAT PLUS BIO-MANGUINHOS. As variáveis analisadas foram: sexo, idade, cidade de procedência e número de doações realizadas pré-diagnóstico. A coleta de dados foi realizada no sistema informatizado. Resultados: : Das 134.507 doações no período analisado, 36 (0,026%) apresentaram teste sorológico reagente e NAT detectável para HIV. Destes, 18 (50%) do sexo feminino e 18 (50%) masculino, a média de idade foi 33 anos (mínima 19 e máxima 49); 18 (50%) procedentes do município de Passo Fundo/RS e outros 18 (50%) de outros municípios do Rio Grande do Sul. Discussão: : Segundo o Hemoprod (2020) para a região Sul a prevalência de sorologia reagente para HIV é de 0,16%, em nosso estudo encontramos taxa inferior, contudo analisamos apenas as doações com sorologia e NAT detectável paar HIV. No município de Passo Fundo a taxa de detecção (por 100.000 hab.) de casos de HIV notificados no SINAN (Sistema de Informação de Agravos de Notificação) foi de 0,028%, semelhante ao encontrado neste estudo. A homogeneidade entre os sexos encontrada neste estudo diferiu em relação ao restante do território nacional, em que o sexo masculino, em geral, possui prevalência sobre o feminino, como citado em Siqueira et al. (2020) e Oliveira et al. (2021). Conclusão: : Apesar dos avanços no diagnóstico e na terapêutica disponível, o HIV ainda representa um problema de saúde pública, pois a taxa de detecção em indivíduos saudáveis e doadores de sangue são semelhantes aos encontrado na população geral do município. A compreensão do perfil dos doadores é necessária para o desenvolvimento de políticas de saúde mais eficazes, criação de campanhas de prevenção e educação permitindo o planejamento adequado de recursos para o tratamento e a gestão da doença.

Objetivo: Realizar análise comparativa entre eficácia e segurança do zanubrutinibe e ibrutinibe no tratamento da Macroglobulinemia de Waldenström pela avaliação de estudos clínicos. Materiais e métodos: Foram utilizadas as bases de dados ClinicalTrials.gov e PubMed, filtrando pelas palavras-chave: “Lymphoplasmacytic Lymphoma”, “Waldenström's Macroglobulinemia”, “Zanubrutinib”, “Ibrutinib”e “Bruton's tyrosine kinase”. A partir da lista de artigos gerados, foram excluídos os estudos que: (I) não estavam relacionados à Macroglobulinemia de Waldenström; (II) não utilizaram os medicamentos zanubrutinibe e ibrutinibe. Resultados: Observamos uma eficácia semelhante entre zanubrutinibe e ibrutinibe, porém o primeiro apresenta um perfil de segurança mais aprimorado devido sua menor quantidade de efeitos adversos como neutropenia, infecção respiratória e diarréia quando comparado aos efeitos colaterais do ibrutinibe que são além desses, também: espasmos musculares, edema periférico e fibrilação cardíaco. Em um dos estudos, 23% dos pacientes que utilizaram ibrutinibe precisaram reduzir a dose devido aos efeitos adversos, enquanto apenas 14% dos pacientes que receberam zanubrutinibe necessitaram reduzir a dose. Em outro estudo, os níveis médios de IgM foram reduzidos em 79% e 72% para pacientes com zanubrutinibe e ibrutinibe, respectivamente. Discussão: O linfoma linfoplasmocitário/tipo macroglobulinemia de Waldestrom é uma doença rara das células B caracterizada pela produção monoclonal de imunoglobulinas M, conhecidas como macroglobulinas. É uma forma indolente de linfoma não-Hodgkin de células B e manifesta-se com sintomas brandos como astenia, problemas de visão, sangramento purpúrico, linfoadenomegalia e alterações neurológicas. O tratamento inicialmente previsto para essa doença é o ibrutinibe, um inibidor de tirosina quinase de Bruton (BTK) de primeira geração, uma quinase que apresenta um papel de sinalização oncogênica essencial na sobrevivência de células B leucêmicas. Entretanto, devido aos efeitos adversos e ao desenvolvimento de resistência na maioria dos pacientes que o utilizam, fez-se necessário novos estudos com medicamentos. O zanubrutinibe foi liberado pela Agência Nacional de Vigilância Sanitária no Brasil em 2023. Ele primeiramente foi previsto para outras doenças malignas, mas devido seu mecanismo de inibição da tirosina quinase de Bruton (BTK) e redução do crescimento tumoral, também pode ser recomendado nesse caso. Isso por conta da ligação do medicamento ao sítio ativo da BTK onde há resíduos de cisteína, formando ligações covalentes e tendo por consequência a inibição da proliferação de células B malignas. Além de apresentar uma seletividade maior que o ibrutinibe, podendo atingir uma disponibilidade plasmática mais elevada e um potencial reduzido para interação medicamentosa. Dado o exposto, o ibrutinibe como resistência e intolerância, torna-se importante medicamento para análise comparativa entre os dois. Conclusão: Os dados apresentados indicam uma eficácia semelhante entre os medicamentos zanubrutinibe e Ibrutinibe. Entretanto, o perfil de segurança do primeiro se revelou mais aprimorado. Pacientes com mutação no receptor de quimiocina CXC4 apresentaram melhores taxas de resposta, destacando a capacidade do medicamento zabrutinibe de melhorar a qualidade de vida e otimizar o prognóstico dos pacientes.

Objetivos: Explorar o mimetismo molecular entre o vírus da dengue (DENV) e fatores de coagulação humanos, e como essa interação pode levar à produção de autoanticorpos que alteram o equilíbrio da hemostasia. Além disso, analisar as evidências experimentais que mostram como anticorpos induzidos por infecção com DENV se ligam a trombina e plasminogênio, e como esses anticorpos podem interferir na coagulação e fibrinólise. Assim, pretendemos identificar o impacto clínico deste mimetismo molecular na patogênese de complicações graves da dengue, como a febre hemorrágica. Metodologia: Foram utilizadas as bases de dados ClinicalTrials.gov e PubMed, filtrando pelas palavras-chave: “dengue virus”, “molecular mimicry”, “hemostasis” e “dengue pathogenesis”. A lista de artigos gerados foi adequadamente organizada, excluindo-se os estudos que: (I) não estavam relacionados à infecção pelo vírus da dengue; (II) não envolviam mimetismo molecular. Resultados: Entre as reações relacionadas à produção de anticorpos anti-DENV por mimetismo molecular, encontramos a produção de autoanticorpos que se ligam a trombina e plasminogênio, interferindo na coagulação e fibrinólise. Além disso, podem reagir de forma cruzada com plaquetas, fatores de coagulação e células endoteliais. Foi relatado, por meio de western blotting, que anticorpos anti-trombina (ATAs) de coelho mostraram atividade cruzada com trombina bovina/humana e plasminogênio. Foi realizado um ensaio cromogênico utilizando o substrato específico da trombina (S-2238), dessa forma viram que as ATAs de coelhos foram capazes de inibir significativamente a atividade da trombina humana em comparação com o grupo controle de Igs de coelho. Discussão: A partir dos resultados observados nesses estudos, sugere-se que os autoanticorpos produzidos pelo mimetismo molecular produz anticorpos anti-trombina humanos que podem alterar o equilíbrio hemostático e tender ao sangramento em pacientes com dengue hemorrágica, pois além de inibirem a trombina, aumentam a fibrinólise, sugerindo ser um fator relacionado à patogênese da dengue hemorrágica. Além disso, a literatura destaca que fatores virais somados a fatores do hospedeiro, como a produção de autoanticorpos, também podem afetar fatores da coagulação de maneira direta e indireta. Dessa forma, vimos que o mimetismo molecular foi proposto para explicar a indução de anticorpos reativos cruzados aos distúrbios da hemostasia relacionado a dengue hemorrágica, uma vez que previamente foi relatado que existem regiões de proteínas DENV que compartilham homologia de sequências de vários fatores da coagulação. Conclusão: Mesmo que a interação entre hemostasia, resposta imune e inflamação seja de difícil entendimento, a partir dos dados apresentados podemos observar o agravamento de quadros de pacientes com dengue devido a relação de fatores tanto virais quanto do próprio hospedeiro com a patogenicidade da doença. E neste caso, o uso das técnicas biológicas moleculares e modelos animais podem nos ajudar na análise dessas interações visto que há um desequilíbrio notável causado no organismo por anticorpos e autoanticorpos que interferem em fatores importantes da coagulação.

A sepse, uma das síndromes mais antigas estudadas pela medicina, é responsável por aproximadamente 11 milhões de mortes anuais no mundo, segundo a World Health Organization (WHO), no Brasil, são cerca de 240 mil mortes anuais, com uma taxa de mortalidade de 65%. O diagnóstico mais rápido e preciso de sepse atualmente é feito pela reação em cadeia da polimerase (PCR), embora o padrão ouro ainda seja a cultura microbiológica, provas bioquímicas e antibiograma; a PCR permite um diagnóstico precoce e mais sensível, detectando até quantidades mínimas de patógenos, sendo mais eficaz, permitindo a identificação específica de microrganismos e genes de resistência a antibióticos, auxiliando na escolha da antibioticoterapia adequada e evitando danos ao paciente. A Santa Casa da Misericórdia de Ourinhos (ASCMO) implementou essa tecnologia devido ao aumento de casos de sepse durante a pandemia de COVID-19, especialmente em pacientes em ventilação mecânica. A microbiologia convencional tem um tempo de resposta mais longo, o que motivou a busca por metodologias mais rápidas e confiáveis, como a detecção de marcadores genéticos de patógenos. Objetivos: Implantar diagnóstico molecular para a detecção de patógenos e seus genes de resistência, colaborando na prevenção e/ou melhoria dos quadros de sepse em pacientes da UTI da Santa Casa de Ourinhos, propondo uma abordagem mais eficaz às infecções. Metodologia: O estudo foi realizado com 30 amostras de pacientes da UTI da Santa Casa de Ourinhos entre maio e novembro de 2022, utilizando culturas bacterianas para a análise molecular. O método envolve amplificação simultânea de patógenos e genes de resistência via PCR, seguida de hibridização reversa com sondas específicas (Flow Chip), o software HybriSoft analisa os resultados, identificando patógenos e genes de resistência. Resultados: Das 30 amostras, 26 foram positivas para patógenos como Staphylococcus spp., Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus spp., Enterobacteriaceae, Klebsiella pneumoniae, Enterococcus spp. e Escherichia coli. Os genes de resistência detectados incluíram MecA, β-Lactamase SHV e β-Lactamase CTX-M. Discussão: O gene MecA, resistente à meticilina, foi o mais prevalente, encontrado em 16 amostras de Staphylococcus spp. Genes β-Lactamase SHV e CTX-M foram detectados em um paciente com Klebsiella pneumoniae, indicando resistência a várias penicilinas e cefalosporinas. A técnica Flow Chip mostrou alta sensibilidade na detecção de patógenos e genes de resistência, mas pode falhar em identificar genes na membrana ou parede celular das bactérias, o que o antibiograma pode detectar. Conclusão: O diagnóstico por PCR é mais rápido (cerca de 4 horas) comparado ao antibiograma (24-48 horas), sendo decisivo para o tratamento eficaz e rápido da sepse. O custo elevado do teste automatizado é justificado pelo melhor prognóstico e menor tempo de tratamento, destacando a importância da tecnologia molecular na gestão da sepse.

A hallmark of biomolecular condensates formed via liquid-liquid phase separation is that they dynamically exchange material with their surroundings, and this process can be crucial to condensate function. Intuitively, the rate of exchange can be limited by the flux from the dilute phase or by the mixing speed in the dense phase. Surprisingly, a recent experiment suggests that exchange can also be limited by the dynamics at the droplet interface, implying the existence of an ‘interface resistance’. Here, we first derive an analytical expression for the timescale of condensate material exchange, which clearly conveys the physical factors controlling exchange dynamics. We then utilize sticker-spacer polymer models to show that interface resistance can arise when incident molecules transiently touch the interface without entering the dense phase, i.e., the molecules ‘bounce’ from the interface. Our work provides insight into condensate exchange dynamics, with implications for both natural and synthetic systems.

Abstract Background Demand for healthcare outweighs available resources, making priority setting a critical issue. ‘Severity’ is a priority-setting criterion in many healthcare systems, including in Norway, Sweden, the Netherlands, and the United Kingdom. However, there is a lack of consensus on what severity means in a healthcare context, both in the academic literature and in policy. Further, while public preference elicitation studies demonstrate support for severity as a relevant concern in priority setting, there is a paucity of research on what severity is taken to mean for the public. The purpose of this study is to explore how severity is conceptualised by members of the general public. Methods Semi-structured group interviews were conducted from February to July 2021 with members of the Norwegian adult public (n = 59). These were transcribed verbatim and subjected to thematic analysis, incorporating inductive and deductive elements. Results Through the analysis we arrived at three interrelated main themes. Severity as subjective experience included perceptions of severity as inherently subjective and personal. Emphasis was on the individual’s unique insight into their illness, and there was a concern that the assessment of severity should be fair for the individual. The second theme, Severity as objective fact, included perceptions of severity as something determined by objective criteria, so that a severe condition is equally severe for any person. Here, there was a concern for determining severity fairly within and across patient groups. The third theme, Severity as situation dependent, included perceptions of severity centered on second-order effects of illness. These included effects on the individual, such as their ability to work and enjoy their hobbies, effects on those surrounding the patient, such as next of kin, and effects at a societal level, such as production loss. We also identified a concern for determining severity fairly at a societal level. Conclusions Our findings suggest that severity is a polyvalent notion with different meanings attached to it. There seems to be a dissonance between lay conceptualisations of severity and policy operationalisations of the term, which may lead to miscommunications between members of the public and policymakers.

Habiba Ejabo Ali,1 Tamrat Assefa Tadesse,1 Dessale Abate Beyene,2 Girma Tekle Gebremariam1 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Pharmacy, Asrat Woldeyes Health Science Campus, Debre Berhan University, Debre Berhan, EthiopiaCorrespondence: Girma Tekle Gebremariam, Email girma.tekle@aau.edu.etBackground: Menstrual-related headache (MRH) is the most prevalent health condition among young females that limits productivity and social life. However, the magnitude of the problem and its characteristics have not been studied in Ethiopia.Objective: This study aimed to assess the prevalence, characteristics, and treatment of MRH among undergraduate female students at the College of Health Sciences, Addis Ababa University, Ethiopia.Methods: A cross-sectional study was conducted among undergraduate female students from May to June 2023. A random sample of 1000 females were approached who fulfilled the eligibility criteria using the online electronic method. Descriptive statistics were used to summarize participant characteristics. Multivariate logistic regression analysis was performed to identify factors associated with the severity of pain. All statistical analyses were performed using SPSS version 26. A p-value ≤ 0.05 was considered statistically significant.Results: Of the 1000 students who approached online, 757 were included in the final analyses. The prevalence of MRH was (86, 11.4%) and 32.6% of them has experienced the headache before two to three days of menses. The median number of days of missed social activities and reduced productivity was three and one day, respectively. Being single was 6.24 times more likely to have severe MRH (AOR = 6.24, 95% CI: 2.73– 14.26, p=0.001) and pharmacy students were less likely (AOR = 0.31, 95% CI: 0.16– 0.61, p = 0.001) to have severe pain.Conclusion: Our findings illustrated that MRH among young female students adversely affects students’ productivity and social life. This demands interventions to reduce the impact and should pay attention in the future, particularly to create awareness to enhance screening and rendering various treatment options for the target population.Keywords: prevalence, characteristics, menstrual-related headache, treatment pattern, Ethiopia

Abstract Background Quality of life is an important quality indicator for health and aged care sectors. However, self-reporting of quality of life is not always possible given the relatively high prevalence of cognitive impairment amongst older people, hence proxy reporting is often utilised as the default option. Internationally, there is little evidence on the impact of proxy perspective on interrater agreement between self and proxy report. Objectives To assess the impacts of (i) cognition level and (ii) proxy perspective on interrater agreement using a utility instrument, the Quality of Life-Aged Care Consumers (QOL-ACC). Methods A cross-sectional study was undertaken with aged care residents and family member proxies. Residents completed the self-report QOL-ACC, while proxies completed two proxy versions: proxy-proxy perspective (their own opinion), and proxy-person perspective (how they believe the resident would respond). Interrater agreement was assessed using quadratic weighted kappas for dimension-level data and concordance correlation coefficients and Bland-Altman plots for utility scores. Results Sixty-three residents (22, no cognitive impairment; 41, mild-to-moderate cognitive impairment) and proxies participated. In the full sample and in the mild-to-moderate impairment group, the mean self-reported QOL-ACC utility score was significantly higher than the means reported by proxies, regardless of perspective (p

Benjamin D Sullivan,1 Guy T Smith,2 Arun Gupta,3 Francesca Harman,4 Ejaz Ansari5 1Trukera Medical, Southlake, TX, USA; 2The Great Western Hospital NHS Trust, Swindon, UK; 3Ashford and St Peters NHS Trust, Ashford, UK; 4Hillingdon Hospital NHS Foundation, Uxbridge, UK; 5Department of Ophthalmology, Maidstone & Tunbridge Wells Hospitals, Maidstone, Kent, UKCorrespondence: Benjamin D Sullivan, Email bdsulliv@trukera.comPurpose: To understand the impact of subjectivity on diagnosis rates of dry eye disease (DED) in an unbiased population.Patients and Methods: A multicenter study enrolled 818 subjects with complete report forms (465 females, 67.1 ± 16.7 years, 353 males, 65.0 ± 15.9 years). Subjects were evaluated for staining, TBUT, tear osmolarity, meibomian gland disease, and OSDI.Results: Physicians diagnosed 48.7% of subjects as having DED, ranging from 42.9% to 62.3% between sites. Positivity rates for staining (≥ grade 1) ranged from 41.3% to 84.1% (mean = 0.8 ± 0.9 grade), TBUT (< 10s) ranged from 39.1% to 61.6% (mean = 10.4 ± 6.6 seconds), osmolarity (> 308 mOsm/L) ranged from 63.7% to 72.4% (mean = 319.7 ± 20.8), MGD grading ranged from 28.9% to 51.3% (mean = 0.5 ± 0.7), and symptoms measured by OSDI ranged from 57.6% to 71.0% (mean = 23.5 ± 20.5) between sites. Tear osmolarity was the most consistent between sites (max/min positivity = 114%), followed by OSDI (123%), TBUT (158%), MGD (178%), and staining (204%). DED markers were uncorrelated (average r2 = 0.05 ± 0.07). A substantial number of subjects (N = 110) exhibited positive symptoms (OSDI = 32.4 ± 15.7) and hyperosmolarity (338.1 ± 20.1 mOsm/L) but no other obvious signs of DED (MGD grade = 0.2 ± 0.4, TBUT = 13.5 ± 7.0 seconds, staining grade = 0.4 ± 0.5).Conclusion: Subjective signs of DED varied considerably, whereas objective measurements of OSDI and osmolarity were the most consistent between sites. A large proportion of subjects exhibited high symptoms and hyperosmolarity but no other obvious signs of dry eye disease, most of whom were undiagnosed by clinical assessment without access to the osmolarity measurement.Keywords: corneal fluorescein staining, dry eye disease, meibomian gland disease, tear osmolarity, hyperosmolarity

Su Hyun Lim,1,2 Gi Taek Yee,3 Dongwoo Khang1,2,4 1Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, South Korea; 2Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, South Korea; 3Department of Neurosurgery, Gil Medical Center, Gachon University, School of Medicine, Incheon, 21565, South Korea; 4Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, South KoreaCorrespondence: Dongwoo Khang, Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, South Korea, Tel +82 32 899 1525, Email dkhang@gachon.ac.kr Gi Taek Yee, Department of Neurosurgery, College of Medicine, Gil Medical Center, Gachon University, Incheon, 21565, South Korea, Tel +82-32-460-3304, Email gtyee@gilhospital.comAbstract: The blood-brain barrier (BBB) and blood-tumor barrier (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities to overcome these barriers and enhance drug penetration into the brain parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic field, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery involves using engineered cells as carriers for nanoparticles, taking advantage of their intrinsic migratory and homing capabilities to facilitate the transport of therapeutic payloads across BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, coupled with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery exploits magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive avenue to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM. Keywords: glioblastoma, blood-brain barrier, blood-tumor barrier, nanoparticle, combination strategy, ultrasound-wave, magnetic field, intranasal drug delivery

Kebede Araya Abay,1 Girmay Desalegn,2 Yemane Weldu,2 Gebrecherkos Teame Gebrehiwot,3 Gebreselema Gebreyohannes,4 Letemicheal Negash Welekidan,2 Kibra Hailu Desta,2 Yohanns Tekle Asfaw,5 Ataklti Gessese Teka,3 Mulugeta Tilahun Gebremedhin3 1Department of Microbiology and Immunology, Dr. Tewelde Legesse College of Health Sciences, Mekelle, Tigray, Ethiopia; 2Department of Medical Microbiology and Immunology, College of Health Sciences, Mekelle University, Mekelle, Tigray, Ethiopia; 3Department of Biomedical Research and Technology Transfer, Tigray Health Research Institute, Mekelle, Tigray, Ethiopia; 4Department of Biological and Chemical Engineering, Mekelle Institute of Technology, Mekelle University, Mekelle, Tigray, Ethiopia; 5Department of Veterinary Medicine, College of Animal Health, Mekelle University, Mekelle, Tigray, EthiopiaCorrespondence: Gebrecherkos Teame Gebrehiwot, Email cherkos77kga@gmail.comBackground: Campylobacter species are the most predominant bacterial agents to cause diarrhea in under-five children. It poses a serious challenge to public health worldwide with ongoing acquisition of resistance to different antimicrobials with multiple patterns. Thus, this study aimed to determine the prevalence, and antimicrobial resistance of Campylobacter species, and associated factors among under-five children with diarrhea in selected public health facilities.Methods: A cross-sectional study was conducted among under-five children with diarrhea using convenient sampling. Health facilities were selected using a simple random sampling method. The stool samples collected from 214 study participants were transported and processed following standard microbiological protocols. Campylobacter isolates were identified using Gram staining, biochemical test, serological test, and aerobic growth at 25°C. Antimicrobial susceptibility profiles of isolates were performed using the Kirby–Bauer method. Data were analyzed using SPSS ver. 25.0. Association between variables was assessed using Chi-square test and Logistic regression, with P ≤ 0.05.Results: The subject’s mean age was 31.3 (± 3.9) months. Of the 214 samples cultured, 14 (6.5%) of them were positive for Campylobacter species with 95% CI (3.3– 10.3). Out of the isolated species, 12 (85.7%) were Campylobacter jejuni /Campylobacter coli and 2 (14.3%) were other Campylobacter species. Bottle feeding and history of direct contact to domestic animals were associated with Campylobacter species (AOR=5.13, CI=1.21– 21.6, p=0.026 and AOR=4.93, CI=1.33– 18.17, P=0.016), respectively. Campylobacter isolates were highly resistant to ciprofloxacin 5 (35.7%), and tetracycline 3 (21.4%).Conclusion: A higher incidence of Campylobacter species was obtained in children who were bottle-fed and who had a history of direct contact with domestic animals. The isolates were highly resistant to ciprofloxacin and tetracycline. These findings indicate that special attention is needed for better management of Campylobacter drug resistance in under-five children. To enhance and support our current findings, further research using molecular techniques is needed to identify the resistant and virulent genes of the bacterial isolates.Keywords: Campylobacter species, drug susceptibility, gastroenteritis, Mekelle city, prevalence, risk factors, under-five children

Tilahun Dessie Alene,1 Getacher Tessema Engidaye,2 Tesfaye Birhane,3 Sisay Gedamu4 1Department of Pediatrics and Child Health, Wollo University, Dessie, Amhara, Ethiopia; 2Department of Medicine, Mekoy Primary Health Care Unit, Mekoy, Amhara, Ethiopia; 3Department of Reproductive and Family Health, Wollo University, Dessie, Amhara, Ethiopia; 4Department of Comprehensive Nursing, Wollo University, Dessie, Amhara, EthiopiaCorrespondence: Sisay Gedamu, Tel +251935574801 ; +251920553732, Email sgsisay4@gmail.comIntroduction: Epilepsy is a chronic non-communicable disease of the brain that affects millions of people worldwide. A significant number of children are affected globally, and most live in developing countries, often with physical and cognitive disabilities. Regardless of these factors, epilepsy is poorly controlled, particularly in the developing countries. Thus, this study aimed to assess the magnitude of treatment outcomes and its predictors among pediatrics patients with epilepsy who were followed-up at the Dessie Comprehensive Specialized Hospital, Northeast Ethiopia.Methods: Hospital-based cross-sectional study was conducted from 1 June 2022 to 30 August 2022. A total of 200 patients with epilepsy were included in this study. Data were collected through face-to-face interviews, and by reviewing medical records. The collected data were entered into Epi-data version 4.6 and exported to SPSS version 25.0. Descriptive statistics such as frequencies, percentages, means and standard deviations were computed. Binary and multivariate logistic regression analyses were performed. Variables with p < 0.25 in bivariate analysis were entered into multivariable logistic regression. In multivariable analysis, adjusted odd ratio with 95% CI and p-value less than 0.05 were considered statistically significant.Results: Of 200 pediatric patients with epilepsy, 66 (34.5%) had poor treatment outcomes. In the multivariate analysis, 11– 15 years of age (AOR = 4.08; 95% CI = 1.202, 13.848), poor treatment adherence (AOR = 3.21; 95% CI = 1.421, 7.249), history of more seizure frequency before starting treatment (AOR = 4.19; 95% CI = 1.984, 8.834) and history of head injury (AOR = 3.03; 95% CI = 1.502, 6.112) were significantly associated with poor treatment outcomes in pediatric patients with epilepsy.Conclusion: Significant proportion of pediatric patients with epilepsy had poor treatment outcomes. Therefore, health-care workers should strictly follow patient treatment especially for pediatric epileptic patients’ who have poor treatment adherence, more seizure frequency history, head injury history and whose age were 11– 15 years old.Keywords: epilepsy, treatment outcome, children, chronic follow up, Dessie Comprehensive Specialized Hospital

Reconstituting functional transmembrane (TM) proteins into model membranes is challenging due to the difficulty of expressing hydrophobic TM domains, which often require stabilizing detergents that can perturb protein structure and function. Recent model systems solve this problem by linking the soluble domains of membrane proteins to lipids, using noncovalent conjugation. Herein, we test an alternative solution involving the in vitro assembly of TM proteins from synthetic TM domains and expressed soluble domains using chemoselective peptide ligation. We developed an intein mediated ligation strategy to semisynthesize single-pass TM proteins in synthetic giant unilamellar vesicle (GUV) membranes by covalently attaching soluble protein domains to a synthetic TM polypeptide, avoiding the requirement for detergent. We show that the extracellular domain of programmed cell death protein 1, a mammalian immune checkpoint receptor, retains its ligand-binding function at a membrane interface after ligation to a synthetic TM peptide in GUVs, facilitating the study of receptor-ligand interactions.

Tamirat Ersino Kebamo,1 Tilahun Yemane,2 Mesay Arkew,3 Getachew Alemu Walano,1 Abinet Tantu,1 Ageze Abose,4 Kassahun Haile,5 Solomon Gebre Bawore,4 Girum Tesfaye Kiya2 1School of Medical Laboratory Sciences, College of Health Sciences and Medicine, Wolaita Sodo University, Wolaita Sodo, Ethiopia; 2School of Medical Laboratory Sciences, Institute of Health, Jimma University, Jimma, Ethiopia; 3School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia; 4Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wachamo University, Hassana, Ethiopia; 5Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wolkite University, Wolkite, EthiopiaCorrespondence: Tamirat Ersino Kebamo, School of Medical Laboratory Sciences, College of Health Sciences and Medicine, Wolaita Sodo University, P.O. Box: 138, Wolaita Sodo, Ethiopia, Tel +251919675172, Email tamiratersino128@gmail.comBackground: Human exposure to benzene is associated with many adverse health effects. It is mainly related to impairment of the hematopoietic system and bone marrow suppression, causing abnormalities in hematological parameters. However, the reports obtained from different studies are contradictory, and there are little data regarding the hematological parameters of gas station workers in the study area. Therefore, this study aimed to evaluate the hematological parameters of gas station workers in Hosanna town, southwest Ethiopia, from May 01 to June 15, 2020.Methods: A comparative cross-sectional study was conducted by involving 180 (60 gas-stations workers and 120 controls) participants. Socio-demographic and related data of the study participants were collected using a pre-tested structured questionnaire through face-to-face-interviews. All phases of quality assurance were maintained, and hematological parameters were determined using Uni-Cel DxH 800 automated hematological analyzer. Independent sample T-test, Mann–Whitney U-test, and one-way ANOVA were used for data analysis. Statistical significance was declared at P< 0.05.Results: Statistically significant difference was observed in hematological parameters of gasoline-workers and control groups. The mean of red blood cell count among gasoline-workers was significantly reduced as compared to control groups (p=0.007). In addition, the median of hemoglobin levels among gasoline-workers was significantly decreased as compared to the control groups (p=0.001). In contrast, a significant increase was observed in median of absolute eosinophil count among the gasoline-workers as compared to control groups (p=0.01). The mean of mean cell volume was significantly decreased with respect to the duration of work experience (p=0.04).Conclusion: In this study, a statistically significant difference was observed in some hematological parameters of gas station workers compared to the control group. Therefore, medical observation and periodic medical check-ups of the hematological profile should be considered to prevent the development of medical complications.Keywords: benzene, Ethiopia, gasoline workers, hematological parameters, Hossana

Jelena Lilic,1 Vesna G Marjanovic,1,2 Ivana Budic,1,2 Nikola Stefanovic,3 Dragana Stokanovic,4 Goran T Marjanovic,5,6 Tatjana Jevtovic-Stoimenov,7 Mladjan Golubovic,2,8 Maja Zecevic,9 Radmila Velickovic-Radovanovic4,10 1Clinic for Anesthesia and Intensive Therapy, University Clinical Centre Nis, Nis, Serbia; 2Department of Surgery and Anesthesiology with Reanimatology, Faculty of Medicine, University of Nis, Nis, Serbia; 3Department of Pharmacy, Faculty of Medicine, University of Nis, Nis, Serbia; 4Department of Pharmacology with Toxicology, Faculty of Medicine, University of Nis, Nis, Serbia; 5Department of Immunology, Faculty of Medicine, University of Nis, Nis, Serbia; 6Department of Hematology and Clinical Immunology, University Clinical Centre Nis, Nis, Serbia; 7Institute of Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia; 8Clinic of Cardiovascular and Transplant Surgery, University Clinical Centre Nis, Nis, Serbia; 9Clinic of Pediatric Surgery, University Clinical Centre Nis, Nis, Serbia; 10Clinic of Nephrology, University Clinical Centre Nis, Nis, SerbiaCorrespondence: Jelena Lilic, Clinic for Anesthesia and Intensive Therapy, University Clinical Centre Nis, Zorana Djindjica Blvd 48, Nis, 18000, Serbia, Tel +381605118400, Email jjeca8451@gmail.comIntroduction: The polymorphism of the gene coding mu-opioid receptor (OPRM1) is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages.Methods: This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil. Postoperative pain was rated using Numerical Rating Scale (0– 10). All the patients were genotyped forOPRM1 118A>G (rs1799971) gene polymorphism.Results: School children under the age of 11 with the OPRM1 AA genotype were shown to have a higher BMI (p< 0.05). Children over the age of 12 carrying G allele OPRM1, had increased postoperative pain sensitivity and intensity (3.28± 1.95 vs 4.91± 2.17; p< 0.05), as compared to AA allele carriers.Discussion: OPRM1 118A>G polymorphism may explain the variation in the perception of postoperative pain in children over the age of 12 and may be a useful predictor for adjusting the dose of analgesics, but the dose is relative to the patient’s needs regardless of his genetic characteristics. In younger children, carriers of polymorphic OPRM1 118G allele may be protected from obesity, due to diminished MOP expression.Keywords: polymorphism, OPRM1, opioid, pain, children

Tsegaab Yoseph Yirba,1,2 Girma Tekle Gebremariam,1 Tamrat Assefa Tadesse,1 Amsalu Degu,3 Desalew Mekonnen,4 Getachew Alemkere1 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa Univerisity, Addis Ababa, Ethiopia; 2Department of Pharmacy, College of Health and Medical Science, Dilla Univerisity, Dilla, Ethiopia; 3School of Pharmacy and Health Sciences, United States International University-Africa, Nairobi, Kenya; 4Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Health and Medical Science, Addis Ababa Univerisity, Addis Ababa, EthiopiaCorrespondence: Tamrat Assefa Tadesse, Email tamrat.assefa@aau.edu.etBackground: Hypertension is the leading cause of death from cardiovascular disease. Non-adherence to treatment and lifestyle modification are the key drivers of suboptimal blood pressure control and cardiovascular events.Objective: To assess the reliability and validity of the Amharic version of the Hill–Bone Adherence to High Blood Pressure Therapy Scale (HBTS) among Ethiopian hypertensive patients.Methods: A cross-sectional study was conducted among 294 hypertensive patients at two health facilities from 1st October to 30th December 2021 using the culturally adapted HBTS. Psychometric properties were assessed in terms of acceptability, internal consistency, construct validity, and predictive validity. Statistical Package for Social Sciences version 26 was used to perform statistical tests at a significance level of p-value < 0.05. The Statistical Package for Social Sciences AMOS version 26 was used for the confirmatory factor analysis.Results: Cronbach of the 14-item HBTS was initially 0.801. After excluding one item from the appointment-keeping subscale, Cronbach of the modified 13-item HBTS was 0.806. The initial principal component analysis revealed four constructs for the 14-item and three for the 12-item with a total explained variance of 58.65% and 55.73%, respectively. The confirmatory factor analysis failed to fit the observed items with the latent subscales. The predictive validity test showed that the modified 12-item Amharic version was correlated (r= 0.118;p< 0.043) with systolic blood pressure.Conclusion: The modified 13-item Amharic version of the HBTS is a reliable and valid tool with adequate psychometric properties. It can be used to assess adherence to antihypertensive medications in Amharic-speaking patients in Ethiopia.Keywords: hypertension, reliability, Hill-Bone adherence to high blood pressure therapy scale, validity, Ethiopia

Dereje Abebe Regassa,1 Girum Tesfaye Kiya,2 Regassa Alemu Kebede,2 Woyesa Beyene3 1Department of Medical Laboratory Science, Wolkite University, Wolkite, Ethiopia; 2School of Medical Laboratory Sciences, Jimma University, Jimma, Ethiopia; 3Department of Medical Laboratory Science, Dire Dawa University, Dire Dawa, EthiopiaCorrespondence: Dereje Abebe Regassa, Department of Medical Laboratory Science, Wolkite University, PO.Box 07, Wolkite, Ethiopia, Tel +251933864800 ; +251903036210, Email sifaanabebe@gmail.com; dereje.abebe@wku.edu.etBackground: Diabetes is a chronic metabolic syndrome that is a global public health problem. Studies have used hematological parameters and hemogram-derived markers as predictors of poor glycemic and microvascular complications status in diabetics. However, the tendency to use these parameters is not fully evaluated in our context, and the evidence is inadequate. This study aimed to assess the hematological profiles and prognostic role of hemogram-derived novel markers in diabetes mellitus and its complications among DM patients at Bishoftu General Hospital, Ethiopia.Methods: A comparative cross-sectional study was conducted among 261 participants from June 15 to August 12, 2022. A systematic random sampling technique was used to select participants. Data were collected using structured questionnaires, physical measurements, checklists, and laboratory tests. Hematological parameters and fasting blood glucose levels were determined from blood using Sysmex-XN550 and Cobas C311 analyzers, respectively. Blood smear was used to check Hematology analyzer output, and to screen participants for malaria parasites. Collected data were entered into Epi-data 3.1 and exported to SPSS-25. Data were analyzed by Chi-square, Mann–Whitney U-test, Kruskal–Wallis test, Post hoc test, and ROC curve. A P-value < 0.05 was considered statistically significant.Results: Total WBC, neutrophils, Monocyte, NLR, MLR, MPVLR, and PLR were significantly higher in poor glycemic and complicated T2DM; meanwhile, measured RBC parameters, RBC indices values were significantly lower in poor glycemic and complicated T2DM. The NLR, MLR, MPVLR, PLR, and NLR, MLR, MPVLR, RPR values were identified as predictors of poor glycemic and complication status in diabetic patients, respectively.Conclusion: Significant increment of some hematological parameters and hemogram-derived markers, and their role in predicting poor glycemic and microvascular complications were identified in diabetic patients. Routine screening of hematological parameters and use of hemogram-derived markers for monitoring of altered health status in DM is very important in the improvement of patient quality of life.Keywords: hematological parameters, hemogram-derived markers, type 2 diabetes, Ethiopia

We are now facing a tsunami wave of social media development. Anyone and anywhere can access religious information. The impact of this correlates with the vital flow of globalization to all levels of society. The negative influence from the media development side gives a strong impetus for social insecurity. Our integrity as citizens will be at stake because of the appeal of social media. To maintain this, it is essential to strengthen and foster so as not to get out of the path of the nation's ideals. This research discusses how students establish relationships with God and each other in the frame of love for the homeland, surrounded by a plurality of religions, tribes, ethnicities, and cultures, to create an attitude of religious moderation. This type of research is included in field research with quantitative and qualitative approaches. Internalization of spiritual values and love for the homeland in students showed positive results. The results of respondent data show that the strong tendency of religious influence has a positive impact and correlates with love for the homeland. Based on the data, 60% strongly agree, and 28% agree with maintaining relationships with others regardless of anything. This reflects that students' religious understanding has shown an inclusive category, which means they can openly accept differences irrespective of religion, ethnicity, and culture, which is necessary in the Republic of Indonesia.

Aster Wakjira Garedow,1 Mekonnen Damessa Mamo,1 Gorfineh Teshome Tesfaye2 1Jimma University, School of Pharmacy, Jimma, Ethiopia; 2Jimma University Medical Center, Department of Pharmacy, Jimma, EthiopiaCorrespondence: Aster Wakjira Garedow, Email asterwakjira@gmail.com; aster.garedow@ju.edu.etBackground: Hypertension affects more than 1.4 billion people worldwide currently, with that number anticipated to climb to 1.6 billion by 2025 with high mortality and morbidity effects. Medication related problems in cardiovascular disease patients, especially among hypertension patients were found to be high and a critical problem which is associated with high mortality, complication, prolonged hospital stay, compromised quality of life and increase health care cost.Objective: To determine medication related problems and its predictors among hypertension patients on chronic follow-up at Jimma Medical Center.Methods: A prospective interventional study was conducted among hypertension patients from November 28, 2021 to June 30, 2022 at Jimma Medical Center. Medication related problems were classified and identified based on Pharmaceutical care network Europe drug classification tool version 9.0. Interventions were done through discussion with individual prescriber and patients. Consecutive sampling technique was used. Binary Logistic regression was used to identify independent predictors of medication related problems. Variables having P-values < 0.05 were considered statistically significant.Results: Among 384 hypertension patients included in the study, 219 (57.1%) were male. The mean (SD) age was 49.06+17.79. Two thirds of study participants had at least one medication related problem. A total of 483 MRPs were identified among 231 (60.15%) patients. Treatment effectiveness related problem (55.48%) was the most common observed medication related problems. Alcoholism (AOR; 3.15, 95% CI [1.46– 7.23]), stage II hypertension (AOR=2.77, 95% CI= [3.53– 4.66]); comorbidity (AOR=2.88, 95% CI= [1.47– 5.66]) and polypharmacy (AOR=3.07, 95% CI= [1.57– 5.99]) were the independent predictors of medication related problems.Conclusion: The prevalence of medication related problems was high among hypertensive patients. Alcoholism, stage II hypertension, comorbidity and poly-pharmacy were the predictors of medication related problems. Therefore, to overcome the problems, clinical pharmacists, physicians and other health care professionals have to work in collaboration.Keywords: medication related problems, interventions, hypertension, Jimma

Puffer and porcupine fishes (families Diodontidae and Tetraodontidae, order Tetradontiformes) are known for their extraordinary ability to triple their body size by swallowing and retaining large amounts of seawater in their accommodating stomachs. This inflation mechanism provides a defence to predation; however, it is associated with the secondary loss of the stomach's digestive function. Ingestion of alkaline seawater during inflation would make acidification inefficient (a potential driver for the loss of gastric digestion), paralleled by the loss of acid-peptic genes. We tested the hypothesis of stomach inflation as a driver for the convergent evolution of stomach loss by investigating the gastric phenotype and genotype of four distantly related stomach inflating gnathostomes: sargassum fish, swellshark, bearded goby and the pygmy leatherjacket. Strikingly, unlike in the puffer/porcupine fishes, we found no evidence for the loss of stomach function in sargassum fish, swellshark and bearded goby. Only the pygmy leatherjacket (Monochanthidae, Tetraodontiformes) lacked the gastric phenotype and genotype. In conclusion, ingestion of seawater for inflation, associated with loss of gastric acid secretion, is restricted to the Tetraodontiformes and is not a selective pressure for gastric loss in other reported gastric inflating fishes.

We modified and combined an open-source spatial frequency domain imaging (openSFDI) build with laser speckle imaging (LSI) into a widefield rodent cortical hemodynamic imaging system. Here, we present system specifications and in-vitro phantom measurement results.

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or "omics," quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

We report a layered ternary selenide BaPt4Se6 featuring sesqui-selenide Pt2Se3 layers sandwiched by Ba atoms. The Pt2Se3 layers in this compound can be derived from the Dirac-semimetal PtSe2 phase with Se vacancies that form a honeycomb structure. This structure results in a Pt (VI) and Pt (II) mixed-valence compound with both PtSe6 octahedra and PtSe4 square net coordination configurations. Temperature-dependent electrical transport measurements suggest two distinct anomalies: a resistivity crossover, mimic to the metal-insulator (M-I) transition at ~150 K, and a resistivity plateau at temperatures below 10 K. The resistivity crossover is not associated with any structural, magnetic, or charge order modulated phase transitions. Magnetoresistivity, Hall, and heat capacity measurements concurrently suggest an existing hidden state below 5 K in this system. Angle-resolved photoemission spectroscopy measurements reveal a metallic state and no dramatic reconstruction of the electronic structure up to 200 K.