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1.
Blood ; 142(25): 2175-2191, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-37756525

RESUMO

ABSTRACT: Growth factor independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of hematopoiesis. GFI1-36N is a germ line variant, causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10% to 15% among patients with acute myeloid leukemia (AML) and 5% to 7% among healthy Caucasians and promotes the development of this disease. Using a multiomics approach, we show here that GFI1-36N expression is associated with increased frequencies of chromosomal aberrations, mutational burden, and mutational signatures in both murine and human AML and impedes homologous recombination (HR)-directed DNA repair in leukemic cells. GFI1-36N exhibits impaired binding to N-Myc downstream-regulated gene 1 (Ndrg1) regulatory elements, causing decreased NDRG1 levels, which leads to a reduction of O6-methylguanine-DNA-methyltransferase (MGMT) expression levels, as illustrated by both transcriptome and proteome analyses. Targeting MGMT via temozolomide, a DNA alkylating drug, and HR via olaparib, a poly-ADP ribose polymerase 1 inhibitor, caused synthetic lethality in human and murine AML samples expressing GFI1-36N, whereas the effects were insignificant in nonmalignant GFI1-36S or GFI1-36N cells. In addition, mice that received transplantation with GFI1-36N leukemic cells treated with a combination of temozolomide and olaparib had significantly longer AML-free survival than mice that received transplantation with GFI1-36S leukemic cells. This suggests that reduced MGMT expression leaves GFI1-36N leukemic cells particularly vulnerable to DNA damage initiating chemotherapeutics. Our data provide critical insights into novel options to treat patients with AML carrying the GFI1-36N variant.


Assuntos
Proteínas de Ligação a DNA , Leucemia Mieloide Aguda , Humanos , Camundongos , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Temozolomida , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Dano ao DNA , Reparo do DNA , Células Germinativas/metabolismo , DNA , Fatores de Transcrição/genética
2.
J Cell Mol Med ; 28(4): e18105, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339761

RESUMO

Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs. non-ICU admission). A recently introduced alpha-index identified the 30 most predictive genetic variants. DERGA algorithm, which employs multiple classification algorithms, determined the optimal pattern of these key variants, resulting in 97% accuracy for predicting disease outcome. Individual variations ranged from 40 to 161 variants per patient, with 977 total variants detected. This study demonstrates the utility of alpha-index in ranking a substantial number of genetic variants. This approach enables the implementation of well-established classification algorithms that effectively determine the relevance of genetic variants in predicting outcomes with high accuracy.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/genética , Inteligência Artificial , Algoritmos
3.
J Biol Chem ; 299(1): 102750, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436563

RESUMO

Type IIB receptor protein tyrosine phosphatases are cell surface transmembrane proteins that engage in cell adhesion via their extracellular domains (ECDs) and cell signaling via their cytoplasmic phosphatase domains. The ECDs of type IIB receptor protein tyrosine phosphatases form stable, homophilic, and trans interactions between adjacent cell membranes. Previous work has demonstrated how one family member, PTPRM, forms head-to-tail homodimers. However, as the interface was composed of residues conserved across the family, the determinants of homophilic specificity remain unknown. Here, we have solved the X-ray crystal structure of the membrane-distal N-terminal domains of PTPRK that form a head-to-tail dimer consistent with intermembrane adhesion. Comparison with the PTPRM structure demonstrates interdomain conformational differences that may define homophilic specificity. Using small-angle X-ray scattering, we determined the solution structures of the full-length ECDs of PTPRM and PTPRK, identifying that both are rigid extended molecules that differ in their overall long-range conformation. Furthermore, we identified one residue, W351, within the interaction interface that differs between PTPRM and PTPRK and showed that mutation to glycine, the equivalent residue in PTPRM, abolishes PTPRK dimer formation in vitro. This comparison of two members of the receptor tyrosine phosphatase family suggests that homophilic specificity is driven by a combination of shape complementarity and specific but limited sequence differences.


Assuntos
Proteínas Tirosina Fosfatases , Transdução de Sinais , Humanos , Adesão Celular , Linhagem Celular , Proteínas Tirosina Fosfatases/metabolismo , Tirosina
4.
Am J Physiol Gastrointest Liver Physiol ; 326(5): G591-G606, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469632

RESUMO

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.


Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Mucosa Intestinal , Camundongos Endogâmicos C57BL , Animais , Feminino , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/patologia , Colite/imunologia , Colite/microbiologia , Álcoois Graxos/farmacologia , Di-Inos/farmacologia , Modelos Animais de Doenças , Colo/efeitos dos fármacos , Colo/patologia , Colo/imunologia , Colo/microbiologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/microbiologia
5.
Ann Surg ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38348652

RESUMO

OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.

6.
Ann Hematol ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028356

RESUMO

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38224415

RESUMO

BACKGROUND: In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI). METHODS: This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784. RESULTS: Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively). CONCLUSION: NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

8.
Epilepsy Behav ; 153: 109731, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452516

RESUMO

BACKGROUND: Despite significant advancements in the understanding and treatment of epilepsy, the quality of life for persons diagnosed with Epilepsy (PdwE) can still be negatively impacted due to prevalent misconceptions and societal attitudes. This study aimed to investigate the knowledge, misconceptions, and attitudes towards epilepsy in Bahrain. METHODS: This cross-sectional study involved 1079 participants aged ≥ 18 years living in Bahrain. Data collection occurred between June and December 2023 through an online questionnaire. The questionnaire consisted of four sections: sociodemographic characteristics, sources of information, knowledge about epilepsy, and attitudes toward PdwE. RESULTS: Most participants (1063 out of 1179) were familiar with epilepsy, with social media being the main source of information (56.7%). While 75.6% correctly recognized epilepsy as a nervous system disorder. About 30% of participants believed that body shaking and falling to the ground were the only types of seizures. In terms of attitudes, 47.9% believed that PdwE could achieve high levels of education, but 40% thought they might face job loss due to their condition. Additionally, 27.5% disagreed with the idea of marrying someone with epilepsy or allowing a family member to do so. Being female, young, highly educated, and having a family member with epilepsy were associated with significantly more positive attitudes compared to other groups. CONCLUSION: The studied sample of the Bahraini public demonstrated a satisfactory level of knowledge about epilepsy. However, they still held certain misconceptions that could impact their attitudes towards PdwE. Community awareness campaigns can address this knowledge gap and reduce epilepsy stigma.


Assuntos
Epilepsia , Qualidade de Vida , Humanos , Feminino , Masculino , Estudos Transversais , Barein/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Epilepsia/epidemiologia , Inquéritos e Questionários
9.
BMC Vet Res ; 20(1): 329, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033105

RESUMO

BACKGROUND: In the livestock industry, Foreign Body Syndrome is a devastating disease condition. Feeding management, lacking of food discrimination, and eating chopped food increase the risk of swallowing sharp foreign bodies in bovine species. In addition to the honeycomb cells shape of the reticulum, the contractions of the reticular wall, gravid uterine pressure, and parturition efforts, foreign bodies can penetrate the reticular wall, causing cascade of problems including traumatic reticulitis, traumatic reticuloperitonitis, and traumatic pericarditis. The present study was carried out to evaluate the diagnostic significance of cardiac troponin I rapid test cassette and other cardiac biomarkers including serum cardiac troponin I (cTn I), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase enzyme (AST), in confirmed cases of traumatic pericarditis (TP) and/or traumatic reticuleoperitonitis (TRP) in cattle and buffaloes. METHODS: A total number of 30 animals (22 cattle and 8 buffaloes) with different signs such as anorexia, jugular distension, brisket edema, and signs of pain (reluctance to move, arching back, and abduction of the forelimbs) were included in the present study. Based on case history, clinical signs, ferroscopic, pericardiocentesis, radiographic and ultrasonographic examinations, TP were confirmed in cattle (n = 10) and buffaloes (n = 8) while TRP were confirmed only in cattle (n = 12). Additionally, 20 clinically healthy animals (n = 10 cattle and 10 buffaloes) were used as a control group. Blood samples were collected for determination of blood level of Tn-I, and activity of CK-MB, LDH, and AST. RESULTS: The obtained results revealed a highly significant increase in serum cTn I in diseased cattle with TP and TRP (P = 0.00), while buffaloes with TP showed no significant changes in serum cTn I (P = 0.111). Both diseased cattle and buffaloes showed increased serum activities of CK-MB, AST, and LDH enzyme. On the other hand, cardiac troponin I rapid test cassette failed to detect cTn I in diseased animals. CONCLUSION: The study concluded that the cardiac troponin I rapid test cassette did not have a diagnostic significance and could not be used as a point-of-care under field condition for diagnosis of TP and TRP in large ruminants. However, the serum troponin I level is helpful in diagnosis of TP and TRP in cattle. Although cardiac biomarkers have some diagnostic values in TP and TRP, the traditional diagnostic methods (clinical, radiography and ultrasonography examinations) are crucial for thorough evaluation of TP/TRP cases in bovine.


Assuntos
Biomarcadores , Búfalos , Doenças dos Bovinos , Creatina Quinase Forma MB , Pericardite , Retículo , Troponina I , Animais , Pericardite/veterinária , Pericardite/diagnóstico , Pericardite/sangue , Bovinos , Biomarcadores/sangue , Troponina I/sangue , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/sangue , Creatina Quinase Forma MB/sangue , Feminino , Peritonite/veterinária , Peritonite/diagnóstico , Peritonite/sangue , L-Lactato Desidrogenase/sangue , Aspartato Aminotransferases/sangue , Masculino , Corpos Estranhos/veterinária , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico
10.
BMC Psychiatry ; 24(1): 344, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714984

RESUMO

BACKGROUND: Female sex workers (FSWs) face an elevated risk of developing mental health disorders and alcohol use disorders (AUD), which in turn increase their vulnerability to HIV and other sexually transmitted infections (STIs) and other negative outcomes. To effectively address both of these health issues, it is crucial to understand the shared key determinants underlying these illnesses, which is a substantial knowledge gap in Ethiopia and elsewhere in the world. Therefore, this study aimed to identify the common key determinants of depression and AUD among FSWs in Ethiopia using a bivariate multivariable ordinal logistic model. METHODS: We analyzed cross-sectional biobehavioral data collected in 2020 from 16 cities and major towns in Ethiopia using the respondent-driven sampling (RDS) technique, which involved a total of 6,085 FSWs. FSWs who had lived at the study sites for at least a month before the study period were deemed eligible for recruitment. Major depressive disorder (DD) and AUD were screened using the Patient Health Questionnaire (PHQ9) and alcohol use disorder identification test (AUDIT), respectively. We used descriptive statistics to summarize study population characteristics and bivariate multivariable ordinal logistic regression (BMOLR) to identify common determinants of DD and AUD combined and their nonnormal correlation. RESULTS: Among 6085 FSWs screened for DD and AUD, 13.5% and 4.0% have met the criteria for moderate and severe depressive disorder, respectively, and 20.3% and 34.7% have met the AUDIT criteria for harmful or hazardous behavior and alcohol dependence, respectively. FSW with experience of inconsistent condom use, condom failure, violence, mobility, use of any drugs, non-paying partners, abortion, and selling sex for more than five years were associated with an increase in the severity of both disorders. A high average income from selling sex and the number of paying partners reduced the severity of depression and increased the level of alcohol dependence. Being HIV positive and ever having anal sex were associated only with an increase in depression. CONCLUSION: Major DD and AUD are prevalent among FSWs in Ethiopia. The findings revealed that common key determinants, which exacerbated the severity of both disorders, were also risk factors for HIV and other STIs. Consequently, integrated STI strategies are essential in the screening, referral, and treatment of depression and AUD. Intervention packages should encompass determinants of depression and AUD, including condom utilization, drug use, mobility between towns, abortion, violence, and counseling services. Additionally, strategies to ensure economic security should be incorporated.


Assuntos
Alcoolismo , Profissionais do Sexo , Humanos , Feminino , Etiópia/epidemiologia , Profissionais do Sexo/estatística & dados numéricos , Profissionais do Sexo/psicologia , Adulto , Estudos Transversais , Adulto Jovem , Alcoolismo/epidemiologia , Adolescente , Transtorno Depressivo Maior/epidemiologia , Fatores de Risco , Prevalência
11.
BMC Psychiatry ; 24(1): 17, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172755

RESUMO

BACKGROUND: Depressive disorder is one of the severe and common mental illnesses in the general population. Bipolar disorder is a severe, persistent mental illness associated with significant morbidity and mortality. However, there is a paucity of data on the prevalence of depressive disorder, and bipolar disorder in our study area. OBJECTIVE: This study aimed to assess the prevalence of depressive and bipolar disorders among adults in Kersa, Haramaya, and Harar Health and Demographic Surveillance Sites in Eastern Ethiopia. METHODS: A community-based cross-sectional study was conducted among 1,416 participants. A multi-stage sampling was employed to select the participants. DSM-5 diagnostic criteria was used to assess depressive disorder and bipolar disorder. Data was collected using a standard questionnaire. Data were entered into Epi-Data 3.1 and analyzed using SPSS version 26. Both binary and multivariate logistic regression analyses were done. Those with a p-value < 0.05 in the final model were considered statistically significant. RESULTS: The overall prevalence of depressive and bipolar disorders among our study participants was 6.7% (95% CI: 5.40, 8.20) and 2.1% (95% CI: (1.40, 3.00), respectively. The independent predictors of depressive disorder included a family history of mental illness, chronic medical illnesses, unemployment, low educational status, divorced or widowed, poor social support, and current alcohol use or khat chewing. Single, males, divorced or widowed, and current consumers of alcohol were independent predictors for bipolar disorder. CONCLUSIONS AND RECOMMENDATION: The results of our investigation showed that bipolar illness and depression were significant public health issues. It was shown that although bipolar disorder is highly prevalent in the society, depression is a widespread concern. As a result, it is imperative that the relevant body grow and enhance the provision of mental health services. Furthermore, research on the effects and burdens of bipolar disorder in the community is required.


Assuntos
Transtorno Bipolar , Transtorno Depressivo , Adulto , Masculino , Humanos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Estudos Transversais , Etiópia/epidemiologia , Consumo de Bebidas Alcoólicas , Prevalência
12.
Eur J Pediatr ; 183(4): 1637-1643, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38193997

RESUMO

Pulmonary arterial hypertension (PAH) in pediatrics is a progressive disease with significant vascular remodeling, right sided heart failure, and death if left untreated. Elevated interleukin-6 (IL-6) level in PAH patients is taken as an independent predictor of adverse outcome including mortality. The aim of this study was to investigate and compare serum levels of IL-6 in children with PAH and healthy matched controls, and correlate between IL-6 and degree of PAH, as well as mortality. IL-6 was measured by ELISA in serum samples in 40 children with PAH (age 1-12 years) and 40 age and sex-matched healthy controls. There was a statistically significant increase in IL-6 level among PAH cases compared with the controls (1.85 ng/L vs 1.30 ng/L, p-value = 0.004). IL-6 at cut off point 1.45 ng/L significantly predict pulmonary hypertension in children (AUC = 0.685, 75% sensitivity, and 65% specificity with p = 0.002). There was no statistically significant association between IL-6 level and degree of PAH (p = 0.218). There was no statistically significant association between IL-6 level and mortality (p = 0.662).    Conclusion: IL-6 significantly predict PAH in pediatrics but there is no association between IL-6 level and degree of PAH or mortality. IL-6 may provide a less costly and less invasive method for disease detection. What is Known: • Definitive diagnosis of PAH is made by right heart catheterization, while echocardiography is the gold standard for tracking the course of the disease. What is New: • It was assumed that children with a diagnosis of PAH would have higher serum IL-6 levels than controls. Furthermore, an adverse relationship between the blood IL-6 level and PPAH was predicted.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Criança , Lactente , Pré-Escolar , Interleucina-6 , Estudos de Casos e Controles , Prognóstico , Hipertensão Pulmonar/diagnóstico
13.
Neurol Sci ; 45(5): 1945-1951, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38146012

RESUMO

BACKGROUND: There is evidence that individuals of African ancestry, particularly those residing in Africa, suffer from an unfortunate amount of under-representation in cancer research worldwide. AIM: We aimed to analyze current research output and potentially predict future trends in neuro-oncological research in Africa. Investigating deficits in the field will assist in identifying top-performing countries, which ones face challenges, and how to solve them. Therefore, targeted interventions can be applied to overcome these challenges. METHODS: We conducted a systematic computer-based search on the following databases (PubMed, Scopus, Web of Science, and Embase) for research articles related to the neuro-oncological field in Africa. We aimed to retrieve any article published in the period between 1 January 2000 and 10 January 2023. RESULTS: We included 200 eligible articles in our study. The output of neuro-oncological research has been increasing over the past two decades, peaking in 2019. Among the included articles, clinical practice issues constituted the majority (80%), while public health-related topics accounted for 20% of the publications. Regarding the type of neurological tumor, neuroblastoma was the most common, with 26 articles (13%), meningioma with 21 (10.5%), and glioma with 16 articles (8%). CONCLUSION: The interest in African neuro-oncological research is increasing. Hence, there is a need for ongoing efforts to address issues with clinical practice and public health related to neurological tumors in the continent. Future studies should concentrate on filling in knowledge gaps and investigating novel methods for neuro-oncological conditions that affect African populations in terms of prevention, diagnosis, treatment, and management strategies.


Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Humanos , África/epidemiologia , Neoplasias Encefálicas/terapia
14.
Med Educ ; 58(8): 930-938, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38888045

RESUMO

CONTEXT: Politics is characterised by power relations, and the deployment of power is inescapably political. In an increasingly globalised and interconnected modern world, politics is shaping the field of medical education more than ever before. Global frameworks that classify peoples and places are political tools that are fundamentally shaped by hegemonic knowledge systems. Despite this, they continue to form the basis for global thinking and practices, including in medical education. Political analysis can help to expose and challenge such thinking. APPROACH: To better understand impacts of globalisation in medical education, we explore the previously under-examined political dimensions that underpin it, focusing particularly on deconstructing power relations. We situate our analysis of global medical education in political terms, including through examination of ideology, economics, market and the enduring effects of colonialism. We interrogate the construct of the Global South (GS), considering the geopolitical and historical ideas that have enabled it to be widely propagated. We go on to examine the consequences of the GS construct in medical education and consider what this tells us about how power is enacted in the field. CONCLUSIONS: In analysing the politics of global medical education, we shed light on how power is exerted and draw attention to forces that permit and enable trends, policies and positions. Notwithstanding the emancipatory rhetoric that has been associated with the GS construct, we highlight its reductive potential and argue that it can lead to an oversimplification of power relations and vested interests. Given the growing recognition that educational approaches do not transfer well across countries and cultures, we encourage the medical education community to consider why ideas from more dominant countries continue to be imitated so routinely. In doing so, we urge them to use political lenses to recognise the influence of multiple complex and interconnected forces of global power that shape all aspects of medical education.


Assuntos
Educação Médica , Internacionalidade , Política , Humanos , Poder Psicológico , Saúde Global , Colonialismo
15.
BMC Womens Health ; 24(1): 377, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943118

RESUMO

BACKGROUND: Cervical cancer is the second most common malignancy in Ethiopia and first in some African countries. It is six times more likely to occur in positive cases of the human immunodeficiency virus than in the general population. If diagnosed and treated early enough, cervical cancer is both treatable and preventable. However, among Ethiopian women who test positive for HIV, the uptake of cervical cancer screening is low. Its determinant factors were not well studied in the study area. Hence, this study was aimed at filling this information gap. OBJECTIVE: To assess uptake of cervical cancer screening services and associated factors among HIV-positive women attending an adult antiretroviral treatment clinic at public hospitals in Addis Ababa, Ethiopia, June 1-30, 2022. METHODS: A cross-sectional investigation was carried out in a hospital. 407 participants in all were chosen using the systematic sampling technique. A pretested interviewer-administered questionnaire was used to collect the data from respondents. The data were entered into Epi data version 4.6 and exported to SPSS version 25 for analysis. Bivariable and multivariable logistic regression analysis was employed. Adjusted odds ratio with its 95% confidence interval and p value < 0.05 were used to estimate the strength and significance of the association. RESULT: Among a total of 407 respondents, 238 (58.5%), 95% CI (53.5-63.3), HIV-positive women were screened at least once in the last five years. In multivariable analysis, age > 45 years old (AOR = 0.18, 95% CI: 0.053-0.644), number of children (3 children) (AOR = 0.19, 95% CI:0.036-0.979), perception of being susceptible to cervical cancer (AOR = 6.39, 95% CI: 1.79-22.74), knowledge of cervical cancer and its screening (AOR = 19.34, 95% CI: 7.87-47.75), and positive attitude towards cervical cancer screening (AOR = 8.06, 95% CI:3.62-17.91) were significantly associated factors with the uptake of cervical cancer screening. CONCLUSION AND RECOMMENDATION: in this study, Age > 45 years, having less than three children, feeling susceptible, knowing about cervical cancer and screening, and having a positive attitude toward cervical cancer screening were significant factor of uptake of cervical cancer screening service. There is a need to strengthen the policy and health education on safe sexual practices and healthy lifestyles through information dissemination and communication to scale up screening service utilization.


Assuntos
Detecção Precoce de Câncer , Infecções por HIV , Hospitais Públicos , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Etiópia/epidemiologia , Adulto , Estudos Transversais , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/psicologia , Hospitais Públicos/estatística & dados numéricos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adulto Jovem , Inquéritos e Questionários , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/métodos
16.
Photodermatol Photoimmunol Photomed ; 40(3): e12964, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38616405

RESUMO

INTRODUCTION: Pityriasis lichenoides chronica is the chronic end of the spectrum of pityriasis lichenoides which have several forms of papulosuamous conditions. Several treatments obtained complete clearance of the condition including phototherapy and specifically narrow band ultraviolet B. The Excimer light 308 is a monochromatic light that acts within the ultraviolet B wavelength and used as a targeted phototherapy in several skin conditions. METHODS: Thirty-four patients with histopathologically diagnosed pityriasis lichenoides chronica underwent treatment with biweekly sessions of excimer light 308 nm. Treatment continued until complete clearance was obtained or to a maximum of 48 sessions (24 weeks). RESULTS: Thirty-one patients obtained complete clearance with no recurrence till the end of the study period, two patients had partial response and only one patient showed poor response to treatment. CONCLUSION: Excimer light can be a safe and effective treatment of pityriasis lichinoides chronica in different ages and genders.


Assuntos
Pitiríase Liquenoide , Humanos , Feminino , Masculino , Pitiríase Liquenoide/radioterapia , Fototerapia , Cinética
17.
BMC Public Health ; 24(1): 910, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539158

RESUMO

BACKGROUND: HIV/AIDS is one of the top global public health threats that causes significant cases, deaths, and socioeconomic impact. Even though both HIV testing and counseling are identified as essential HIV interventions during pregnancy, large population-representative data shows that service coverage and determinants are limited. Therefore, this study aimed to assess the coverage and determinants of HIV testing and counseling services among pregnant mothers attending antenatal care services in sub-Saharan African countries using different nationwide data. METHODS: This study was conducted on large national-representative data from the Demographic Health Survey (DHS) using multilevel analysis. Data extraction, cleaning, coding, and statistical analysis were performed using STATA version 17. Weighting was used to ensure the representativeness of the sample and to obtain reliable estimates and standard errors. The multivariable multilevel logistic regression model was used to identify the determinants of HIV testing and counseling during the antenatal care visit. Adjusted odds ratios with 95% confidence intervals were used to measure statistical significance. RESULTS: A total of 83,584 women attending antenatal care were included in this study. HIV testing and counseling coverage in sub-Saharan Africa was found to be 62.87% with a 95% CI of 62.54-63.19%. The HIV testing and counseling determinants included being in the age group of 35-49 (AOR = 1.64; 95% CI: 1.46-1.83), secondary and above education levels (AOR = 1.50; 95% CI: 1.39-1.60), having at least four ANC visits (AOR = 1.85; 95% CI: 1.68-2.02), living in an urban area (AOR = 1.40; 95% CI: 1.30-1.52), and living in countries such as Rwanda (AOR = 6.19; 95% CI: 5.19-7.38) and Mauritania (AOR = 0.02; 95% CI: 0.01-0.03). CONCLUSION: This study revealed that HIV testing and counseling coverage was 62.87% in sub-Saharan Africa. Factors affecting the HIV testing and counseling coverage were age, education, frequency of antenatal care visits, residence area, and living in Rwanda and Mauritania. Therefore, to increase HIV testing and counseling coverage in sub-Saharan Africa, policymakers on maternal health and other stakeholders should work with an integrated approach with other sectors and give prior attention to modifiable factors such as promoting women's education and the comprehensiveness of antenatal care follow-up services during the follow-up.


Assuntos
Síndrome da Imunodeficiência Adquirida , Cuidado Pré-Natal , Feminino , Gravidez , Humanos , Adulto , Pessoa de Meia-Idade , Análise Multinível , Inquéritos Epidemiológicos , África Subsaariana , Aconselhamento , Teste de HIV
18.
J Adolesc ; 96(4): 874-885, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38385858

RESUMO

INTRODUCTION: Adolescents' attachment security toward parental figures has been assessed in multiple cultures and languages. In some cultural contexts, the presence of a secondary parental figure is ubiquitous, though its effect on children's and adolescents' well-being has been understudied. The present study aimed to validate a culture-specific Arabic instrument of attachment security, in an adolescent sample of Qatar. Since foreign domestic workers (Khadama) play a key role as secondary caring figures in Middle Eastern countries, the new instrument included parents (i.e., mother and father) and domestic workers as providers of attachment security. METHODS: A sample of 387 adolescents (ages 12-17 years; 48.3% females) participated in the study in the 2020-2021 school term. While 286 students completed the version in modern Arabic, 101 counterparts attending international schools filled in the English version for comparison purposes. RESULTS: Confirmatory Factor Analysis for all three forms (i.e., mother, father, and domestic worker) showed the one-dimension of the Arabic tool. Optimal Tucker's Phi coefficient indicated a comparable one-factor structure of attachment security across linguistic versions. Moderate correlations (positive and negative, respectively) of attachment security towards father and mother (but not towards domestic workers) with family cohesion and family conflict dimensions of the Family Environment Scale provided evidence for the concurrent validity. DISCUSSION: Gender differences in the links between adolescents' attachment security and family conflict were observed; culturally relevant relationship family patterns are stressed. The practical implications of the Arabic Inventory of Parent and Domestic Worker Attachment (A-IPDWA) validation are discussed.


Assuntos
Apego ao Objeto , Relações Pais-Filho , Humanos , Feminino , Masculino , Adolescente , Catar , Relações Pais-Filho/etnologia , Criança , Inquéritos e Questionários/normas , Psicometria/instrumentação , Reprodutibilidade dos Testes
19.
Chem Biodivers ; 21(7): e202400637, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38740555

RESUMO

One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. Using computational simulations and models, we investigate the structure-activity relationships of 1,2,4-triazoles, showing how various modifications to the triazole core yield a variety of clinical therapeutic benefits. The review highlights the anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles' capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Coordinated efforts are required to translate the efficacy of 1,2,4-triazole compounds in preclinical models into practical therapeutic benefits. Based on the information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and the medical community as a whole. This comprehensive research, which is further reinforced by in-silico investigations, highlights the great medicinal potential of 1,2,4-triazoles. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development.


Assuntos
Antineoplásicos , Desenho de Fármacos , Triazóis , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Química Farmacêutica , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Relação Estrutura-Atividade , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
20.
BMC Med Educ ; 24(1): 61, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216906

RESUMO

BACKGROUND: Healthcare workers must maintain their knowledge, attitude, and skills regarding the most recent technology and competencies to deliver quality health care. The Ministry of Health, Ethiopia developed guidelines and directives for the utilization of continuous professional development programs. However, there is limited evidence on utilization and barriers to utilization in the study area. Therefore, this study aimed to assess the utilization and barriers to the utilization of continuous professional development among health professionals working in health facilities in eastern Ethiopia. METHODS: A health facility-based cross-sectional quantitative study was conducted among 731 healthcare professionals from September 01, 2022, and October 30, 2022. A multistage sampling technique was utilized. A simple random sampling technique selected health facilities and study participants. A self-administered questionnaire developed from national continuous professional development guidelines was disseminated to healthcare professionals working in the selected forty health centers and four hospitals. STATA statistical package version 14 was used for data analysis. A descriptive summary was used to summarize the variables. A logistic regression model was used to assess the association between independent variables and the outcome variable. Adjusted odds ratios along with 95% CIs were estimated to assess the strength of the association, and a p-value < 0.05 was used to declare the level of statistical significance in the analysis. RESULTS: Continuous professional development utilization was determined for 731 healthcare professionals, of whom 241 (32.97%) [(95% CI: (29.55, 36.38)] had utilized continuous professional development. Lack of continuous professional development knowledge AOR 0.23 [(95% CI: 0.14, 0.37)], being female AOR 0.58 [(95% CI: 0.39, 0.86)], lack of internet access AOR 0.62 [(95% CI: 0.43, 0.89)], greater than 20 km distance from main road AOR 0.58 [(95% CI: 0.37, 0.91)], not heard importance of continuous educational units AOR 0.45 [(95% CI: 0.31, 0.65)], and poor perceived need of continuous professional development AOR 0.61 [(95% CI: 0.38, 0.97)], had a negative statistically significant association with the utilization of continuous professional development. CONCLUSION: The utilization of continuous professional development in the study area was low. Health sectors and stakeholders working on continuous professional development programs are required to focus on developing strategies for knowledge creation, female health workers, and access to the internet, remote areas, information on the importance of continuous educational units, and the variety of needs of professionals for continuous professional development implementation.


Assuntos
Instalações de Saúde , Pessoal de Saúde , Humanos , Feminino , Masculino , Estudos Transversais , Etiópia , Modelos Logísticos
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