Unveiling ferroptosis as a promising therapeutic avenue for colorectal cancer and colitis treatment.

Ferroptosis is a novel type of regulated cell death (RCD) involving iron accumulation and lipid peroxidation. Since its discovery in 2012, various studies have shown that ferroptosis is associated with the pathogenesis of various diseases. Ferroptotic cell death has also been linked to intestinal dysfunction but can act as either a positive or negative regulator of intestinal disease, depending on the cell type and disease context. The continued investigation of mechanisms underlying ferroptosis provides a wealth of potential for developing novel treatments. Considering the growing prevalence of intestinal diseases, particularly colorectal cancer (CRC) and inflammatory bowel disease (IBD), this review article focuses on potential therapeutics targeting the ferroptotic pathway in relation to CRC and IBD.

The mechanisms and drug therapies of colorectal cancer and epigenetics: bibliometrics and visualized analysis.

Background: Numerous studies have demonstrated a link between epigenetics and CRC. However, there has been no systematic analysis or visualization of relevant publications using bibliometrics. Methods: 839 publications obtained from the Web of Science Core (WoSCC) were systematically analyzed using CiteSpace and VOSviewer software. Results: The results show that the countries, institutions, and authors with the most published articles are the United States, Harvard University, and Ogino and Shuji, respectively. SEPT9 is a blood test for the early detection of colorectal cancer. Vitamin D and gut microbiota mediate colorectal cancer and epigenetics, and probiotics may reduce colorectal cancer-related symptoms. We summarize the specific epigenetic mechanisms of CRC and the current existence and potential epigenetic drugs associated with these mechanisms. It is closely integrated with clinical practice, and the possible research directions and challenges in the future are proposed. Conclusion: This study reviews the current research trends and hotspots in CRC and epigenetics, which can promote the development of this field and provide references for researchers in this field.

Quadruple therapies show a higher eradication rate compared to standard triple therapy for Helicobacter pylori infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries.

INTRODUCTION: Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations. OBJECTIVE: To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America. METHODS: A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed H. pylori infection who received eradication therapy and confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country-specific variables, including prevalence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and CYP2C19 polymorphisms. RESULTS: 772 patients were incorporated (64.64% females; mean age of 52.93 years). The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT-QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively. The antibiotic-resistance prevalence by country, but not the prevalence of CYP2C19 polymorphism, showed a statistically significant impact on eradication success. CONCLUSIONS: Both QCT and QBT are superior to STT for H. pylori eradication when adjusted for country-specific antibiotic resistance and CYP2C19 polymorphism in a sample of individuals residing in five countries within two continents.

Comparing efficacy and safety of mirabegron, tamsulosin, and solifenacin in ureteral stent-related symptoms: outcomes from a network meta-analysis.

Background: Although ureteral stents are a well-established and commonly used method for renal drainage, the ureteral stent-related symptoms (SRSs) they cause in patients cannot be ignored. It is currently unclear whether mirabegron has a place in the treatment of SRSs. Our study aims to systematically evaluate the efficacy and safety of mirabegron in treating SRSs in adult patients. Methods: Through a systematical search of multiple scientific databases before August 2023, we performed a systematic review and meta-analysis of the primary outcomes of interest according to the PRISMA. Analysis was performed under multivariate random-effects network models and effects of drugs was ranked with surface under the cumulative ranking curves (SUCRA) probabilities. Results: Sixteen studies involving 2,002 patients were included. All regimens (including mirabegron, solifenacin, and tamsulosin) were significantly better than placebo in urinary symptoms. Solifenacin was associated with more adverse drug events than mirabegron and tamsulosin. The SUCRA values showed that mirabegron was the best in the outcomes of body pain (71.5%), sexual matters (76.4%), and adverse events (70.5%). Solifenacin was the best in the outcomes of urinary symptoms (73.1%), general health (81.0%), and work performance (85.1%). Tamsulosin had the lowest rate of all outcomes. Conclusions: Compared with traditional drugs for relieving SRSs, mirabegron performs best in terms of alleviating body pain, sexual matters, and adverse events, with little difference in urinary symptoms and general health. Further high-quality prospective double-blinded randomized controlled trials (RCTs) are required to provide sufficient evidence supporting our observations.

Comprehensive risk factor predictions for 3-year survival among HIV-associated and disseminated cryptococcosis involving lungs and central nervous system.

BACKGROUND: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. METHODS: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. RESULTS: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). CONCLUSIONS: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.

Exploring Myc puzzle: Insights into cancer, stem cell biology, and PPI networks.

"The grand orchestrator," "Universal Amplifier," "double-edged sword," and "Undruggable" are just some of the Myc oncogene so-called names. It has been around 40 years since the discovery of the Myc, and it remains in the mainstream of cancer treatment drugs. Myc is part of basic helix-loop-helix leucine zipper (bHLH-LZ) superfamily proteins, and its dysregulation can be seen in many malignant human tumors. It dysregulates critical pathways in cells that are connected to each other, such as proliferation, growth, cell cycle, and cell adhesion, impacts miRNAs action, intercellular metabolism, DNA replication, differentiation, microenvironment regulation, angiogenesis, and metastasis. Myc, surprisingly, is used in stem cell research too. Its family includes three members, MYC, MYCN, and MYCL, and each dysfunction was observed in different cancer types. This review aims to introduce Myc and its function in the body. Besides, Myc deregulatory mechanisms in cancer cells, their intricate aspects will be discussed. We will look at promising drugs and Myc-based therapies. Finally, Myc and its role in stemness, Myc pathways based on PPI network analysis, and future insights will be explained.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam.

OBJECTIVES: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. METHODS: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan-Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). RESULTS: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. CONCLUSION: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVE: Summarize the evidence on drug therapies for obstructive sleep apnea. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. RESULTS: 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. CONCLUSION: The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO REGISTRATION NUMBER: CRD42022362639.

Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis

Abstract Objective Summarize the evidence on drug therapies for obstructive sleep apnea. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. Results 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. Conclusion The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO registration number CRD42022362639.

A Comprehensive Review on Drug Therapies and Nanomaterials used in Orthodontic Treatment.

Orthodontic treatment typically requires an extended duration of 1-2 years to complete the treatment. Accelerating the rate of tooth movement during orthodontic treatment is essential for shortening the overall treatment duration. After the completion of orthodontic treatment, a prominent concern arises in the form of orthodontic relapse, where the teeth tend to revert to their original positions. This issue affects approximately 60% of the global population, underscoring the importance of implementing effective measures to address orthodontic relapse. An approach in this regard involves the targeted administration of herbal and synthetic drugs applied directly to the specific area of interest to facilitate tooth movement and prevent orthodontic relapse. Apart from this, researchers are investigating the feasibility of utilizing different types of nanoparticles to improve the process of orthodontic tooth movement. In recent years, there has been a noticeable increase in the number of studies examining the effects of various drugs on orthodontics. However, the currently available literature does not provide significant evidence relating to orthodontic tooth movement. In this review, the authors provide valuable information about the drugs and nanomaterials that are capable of further enhancing the rate of orthodontic tooth movement and reducing the risk of orthodontic relapse. However, a notable hurdle remains, i.e., there is no marketed formulation available that can enhance orthodontic tooth movement and reduce treatment time. Therefore, researchers should try herbal-synthetic approaches to achieve a synergistic effect that can enhance orthodontic tooth movement. In this nutshell, there is an urgent need to develop a non-invasive, patient-compliant, and cost-effective formulation that will provide quality treatment and ultimately reduce the treatment time. Another critical issue is orthodontic relapse, which can be addressed by employing drugs that slow down osteoclastogenesis, thereby preventing tooth movement after treatment. Nevertheless, extensive research is still required to overcome this challenge in the future.

Psoriasis: Striving for Potential Biomarkers.

Psoriasis is a chronic disease that is caused by multiple factors and is identified by itchiness, unpleasant, red, or white scaly patches on the skin, particularly on regularly chafed body regions such as the lateral areas of the limbs. Reports suggest that globally around 2%-3% of the population suffers from psoriasis. In this review, we have discussed the clinical classification of psoriasis and also the ideal characteristics of the biomarkers. An overview regarding the discovery of the biomarker and method for validating the study has been discussed. A growing body of research suggests a link to certain other systemic symptoms such as cardiovascular disorder, metabolic syndrome, and few other comorbidities such as hypertension and nonalcoholic fatty liver disease. Natural killer (NK) cells are lymphocyte cells that concentrate on the destruction of virally infected and malignant cells; these tend to produce a wide range of inflammatory cytokines, some of which are associated with the etiology of psoriasis. Detailed information on the molecular pathogenesis of psoriasis in which interleukin (IL)-17, IL-23, tumor necrosis factor-α (TNF-α), and CCL20 play a very significant role in the development of psoriasis. In this review, we have discussed an overview of the recent state of the biomarkers available for the diagnosis and treatment of psoriasis by emphasizing on the available biomarkers such as epigenomic, transcriptomic, glycomic, and metabolomic. The most recent advancements in molecular-targeted therapy utilizing biologics and oral systemic therapy (methotrexate, apremilast) enable to adequately treat the most serious psoriatic symptoms and also the studies have validated the efficacy of biologic therapy such as TNF-α antagonist (infliximab, adalimumab), IL-23 antagonist (guselkumab, risankizumab), and IL-17 antagonist (secukinumab, ixekizumab). Finally, an overview about the technological opportunities as well as various challenges has been discussed.

[Predictors of the efficacy of non-drug treatments for non-dementia vascular cognitive impairment]. / Prediktory effektivnosti nelekarstvennykh metodov lecheniya nedementnykh sosudistykh kognitivnykh narushenii.

OBJECTIVE: To study the predictors of the efficacy of non-drug multimodal therapy in the treatment of mild vascular cognitive impairment. MATERIAL AND METHODS: Thirty patients with mild vascular cognitive impairment, under the supervision of their physician, received a 1-month non-drug treatment program including cognitive training, detailed recommendations for physical activity, and dietary planning. RESULTS: After the end of the course of treatment, improvements in the MoCa test were achieved by 22 patients (73%), which made up Group 1. In the remaining 8 patients, the treatment had no effect (Group 2). In Group 1, the dynamics of the MoCa test averaged 1.7±0.9, in the Group 2 it was (-0.4)±0.5. Patients of Group 1 had a significantly lower level of education (10.9±2.3) compared with Group 2 (14.9±2.0), a higher initial MoCa score, and a less pronounced white matter lesion on the Fazekas scale. After the regression analysis, the level of education (B -0.999, p<0.05) and white matter damage (B -2.761, p<0.01) were significant predictors. CONCLUSION: When using non-drug multimodal therapy in the treatment of mild vascular cognitive impairment, lower levels of education and a lower degree of white matter vascular damage are reliable predictors of treatment efficacy.

Dementia with Lewy Bodies Drug Therapies in Clinical Trials: Systematic Review up to 2022.

INTRODUCTION: Reviews of randomized clinical trials (RCTs) in dementia with Lewy bodies (DLB) are essential for informing ongoing research efforts of symptomatic therapies and potentially disease-modifying therapies (DMTs). METHODS: We performed a systematic review of all clinical trials conducted until September 27, 2022, by examining 3 international registries: ClinicalTrials.gov, the European Union Drug Regulating Authorities Clinical Trials Database, and the International Clinical Trials Registry Platform, to identify drugs in trials in DLB. RESULTS: We found 25 agents in 40 trials assessing symptomatic treatments and DMTs for DLB: 7 phase 3, 31 phase 2, and 2 phase 1 trials. We found an active pipeline for drug development in DLB, with most ongoing clinical trials in phase 2. We identified a recent trend towards including participants at the prodromal stages, although more than half of active clinical trials will enroll mild to moderate dementia patients. Additionally, repurposed agents are frequently tested, representing 65% of clinical trials. CONCLUSION: Current challenges in DLB clinical trials include the need for disease-specific outcome measures and biomarkers, and improving representation of global and diverse populations.

Metabolic dysfunction-associated fatty liver disease (MAFLD): an update of the recent advances in pharmacological treatment.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is nowadays considered the liver manifestation of metabolic syndrome. Its prevalence is increasing worldwide in parallel to the epidemic of diabetes and obesity. MAFLD includes a wide spectrum of liver injury including simple steatosis and non-alcoholic steatohepatitis (NASH) that may lead to serious complications such as liver cirrhosis and liver cancer. The complexity of its pathophysiology and the intricate mechanisms underlying disease progression explains the huge variety of molecules targeting diverse biological mechanisms that have been tested in preclinical and clinical settings in the last two decades. Thanks to the large number of clinical trials of the last few years, most of them still ongoing, the pharmacotherapy scenario of MAFLD is rapidly evolving. The three major components of MAFLD, steatosis, inflammation, and fibrosis seem to be safely targeted with different agents at least in a large proportion of patients. Likely, in the next few years more than one drug will be approved for the treatment of MAFLD at different disease stages. The aim of this review is to synthesize the characteristics and the results of the most advanced clinical trials for the treatment of NASH to evaluate the recent advances of pharmacotherapy in this disease.

Advancements in Hepatocellular Carcinoma: Potential Preclinical Drugs and their Future.

Hepatocellular carcinoma (HCC) is one of the foremost causes of tumor-affiliated demises globally. The HCC treatment has undergone numerous developments in terms of both drug and non-drug treatments. The United States Food and Drug Administration (FDA) has authorized the usage of a variety of drugs for the treatment of HCC in recent years, involving multi-kinase inhibitors (lenvatinib, regorafenib, ramucirumab, and cabozantinib), immune checkpoint inhibitors (ICIs) (pembrolizumab and nivolumab), and combination therapies like atezolizumab along with bevacizumab. There are currently over a thousand ongoing clinical and preclinical studies for novel HCC drugs, which portrays a competent setting in the field. This review discusses the i. FDA-approved HCC drugs, their molecular targets, safety profiles, and potential disadvantages; ii. The intrial agents/drugs, their molecular targets, and possible benefits compared to alternatives, and iii. The current and future status of potential preclinical drugs with novel therapeutic targets for HCC. Consequently, existing drug treatments and novel strategies with their balanced consumption could ensure a promising future for a universal remedy of HCC in the near future.

Osteoporosis guidelines on TCM drug therapies: a systematic quality evaluation and content analysis.

Objective: The aims of this study were to evaluate the quality of osteoporosis guidelines on traditional Chinese medicine (TCM) drug therapies and to analyze the specific recommendations of these guidelines. Methods: We systematically collected guidelines, evaluated the quality of the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool, and summarized the recommendations of TCM drug therapies using the Patient-Intervention-Comparator-Outcome (PICO) model as the analysis framework. Results and conclusions: A total of 20 guidelines were included. Overall quality evaluation results revealed that four guidelines were at level A, four at level B, and 12 at level C, whose quality needed to be improved in the domains of "stakeholder involvement", "rigor of development", "applicability" and "editorial independence". Stratified analysis suggested that the post-2020 guidelines were significantly better than those published before 2020 in the domains of "scope and purpose", "stakeholder involvement" and "editorial independence". Guidelines with evidence systems were significantly better than those without evidence systems in terms of "stakeholder involvement", "rigor of development", "clarity of presentation" and "applicability". The guidelines recommended TCM drug therapies for patients with osteopenia, osteoporosis and osteoporotic fracture. Recommended TCM drugs were mainly Chinese patent medicine alone or combined with Western medicine, with the outcome mainly focused on improving bone mineral density (BMD).

End-to-End n-ary Relation Extraction for Combination Drug Therapies.

Combination drug therapies are treatment regimens that involve two or more drugs, administered more commonly for patients with cancer, HIV, malaria, or tuberculosis. Currently there are over 350K articles in PubMed that use the combination drug therapy MeSH heading with at least 10K articles published per year over the past two decades. Extracting combination therapies from scientific literature inherently constitutes an n-ary relation extraction problem. Unlike in the general n-ary setting where n is fixed (e.g., drug-gene-mutation relations where n = 3), extracting combination therapies is a special setting where n ≥ 2 is dynamic, depending on each instance. Recently, Tiktinsky et al. (NAACL 2022) introduced a first of its kind dataset, CombDrugExt, for extracting such therapies from literature. Here, we use a sequence-to-sequence style end-to-end extraction method to achieve an F1-Score of 66.7% on the CombDrugExt test set for positive (or effective) combinations. This is an absolute ≈ 5% F1-score improvement even over the prior best relation classification score with spotted drug entities (hence, not end-to-end). Thus our effort introduces a state-of-the-art first model for end-to-end extraction that is already superior to the best prior non end-to-end model for this task. Our model seamlessly extracts all drug entities and relations in a single pass and is highly suitable for dynamic n-ary extraction scenarios.

Intermittent high intensity exercise associated with drugs in patients with type 2 diabetes / Exercício intermitente de alta intensidade associado aos fármacos em pacientes com diabetes tipo 2 / Ejercicio intermitente de alta intensidad asociado a fármacos en pacientes con diabetes tipo 2

ABSTRACT Introduction: Some studies point out that high-intensity intermittent training exercises combined with drugs may improve the endurance of patients with type 2 diabetes. However, the information concerning blood glucose control still needs to be better evidenced. Objective: Explore further the effect of intermittent high-intensity exercise combined with drugs on blood glucose control in patients with type 2 diabetes. Methods: Through a control experiment, 100 patients were selected from volunteers, and divided equally into two groups for this experiment. A protocol with high-intensity intermittent exercise for intervention associated with drug treatment was added to the experimental group, while the control received standard drug treatment. Results: The results of each index in the experimental group were: TC pre 4.80±1.00, post 4.56±0.78; TG pre 1.77±1.15, post 1.49±1.16; LDL pre 2.94±0.83, post 2.51±0.73. The experimental results proved that all indices in the experimental group were improved, but the changes in the control group were not evidenced. Conclusion: Intermittent high-intensity exercise combined with drugs positively affected blood glucose control in patients with type 2 diabetes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Alguns estudos apontam que exercícios com treinamento intermitente de alta intensidade combinados aos fármacos possam melhorar a resistência dos pacientes com diabetes tipo 2. No entanto, as informações relativas ao controle da glicemia ainda são pouco evidentes. Objetivo: Explorar melhor o efeito do exercício intermitente de alta intensidade combinado com fármacos no controle glicêmico sanguíneo em pacientes com diabetes tipo 2. Métodos: Através de um experimento de controle, 100 pacientes foram selecionados entre os voluntários, divididos igualmente em dois grupos para este experimento. Ao grupo experimental foi adicionado um protocolo com exercício intermitente de alta intensidade para intervenção associado ao tratamento medicamentoso, enquanto o controle recebeu tratamento medicamentoso padrão. Resultados: Os resultados de cada índice no grupo experimental foram: TC pré 4,80±1,00, pós 4,56±0,78; TG pré 1,77±1,15, pós 1,49±1,16; LDL pré 2,94±0,83, pós 2,51±0,73. A partir dos resultados experimentais, comprovou-se que todos os índices no grupo experimental foram aprimorados, porém as mudanças no grupo de controle não foram evidenciadas. Conclusão: O exercício intermitente de alta intensidade combinado com fármacos apresentaram um efeito positivo no controle da glicose sanguínea em pacientes com diabetes tipo 2. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Algunos estudios señalan que los ejercicios de entrenamiento intermitente de alta intensidad combinados con fármacos pueden mejorar la resistencia de los pacientes con diabetes de tipo 2. Sin embargo, la información relativa al control de la glucemia sigue siendo escasa. Objetivo: Profundizar en el efecto del ejercicio intermitente de alta intensidad combinado con fármacos sobre el control de la glucemia en pacientes con diabetes tipo 2. Métodos: Mediante un experimento de control, se seleccionaron 100 pacientes voluntarios, divididos equitativamente en dos grupos para este experimento. Al grupo experimental se le añadió un protocolo con ejercicio intermitente de alta intensidad para la intervención asociado al tratamiento farmacológico, mientras que el control recibió el tratamiento farmacológico estándar. Resultados: Los resultados de cada índice en el grupo experimental fueron: TC pre 4,80±1,00, post 4,56±0,78; TG pre 1,77±1,15, post 1,49±1,16; LDL pre 2,94±0,83, post 2,51±0,73. A partir de los resultados experimentales, se comprobó que todos los índices del grupo experimental mejoraron, pero no se evidenciaron cambios en el grupo de control. Conclusión: El ejercicio intermitente de alta intensidad combinado con fármacos tuvo un efecto positivo sobre el control de la glucemia en pacientes con diabetes tipo 2. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review.

Post-stroke depression (PSD) is a biopsychosocial disorder that affects individuals who have suffered a stroke at any point. PSD has a 20 to 60 percent reported prevalence among stroke survivors. Its effects are usually adverse, can lead to disability, and may increase mortality if not managed or treated early. PSD is linked to several other medical conditions, including anxiety, hyper-locomotor activity, and poor functional recovery. Despite significant awareness of its adverse impacts, understanding the pathogenesis of PSD has proved challenging. The exact pathophysiology of PSD is unknown, yet its complexity has been definitively shown, involving mechanisms such as dysfunction of monoamine, the glutamatergic systems, the gut-brain axis, and neuroinflammation. The current effectiveness of PSD treatment is about 30-40 percent of all cases. In this review, we examined different pathophysiological mechanisms and current pharmacological and non-pharmacological approaches for the treatment of PSD.