5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Association between burnout and empathy in medical residents.

BACKGROUND: Burnout is a work-related syndrome that can affect physicians' performance. Empathy is one of the clinical competencies in whose formation many factors play a role. Empathy and burnout are important topics of research in medical sciences, and both are related to the communication between the patient and the physician. This study investigated the relationship between occupational burnout and empathy among medical residents. METHOD: This cross-sectional study was conducted on 297 medical residents in Ahvaz Jundishapur University of Medical Sciences from January to March 2021. The data collection tools were the Jefferson Scale of Empathy (JSE) and the Maslach Burnout Inventory (MBI). The reliability of the instruments was measured by calculating Cronbach's alpha. Data were analyzed by SPSS-18, using the Pearson correlation test and linear regression models. RESULTS: The average age of the study population was 33.06 ±4.7 years, with more than half being females (57.6%) and married (51.9%). The residents' mean scores of empathy and overall burnout were 102.87 out of 140 and 55.90 out of 132, respectively. The burnout scores showed an inverse correlation with the overall empathy scores (r = -0.123, P = 0.035), and the score of standing in the patient's shoes (r = -0.165, P = 0.004). Linear regression test was used to detect which dimension of empathy was a better predictor for the reduction of burnout scores. Results showed that the best predictor was standing in the patient's shoes (P = 0.014). CONCLUSION: The findings showed a negative association between empathy and burnout among medical residents, which suggests the need for adjustment of the existing burnout management at the institutional level. Therefore, residents should be supported by managers to reduce burnout and improve their empathic behavior.

Crosstalk between Alzheimer's disease and diabetes: a focus on anti-diabetic drugs.

Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) are two of the most common age-related diseases. There is accumulating evidence of an overlap in the pathophysiological mechanisms of these two diseases. Studies have demonstrated insulin pathway alternation may interact with amyloid-ß protein deposition and tau protein phosphorylation, two essential factors in AD. So attention to the use of anti-diabetic drugs in AD treatment has increased in recent years. In vitro, in vivo, and clinical studies have evaluated possible neuroprotective effects of anti-diabetic different medicines in AD, with some promising results. Here we review the evidence on the therapeutic potential of insulin, metformin, Glucagon-like peptide-1 receptor agonist (GLP1R), thiazolidinediones (TZDs), Dipeptidyl Peptidase IV (DPP IV) Inhibitors, Sulfonylureas, Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors, Alpha-glucosidase inhibitors, and Amylin analog against AD. Given that many questions remain unanswered, further studies are required to confirm the positive effects of anti-diabetic drugs in AD treatment. So to date, no particular anti-diabetic drugs can be recommended to treat AD.

The critical role of circular RNAs in drug resistance in gastrointestinal cancers.

Nowadays, drug resistance (DR) in gastrointestinal (GI) cancers, as the main reason for cancer-related mortality worldwide, has become a serious problem in the management of patients. Several mechanisms have been proposed for resistance to anticancer drugs, including altered transport and metabolism of drugs, mutation of drug targets, altered DNA repair system, inhibited apoptosis and autophagy, cancer stem cells, tumor heterogeneity, and epithelial-mesenchymal transition. Compelling evidence has revealed that genetic and epigenetic factors are strongly linked to DR. Non-coding RNA (ncRNA) interferences are the most crucial epigenetic alterations explored so far, and among these ncRNAs, circular RNAs (circRNAs) are the most emerging members known to have unique properties. Due to the absence of 5' and 3' ends in these novel RNAs, the two ends are covalently bonded together and are generated from pre-mRNA in a process known as back-splicing, which makes them more stable than other RNAs. As far as the unique structure and function of circRNAs is concerned, they are implicated in proliferation, migration, invasion, angiogenesis, metastasis, and DR. A clear understanding of the molecular mechanisms responsible for circRNAs-mediated DR in the GI cancers will open a new window to the management of GI cancers. Hence, in the present review, we will describe briefly the biogenesis, multiple features, and different biological functions of circRNAs. Then, we will summarize current mechanisms of DR, and finally, discuss molecular mechanisms through which circRNAs regulate DR development in esophageal cancer, pancreatic cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma.

Comparative Study on Clinical Characteristics of COVID-19 Patients with or without Digestive Symptoms in Razi Hospital, Ahvaz, Khuzestan.

BACKGROUND: Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms, with the most common being anorexia, diarrhea, nausea and vomiting. We aimed to conduct a comparative study on COVID-19 patients with or without gastrointestinal patients (GI). AIMS: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a dire health problem, causing a massive crisis for global health. METHODS: Collective data of clinical manifestations and laboratory reports of patients admitted to Razi Hospital, Ahvaz, Khuzestan, Iran, for two weeks were analyzed. RESULTS: Our results showed that GI symptoms are not statistically significant criteria to be predictive or prognostic factors in COVID-19 patients, although they are probably related to the acute or non-acute phase of the disease. Moreover, non-specific GI symptoms seem to result from cytokine storm that occurred during the disease. CONCLUSION: Therefore, our results did not support GI tract involvement as a common route of COVID- 19 infection. Maybe future research will shed light on why and how the gastrointestinal system becomes infected by COVID-19.

Multiple novel functions of circular RNAs in diabetes mellitus.

Circular RNAs (circRNAs), as an emerging group of non-coding RNAs (ncRNAs), have received the attention given evidence indicating that these novel ncRNAs are implicated in various biological processes. Due to the absence of 5' and 3' ends in circ-RNAs, their two ends are covalently bonded together, and they are synthesised from pre-mRNAs in a process called back-splicing, which makes them more stable than linear RNAs. There is accumulating evidence showing that circRNAs play a critical role in the pathogenesis of diabetes mellitus (DM). Moreover, it has been indicated that dysregulation of circRNAs has made them promising diagnostic biomarkers for the detection of DM. Recently, increasing attention has been paid to investigate the mechanisms underlying the DM process. It has been demonstrated that there is a strong correlation between the expression of circRNAs and DM. Hence, our aim is to discuss the crosstalk between circRNAs and DM and its complications.

Determining massage dose-response to improve cancer-related symptom cluster of pain, fatigue, and sleep disturbance: A 7-arm randomized trial in palliative cancer care.

BACKGROUND: The efficacy of various massage doses in palliative cancer care settings is still debated, and no specific protocol is available. AIM: Evaluating response to various massage doses for symptom cluster of pain-fatigue-sleep. DESIGN: A 7-arm randomized-controlled trial with weekly massage for 4 weeks depending on the prescribed dose (15-, 30-, or 60-min; 2× or 3×/week) and a 4-week follow-up. The intensities of pain, fatigue, and sleep disturbance were measured using a 0-10 scale at nine-timepoint; baseline, weekly during the intervention, and the follow-up period. Then, the mean scores of the three symptoms were calculated as the symptom cluster intensity at each timepoint. IRCT.ir IRCT20150302021307N5. SETTING/PARTICIPANTS: Adults with cancer (n = 273) who reported all three symptoms at three oncology centers in Iran. RESULTS: The odds of clinical improvement (at least 30% reduction in symptom cluster intensity from baseline) increased with dose-escalation significantly [(OR = 17.37; 95% CI = 3.87-77.90 for 60-min doses); (OR = 11.71; 95% CI = 2.60-52.69, for 30-min doses); (OR = 4.36; 95% CI = 0.94-20.32, for 15-min doses)]. The effect durability was significantly shorter at 15-min doses compared to 30- and 60-min doses. The odds of improvement for doses 3×/week was not significant compared to doses 2×/week (OR = 12.27 vs OR = 8.34); however, the effect durability for doses 3×/week was significantly higher. CONCLUSIONS: The findings indicated that dose-escalation increases the efficacy of massage for the pain-fatigue-sleep symptom cluster. Although the 60-min doses were found to be more effective, the 30-min doses can be considered more practical because they are less costly and time-consuming. Our findings can be helpful to develop massage guidelines in palliative care settings. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20150302021307N5.

High levels of FBS and HbA1c and their association with diabetic retinopathy: a study in the north of Iran.

Background: Diabetic retinopathy, which is a common complication of diabetes, is one of the most common reasons of blindness in adults. There are several potential risk factors for diabetic retinopathy such as hypertension (HTN), hyperlipidemia (HLP), high fasting blood sugar (FBS), and high Hemoglobin A1c (HbA1c). Yet, ethnicity is another factor which may contribute to diabetic retinopathy regardless of the potential risk factors mentioned. The aim of this study, therefore, is to find the risk factors associated with diabetic retinopathy in the north of Iran. Methods: This was a retrospective cohort study including a total of 1,125 patients divided into three groups as follows: (i) patients with no diabetic retinopathy (NDR group; n = 398); (ii) patients with non-proliferative diabetic retinopathy (non-PDR group; n = 408); (iii) patients with proliferative diabetic retinopathy (PDR group; n = 319). The laboratory data were collected from patients for analysis. Results: Diabetic patients with retinopathy had significantly higher levels of FBS compared with those without retinopathy (p = 0.001). Patients with PDR or non-PDR had higher levels of HbA1c compared with patients without retinopathy (p = 0.001). In contrast, no association was observed between HTN or HLP and diabetic retinopathy. On the other hand, duration of diabetes was another important factor affecting diabetic retinopathy. Conclusions: Higher levels of FBS and HbA1c were observed in patients with diabetic retinopathy. Monitoring and controlling of FBS and HbA1c of diabetic patients could prevent the occurrence of diabetic retinopathy.

Developing a new academic wordlist for medical purposes - a viable tool for educators.

Objective: This study aims at developing a list of academic and technical words commonly used in medical research articles. It is conducted in line with the specificity of academic literacy and vocabulary practices in every individual discipline. Methods: The corpus of this study consisted of 18,462,820 words extracted from 1,784 research articles accessed from three prestigious and widely known journals, i.e., The Lancet, The British Medical Journal (BMJ), and The New England Journal of Medicine (NEJM), published between 2015 and 2019. To analyze the data, the RANGE program as a robust tool for developing viable academic word lists was used. Results: Our quantitative and qualitative data analysis yielded a final academic wordlist which consisted of 1,003 words, covered 1,972,420 words in the corpus, and accounted for 10.68% of the medical research articles. Discussion: The high coverage of the extracted academic and technical words provides a reliable source for medical students, medical educators, material designers, and those who are deeply involved in medical English education.

Gastrointestinal disorder biomarkers.

Gastrointestinal (GI) disorders refer to gastrointestinal tract conditions, ranging from dyspepsia to inflammatory bowel diseases (IBDs) and malignant tumors. Biomarkers, which are assessable indicators of the presence or severity of the disorders, are indispensable agents to diagnose GI conditions. Diagnostic biomarkers, including serological biomarkers, antibodies, immunological biomarkers, fecal biomarkers, and genetic biomarkers (Non-encoding RNAs), are investigated and categorized in this review. Furthermore, we have discussed the essential biological functions and diagnostic roles and the advantages and disadvantages of these biomarkers, besides novel genetic biomarkers such as miRNA-146a and their role in GI diseases.

Gene therapy: A promising approach for breast cancer treatment.

Breast cancer (BC) is the most prevalent malignancy and the second leading cause of death among women worldwide that is caused by numerous genetic and environmental factors. Hence, effective treatment for this type of cancer requires new therapeutic approaches. The traditional methods for treating this cancer have side effects, therefore so much research have been performed in last decade to find new methods to alleviate these problems. The study of the molecular basis of breast cancer has led to the introduction of gene therapy as an effective therapeutic approach for this cancer. Gene therapy involves sending genetic material through a vector into target cells, which is followed by a correction, addition, or suppression of the gene. In this technique, it is necessary to target tumour cells without affecting normal cells. In addition, clinical trial studies have shown that this approach is less toxic than traditional therapies. This study will review various aspects of breast cancer, gene therapy strategies, limitations, challenges and recent studies in this area.

Long non-coding RNAs and microorganism-associated cancers.

Cancerous cells are abnormal cells characterized by aberrant growth and proliferation, which can involve various types of cells and tissues. Through numerous signalling pathways, many mechanisms are involved in cells that keep them normal. These signalling pathways are tightly set by different proteins whose expression is regulated by a large number of factors. In other words, when a regulating factor does not act properly or undergoes a change in its function or expression, the result will be that the subordinate gene and subsequently the related protein will show deranged expression and activity. This leads to disordered signalling pathways which bring about uncontrolled proliferation in cells. One of the most significant factors in adjusting the expression of genes is noncoding RNAs. It should be noted that all underlying causes initiating malignancy try to alter the main regulatory factors in cellular processes and gene expression and direct the cell to an unregulated state. Microorganisms have been identified as one of the important elements to direct normal cells to abnormality. That is, they probably agitate the malignant traits through manipulating significant factors such as ncRNAs in given cells using their own or host-related factors. The present study is aimed at examining how the long noncoding RNAs are involved in microorganism-mediated cancers.

Prevalence and viral load determination of BK polyomavirus among Iranian patients with brain tumors.

BACKGROUND: Due to persistent infections of human central nervous system (CNS), polyomaviruses have been identified as one of the risk factors for brain tumor development. Human BK virus is of significant interest due to its experimental neuro-oncogenic potential and the possible association with CNS neoplasms. However, the results of different studies are discrepant. In the present study, we aimed to investigate the prevalence of BK virus genome and quantify BK viral load in Iranian patients with primary and metastatic brain malignancies. METHODS: To assess the prevalence of BK virus sequences, a total of 58 fresh brain tumors were examined by quantitative real-time PCR. The BK viral load was determined as viral copy number per cell. RESULTS: Of the 58 brain tumor samples BK tumor antigen (TAg) sequences were detected in 26 (44.8%) of cases. In primary brain tumors, BK virus sequences were recognized more frequently in schwannomas (15.5%) and meningiomas (12.1%). The mean BK virus TAg copy number in positive cases was 0.20×10-3±0.27×10-3 (range 0.01×10-3- 0.8×10-3) copies per cell. CONCLUSION: Taken together, in the present study low copy numbers of BK virus TAg gene was detected in brain tumor cells, which can indicate that BK virus may contribute to tumor induction by indirect mechanisms or neuro-persistence of this virus without any pathological consequences.

COVID-19: imbalance of multiple systems during infection and importance of therapeutic choice and dosing of cardiac and anti-coagulant therapies.

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.

In Vitro Antileishmanial Effects of Saffron Compounds, Crocin and Stigmasterol, on Iranian Strain of Leishmania major (MHOM/IR/75/ER).

BACKGROUND: Due to numerous side effects of common drugs in treatment of leishmaniasis, new therapeutic approaches focus on herbal compounds. Therefore, we aimed to determine the effect of crocin and stigmasterol on in-vitro growth of promastigotes and amastigotes of Leishmania major in the Department of Parasitology, Pasteur Institute, Tehran, Iran in 2018. METHODS: The effect of different concentrations of crocin and stigmasterol were evaluated by determining their in-vitro inhibitory effects on promastigotes and amastigotes of the L. major using MTT assay. RESULTS: The fatality rate was 65.27% and 71.96% for crocin and stigmasterol respectively at 24 h post-culture in concentration of 50 µg/mL. The mean inhibitory effect of crocin and stigmasterol on L major amastigotes after 72 h were 52.22% and 38.96%. CONCLUSION: The crocin and stigmasterol had efficient adverse effects on promastigote and amastigotes of L. major, hence, further studies on the anti-leishmanial effects of these herbal compounds in human and animal models are recommended.

The effects of natural compounds on wound healing in Iranian traditional medicine: A comprehensive review.

Wounds are physical and anatomical disruption in healthy skin and represent an important healthcare concern around the world. Wound healing is a complex and dynamic cascade of cellular and molecular interactions which include four main phases: hemostasis, inflammatory, proliferative, and remodeling. Therefore, some pharmacological activities such as anti-inflammatory, antioxidant, and antimicrobial activities can play a key role in the process of wound healing. Iranian Traditional Medicine (ITM) has a rich background of practice and a wealth of ancient medicine scientists from the Old Persian days until today. This paper presents and characterizes pure data from original references of ITM about wound remedies and verifies their function by reviewing articles from three databases (Google Scholar, PubMed, and Scopus), which could be an interesting and comprehensive resource for future researchers interested in traditional medicine (TM) generally and in ITM in particular. Selected natural compounds from the references were divided into 5 groups, including herbs, herbal products, animal products, minerals, and animals. In total, 23 natural compounds with regard to the current state of knowledge and ITM were introduced and verified. The present review will provide better insights into ITM and its extensive experience in topics such as wound healing.

Designing an Outer Membrane Protein (Omp-W) Based Vaccine for Immunization against Vibrio and Salmonella: An in silico Approach.

BACKGROUND: Cholera triggered by Vibrio cholerae remains the main reason for morbidity and mortality all over the world. In addition, salmonellosis is regarded as an infectious disease that makes it essential for the identification and detection of Salmonella. With a beta-barrel structure consisting of eight non-parallel beta strands, OmpW family is widely distributed among gram-negative bacteria. Moreover, OmpW isolated from S. typhimurium and Vibrio cholerae can be used in vaccine design. METHODS: Topology prediction was determined. T-cell and B-cell epitopes were selected from exposed areas, and sequence conservancy was evaluated. The remaining loops and inaccessible residues were removed to prepare OmpW-1. High antigenicity peptides were detected to replace inappropriate residues to obtain OmpW-2. Physicochemical properties were assessed, and antigenicity, hydrophobicity, flexibility, and accessibility were compared to the native Omp-W structure. Low score areas were removed from the designed structure for preparing the OmpW-3. To construct OmpW-4, TTFrC was used as T-CD4+ cell-stimulating factor and CTB as adjuvant to the end of the C-terminal of this sequence, which can increase the antigenicity and sequence density. The sequences were re-analyzed to delete the unfavorable residues. Besides, the solubility of the mature OmpW and the designed structure were predicted while overexpressed in E. coli. RESULTS: The designed vaccine is a stable protein that has immune cells recognizing epitopes and is considered as an antigen. The construct can be overexpressed in an E. coli. CONCLUSION: The multi-epitope vaccine is a suitable stimulator for the immune system and would be a candidate for experimental research. Recent patents describe numerous inventions related to the clinical facets of vaccine peptide against human infectious disease.

Correction to: The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach.

The article "The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach", written by Seyed Farzad Hosseini · Mehdi Forouzesh · Mohsen Maleknia · Samira Valiyari · Mahmood Maniati · Azin Samimi, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 25th July 2020 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 29th July 2020 to © Springer Science+Business Media, LLC, part of Springer Nature 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.

Calprotectin in inflammatory bowel disease.

The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.

The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach.

Nowadays, poisoning with metal phosphides, especially aluminum phosphide (ALP), is one of the main health threats in human societies. Patients suffer from significant complications due to this type of poisoning, and the heart is one of the main organs targeted by ALP. Therefore, in this study, we discussed the effect of phosphine on cardiac function. This study is based on data obtained from PubMed, between 2002 and 2020. The key keywords included "Aluminum phosphide," "Oxidative Stress," "Mitochondria," "Cardiovascular disease," and "Treatment." The results showed that ALP produced reactive oxygen species (ROS) due to mitochondrial dysfunction. ROS production leads to red blood cell hemolysis, decreased ATP production, and induction of apoptosis in cardiomyocytes, which eventually results in cardiovascular disease. Since ALP has the most significant effect on cardiomyocytes, the use of appropriate treatment strategies to restore cell function can increase patients' survival.