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.

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.

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.

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.

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.

CRISPR/Cas9 gene editing: A new therapeutic approach in the treatment of infection and autoimmunity.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein9) may be viewed as an adaptive bacterial immune system. When a virus infects a bacterium, a fragment of the virus genome is inserted into the CRISPR sequence of the bacterial genome as a memory. When the bacterium becomes infected again with the same virus, an RNA molecule that is a transcript of the memory sequence, directs Cas9, an endonuclease, to the complementary region of the virus genome, and Cas9 disables the virus by a double-strand break. In recent years, studies have shown that by designing synthetic RNA molecules and delivering them along with Cas9 into eukaryotic cells, different regions of the cell's genome can be targeted and manipulated. These findings have drawn much attention to this new technology and it has been shown that CRISPR/Cas9 gene editing can be used to treat some human diseases. These include infectious diseases and autoimmune diseases. In this review article, in addition to a brief overview of the biology of the CRISPR/Cas9 system, we collected the most recent findings on the applications of CRISPR/Cas9 technology for better investigation of the pathogenesis and treatment of viral infections (human immunodeficiency virus infection, hepatitis virus infections, and onco-virus infections), non-viral infections (parasitic, fungal, and bacterial infections), and autoimmune diseases.

The interplay of Klotho with signaling pathway and microRNAs in cancers.

Klotho (KL) gene has been accepted as an "aging suppressor" gene that encodes a single transmembrane protein in human known as Klotho which is commonly expressed in renal tubes. The interruption in the secretion of Klotho protein expedites aging whereas its high expression extends lifespan. The family of Klotho proteins has been reported to act as distinct receptors for endocrine fibroblast growth factors (FGFs), which manage multifarious metabolic processes. Further, the secreted Klotho is a hormonal factor that takes part in the ion channel organization. Numerous studies determined that this protein affects the function of a number of important signaling pathways, which may present an impact in tumorigenesis via the coordination of receptors located on them. This review article focuses on the effects of microRNAs on the performance of Klotho and how the interplay between Klotho and certain pathways like insulin-like growth factor, FGF, Wnt, and transforming growth factor ß contribute to the biogenesis of cancer. The present study is also pointed at defining the molecular mechanisms of these interactions.

Modulation of cancer cell signaling by long noncoding RNAs.

Cellular signaling pathways play a very important role in almost all molecular processes in the cell, and are generally composed of a complex set of cascades in which enzymes and proteins play a key role. These signaling pathways include different types of cellular signaling classified based on their receptors and effector proteins such as enzyme-linked receptors, cytokine receptors, and G-protein-coupled receptors each of which is subdivided into different classes. Signaling pathways are tightly controlled by different mechanisms mostly thorough inhibiting/activating their receptors or effector proteins. In the last two decades, our knowledge of molecular biology has changed dramatically and today we know that more than 85% of the human genome expresses noncoding RNAs most of which are crucial in the cellular and molecular mechanisms of cells. One of these noncoding RNAs are long noncoding RNAs (lncRNA) containing more than 200 nucleotides. LncRNAs participate in the progression of cancer growth through several mechanism including signaling pathways. In this review, we summarize some of the most important of lncRNAs and their effect on important signaling pathways.

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a diversity of neurological disorders characterized by the progressive degeneration of the structure and function of the central nervous system (CNS). The most common NDs are Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Recently, many studies have investigated associations between common NDs with noncoding RNAs (ncRNAs) molecules. ncRNAs are regulatory molecules in the normal functioning of the CNS. Two of the most important ncRNAs are microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). These types of ncRNAs are involved in different biological processes including brain development, maturation, differentiation, neuronal cell specification, neurogenesis, and neurotransmission. Increasing data has demonstrated that miRNAs and lncRNAs have strong correlations with the development of NDs, particularly gene expression. Besides, ncRNAs can be introduced as new biomarkers for diagnosis and prognosis of NDs. Hence, in this review, we summarized the involvement of various miRNAs and lncRNAs in most common NDs followed by a correlation of ncRNAs dysregulation with the AD, PD, and HD.

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer.

DNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell-cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer.

The roles of FGF21 in atherosclerosis pathogenesis.

FGF21 is a peptide hormone that regulates homeostasis of lipid and glucose as well as energy metabolism. It is mainly expressed and secreted in liver and adipose tissues, and it is expressed in lower amounts in the aorta. Recent clinical and preclinical studies indicate increased serum FGF21 levels in atherosclerosis patients. Also, FGF21 therapy has been reported to reduce the initiation and progression of atherosclerosis in animal models and in vitro studies. Moreover, growing evidence indicates that administration of exogenous FGF21 induces anti-atherosclerotic effects, because of its ability to reduce lipid profile, alleviation of oxidative stress, inflammation, and apoptosis. Therefore, FGF21 can not only be considered as a biomarker for predicting atherosclerosis, but also induce protective effects against atherosclerosis. Besides, serum levels of FGF21 increase in various diseases including in diabetes mellitus, hypertension, and obesity, which may be related to initiating and exacerbating atherosclerosis. On the other hand, FGF21 therapy significantly improves lipid profiles, and reduces vascular inflammation and oxidative stress in atherosclerosis related diseases. Therefore, further prospective studies are needed to clarify whether FGF21 can be used as a prognostic biomarker to identify individuals at future risk of atherosclerosis in these atherosclerosis-associated diseases. In this review, we will discuss the possible mechanism by which FGF21 protects against atherosclerosis.

The role of microRNAs in the healing of diabetic ulcers.

MicroRNAs (miRNAs) are small protected molecules with a length of 18 to 25 nucleotides. Many studies have recently been conducted on miRNAs, illustrating their role in regulating many biological, physiological, and pathological activities, such as maintaining cellular signalling and regulating cellular pathways. The main role of miRNAs is to regulate the expression of genes after translation, which can lead to the destruction or suppression of translation by binding to mRNAs. As any change in the regulation of miRNAs is associated with several physiological abnormalities, such as type 2 diabetes and its complications, these molecules can be used for therapeutic purposes or as biomarkers for the diagnosis of diseases such as diabetes and its complications. In this review article, we will discuss important findings about the miRNAs and the role of these molecules in different phases of the wound-healing process of chronic wounds, especially diabetic ulcer.

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.

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.

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.

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.

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.