Melatonin and bone-related diseases: an updated mechanistic overview of current evidence and future prospects.

PURPOSE: Bone diseases account for an enormous cost burden on health systems. Bone disorders are considered as age-dependent diseases. The aging of world population has encouraged scientists to further explore the most effective preventive modalities and therapeutic strategies to overcome and reduce the high cost of bone disorders. Herein, we review the current evidence of melatonin's therapeutic effects on bone-related diseases. METHODS: This review summarized evidences from in vitro, in vivo, and clinical studies regarding the effects of melatonin on bone-related diseases, with a focus on the molecular mechanisms. Electronically, Scopus and MEDLINE®/PubMed databases were searched for articles published on melatonin and bone-related diseases from inception to June 2023. RESULTS: The findings demonstrated that melatonin has beneficial effect in bone- and cartilage-related disorders such as osteoporosis, bone fracture healing, osteoarthritis, and rheumatoid arthritis, in addition to the control of sleep and circadian rhythms. CONCLUSION: A number of animal and clinical studies have indicated that various biological effects of melatonin may suggest this molecule as an effective therapeutic agent for controlling, diminishing, or suppressing bone-related disorders. Therefore, further clinical studies are required to clarify whether melatonin can be effective in patients with bone-related diseases.

MiR-20b Tissue Expression Level Displays the Diagnostic Value in Papillary Thyroid Carcinoma.

Background: Detection of cancer in patients with thyroid nodules requires sensitive and specific diagnostic modalities that are accurate and inexpensive. This study aimed to identify a potential microRNA(miRNA) panel to detect papillary thyroid carcinoma (PTC). Methods: Following a comprehensive literature review as well as miRNA target predictor databases, Real-time PCR was used to quantify the expression of candidate miRNAs in 59 tissue specimens from 30 patients with PTC and 29 patients with benign nodules. A receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of miRNA expression levels compared to the pathology report as the gold standard. Based on prediction results, four miRNAs, including miR-9, miR-20b, miR-221, and miR-222, were selected to evaluate their expression level in Iranian thyroid samples. Results: A significant difference between the tissue expression level of miR-20b, miR-9, miR-222, and miR-221 was detected in the PTC group compared with non-PTC (P < 0.05). The area under the curves for the included miRs were 1, 0.98, 0.99, 0.98, and 1, respectively. Conclusion: Our results confirmed deregulations of miR-20b as well as miR-222, miR-221, and miR-9 in PTC and, therefore, could be used as a helpful miRNA panel to differentiate PTC from benign nodules, which results in the more efficient clinical management of PTC patients.

Assessment of normal hemodynamic profile of mechanical pulmonary prosthesis by doppler echocardiography: a prospective cross-sectional study.

OBJECTIVES: Very few reports have described the Doppler-derived echocardiographic parameters for mechanical pulmonary valve prosthesis (MPVP). This study aims to describe the normal Doppler hemodynamic profile of MPVP using Doppler echocardiography. METHODS: The current prospective, single center observational study enrolled 108 patients who underwent pulmonary valve replacement (PVR) surgery for the first time and had a normally functioning prosthesis post-operation. The hemodynamic performance of MPVPs, considering flow dependent and flow independent parameters, was evaluated at two follow-up points, at week one and week four post-operation. All assessments were conducted by an experienced echocardiographer. RESULTS: The mean age (±SD) of the participants was 26.4 (±8.98). Tetralogy of Fallot (ToF) was the most common underlying disease leading to PVR, with a prevalence of 88%. At first week post-operation, measurement of indices reported the following values (±SD): peak pressure gradient (PPG): 18.51(±7.64) mm Hg; mean pressure gradient (MPG): 10.88(±5.62) mm Hg; peak velocity (PV): 1.97(±0.43)m/s; doppler velocity index (DVI): 0.61(±18); pulmonary velocity acceleration time (PVAT): 87.35(±15.16) ms; effective orifice area (EOA): 2.98(±1.02) cm2;and effective orifice area to body surface area ratio (EOA/ BSA): 1.81(±0.62) cm2/m2. Comparing these measurements with those obtained from the second follow-up (at week four post-op) failed to hold significant difference in all values except for PVAT, which had increased from its primary value (p = 0.038). Also, right ventricular (RV) function showed significant improvement throughout the follow up period. CONCLUSION: The findings of this study help strengthen the previously scarce data pool and better establish the normal values for Doppler hemodynamics in mechanical pulmonary prosthesis.

A randomized controlled trial of pegylated interferon-alpha with tenofovir disoproxil fumarate for hepatitis B e antigen-negative chronic hepatitis B: A 48-week follow-up study.

BACKGROUND: Recent studies report incongruent finds regarding the addition of pegylated interferon -alpha (Peg- IFNα) to nucleos(t)ide analogues. This study was designed to compare the efficacy of Peg- IFNα and tenofovir disoproxil fumarate (TDF) combination therapy with each of the treatments separately. METHODS: In this open-label, randomized clinical trial, treatment-naive hepatitis B e antigen (HBeAg)-negative patients were randomly assigned to three treatment groups: Group A: Peg- IFNα (180 mcg/week) with TDF (300 mg/day); Group B: TDF (300 mg/day); and Group C: Peg- IFNα (180 mcg/week). The intervention spanned 48 weeks and patients were followed up every 12 weeks. The primary end-point was HBV DNA load <20 IU/mL. RESULTS: Groups A, B and C each comprised of 22, 23 and 22 patients, respectively. The number of patients with HBV DNA suppression in group A was significantly higher compared to groups B and C (P = 0.034). No significant difference was observed in the normalization trends of serum ALT levels between the three groups (P = 0.082). At week 48, combination therapy was significantly more effective in suppressing HBV DNA concentration to below the level of detection than TDF monotherapy (OR = 2.1, 95%CI: 1.18-4.15; P = 0.034). Furthermore, a comparison between monotherapy arms revealed that both interventions had similar effects on the overall outcome (OR = 1.24, 95%CI: 1.02-5.8; P = 0.062). CONCLUSION: A Peg- IFNα and TDF combination therapy resulted in improved virologic response and was safe in HBeAg negative patients. Monotherapy with Peg-IFNα or TDF procured limited benefits in comparison. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT20181113041635N1).

Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions.

The trend in the incidence rate of bone fractures has been upward and as a result, the burden associated with orthopedic fractures has increased significantly. Titanium (Ti) implants are considered a preferred method of managing long bone fractures. However, no benefit comes without some downside, and using Ti implants is associated with several complications. In this respect, it was observed that in bones, Ti can disrupt the bone healing process by disturbing the balance of osteoclast and osteoblast activation and also increasing the production of inflammatory cytokines. Melatonin is a widely-acting molecule that possesses strong anti-oxidant features. This molecule reinforces mineral density and improves bone formation processes. In this review, we focused on the protective effect of melatonin in mitigating the Ti-related complications.

Pre- and Post-surgical Prevalence of Thiamine Deficiency in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

Thiamine deficiency is a life-threatening nutritional abnormality observed in the patients with obesity and following bariatric surgery. The aim of the present study is to determine the prevalence of thiamine deficiency prior to and after bariatric procedures. PubMed, Web of Science, Google scholar, CENTRAL, ProQuest, and Scopus were searched to retrieve relevant studies containing data on thiamine deficiency in patients with obesity who underwent bariatric surgery. A proportional meta-analysis approach was used to pool the prevalence of thiamine deficiency prior and after surgery. Our comprehensive literature search retrieved 41 studies with relevant data. The pooled prevalence of thiamine deficiency was 7% (95% CI: 4-12%) at baseline. We observed that 19% (95% CI: 0-68%), 9% (95% CI: 3-17%), and 6% (95% CI: 3-9%) of patients had developed thiamine deficiency at 3 months, 6 months, and 1 year after surgery, respectively. We also report that the prevalence of thiamine deficiency in pregnant women who had history of bariatric surgery. The rate was highest in the first trimester (12%) compared to that in the second (8%) and third (10%) trimesters. The baseline prevalence is 7% for thiamine deficiency in bariatric surgery candidates. The prevalence rate of thiamin deficiency increased to 19% and 9% 3 and 6 months after surgery; however, the rate decreased to 6% 1 year after surgery. Due to the higher prevalence of thiamine deficiency in the early post-operative phase, close monitoring during this period is recommended. A similar strategy should be implemented for pregnant women with history of bariatric surgery in their first trimester.

Laparoscopic small bowel length measurement: nonassociative nature of total small bowel length with anthropometric and clinical characteristics in patients undergoing bariatric surgery.

BACKGROUND: Small bowel length (SBL) may have an impact on the outcomes of bariatric surgeries, but it can be difficult to make a direct association between SBL and the safety and outcome of bariatric surgeries. OBJECTIVES: To address this issue, we set out to devise a predictive model for SBL determination based on clinical and anthropometric variables. SETTING: An academic tertiary medical center. METHODS: Anthropometric and clinical data, including age, sex, height, weight, and past medical history, were collected upon enrollment. SBL was measured twice during the surgery using a marked grasper. In all cases, measurements were carried out by a single surgeon. To create a predictive model, a 2-step approach was employed. In the first step, linear regression was used to determine influential variables. In the second step, all variables with a P value < .2 were entered into a multivariate regression model. RESULTS: Overall, 961 bariatric candidates were enrolled. The mean age of the participants was 40.08 years, and 77.5% (n = 745) were female. The mean SBL was 748.90 centimeters. There was a weak but statistically significant positive correlation between SBL with both weight and height. Our univariate linear model determined only anthropometric parameters as a predictor of SBL. The multivariate model also yielded that none of the entered parameters were shown to be accurate predictors of SBL. Moreover, only 4.3% of variances were explainable by this model. CONCLUSION: Although we found a weak positive association between height and SBL, this association lacked clinical practicality.

Melatonin effect on platelets and coagulation: Implications for a prophylactic indication in COVID-19.

Severe COVID-19 is associated with the dynamic changes in coagulation parameters. Coagulopathy is considered as a major extra-pulmonary risk factor for severity and mortality of COVID-19; patients with elevated levels of coagulation biomarkers have poorer in-hospital outcomes. Oxidative stress, alterations in the activity of cytochrome P450 enzymes, development of the cytokine storm and inflammation, endothelial dysfunction, angiotensin-converting enzyme 2 (ACE2) enzyme malfunction and renin-angiotensin system (RAS) imbalance are among other mechanisms suggested to be involved in the coagulopathy induced by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The activity and function of coagulation factors are reported to have a circadian component. Melatonin, a multipotential neurohormone secreted by the pineal gland exclusively at night, regulates the cytokine system and the coagulation cascade in infections such as those caused by coronaviruses. Herein, we review the mechanisms and beneficial effects of melatonin against coagulopathy induced by SARS-CoV-2 infection.

Therapeutic potentials of melatonin in the treatment of lymphoma: A review of current evidence.

Hematological malignancies including leukemia, multiple myeloma, and lymphoma are known as leading causes of death around the world. Despite all developments in cancer management, current therapeutic methods are still relatively inefficient, leading to the heavy financial burdens for public health systems. Strategic attempts in clinical practice must be based on three serious goals including (1) increasing the efficacy of treatments and decreasing their side-effects; (2) decreasing financial price of treatments and related morbidity and mortality rates; and (3) improving life quality and survival of affected patients. Melatonin, a multipotential neurohormone mainly secreted by the pineal gland, has recently been shown to play essential roles in the treatment of various human diseases. Moreover, it possesses anticancer impacts and acts through regulation of underlying cellular and molecular mechanisms. In this article, we review mechanistic roles and beneficial effects of melatonin against hematological cancers, especially lymphoma.

How the Choice of Osteosynthesis Affects the Complication Rate of Intercalary Allograft Reconstruction? A Systematic Review and Meta-analysis.

Background: There is no clear consensus on the optimal type of fixation in intercalary allograft reconstruction. In this study, we aimed to compare the rate of most common complications following the plate and nail fixation of the intercalary allograft. Materials and Methods: We searched PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library. Studies in which the complication rate of the single bridging plate and intramedullary nail fixation was extractable were included. Studies that used extra procedures such as cementation and fibular vascular graft augmentation were excluded. The primary outcome was the fixation-specific rate of nonunion. Secondary outcomes were the fixation-specific rate of fracture, infection, and local recurrence. Results: In total, 13 studies with 431 reconstructions (352 reconstructions in the plate group and 79 reconstructions in the intramedullary nailing group) were included in this study. In the plate fixation, the rate of nonunion, fracture, infection and local recurrence was 12%, 11%, 11%, and 3%, respectively. In the intramedullary nail fixation, the rate of nonunion, fracture, infection, and local recurrence was 37%, 5%, 4%, and 0%, respectively. The rate of nonunion was significantly higher in the intramedullary nail group (OR = 6.34; 95% CI 2.98-13.49, P < 0.001). The rate of fracture, infection, and local recurrence was not significantly different between the two fixation methods. Conclusions: Intramedullary nail is associated with a significantly higher rate of nonunion. Since the rate of other complications was not significantly different between the two osteosynthesis types, plate fixation could be considered as a better type of fixation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-021-00563-7.

Evaluation of the Association between Fetal Cardiac Disorders with Choroid Plexus Cyst in Fetuses.

Choroid plexus cysts (CPCs) are often transient and benign findings observed in pregnancy screenings. This study aimed to examine the association between the frequency of congenital heart diseases and the detection of CPCs. In this prospective case-control study, pregnant mothers with no predisposing risk factors for the development of fetal cardiac abnormalities were eligible for entry. Based on the presence or absence of CPCs on ultrasound, the enrolled fetuses were divided into two groups. All patients (n = 100) underwent two-dimensional and color Doppler echocardiography to identify potential cardiac anomalies. Overall, CPCs were detected in 53 enrolled fetuses, and the remainder were enrolled as controls (n = 47). Pathological findings, such as echogenic intracardiac focus (EIF), ductal spasm, atrial septal defect (ASD), pericardial effusion, cardiomyopathy, and congenital heart disease were found in neither group. In the CPC group, two mild and six trivial cases of tricuspid regurgitation (TR) were detected. In the controls, five cases of trivial TR were identified. In conclusion, the presence of CPCs was not associated with significant functional or structural fetal cardiac abnormalities, which may be due to altered developmental mechanisms.

Risk of Bias in Iranian Randomized Trials Included in Cochrane Reviews.

BACKGROUND: Among interventional studies, randomized controlled trials (RCTs) provide the highest level of evidence. However, RCTs can be susceptible to the risk of bias (RoB). Systematic reviews can be performed to appraise RoB in the included articles using evaluative tools. This study aimed to describe the main characteristics and focus on the RoB of RCTs conducted in Iran and included in Cochrane Reviews (CRs). METHODS: We searched "Iran" by selecting the "Search All Text" and "Review" fields in the Cochrane Database of Systematic Reviews within Ovid. CRs that included the RCTs conducted in Iran were retrieved. A trial was selected only if it was included in CRs, described as a controlled clinical trial, involved human subjects and CR authors assessed its RoB. The trials were characterized by investigating the relevant articles and the table "Characteristics of included studies" in each CR. The RoB was investigated by collecting the review authors' judgments based on RoB assessment tables in the CRs. RESULTS: Out of 1166 Iranian RCTs included by 571 CRs, low RoB was found in 44.9% for random sequence generation, 20.8% for allocation concealment, 32.3% for blinding of participants/personnel, 36.5% for blinding of outcome assessors, 56.3% for incomplete outcome data, 41.3% for selective outcome reporting and 53.8% for other sources of bias. CONCLUSION: The RoB in Iranian RCTs was found to be mostly high or unclear. While this is similar to the global situation, it is recommended that the methodological quality of conducting and reporting RCTs be addressed in Iran.

Comparing the Severity of Injury and Trauma Pattern between Scooter and Street Motorcycle Riders; a Prospective Cohort Study.

INTRODUCTION: The popularity of motorcycle riding in Iran is increasing. However, there is a lack of information about the safety of different motorcycle types. This study aimed to compare the severity of injury and trauma pattern between scooter (vespa) and street (standard) motorcycle riders. METHOD: In a prospective cohort study, a comparison of demographics, injury severity, trauma pattern, and clinical characteristics between 324 riders (162 Vespa and 162 standard motorcycles) admitted to emergency departments was undertaken. The risk factors associated with severe injuries in the two groups were also determined. An emergency medicine specialist determined the severity of trauma based on the abbreviated injury scale (AIS). RESULTS: The Odds Ratio (OR) of severe injuries was significantly higher in the standard motorcycle riders' group (OR: 3.09; 95% CI: 1.9-4.21; p: 0.013). The frequency of lower extremity fractures was significantly lower in the Vespa group (OR: 4.11; 95% CI: 2.01-6.25; p = 0.012). The frequency of admission to the intensive care unit was significantly higher in the standard motorbike riders' group (OR: 1.64; 95% CI: 1.11-2.51; p = 0.033). The multivariate analysis indicated that motorcycle type, the speed at the time of the accident, use of helmet, and age of riders are the most important predictors of trauma severity in riders (p<0.05). CONCLUSION: The pattern of injury varies between standard and Vespa motorcycles. The standard motorcycle riders were prone to a higher risk of adverse outcomes such as severe injuries. Due to the particular structure of scooters, the rate of lower limb injuries was significantly lower than standard motorcycles.

Waist-To-Height Ratio Is a More Accurate Tool for Predicting Hypertension Than Waist-To-Hip Circumference and BMI in Patients With Type 2 Diabetes: A Prospective Study.

Background: Anthropometric measures [i.e., body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)] have been used as prediction factors for incident hypertension. However, whether any of these measures is superior to another in the matter of accuracy in predicting hypertension in diabetic patients has been controversial. The present prospective study aimed to determine whether WHtR is a more accurate tool for predicting hypertension than WHR and BMI in patients with type 2 diabetes. Methods: The study population consisted of 1,685 normotensive patients with type 2 diabetes. BMI, WHR, and WHtR were assessed at baseline and followed up for hypertension incidence for a mean of 4.8 years. A cox regression analysis was performed to assess the association between anthropometric measures (i.e., BMI, WHR, and WHtR) and incident hypertension during the follow-up period. The area under the ROC curve analysis was performed and optimal cutoff values were calculated for each anthropometric measure for hypertension prediction. Results: WHtR and BMI were significantly associated with an increased incidence of hypertension (HR = 3.296 (0.936-12.857), P < 0.001, and HR = 1.050 (1.030-1.070), P < 0.001, respectively). The discriminative powers for each anthropometric index for hypertension were 0.571 (0.540-0.602) for BMI, 0.518 (0.486-0.550) for WHR, and 0.609 (0.578-0.639) for WHtR. The optimal cutoff points for predicting hypertension in patients with type 2 diabetes were 26.94 (sensitivity = 0.739, specificity = 0.380) for BMI, 0.90 (sensitivity = 0.718, specificity = 0.279) for WHR, and 0.59 (sensitivity = 0.676, specificity = 0.517) for WHtR. Conclusion: WHtR was a more accurate tool for predicting hypertension compared to WHR and BMI in patients with type 2 diabetes.

Angiotensin enzyme inhibitors and angiotensin receptor blockers as protective factors in COVID-19 mortality: a retrospective cohort study.

Targeting the renin-angiotensin system is proposed to affect mortality due to coronavirus disease 2019 (COVID-19). We aimed to compare the mortality rates in COVID-19 patients who received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) and those who did not. In this retrospective cohort study, mortality was considered as the main outcome measure. All underlying diseases were assessed by the chronic use of medications related to each condition. We defined two main groups based on the ACEIs/ARBs administration. A logistic regression model was designed to define independent predictors of mortality as well as a Cox regression analysis. In total, 2553 patients were included in this study. The mortality frequency was higher in patients with a history of underlying diseases (22.4% vs 12.7%, P value < 0.001). The mortality rate in patients who received ACEIs/ARBs were higher than non-receivers (29.3% vs. 19.5%, P value = 0.013, OR = 1.3, 95% CI 1.1, 1.7) in the univariate analysis. However, the use of ACEIs/ARBs was a protective factor against mortality in the model when adjusted for underlying conditions, length of stay, age, gender, and ICU admission (P value < 0.001, OR = 0.5, 95% CI 0.3, 0.7). The Kaplan-Meier curve showed an overall survival of approximately 85.7% after a 120-day follow-up. ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease. The survival probability is higher in ACEIs/ARBs receivers than non-receivers.

Comparison of the effect of argon, hydrogen, and nitrogen gases on the reduced graphene oxide-hydroxyapatite nanocomposites characteristics.

In this study, the effect of the argon, nitrogen, and hydrogen gases on the final properties of the reduced graphene oxide- hydroxyapatite nanocomposites synthesized by gas injected hydrothermal method was investigated. Four samples were synthesized, which in the first sample the pressure was controlled by volume change at a constant concentration. In subsequent samples, the pressure inside the autoclave was adjusted by the injecting gases. The initial pressure of the injected gases was 10 bar and the final pressure considered was 25 bar. The synthesized powders were consolidated at 950 °C and 2 MPa by spark plasma sintering method. The final samples were subjected to Vickers indentation analysis. The findings of this study indicate that the injection of argon, hydrogen, and nitrogen gases improved the mechanical properties of the nanocomposites. Injection of gases increased the crystallinity and particle size of hydroxyapatite, and this increase was greater for nitrogen gas than for others. Injection of these gases increased the rate of graphene oxide reduction and in this case the effect of nitrogen gas was greater than the others.