Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

BACKGROUND: Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. METHODS: This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3 mg/day, clonazepam 1 mg/day, or trazodone 50 mg/day for 4 weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. RESULTS: A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4 weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. CONCLUSIONS: Trazodone 50 mg/day, clonazepam 1 mg/day, and melatonin 3 mg/day were all tolerable and effective in improving sleep quality in patients with PD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Ammonia removal from industrial effluent using zirconium oxide and graphene-oxide nanocomposites.

The present study developed and evaluated nano-adsorbents based on zirconium oxide and graphene oxide (ZrO2/GO) as a novel adsorbent for the efficient removal of ammonia from industrial effluents. Fourier transform infrared (FTIR) spectroscopy, Field Emission Scanning Electron Microscope, Energy-dispersive X-ray Spectroscopy, and X-ray diffraction were used to evaluate and identify the novel adsorbent in terms of morphology, crystallography, and chemical composition. The pH (7), adsorbent quantities (20 mg), adsorbent contact time (30 min) with the sample, and initial ammonia concentration were all tuned for ammonia uptake. To validate ammonia adsorption on the ZrO2/GO adsorbent, several kinetic models and adsorption isotherms were also utilized. The results showed that the kinetics of ammonia adsorption are of the pseudo-second order due to high R2 (>0.99) value as compared first-order (R2 = 0.52). The chemical behavior and equilibrium isotherm were analyzed using the isotherm models and Langmuir model provided high R2 (>0.98) as compared Freundlich (>0.96). Hence, yielding a maximum uniform equilibrium adsorption capacity of 84.47 mg g-1. The presence of functional groups on the surface of graphene oxide and ZrO2 nanoparticles, which interact efficiently with ammonia species and provide an efficient surface for good ammonia removal, is most likely to be responsible.

A rare case of coexistence of Wegener's granulomatosis and pulmonary tuberculosis with subsequent development of thrombosis of the cerebral veins.

BACKGROUND: Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis, is an idiopathic systemic disease typically affecting the lungs, although other organs may also be involved. CASE PRESENTATION: A 28-year-old male was admitted to Baqiyatallah university hospital in Teheran (Iran) after a 3-week history of fever and productive cough. The patient gradually developed fatigue, arthralgia, hematuria, nausea, vomiting, dyspnea, hemoptysis, weight loss, oliguria and then anuria. Chest-X-ray (CXR) and computerized tomography scan revealed cavitating nodular opacities in the right lung lobe. Furthermore, plasma creatinine increased from 2.2 to 4 mg/dl in a few days. Histopathological examination of kidney biopsy revealed peri-glomerular and peri-vascular inflammation, degeneration and necrosis of the tubular epithelial lining, red blood cell casts, distorted glomerular structure, fibrin thrombi, segmental breaks of the glomerular basal membrane, disruption of Bowman's capsular membrane and crescent formation of the affected glomeruli. An abnormal CXR, an abnormal urinary sediment and a typical kidney histology were used as criteria to diagnose glomerulonefritis with poliangiitis (GPA). Bronchoalveolar lavage smear and PCR turned out positive for mycobacterium tuberculosis. After 3 months of treatment for (GPA) and tuberculosis the patient developed headache and seizure. Cerebral Magnetic Resonance Venography revealed cerebral venous thrombosis of the sinus transverse and sigmoid. CONCLUSIONS: Tuberculosis may coexist with GPA, as it occurred in our patient. Since a crescentic glomerulonephritis can progress to renal failure, clinicians should always be aware of potential multiple conditions when considering differential diagnoses.

Investigating the possible association between NLRP3 gene polymorphisms and myasthenia gravis.

INTRODUCTION: In this case-control study, we investigated the association between nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) single-nucleotide polymorphisms (SNPs) rs10754558, rs3806265, rs4612666, and rs35829419 and myasthenia gravis (MG). METHODS: Samples from MG patients were selected from a previous study conducted in our neuromuscular clinic, which investigated the association between human leukocyte antigen (HLA) class II genes and MG. Genetic data of controls were also available from another study. The NLRP3 SNPs genotyping was performed using the TaqMan method. RESULTS: A total of 93 blood samples from eligible Iranian patients with MG and 56 samples from healthy controls were obtained. The NLRP3 rs3806265 "C" allele was significantly more frequent in MG patients (P < .001; odd ratio [OR] = 2.33, 95% confidence interval [CI]: 1.4-4.0) than controls. The "CC" genotype of this SNP was found in 18.27% of patients, but none of the controls (P < .001). The distribution of other SNPs was similar between the groups. DISCUSSION: These preliminary results suggest that there might be some associations between the NLRP3 gene polymorphism and MG.

The safety and efficacy of transcranial direct current stimulation as add-on therapy to fluoxetine in obsessive-compulsive disorder: a randomized, double-blind, sham-controlled, clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is an anxiety disorder that causes impairment in daily activities. This study aimed to assess the safety and efficacy of transcranial direct current stimulation (tDCS) as adjunctive therapy with fluoxetine in individuals diagnosed with moderate to severe OCD. METHODS: This is a randomized, double-blind sham-controlled trial. Individuals with OCD who had baseline Yale-Brown obsessive-compulsive scale (Y-BOCS) of > 15 were enrolled. Eligible cases were randomly assigned in 1:1 ratio to receive either 20-min-period of stimulation with tDCS and fluoxetine (experimental arm) or fluoxetine only (sham control arm). The anodal electrode of tDCS was placed over the left dorsolateral prefrontal cortex (Fp3) and the cathodal electrode was placed over the right orbitofrontal cortex (F8). Two mA electrical stimulation with the tDCS was used for 20 min in individuals of experimental group. In the control group, electrodes were placed and stimulation was administered for 30 s to induce the same skin sensation as in experimental group. This procedure was performed three times per week for 8 weeks. Y-BOCS test was assessed at baseline, week 4 (after 12th stimulation), week 8 (after 24th stimulation), and 1 month after the last stimulation. The primary endpoints were the mean changes in Y-BOCS total score from baseline to the last visit. The secondary endpoints were the mean changes in obsession and compulsion sub-scores from baseline to the last visit. Adverse events were also assessed. Mixed design repeated measures analysis of variance assessed the endpoints. RESULTS: Sixty individuals (30 in each group) were participated. All individuals in control group and 28 cases in experimental arm completed the trial. The mean Y-BOCS (F(1.85) = 30.83; P < 0.001), OCD obsession (F(2.23) = 25.01; P < 0.001), and compulsion (F(2.06) = 10.81; P < 0.001) scores decreased significantly during the study. No statistical differences were, however, detected between experimental and control groups (P > 0.05). The tDCS was well tolerated and no major adverse events were reported. CONCLUSION: This study showed that among individuals with moderate to severe OCD, there was no significant difference regarding OC symptoms between cases used tDCS as adjunctive therapy with fluoxetine and individuals used fluoxetine only. TRIAL REGISTRATION: IRCT2017030632904N1 . Registered 14 July 2017, http://irct.ir/user/trial/44193/view.

Safety and efficacy of memantine for multiple sclerosis-related fatigue: A pilot randomized, double-blind placebo-controlled trial.

BACKGROUND: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS). Currently, there is no approved medication for MS-related fatigue. OBJECTIVE: In this study, we aim to evaluate the safety and efficacy of memantine for improving fatigue in patients with MS. METHODS: This was a pilot randomized, double-blind, placebo-controlled clinical trial. Eligible patients with relapsing-remitting MS (RRMS) according to the McDonald criteria were randomized to receive either memantine (20 mg/day) or placebo and were assessed at baseline and three months after treatment. The change in the severity of fatigue was determined by the Modified Fatigue Impact Scale (MFIS). RESULTS: Sixty-four patients were randomly allocated to the memantine (n = 32) and placebo (n = 32) groups. Sixteen patients in the memantine group and 24 patients in the placebo group completed the study. The mean [95% CI] absolute change in MFIS scores from baseline did not differ significantly between the memantine (-5.8 [-12.7 to 1.0]) and placebo (-4.0 [-10.6 to 2.7]) groups (between-group difference: -1.9 [-11.7 to 7.8], P = .702). No serious adverse events were reported, except for dizziness and sedation in four patients in the experimental arm, which resulted in discontinuation. CONCLUSION: This trial failed to prove any clinical efficacy of memantine for the management of MS-related fatigue. Although memantine was generally well-tolerated, adverse events were among the major causes of dropout in this study.

Demographic, clinical, and virological characteristics of patients with a laboratory-confirmed diagnosis of influenza during three consecutive seasons, 2015/2016-2017/18, in the Islamic Republic of Iran.

BACKGROUND: There are minimal data on the differences in demographics, clinical presentations and outcomes for patients with different types and sub-types of influenza in the Middle East. OBJECTIVES: To use population-based data from Iran to investigate factors associated with unfavorable disease outcome. STUDY DESIGN: Clinical data were compiled from the Iranian Ministry of Health for patients of all ages who fulfilled the severe acute respiratory infections (SARI) definition according to World Health Organization criteriatested for any reason and found to have and had laboratory proven influenza September 21, 2015 through March 20, 2018. Pulmonary, cardiac, renal, hematologic and neurologic complications were recorded. Results were compared by type, age, gender and health status. Multivariate analysis was used to analyze risk factors for complications and death. RESULTS: Of 11,080 enrolled patients, 10,046 (90.7 %) were inpatients, 2254 (20.4 %) were children, 8403 (75.8 %) had influenza A, 2599 (23.5 %) had influenza B, and 78 (0.7 %) had unidentified types. Fever was less common in older patients (OR 0.99; 95 % CI 0.98-0.99, p < 0.001 and in those with comorbidity (OR 0.87; 95 % CI 0.77-0.97, p = 0.013). Although the rate of complications was lower with A(H1N1) pdm09 influenza than with A(H3N2) infection (12.8 % versus 15.6 %, p = 0.001), the mortality rate was higher (7.0 % versus 3.0 %, p < 0.001). Complications occurred more often during late versus early influenza season (OR 1.22; 95 % CI 1.08-1.37, p = 0.002). Patients with type B influenza (OR 0.85; 95 % CI 0.74-0.98, p = 0.025), or who presented with sore throat (OR 0.74; 95 % CI 0.65-0.84, p < 0.001) were less likely to develop complications. The risk of developing complications was increased in patients who had chronic heart disease (OR 1.51; 95 % CI 1.29-1.76, p < 0.001), chronic pulmonary disease (OR 1.62; 95 % CI 1.37-1.91, p < 0.001), diabetes (OR 1.24; 95 % CI 1.03-1.50, p = 022), or epilepsy (OR 1.55; 95 % CI 1.17-2.05). Older age and male gender increased the risk of death but not of complications. CONCLUSIONS: The clinical features, complications and outcomes of influenza vary by age and by viral type and sub-type. Comorbidites appear to be more important than age in predicting complications.

Poly (n-butyl cyanoacrylate) as a nanocarrier for rivastigmine transport across the blood-brain barrier in Alzheimer's disease treatment: a perspective from molecular dynamics simulations.

In this study, molecular dynamics simulations have been used to investigate the behavior of the drug rivastigmine and its carrier so-called poly (n-butyl cyanoacrylate) in the encapsulation process. Polymer modeling, and subsequently the emulsion polymerization model, were applied to analyze drug release in vitro and to justify rivastigmine transport across the blood-brain barrier (BBB) and polymer agglomeration. On the other hand, suitable polymer chain length, encapsulation method, polarity between polymer and drug structure, and finally, pattern of drug released in vitro and in vivo have been investigated to analyze the behavior of drug and polymer accurately. Maximum drug loading was determined based on the modeling of drug encapsulation and comparison of the radius of gyration of polymer (Rg) and distance between center of masses (COMs) of rivastigmine molecules and polymer in equilibrium condition (A°). With the aim of better understanding of drug release, we calculated the Flory-Huggins interaction parameter, diffusion coefficient, and intermolecular interaction energy. The results reveal that more drug molecules remain on the surface of the polymeric structure, with increasing the concentration of rivastigmine molecules from 3 up to 7, but the number of encapsulated drug molecules inside of the polymer remains constant. Also, calculated values of Gibbs free energy indicated that intramolecular interactions of the polymer chain overcome the intermolecular interactions between polymer and drug. Therefore, any extra loading of drug resulted in accumulation on the polymer surface. Graphical abstract Poly (n-butyl cyanoacrylate) containing rivastigmine molecules.