Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.

Background: One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS. Methods: We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes. Results: 36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324). Conclusion: The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.

Evaluation of relationship between memory and temperament in 18-28 years old students.

Background: Mizaj (Temperament) is a concept to express individual differences in Persian medicine and according to this theory, there is a relationship between Mizaj type and the abilities of different body organs. This cross-sectional study aimed to investigate the relationship between the type of Mizaj and the memory score (Quotient). Methods: The target population was the 18 to 38 years old students of Babol University of Medical Sciences. Mojahedi's Mizaj questionnaire (MMQ) was used for determining the whole Mizaj. The physical Persian version of Wechsler Memory Scale III (WMS III) was used to assess memory score. The collected data were analyzed by SPSS Version 22 and the chi square (x2) and t-test were run and p- value 0.05 was considered as significant difference. Results: Forty-two of participants were females and 18 were males. The average age of them was 23.6 (21-27). The average of Memory Quotient (MQ) was 122.1 ± 5.7. The average of MQ in warm Mizaj was 125.46 ± 1.2 and in cold Mizaj was 118.79 ± 6.5. The difference between two groups is statistically significant (p< 0.001). The average of MQ in dry Mizaj was 124.16 ± 2.67 and in wet Mizaj was 118.40 ± 7.64. The difference between two groups is statistically significant (P= 0.005). Conclusion: The results showed there are significant relationship between memory score and warm/cold Mizaj and dry /wet Mizaj. It means students with warm or dry Mizaj had better memory score than students with cold or wet Mizaj. This relation was also detected between subtypes of memory and Mizaj expect between working memory and dry/wet Mizaj. These results are in accordance with theories in PM which indicate people with warm Mizaj and dry Mizaj have better memory and people with cold Mizaj and wet Mizaj have weaker memory and are more at risk of memory dysfunction.

Mediatory role of the serum mineral level and discharge disability of stroke survivors.

Background: Possible association between minerals contributing and mortality related to stroke were seen, but prospective data on the relation of vitamin D, magnesium and calcium serum levels with stroke were inconsistent. Consideration about the potential health effects of minerals and nutrients, the current study was conducted. Methods: This analytical cross-sectional study was conducted on 216 stroke survivors who were referred to the Ayatollah Rouhani Hospital of Babol, Iran. Demographic characteristics, clinical variables, and serum mineral levels were completed in the checklist. Admit score and discharge scale of these patients were determined according to the National Institute of Health Stroke Scale. A path model was constructed to explore the interrelationship between variables and to verify the relationship between variables and disability discharges. Results: Of 216 stroke patients, 185 (85.6%) cases were ischemic. The discharge status of 29 (12.9%) cases were severe or expired. The patients with moderate and severe admit scores, hemorrhagic stroke type, diabetes mellitus, hypertension and live in the village significantly had a poor discharge disability scale (all of p<0.05). Of all direct paths, Mg (ß=-2.85), and among indirect paths, calcium(ß=-3.59) had the highest effect on the discharge scale. Only mg had affected the discharge scale through direct and indirect (ß=-2.45) paths and had the greatest reverse effect on the discharge scale (ß=-5.30; totally). Conclusion: Hypomagnesemia and hypocalcemia play a mediatory role in poor outcomes. Especially, hypomagnesemia was the direct parameter for poor outcomes. The independent role of each mineral in this issue is difficult to define and suggested for future study.

Potential genetic polymorphism of matrix metalloproteinase (MMP)-9 in Iranian migraine patients with Toxoplasma gondii infection.

Toxoplasma gondii is an intracellular protozoan parasite that causes neuroinflammation in the brain and a constant need for peripheral leukocyte migration. Matrix metalloproteinase 9 (MMP-9) can play a major role in this neuroinflammation and be implicated in some neurological disorders, such as migraines. Therefore, the genetic polymorphism evaluation of MMP-9 in migraine patients with T. gondii infection was performed. One hundred fourteen migraine patients and 114 healthy controls were evaluated for the presence of anti-Toxoplasma IgG antibodies. Seventy-two migraine patients and 40 healthy controls were randomly selected for assessment of the MMP 9-1562C/T genetic polymorphism. In the preliminary examination, 61 (53.5%) migraine patients and 43 (37.3%) healthy controls were positive for IgG antibodies, with a significant association between T. gondii seropositivity and migraine (OR = 1.90; 95% CI = 1.21-3.223; P = 0.012). Genetic distribution for the polymorphism was not in Hardy-Weinberg equilibrium in cases but showed no significant variation in control groups (P = 0.03 and P = 0.180, respectively). A significant preponderance of the CT + TT genotype was found in migraine subjects compared to controls (P = 0.042) (OR, 1.77, CI, 1.013-2.229). The homozygote muted allele TT had a higher rate in migraine patients (6.9%). There were significant differences in CT + TT genotype between T. gondii positive and negative migraine patients (P = 0.024), but T allele frequencies had no significant variation (OR 1.7 CI, 1.084-2.44 and 0.42 CI, 0.044-3.97, respectively). In conclusion, the results may provide the first evidence for the involvement of the MMP-9 gene polymorphism in the mechanism of migraine pathology following Toxoplasma infection.

Key Non-coding Variants in Three Neuroapoptosis and Neuroinflammation-Related LncRNAs Are Protectively Associated with Susceptibility to Parkinson's Disease and Some of Its Clinical Features.

Research findings show that genetic susceptibility to sporadic Parkinson's disease (PD), a common neurodegenerative disorder, is determined through gene variation of loci involved in its development and pathogenesis. A growing body of strong evidence has revealed that dysfunction of long non-coding RNAs (lncRNAs) plays key roles in the pathogenesis and progression of PD through impairing neuronal signaling pathways, but little is known about the relationship between their variants and PD susceptibility. In this research, we intended to study the relationship between functional SNPs rs12826786C>T, rs3200401C>T, and rs6931097G>A in the key lncRNAs stimulating neuroapoptosis and neuroinflammation in PD, including HOTAIR, MALAT1, and lincRNA-P21, respectively, with susceptibility to PD as well as its clinical symptoms.The population of this study consisted of 240 individuals, including 120 controls and 120 cases, and the sample taken from them was peripheral blood. Genotyping of the target SNPs was done using PCR-RFLP. We found that the healthy individuals carry more T allele of MALAT1-rs3200401C>T compared to the patients (P= 0.019). Furthermore, it was observed that in the dominant genetic model, subjects with genotypes carrying the T allele have a lower risk of PD (OR= 0.530; CI= 0.296-0.950; P= 0.033). Regarding the lincRNA-P21-rs6931097G>A, we observed a significant protective relationship between its GA (OR= 0.144; CI= 0.030-0.680; P= 0.014) and AA (OR= 0.195; CI= 00.047-0.799; P= 0.023) genotypes with the manifestation of tremor and bradykinesia symptoms, respectively. Furthermore, the findings indicated that the minor TT genotype of HOTAIR-rs12826786C>T was significantly associated with a reduced risk of bradykinesia symptoms (OR= 0.147; CI= 0.039-0.555; P= 0.005). Collectively, these findings suggest that MALAT1-rs3200401C>T may be an important lncRNA SNP against the development of PD, while the other two SNPs show protective effects on the clinical manifestations of PD in a way that lincRNA-P21-rs6931097G>A has a protective effect against the occurrence of tremor and bradykinesia symptoms in PD patients, and HOTAIR -rs12826786C>T indicates a protective effect against the display of bradykinesia feature. Therefore, they can have valuable potential as biomarkers for clinical evaluations of this disease.

Modeling of cerebellar transcranial electrical stimulation effects on hand tremor in Parkinson's disease.

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder with different motor and neurocognitive symptoms. Tremor is a well-known symptom of this disease. Increasing evidence suggested that the cerebellum may substantially contribute to tremors as a clinical symptom of PD. However, the theoretical foundations behind these observations are not yet fully understood. Methods: In this study, a computational model is proposed to consider the role of the cerebellum and to show the effectiveness of cerebellar transcranial alternating current stimulation (tACS) on the rest tremor in participants with PD. The proposed model consists of the cortex, cerebellum, spinal circuit-muscular system (SC-MS), and basal ganglia blocks as the most critical parts of the brain, which are involved in generating rest tremors. The cortex, cerebellum, and SC-MS blocks were modeled using Van der Pol oscillators that interacted through synchronization procedures. Basal ganglia are considered as a regulator of the coupling weights defined between oscillators. In order to evaluate the global behavior of the model, we applied tACS on the cerebellum of fifteen PD patients for 15 min at each patient's peak frequency of their rest tremors. A tri-axial accelerometer recorded rest tremors before, during, and after the tACS. Results and Discussion: The simulation of the model provides a suggestion for the possible role of the cerebellum on rest tremors and how cerebellar tACS can affect these tremors. Results of human experiments also showed that the online and offline effects of cerebellar tACS could lead to the reduction of rest tremors significantly by about %76 and %68, respectively. Our findings suggest that the cerebellar tACS could serve as a reliable, therapeutic technique to suppress the PD tremor.

Determination of plasma transcobalamin-II and zinc levels in newly-diagnosed and long-standing grand mal epileptic patients.

Background: The changes of plasma transcobalamin-II (TCII) and Zinc (Zn) Levels in epileptic patients are not clearly understood. The aim of the current study was to evaluate the plasma contents of TCII and Zn levels in newly-diagnosed epileptic seizure patients, long-standing grand mal epileptic patients following treatment with sodium valproate and healthy control group. Methods: Thirty patients aged 36.76±12.91 years with newly-diagnosed and thirty long-standing grand mal epileptic patients aged 35.56 ±12.77 years were diagnosed based on the clinical symptoms. The control subjects were picked out from healthy individuals and matched to the patients, aged 36.30 ±12.80 years. Plasma Zn and TCN-2 was evaluated via spectrophotometry at 546 nm and 450 nm, respectively, using chimerical kits. Results: Plasma level of TCII in the newly-diagnosed epileptic seizures patients and long-standing grand mal epileptic patients were significantly increased, compared to the healthy controls [14.89 ±3.24 and 21.84± 2.73 vs. 9.55±1.24, (n=30)], respectively. Plasma level of Zn was decreased in the newly-diagnosed epileptic seizure patients, while it was increased in long-standing grand mal epileptic patients compared to the control group [69.28± 6.41 and 80.56 ±6.12 and vs.75.80±1.59, (n=30)], respectively. Conclusion: This study suggests that sodium valproate may disrupt the homeostatic balance of TCII and Zn, and cause abnormality of their serum level in newly-diagnosed epileptic seizure patients and long-standing grand mal epileptic patients. Further research is recommended to identify the underpinning for these changes.

Determination of the effect of repetitive Transcranial Magnetic Stimulation (rTMS) on the primary visual cortex on improving the visual status of patients with subcortical stroke in the area of the posterior cerebral artery.

Background and objective: Repetitive Transcranial Magnetic Stimulation (rTMS)-induced neuroplasticity to induce trans-synaptic transmission at a site away from the stimulus site is one of the recent possible strategies for brain rehabilitation in patients with stroke. This study aimed to determine the effect of rTMS on the primary visual cortex of the lesion side of the brain on improving the visual status of patients with subcortical stroke in the posterior cerebral artery. Methods: After obtaining written consent, this non-randomized clinical trial study was performed on ten eligible patients. The National Eye Institute 25-items Visual Function Questionnaire (NEI-VFQ) and 30-degree automated Perimetry (visual field test) were used to assess patients' vision status before and after ten rTMS sessions. Paired T-test and Student T-test were used to analyze the data using SPSS software. Findings: A comparison of the mean and standard deviation of the total score of the VFQ-25 for each question did not show a significant difference between pre-test and post-test. In perimetry values based on the Visual Field Index (VFI), the correlation of mean deviation (MD) and the pattern standard deviation (PSD) did not differ significantly before and after the intervention. Conclusion: According to the results of this study, the rTMS method cannot be reliable as an effective method in the treatment of visual impairment caused by stroke. Therefore, our study does not definitively support rTMS as the first-choice method by physicians for stroke rehabilitation with visual impairment.

Decreased frequency of regulatory T cells and level of helios gene expression in secondary progressive multiple sclerosis patients: Evidence about the development of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an aggressive disease characterized by central nervous system (CNS) inflammatory and demyelinating lesions. Tolerance failure is implicated in the development of several autoimmune disorders, including MS. Due to their involvement in maintaining environmental tolerance, regulatory T cells (Tregs) are regarded as efficient immune cells. We examined the frequency of Tregs in this study using CD4/CD25/forkhead box protein P3 (FOXP3)/Helios markers. METHODS: Fifty participants, including 25 patients with secondary progressive MS (SPMS) and 25 healthy controls (HCs), were enrolled in this study, and their demographic characteristics were recorded. Peripheral blood samples ranging from 5 to 6 mL were obtained, and the Ficoll technique was used to extract peripheral blood mononuclear cells (PBMCs). Then, the percentage of CD4+CD25+FOXP3+Helios+ regulatory T lymphocytes was examined by flow cytometry in the study groups. Real-time polymerase chain reaction (PCR) was also used to assess the Helios gene expression level. RESULTS: This study showed that the percentage of Tregs with CD4 and CD25 markers did not reveal a significant difference compared with HCs despite the decrease in SPMS patients (P = 0.6). However, lymphocytes with CD4/CD25/FOXP3/Helios markers were significantly reduced in the patients (P = 0.01). Additionally, SPMS patients had statistically significantly lower Helios gene expression levels (P = 0.002). CONCLUSION: In SPMS patients, a decrease in the frequency of the CD4+CD25+FOXP3+Helios+ Treg population can result in an imbalanced immune system. In other words, one of the immunological mechanisms involved in this disease may be a deficiency in Tregs. Helios gene expression was also decreased in these patients, which may exacerbate functional defects in Tregs.

Epilepsy and associated factors in elderly people of Amirkola, North of Iran (The Amirkola Health and Ageing Project).

Background: Knowledge about the associated factors with epilepsy in the elderly in Iran is limited. Therefore, this study aimed to determine the prevalence of epilepsy and associated factors in Amirkola elderly patients. Methods: This cross-sectional study is a part of a comprehensive and cohort research of "The Amirkola Health and Ageing Project". The Mini-mental State Examination was used for cognitive impairment, Geriatric Depression Scale for psychiatric diseases and the Physical Activity Scale for Elderly questionnaire for physical activity. Results: The prevalence of epilepsy was 35 from 1482 participants (24/1000). The significant association between Parkinson's Disease (OR=6.25, 95%CI=1.35-28.4, P=0.001), falls (OR= 3.81, 95%CI=1.62-8.97, P=0.001), depression (P=0.001), hyperphosphatemia (P=0.039) and hypokalemia (P= 0.031) concluded with epilepsy. Past history of stroke (6 % versus 2%, OR= 2.8, 95%CI, 0.97-8.27, P=0.07), increased serum level of triglyceride (OR= 1.96, 95%CI= 0.99-3.88, P=0.06) and low-density lipoprotein (LDL) (P=0. 45) were seen in epileptic patients vs. non-epileptic patients. Conclusion: Parkinson's disease, frequency of falls and depression were the associated factors in epileptic patients and a correlation between past history of stroke, increased serum level of triglyceride and LDL with epilepsy were seen. Associated factors required screening, diagnosis and treatment.

One-year prevalence and the association between SARS-CoV-2 cycle threshold, comorbidity and outcomes in population of Babol, North of Iran (2020-2021).

Background: The present study aimed to investigate the one-year prevalence of SARS-CoV-2, common comorbidities and demographic information among negative- and positive rRT-PCR in health care workers (HCW), hospitalized and outpatients. Also, the association between SARS-CoV-2 cycle threshold (Ct) and the outcomes of patients were analyzed in Babol, northern Iran. Methods: This large retrospective cross-sectional study was performed between March 2020 and March 2021. The records of 19232 hospitalized, outpatients and HCW suspected to COVID-19 were collected from teaching hospitals in the North of Iran. Results: Out of the 19232 suspected to COVID-19 patients, 7251 (37.7%) had a positive rRT-PCR result; 652 (9%), 4599 (63.4%) and 2000 (27.6%) of those were categorized as HCW, hospitalized and outpatients, respectively. Moreover, between the hospitalized and the outpatient group, 10.2 and 0.8% cases died, whereas no death cases were reported in the HCW. Furthermore, it seems that death rate was significantly different between the three groups of Ct value, the highest mortality in those with Ct between 21 and 30 (group B=7.6%) and the lowest in the group with the highest Ct (between 31 and 40 = 5.5%) (p<0.001). Conclusion: In summary, 37.7% of cases were positive for SARS-CoV-2; of which, 63.4, 27.6 and 9% were hospitalized, outpatients and HCW, respectively. With regard to the mortality rate in hospitalized patients and the significant association with Ct under 20 and 30, it seems that the early detection and the initial quantification of SARS-CoV-2 in the first week of the conflict and therapeutic considerations to reduce the relative load can reduce the mortality rate.

Iranian Smell Diagnostic Test in Covid-19 Disease; Report of Covid-19 Center of North of Iran.

Background: SARS-CoV-2 is a pandemic coronavirus that causes the COVID-19 syndrome. In the pandemic of COVID-19 many patients were affected to new onset olfactory dysfunction. Since there is a dearth of research studies regarding the standard smell test, the present study was conducted to fill this gap. Methods: The present retrospective cohort study was conducted on 250 clients with or without diagnosis of Covid-19 disease who referred to Covid-19 centers of North of Iran. Two groups were matched for age and sex. Data were collected by examination, demographic and clinical information questionnaire and Iranian smell diagnostic test. The binary logistic regression to estimate the odds ratio value in SPSS version 23.0 was used. Results: One-hundred cases (42.2%) had hyposmia and 20 cases (8.4%) were found to have anosmia. Type of covid-19 sign and symptom were statistically significant with olfactory dysfunction (41 cases, 31.8%), fever (28 cases, 21.7%), weakness and dyspnea (15 cases, 11.6%), (p=0.0001). The urban residency equal OR=6.42 (3.04-13.53) to rural residency for olfactory dysfunction (p=0.0001). Covid-19 patients' OR=61.25 (27.36-137.11) chance to be affected by the olfactory dysfunction in compare to control group (p=0.0001). Also, with increasing age, chance of olfactory dysfunction changed from OR=0.61(1.16-0.13) to OR=1.89 (0.82-4.33). Furthermore, female chance OR=1.21 (0.72-2.03) and employee patients was OR=2.29 (1.30-4.04) to olfactory dysfunction. Conclusion: Alf of the patients were affected by olfactory dysfunction. Furthermore, Covid-19 patients, urban residency, lower age, female and employee were the prognostic factors for olfactory dysfunction. The standard olfactory tests such as IR-SIT is suggested for screening and detecting the clients probably affected by covid-19 especially in younger ages.

The effect of radial shockwave on the median nerve pathway in patients with mild-to-moderate carpal tunnel syndrome: a randomized clinical trial.

BACKGROUND: This study aimed to evaluate the short-term effect of radial shockwave on the median nerve pathway as a new model method in patients with mild-to-moderate carpal tunnel syndrome. METHODS: In this randomized clinical trial, 60 patients were randomly allocated into three equal groups. The first group received 1500 shocks on the carpal tunnel, the second group received 1500 shocks on the carpal tunnel and median nerve pathways, and the third group was the control group. In all three groups, patients received conventional physiotherapy for ten sessions. In addition, patients in experimental groups received four sessions of radial shockwave. Pain and paresthesia intensity, sensory and motor distal latency were evaluated as primary outcomes. Boston carpal tunnel Questionnaire scores were evaluated as secondary outcomes. Evaluations were performed at baseline, 1 and 4 weeks after the end of the treatment. RESULTS: Pain and paresthesia intensity and Boston questionnaire score significantly decreased in all three groups, but the greater improvement was noted in shockwave groups. Sensory and motor distal latency were only improved in shockwave groups. In terms of clinical and electrophysiological parameters, two groups of shockwaves showed similar results. CONCLUSIONS: Radial shockwave combined with conventional physiotherapy is an effective noninvasive treatment for mild-to-moderate carpal tunnel syndrome that produces greater and longer-lasting results than conventional physiotherapy alone. There were no differences observed between utilizing radial shockwave on the carpal tunnel or median nerve pathways on the palmar surface of the hand, in terms of clinical and electrophysiological measurements. Clinical Trial registration number The study was registered at https://fa.irct.ir/user/trial/49490/view (20200706048028N1) in date of 08/24/2021.

A controlled, randomized phase II clinical trial for efficacy and safety evaluation of mannuronic acid in secondary progressive form of multiple sclerosis.

BACKGROUND: The ß-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has shown positive effects in experimental model of multiple sclerosis (MS). In this study, our aim was to assess efficacy and safety outcomes in MS treated patients with mannuronic acid compared to the conventional drug. METHODS: In a 6-month, randomized controlled, phase II trial, we enrolled patients who had secondary progressive multiple sclerosis (SPMS), were 21-54 years of age, with a score of 1-7 on the Expanded Disability Status Scale (EDSS), and who had at least one relapse in the previous 6 months. Patients were administered orally 1000 mg/day (two 500 mg/capsule daily) of M2000. Endpoints included changes in brain magnetic resonance imaging (MRI) measures and the EDSS score, as compared to the conventional drug (interferon beta-1a, interferon beta-1b). RESULTS: A total of 25 (92.5%) of the M2000 treated patients and 25 conventionally treated patients completed the study. M2000 had better performance compared to the conventional drug regarding to MRI-related measurements, however, the differences between groups were not statistically significant. M2000 decreased the disability progression over the 6-month period. The EDSS score was decreased in the M2000 treated group in the sixth month versus the conventional drug (p < 0.009). Furthermore, we did not observe any short-term side effects. CONCLUSIONS: As compared with the conventional drug, mannuronic acid (M2000) improved the rate of disability progression. This clinical trial demonstrated the efficacy and safety of mannuronic acid in patients with SPMS. (Registered Clinical Trials number, IRCT2016111313739N6).

The Effect of Adding Dry Needling to Physical Therapy in the Treatment of Cervicogenic Headache: A Randomized Controlled Trial.

OBJECTIVE: To compare the long-term effect of adding real or sham dry needling with conventional physiotherapy in cervicogenic headache. DESIGN: A randomized controlled trial. SETTING: Physiotherapy Clinic, Rouhani Hospital of Babol University of Medical Sciences, Iran. SUBJECTS: Sixty-nine patients with cervicogenic headache. METHODS: Patients were randomly assigned into a control group (n = 23) receiving conventional physical therapy; a dry needling group (n = 23) receiving conventional physical therapy and dry needling on the cervical muscles; placebo needling group (n = 23) receiving conventional physical therapy and superficial dry needling at a point away from the trigger point. The primary outcome was the headache intensity and frequency. Neck disability, deep cervical flexor performance, and range of motion were secondary outcomes. Outcomes were assessed immediately after treatment and 1, 3, and 6 months later. RESULTS: Sixty-five patients were finally included in the analysis. Headache intensity and neck disability decreased significantly more in the dry needling compared to sham and control groups after treatment and during all follow-ups. The frequency of headaches also reduced more in the dry needling than in control and sham groups, but it did not reach statistical significance. Higher cervical range of motion and enhancement of deep cervical flexors performance was also observed in the dry needling compared to sham and control groups. CONCLUSION: Dry needling has a positive effect on pain and disability reduction, cervical range of motion, and deep cervical flexor muscles performance in patients with cervicogenic headache and active trigger points, although the clinical relevance of the results was small. TRIAL REGISTRATION: The trial design was registered in the Iranian Registry of Clinical Trials (www.irct.ir, IRCT20180721040539N1) before the first patient was enrolled.

The Effects of Mannuronic Acid on IL-1ß, IL-17A, STAT1, and STAT3 Gene Expressions and TLR2 and TLR4 Molecules in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neurologic disease defined by inflammation and demyelination of the central nervous system that comes with variable degrees of axonal and neuronal damage. The efficacy of ß-D-mannuronic acid (M2000) as a novel drug with immunosuppressive properties (patented: PCT/EP2017/067920), has been shown in an experimental model of MS. In this study, the effects of M2000 on interleukin (IL)-1ß, IL-17A, signal transducer and activator of transcription (STAT) 1, and STAT3 gene expressions and Toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) molecules in patients with secondary progressive MS were evaluated. In this study, 14 patients with secondary progressive MS and 14 healthy subjects (as control group) were entered from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). The gene expressions of IL-1ß, IL-17A, STAT1, and STAT3 were assessed at the baseline and then measured after 6 months of therapy with M2000 by using the quantitative real-time polymerase chain reaction method. Moreover, the expressions of TLR2 and TLR4 molecules on peripheral blood mononuclear cells were evaluated by the flow cytometry method. The gene expressions of IL-17A, STAT1, and STAT3 in patients with MS decreased after 6 months of therapy with M2000 comparing before treatment. Also, the gene expression of IL-1ß decreased numerically after 6 months. Furthermore, the expressions of TLR2 and TLR4 on PBMCs of the patients declined when compared to baseline. The results of this investigation revealed that M2000 could downregulate IL-17, STAT1, and STAT3 genes in patients with secondary progressive MS and also reduce the expressions of TLR2 and TLR4 on PBMCs. Moreover, M2000 declined numerically IL-ß gene expression.

Verbal and oral apraxia in patients with acute stroke: Frequency, relationship, and some risk factors.

Verbal and oral apraxia are two possible consequences of stroke. It seems that there are not sufficient studies regarding the frequency of these disorders. This study aimed to evaluate the frequency of Verbal and oral apraxia. In addition, the relationship between apraxia and some variables such as age, gender, and education, as well as the relationship between types of apraxia with each other, and damaged areas of the brain in apraxia of the oral system in Persian-speaking patients with stroke were studied. In this descriptive-analytical study, 42 patients participated using the convenient sampling method. Verbal and oral apraxia were assessed using the oral and verbal apraxia tasks for adults test. Data were analyzed using independent t-test, Chi-square, and Fisher's exact test. The frequency of patients with oral apraxia was 35.7%, those with verbal apraxia was 2.3%, and the combination of both verbal and oral apraxia was 4.7%. People with apraxia were significantly older than those without apraxia. There was not any significant relationship between apraxia and gender, apraxia and education, and oral apraxia with verbal apraxia (p < 0.05). The present study's findings showed the high frequency of post-stroke apraxia and the high rate of its incidence with age.

Evaluation of Olfactory Function by Iranian Smell Diagnostic Test in Patients with Parkinson's disease in North of Iran.

INTRODUCTION: Parkinson's disease is a neurodegenerative and multisystem disorder affecting systems more than the motor system. The olfactory disorder is an early non-motor symptom of Parkinson's disease. MATERIALS AND METHODS: The present study was conducted on 110 patients aged 50-95 years with a diagnosis of Parkinson's disease referred to the Neurology Clinic of Babol University of Medical Sciences between 2018-2019. The control group consisted of 50-95-year-old non-neurological patients who were matched for age and gender with patients with Parkinson's disease. Data were collected by examination, demographic and clinical information questionnaire (duration of disease, the severity of disease, symptom index), as well as Iranian smell diagnostic test. A p-value less than 0.05 was considered statistically significant. RESULTS: The mean age scores of Parkinson's disease and control groups were obtained at 69±9 and 66±9 years, respectively. The mean duration of the disease was 5 years. Patients with Parkinson's disease scored lower on the Iranian smell test, and olfactory function was significantly reduced in the case group (P<0.001). Based on the results, olfactory function in patients with Parkinson's disease was not significantly correlated with gender, marital status, education, place of residence, and occupation(P<0.05). Only olfactory dysfunction was increased with age (P=0.01). In addition, olfactory dysfunction showed no significant relationship with severity of disease, duration of disease, and clinical index sign. Rapid Iranian smell test with a cut-off of 3.5% had a sensitivity of 87.3% and a specificity of 66.4%. CONCLUSION: According to the obtained results, olfactory dysfunction is an important non-motor and a primary symptom in patients with Parkinson's disease and is not related to the duration and severity of motor symptoms and symptom index.

Evaluation of the Effect of Mannuronic Acid as a Novel NSAID With Immunosuppressive Properties on Expression of SOCS1, SOCS3, SHIP1, and TRAF6 Genes and Serum Levels of IL-6 and TNF-α in Patients With Multiple Sclerosis.

Multiple sclerosis (MS) is described as a chronic inflammatory, demyelinating disease of the central nervous system on an autoimmune basis, which is the most frequent reason for nontraumatic disability in youth. The efficacy and safety of ß-D-nannuronic acid (M2000) as a novel immunosuppressive drug (patented PCT/EP2017/067920) has been shown in an experimental model of MS and also in a phase 2 clinical trial. The effects of M2000 on SOCS1, SOCS3, TRAF6, and SHIP1 gene expression and also serum levels of IL-6 and TNF-α in secondary progressive multiple sclerosis patients have been assessed in this study. In this study, 14 secondary progressive multiple sclerosis patients and 14 healthy subjects (as the control group) were recruited from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). Gene expression of SOCS1, SOCS3, TRAF6, and SHIP1 was measured at baseline and after 6 months of therapy with M2000 using a quantitative real-time polymerase chain reaction method. Furthermore, the serum levels of IL-6 and TNF-α were assessed by the enzyme-linked immunosorbent assay method. Our results showed that the gene expression of SOCS1, SOCS3, and SHIP1 was increased after 6 months of therapy with M2000 in MS patients. Moreover, the serum levels of IL-6 and TNF-α of patients declined compared with baseline, but this was not statistically significant. The results of this study demonstrated that M2000, with immunosuppressive properties, could upregulate SOCS1, SOCS3, and SHIP1 genes in patients with secondary progressive multiple sclerosis.

Analgesic effect of duloxetine compared to nortryptiline in patients with painful neuropathy: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Diabetic neuropathic pain (DNP) is a common complication of diabetes and has a profound effect on patients' quality of life. Therefore. The purpose of the present study was to compare the analgesic effects of duloxetine and nortryptiline in the management of patients with diabetic neuropathy. METHODS: This was a randomized, double-blind, parallel-group, placebo-controlled trial in subjects with a proven diagnosis of DM and suffered from neuropathic pain. Patients were recruited in this study from 20 February 2016 (first patient, first visit) to 22 June 2017 (last patient, last visit), including 5 weeks follow-up. A diagnosis of DNP was based on history, clinical examination, Nerve conduction velocity and Diabetic neuropathy symptom score (more than one point). RESULTS: Both drugs reduced pain when compared with placebo. A significant VAS reduction from 6.4 at baseline to 3.75 at endpoint was observed in the duloxetine group. However, there was no significant difference in the efficacy between nortriptyline and duloxetine based on patient's visual analogue scale (VAS) (p>0.05). No clinically significant changes or serious adverse events were found among treatment groups including changes in vital signs, laboratory assessments, physical examination or electrocardiograms. The decrease in the mean pain intensity was significantly greater in the duloxetine and nortriptyline group compared to the placebo group both in the primary analysis and in the by-visit analysis (p<0.003). CONCLUSION: The present study demonstrates the safety and effectiveness of both duloxetine and nortriptyline in the management of DNP.