Cognitive orientation to daily occupational performance approach in people with multiple sclerosis: A pilot study.

BACKGROUND: Multiple sclerosis is the most important cause of non-injury-related disability in young adults. The disease has unknown causes and distresses and affects daily activities. While therapeutic interventions mainly focus on body function and structure to reduce impairment, Cognitive Orientation to Daily Occupational Performance (CO-OP) is a cognitive approach that provides intervention at the level of activity and participation. PURPOSE: We aim to examine the effects of CO-OP approach on fatigue, quality of life, occupational performance, and satisfaction in people living with multiple sclerosis; and to examine whether they could transfer strategies and skills learned during CO-OP to untrained goals. METHODS: A pre-post design was used. Assessment tools included Montreal Cognitive Assessment, Multiple Sclerosis Impact Scale, Fatigue Impact Scale and the Canadian Occupational Performance Measure. Six individuals living with multiple sclerosis participated in 10 CO-OP sessions twice a week. The sessions were held in an environment of the participants' choice, along with an extra session added to determine the goals. The study was registered in the ethics committee of University of Social Welfare and Rehabilitation Sciences (IR.USWR.REC.1399.089). RESULTS: The performance improved (2-point positive change) in 12 out of 18 trained goals and in three out of six untrained goals (self-report). The improvement was maintained at a 3-month follow-up assessment. There was a statistically significant difference in Canadian Occupational Performance Measure (χ2  = 11.565, p = 0.003 same for performance and satisfaction scores), Fatigue Impact Scale (χ2  = 7.000, p = 0.030), and Multiple Sclerosis Impact Scale scores over time (χ2  = 9.478, p = 0.009) respectively. CONCLUSION: The CO-OP approach has the potential to improve daily activity performance, reduce pain, and improve the quality of life for people living with multiple sclerosis. A definitive randomised controlled trial is required.

TH17/IL23 cytokine gene polymorphisms in bullous pemphigoid.

BACKGROUND: TH17/IL-23 immune axis is considered to be involved in the pathogenesis of autoimmune and chronic inflammatory diseases. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease, characterized by the presence of autoantibodies against the components of the dermal-epidermal junction. Animal studies and characterization of patient samples point toward a contribution of TH17 cells in BP pathogenesis. However, genetic polymorphisms in the genes of TH17/IL-23 cytokines have not yet been well investigated in BP. METHODS: Detection of polymorphisms in IL-17A (rs2275913 and rs3819025), IL-17F (rs2397084 and rs763780), IL-17RA (rs2229151), and IL-23R (rs2201841, rs7530511, rs11209026, and rs10889677) genes were performed following the collection of blood samples and DNA extraction from BP patients and controls. Gene expression of IL-23R was determined by quantitative RT-PCR analysis. RESULTS: The prevalence of IL-23R rs7530511 genotypes and alleles, as well as IL-23R rs2201841 alleles, is significantly different between the BP patients and controls. While the minor C-allele of IL-23R rs7530511 is highly present in the patients, the G-allele distribution of IL-23R rs2201841 is significantly more prevalent in the control individuals compared to the BP patients. Genotypes and alleles of other SNPs in IL-17A, IL-17F, and IL-17RA were similarly distributed in patients and controls. CONCLUSIONS: No alteration was found in the gene expression between wild and polymorphic genotypes of IL-23R (rs2201841 and rs7530511) variations, indicating they do not contribute to altering the levels of gene expression in blood. In summary, our data show that the alleles of two SNPs in IL-23R rs2201841 and rs7530511 are associated with BP.

Single-nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine.

Pemphigus vulgaris (PV) is a rare autoimmune blistering disorder, which could affect both skin and mucosal surfaces. There is increasing evidence that genetics plays a critical role in PV development, severity and prognosis. Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people and have been widely evaluated in most diseases. However, there are few studies regarding the roles of SNPs in the PV. Here, we reviewed both pathogenic and protective roles of the SNPs in non-HLA genes regarding the PV. Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population-specific manner. Moreover, SNPs in glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, including rs11745958, rs17209237, rs33388, rs7701443 as well as rs116855232 at NUDT15, seem to be associated with therapeutic outcomes in PV patients. Additionally, variations in the other genes involved in the drugs' metabolisms, pharmacokinetics and pharmacodynamics such as rs396991 in FCGR3A gene could be used for the prediction of clinical response to drugs and side effects. Taken together, SNPs seem to be valuable tools for better management of PV patients. Further studies need to be conducted to evaluate SNPs in genes that control immune responses and apoptosis.

Cognitive orientation to daily occupational performance approach in adults with neurological conditions: A scoping review.

Background: The Cognitive Orientation to daily Occupational Performance (CO-OP) approach, top-down, client-centered and goal-oriented approach originally developed for children with Developmental Coordination Disorder (DCD) in 2001 and since used in other populations and settings. The purpose of this scoping review was to examine the extent (number) and nature (features and characteristics) of the literature on CO-OP in adult's populations. Methods: In this scoping review, 8 online databases were searched up to April 2018 to identify articles that addressed CO-OP in adult's populations. The articles were selected based on inclusion and exclusion criteria. Two raters reviewed all documents independently. Articles were categorized according to diagnosis. Results: Fifteen studies were identified. To examine application and effectiveness of CO-OP in adult's populations we included individuals with chronic stroke (>6 months post-stroke; n=7), with TBI (n=3), with acute stroke (<6 months post-stroke; n=4) and the older adult populations comprised those with self-reported cognitive difficulties but no diagnosis of dementia, depression, or cognitive impairment (n=1). In all cases, CO-OP showed to be useful and efficient. Conclusion: CO-OP has been applied in TBI, stroke and age-related executive changes appropriately. The results have shown that CO-OP efficiently improved performance and satisfaction in trained and not trained client chosen goals.

The Effect of Filial Therapy on Depressive Symptoms of Children with Cancer and Their Mother's Depression, Anxiety, and Stress: A Randomized Controlled Trial.

BACKGROUND: Childhood cancer is an overwhelming life event that can completely change the lives of the sufferers and their parents. Todays, advances of medical science have shifted the fetal nature of childhood cancer to chronic one exposing children and their family to behavioral and psychosocial problems. The aim of this study was to investigate the effect of filial therapy on children's depressive symptoms and their mother's stress, anxiety, and depression. MATERIALS AND METHODS: In this randomized controlled trial, 32 mothers with their children who suffered from cancer were recruited (16 in each group). During a 10-week training sessions, filial therapy group underwent child-parent relation therapy (CPRT). Training sessions were held once a week. Control group received no training and only individual counseling sessions were held for them we needed. Both groups were assessed before and after the intervention using depression, anxiety, and stress questionnaire-21 (DASS-21), children depression inventory (CDI), and Wong-Baker faces pain rating scale (WBFPRS). Sample randomization and data analysis were conducted by using SPSS (version 20) and running independent t-test and chi-square test. P value< 0.05 was set as the significant level. RESULTS: Mothers in the filial therapy group experienced significant decrease in their level of depression, anxiety, and stress in the posttest (p < 0.001). In contrast to filial therapy group, mothers in the control group did not show an improvement in their level of depression, anxiety, and stress. Moreover, the results of the current investigative showed that depression of children in the filial therapy group significantly reduced at post-test (p < 0.001). On the other hand, the mean of children's depression in the control group remained steady. CONCLUSION: The findings of the present study revealed that using filial therapy could reduce the depression of children with cancer and their parent's depression, anxiety, and stress. Accordingly, we suggest filial therapy programs as a routine for addressing psychosocial problems of children with cancer and their families.

Structural analysis of missense mutations in galactokinase 1 (GALK1) leading to galactosemia type-2.

Galactosemia type 2 is an autosomal recessive disorder characterized by the deficiency of galactokinase (GALK) enzyme due to missense mutations in GALK1 gene, which is associated with various manifestations such as hyper galactosemia and formation of cataracts. GALK enzyme catalyzes the adenosine triphosphate (ATP)-dependent phosphorylation of α-d-galactose to galactose-1-phosphate. We searched 4 different literature databases (Google Scholar, PubMed, PubMed Central, and Science Direct) and 3 gene-variant databases (Online Mendelian Inheritance in Man, Human Gene Mutation Database, and UniProt) to collect all the reported missense mutations associated with GALK deficiency. Our search strategy yielded 32 missense mutations. We used several computational tools (pathogenicity and stability, biophysical characterization, and physiochemical analyses) to prioritize the most significant mutations for further analyses. On the basis of the pathogenicity and stability predictions, 3 mutations (P28T, A198V, and L139P) were chosen to be tested further for physicochemical characterization, molecular docking, and simulation analyses. Molecular docking analysis revealed a decrease in interaction between the protein and ATP in all the 3 mutations, and molecular dynamic simulations of 50 ns showed a loss of stability and compactness in the mutant proteins. As the next step, comparative physicochemical changes of the native and the mutant proteins were carried out using essential dynamics. Overall, P28T and A198V were predicted to alter the structure and function of GALK protein when compared to the mutant L139P. This study demonstrates the power of computational analysis in variant classification and interpretation and provides a platform for developing targeted therapeutics.

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

BACKGROUND: TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. OBJECTIVES: In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. METHODS: Genomic DNA was extracted from the blood of the patients with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. RESULTS: No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. CONCLUSIONS: TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is contributed to altering the levels of gene expression in BP disease.