Cognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?

INTRODUCTION Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). The severity of disability in people with MS (PwMS) is generally measured with the Expanded Disability Status Scale (EDSS). A variant of MS known as 'benign MS' (BMS) has been defined as an EDSS score of 3 or lower, combined with a disease duration of 10 years or longer; however, there is disagreement in the field about whether BMS really exists. Given that the EDSS does not capture cognitive issues, communication dysfunction, fatigue, depression, or anxiety properly, its ability to accurately represent disability in all PwMS, including BMS, remains questionable. METHODS In this study, 141 persons with BMS (PwBMS) were included, consisting of 115 females (82%) and 26 males (18%) with a mean age of 50.8 (±8.68). A computerized test battery (NeuroTrax®) was used to assess cognition, covering seven cognitive domains (memory, executive function, visual-spatial processing, verbal function, attention, information processing, and motor skills). Fatigue was measured using the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was used to assess symptoms of depression. Cognitive impairment was defined for this study as when someone has a score lower than 85 in at least two subdomains of the cognitive test battery. Rates of impairment were compared to 158 persons with non-benign MS (PwNBMS; with a disease duration of 10 years and longer and an EDSS score higher than 3) and 487 PwMS with a disease duration of fewer than 10 years. RESULTS Cognitive impairment was found in 38% of PwBMS and in 66% of PwNBMS (p<0.001). In PwBMS, the lowest rate of impairment was found in the verbal function domain (18%) and the highest rate of impairment in the domain of information processing (32%). Fatigue and depression were found in 78% and 55% of all PwBMS, with no difference in these rates between PwBMS and PwNBMS (p = 0.787 and p = 0.316 resp.) CONCLUSION: Cognitive impairment, fatigue and depression are common among people with an EDSS-based definition of benign MS. These aspects should be incorporated into a new and better definition of truly benign MS

Resilience, resistance, infrapolitics and enmeshment

A great deal has been written in the International Relations literature about the role of resilience in our social world. One of the central debates in the scholarship concerns the relationship between resilience and resistance, which several scholars consider to be one of mutual exclusivity. For many theorists, an individual or a society can either be resilient or resistant, but not both. In this article, we argue that this understanding of the resilience–resistance connection suffers from three interrelated problems: it treats resilience and resistance as binary concepts rather than processes; it presents a simplistic conception of resilient subjects as apolitical subjects; and it eschews the ‘transformability’ aspect of resilience. In a bid to resolve these issues, the article advocates for the usefulness of a relational approach to the processes of resilience and resistance, and suggests an approach that understands resilience and resistance as engaged in mutual assistance rather than mutual exclusion. The case of the Palestinian national liberation movement illustrates our set of arguments

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

1q jumping translocation as a biomarker in myeloid malignancy: frequently mutated genes associated with bad prognosis and low survival

Abstract 1q jumping translocation (JT) is rare and its molecular profiles in myeloid malignancies are not well-known. This study evaluated gene mutations in 1q-JT cohorts (0.38%) from hematological malignant specimens that underwent genetic analysis at the Johns Hopkins Hospital (n = 11,908) and the MD Anderson Cancer Center. 1q-JT had frequent mutations in eleven genes, most of which are associated with worse prognosis. BCOR mutations significantly co-occurred with others. Patients tended to have mutations in DNA-repair, spliceosome, and epigenetic modification pathways, though genes utilized within each of these pathways were not randomly distributed. Multi-, albeit overlapping, pathway interruptions tended to manifest in mutations of two gene sets. One gene set consisted of SF3B1 (spliceosome) and TET2 (epigenetic modification), while the other consisted of STAG2 (DNA repair), SRSF2, U2AF (spliceosome), ASXL1, KMT2D (epigenetic modification), BCOR, and GATA2 (transcription factors). An “intermediate” JT-like rearrangement may represent an early sign of occurring 1q-JT. Treatments (hypomethylating agents) and unique structures of the short arms of acrocentric chromosomes may contribute to 1q-JT formation in myeloid malignancies. The median overall survival after identification of a JT was 10 months (95% confidence interval, 5–15 months). Our cohort represents the largest number of myeloid malignancies from multi-centers with before and after the 1q-JT event analyzed to date. Overall, this study identified specific molecular profiles that are associated with 1q-JT in myeloid malignancies. 1q-JT could serve as a poor prognosis biomarker in myeloid malignancies, which could be important in making well-informed clinical decisions and treatment strategies