Perceived discrimination in patients with multiple sclerosis and depressive symptomatology.

BACKGROUND: Multiple Sclerosis is the central nervous system's most common demyelinating disease and the second leading cause of neurological disability in young adults. Its natural development involves physical and cognitive impairment. Patients commonly perceive discrimination against them, regardless of its occurrence, accepting it as an inherent part of the disease. OBJECTIVE: This study aimed to determine the association between perceived discrimination and the depressive symptoms and physical disability present in patients diagnosed with multiple sclerosis, treated at the Demyelinating Diseases Clinic of the National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez. METHODS: A cross-sectional study was conducted in 98 patients diagnosed with multiple sclerosis. Demographic and clinical variables were obtained through clinical interviews. The severity of the disease was determined using the Extended Disability Status Scale (EDSS), depressive symptoms were assessed with the Beck Depression Inventory (BDI), and perceived discrimination was rated using the King Internalized Stigma Scale. RESULTS: The studied sample's mean age was 36.3 years, schooling 13.6 years, symptoms onset was at 26.2 years (with a delay in diagnosis of 3.2 years), and a disease evolution of 10.9 years. 71.4% were single; 52% had an unpaid work activity and 57.1% were women. The EDSS average was 3.5 points; 24.5% presented moderate to severe depressive symptoms and 53.1% referred perceived discrimination. CONCLUSIONS: Perceived discrimination in patients with multiple sclerosis was associated with earlier disease onset, depressive symptoms, and the lack of caregivers. Medical care and life quality improvement for this vulnerable group require greater education regarding the disease and the establishment of patient support programs.

Molecular dynamics simulations reveal structural differences among wild-type NPC1 protein and its mutant forms.

NPC1 is a 25-exon gene located on the long arm of chromosome 18q11.2 and encodes NPC1, a transmembrane protein comprising 1278 amino acid residues. Mutations in the NPC1 gene can cause Niemann-Pick disease type C (NP-C), a rare autosomal-recessive neurovisceral disease. We assessed mutant protein folding using computer-based molecular dynamics (MD) simulations and molecular docking of the three most common NPC1 mutations, all of which result in changes in a cysteine-rich luminal loop region of the protein: a) I1061T is the most commonly detected variant in patients with NP-C worldwide; b) P1007A is the second most common variant, frequently detected in Portuguese, British and German patients; c) G992W occurs most often in patients of Acadian descent. Analyses of molecular structural information and related cellular physiological processes revealed that mutant NPC1 proteins exhibited altered function despite being far from the N-terminal domain cholesterol binding. MD simulations revealed that mutant I1061T protein shows remarkable instability in comparison the WT and also de other mutants, and interestingly this mutant has been identified as the most common variant. In the case of the mutant P1007A, it is presumed that this substitution promotes larger structural changes than proline due to their greater hydrophobic properties.Structural changes related to the G992W mutation may affect the physicochemical space of G992W variant protein because tryptophan induces hydrophobic interactions. Cholesterol docking studies focused on binding recognition showed differences in the binding positions of variants versus the wild-type protein that go some way to explaining the molecular pathogenesis.Communicated by Ramaswamy H. Sarma.

Quality of life in patients with multiple sclerosis and its association with depressive symptoms and physical disability.

OBJECTIVE: The aim of this work was to evaluate the quality of life of patients with multiple sclerosis and its association with depressive symptoms and physical health. METHOD: A total of 117 patients clinically diagnosed with Multiple Sclerosis (MS) were studied. The MSQOL-54 scale was applied. The depressive symptoms were assessed using the Beck Depression Inventory (BDI), while degree of physical disability was evaluated with the EDSS (Expanded Disability Status Scale). The results of these last two instruments were associated with MSQOL-54 to determine its influence on the perception of quality of life. RESULTS: We evaluated 65 women (56%) and 52 men (44%), with a mean age of 35 years, a mean age of 27 years at the time of diagnosis, and a mean evolution of 8 years. 88% of the patients showed the relapsing-remitting subtype; 42% had paid employment; 29% of the studied patients required help to perform daily activities; 75% took disease-modifying medications. They obtained on average a score of 3.62 ±â€¯2.30 on the EDSS and 11.5 ±â€¯9.21 on the BDI. The general average in MSQOL-54 was 64.67 ±â€¯17.52. CONCLUSIONS: Quality of life, in patients with multiple sclerosis is an issue that worries health personnel, it is essential to implement strategies for reducing the impact of the disease on patients' lives, mainly through the application of programs aimed to decrees depression and improve social support.

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Transduction by phage P1CM clr-100 in Salmonella typhimurium.

Phage P1 does not adsorb to S. typhinurium wild type cells. It does adsorb to rough derivatives including strains with mutations in the galE gene. Phage strain P1CM clr-100 can be efficiently propagated in S. typhimurium derivatives, either by induction of a lysogene, or by lytic infection. Phage P1 lysates are able to mobilize genetic markers in a generalized fashion. The transduction system is essentially identical to that in Escherichia coli, except that CaCl2 is not required for efficient adsorption. Two regions of the S. typhimurium chromosome were mapped by P1-mediated transduction. Several examples of genes linked by P1, and unlinked by P22, are presented. The relative efficiency of P1 over P22 in transduction was not determined, however. Data presented indicate unambigously that the gene order for the trp region is: his ... dad A-hem A-trp-pyrF ... pyrC but known markers in between were not used. The gene order for the cys A region was determined to be as follows: pheA ... purC-cys A-trz A-pts-dsd-aro D-purF ... his, and special mapping problems for this region are discussed.