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1.
J Neurol Sci ; : 117229, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33243431

RESUMO

Neurofilament light chain (NfL) is an emerging biomarker of neural degeneration. NfL is an integral component of axons and is released into the bloodstream and cerebrospinal fluid during neurodegeneration; hence it can be used to monitor disease progression. Given that several neurological disorders are accompanied by cognitive decline, recent literature has investigated the relationship between NfL levels and cognition. The objective of this scoping review was to determine whether a consistent relationship between NfL and cognition exists in the context of variable degrees of neurodegeneration present across several neurological disorders. Four electronic databases were searched for relevant articles and 160 articles were initially identified. After article screening, 37 studies met the final inclusion criteria. Studies were then qualitatively synthesized to determine the relationship between NfL and cognition across a variety of neurological disorders. The large majority of studies found that NfL levels are inversely correlated with cognition, such that higher NfL levels are associated with poorer cognition. This relationship was not universal, however, and this discrepancy was speculated to be due to the nature of the neurological disorder, individual differences between participants, or methodological inconsistencies. Further study is required, and associated recommendations were proposed for the design of future investigations.

2.
J Ultrasound Med ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098581

RESUMO

The Sound Judgment Series consists of invited articles highlighting the clinical value of using ultrasound first in specific clinical diagnoses where ultrasound has shown comparative or superior value. The series is meant to serve as an educational tool for medical and sonography students and clinical practitioners and may help integrate ultrasound into clinical practice.

3.
Womens Health Issues ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32972809

RESUMO

INTRODUCTION: Although previous studies have found a relationship between having a preterm birth and maternal depression, methodologic issues may have limited the generalizability of results. Thus, the purpose of this study was to evaluate the relationship between having a preterm birth and postpartum depressive symptoms using a large, population-based sample of U.S. women. METHODS: This secondary data analysis used 2012-2014 U.S. Pregnancy Risk Assessment Monitoring System data (N = 89,366). Data on the exposure, preterm birth, were obtained from birth certificates. Infants born at 32 to less than 37 weeks' gestation were considered moderate to late preterm, infants born at 28 to less than 32 full weeks' gestation were considered very preterm, and infant born at less than 28 full weeks' gestation were considered extremely preterm. To assess the outcome, two Pregnancy Risk Assessment Monitoring System questions measuring postpartum depressive symptoms were used. Logistic regression was used to calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: After adjustment for confounders, the relationship between having a preterm birth and maternal hopelessness was statistically significant for those who had very preterm and extremely preterm births (moderate to late preterm OR, 1.19; 95% CI, 1.00-1.42; very preterm OR, 1.28; 95% CI, 1.04-1.58; extremely preterm OR, 1.81; 95% CI, 1.31-2.49). In addition, after adjustment, findings indicated no association between preterm birth and maternal loss of interest (extremely preterm OR, 0.85 95% CI, 0.60-1.19; very preterm OR, 1.04; 95% CI, 0.86-1.26; preterm OR, 0.95; 95% CI, 0.82-1.10). CONCLUSIONS: Given the statistically significant increased association between having a preterm birth and postpartum depressive symptoms, health professionals may consider implementing comprehensive screening for depression and other mental illnesses among women who give birth prematurely. Findings may also inform future interventions to emphasize the importance of postpartum care among women who have experienced preterm birth.

4.
Front Immunol ; 11: 1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655562

RESUMO

The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is a heterotrimeric AB2 toxin capable of inducing cell cycle arrest and apoptosis in lymphocytes and other cell types. Recently, we have demonstrated that human macrophages are resistant to Cdt-induced apoptosis but are susceptible to toxin-induced pro-inflammatory cytokine response involving activation of the NLRP3 inflammasome. Exposure to Cdt results in binding to the cell surface followed by internalization and translocation of the active subunit, CdtB, to intracellular compartments. Internalization involves hijacking of retrograde pathways; treatment of cells with Retro-2 leads to a decrease in CdtB-Golgi association. These events are dependent upon toxin binding to cholesterol in the context of lipid rich membrane microdomains often referred to as lipid rafts. We now demonstrate that within 1 h of exposure of macrophages to Cdt, CdtB is internalized and found primarily within lipid rafts; concurrently, cellugyrin (synaptogyrin-2) also translocates into lipid rafts. Further analysis by immunoprecipitation indicates that CdtB associates with complexes containing both cellugyrin and Derlin-2. Moreover, a human macrophage cell line deficient in cellugyrin expression (THP-1Cg-) challenged with Cdt failed to internalize CdtB and was resistant to the Cdt-induced pro-inflammatory response. We propose that lipid rafts along with cellugyrin play a critical role in the internalization and translocation of CdtB to critical intracellular target sites in human macrophages. These studies provide the first evidence that cellugyrin is expressed in human macrophages and plays a critical role in Cdt toxicity of these cells.

5.
Eur Urol ; 78(4): 494-497, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32532514

RESUMO

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97-5.57; hazard ratio = 2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23-72%) by the age of 75 yr and 78% (95% CI 54-94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. PATIENT SUMMARY: In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene.

6.
Ann Clin Transl Neurol ; 7(5): 767-775, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32304358

RESUMO

OBJECTIVE: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. METHODS: Sera were collected from 22 MS patients pre- and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. RESULTS: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). INTERPRETATION: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

7.
Cell Microbiol ; 22(7): e13194, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32068949

RESUMO

Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. We have previously demonstrated that the Aggregatibacter actinomycetemcomitans Cdt induces a pro-inflammatory response from human macrophages which involves activation of the NLRP3 inflammasome. We now demonstrate that in addition to activating caspase-1 (canonical inflammasome), Cdt treatment leads to caspase-4 activation and involvement of the noncanonical inflammasome. Cdt-treated cells exhibit pyroptosis characterised by cleavage of gasdermin-D (GSDMD), release of HMGB1 at 24 hr and LDH at 48 hr. Inhibition of either the canonical (caspase-1) or noncanonical (caspase-4) inflammasome blocks both Cdt-induced release of IL-1ß and induction of pyroptosis. Analysis of upstream events indicates that Cdt induces Syk phosphorylation (activation); furthermore, blockade of Syk expression and inhibition of pSyk activity inhibit both Cdt-induced cytokine release and pyroptosis. Finally, we demonstrate that increases in pSyk are dependent upon Cdt-induced activation of GSK3ß. These studies advance our understanding of Cdt function and provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as A. actinomycetemcomitans.

8.
Pathogens ; 9(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906446

RESUMO

The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) induces lymphocytes to undergo cell-cycle arrest and apoptosis; toxicity is dependent upon the active Cdt subunit, CdtB. We now demonstrate that p21CIP1/WAF1 is critical to Cdt-induced apoptosis. Cdt induces increases in the levels of p21CIP1/WAF1 in lymphoid cell lines, Jurkat and MyLa, and in primary human lymphocytes. These increases were dependent upon CdtB's ability to function as a phosphatidylinositol (PI) 3,4,5-triphosphate (PIP3) phosphatase. It is noteworthy that Cdt-induced increases in the levels of p21CIP1/WAF1 were accompanied by a significant decline in the levels of phosphorylated p21CIP1/WAF1. The significance of Cdt-induced p21CIP1/WAF1 increase was assessed by preventing these changes with a two-pronged approach; pre-incubation with the novel p21CIP1/WAF1 inhibitor, UC2288, and development of a p21CIP1/WAF1-deficient cell line (Jurkatp21-) using clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 gene editing. UC2288 blocked toxin-induced increases in p21CIP1/WAF1, and JurkatWT cells treated with this inhibitor exhibited reduced susceptibility to Cdt-induced apoptosis. Likewise, Jurkatp21- cells failed to undergo toxin-induced apoptosis. The linkage between Cdt, p21CIP1/WAF1, and apoptosis was further established by demonstrating that Cdt-induced increases in levels of the pro-apoptotic proteins Bid, Bax, and Bak were dependent upon p21CIP1/WAF1 as these changes were not observed in Jurkatp21- cells. Finally, we determined that the p21CIP1/WAF1 increases were dependent upon toxin-induced increases in the level and activity of the chaperone heat shock protein (HSP) 90. We propose that p21CIP1/WAF1 plays a key pro-apoptotic role in mediating Cdt-induced toxicity.

9.
Brain Imaging Behav ; 14(6): 2417-2428, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31468375

RESUMO

Cognitive fatigability (CF) can be defined as an inability to maintain performance throughout a sustained cognitive task. Individuals with multiple sclerosis (MS) are more susceptible to CF than healthy controls (HCs); however, the neural correlates underlying CF are still under investigation. Arterial spin labeling (ASL) perfusion imaging provides a non-invasive method of objectively quantifying cerebral blood flow (CBF) during sustained attention tasks. To date, no study has yet evaluated CF in MS using this methodology. 10 MS and 10 HCs completed a 20-min psychomotor vigilance task (PVT). CF was evaluated by dividing the PVT into quintiles and examining performance from the 1st to the last. Mean reaction times (RTs) and number of lapses were recorded. Global and regional CBF changes were evaluated throughout the PVT as well as during pre- and post-task rest. Increased susceptibility to CF was noted in the MS group. Distinct patterns of CBF activation were observed in areas comprising fronto-parietal, cortico-striatal, cerebellar, and basal ganglia regions; however, when and how these regions were engaged differed between the MS and HC groups. In particular, dysfunction in CBF to the middle frontal gyrus may underlie the CF effects observed. In addition, individuals with MS appear to struggle with "switching off" regions of the attentional network at rest following sustained cognitive effort. Findings support the use of ASL as an appropriate methodology for evaluating CF in MS with an overall pattern of attentional network dysfunction being observed. Objectively quantifying CF in this manner can help validate patients' subjective complaints.

10.
Eur Urol ; 77(1): 24-35, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495749

RESUMO

BACKGROUND: BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies. OBJECTIVE: To estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods. RESULTS AND LIMITATIONS: Sixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99-6.61) and absolute PCa risk of 27% (95% CI 17-41%) and 60% (95% CI 43-78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43-3.88); the corresponding SIR at age <65 yr was 3.57 (95% CI 1.68-7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risk for BRCA2 carriers increased with family history (HR per affected relative 1.68, 95% CI 0.99-2.85). BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI 1.07-5.64) compared to population incidences, corresponding to lower PCa risk (HR 0.37, 95% CI 0.14-0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR 5.07, 95% CI 3.20-8.02) than Gleason score ≤6 PCa (SIR 3.03, 95% CI 1.24-7.44), and a higher risk of death from PCa (SMR 3.85, 95% CI 1.44-10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses. CONCLUSIONS: The results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers. PATIENT SUMMARY: In this study we followed unaffected men known to carry mutations in the BRCA1 and BRCA2 genes to investigate whether they are at higher risk of developing prostate cancer compared to the general population. We found that carriers of BRCA2 mutations have a high risk of developing prostate cancer, particularly more aggressive prostate cancer, and that this risk varies by family history of prostate cancer and the location of the mutation within the gene.

11.
J Med Genet ; 57(4): 226-236, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31719169

RESUMO

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

12.
Cancer Epidemiol Biomarkers Prev ; 29(2): 368-378, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792088

RESUMO

BACKGROUND: Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer, but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high breast cancer risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with breast cancer risk is essential. METHODS: Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers and 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers and 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models. RESULTS: For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with breast cancer risk, except smoking for more than 5 years before a first full-term pregnancy (FFTP) when compared with parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HRR) was 1.19 [95% confidence interval (CI), 1.02-1.39] and the HR from prospective analysis (HRP) was 1.36 (95% CI, 0.99-1.87). For BRCA2 mutation carriers, smoking for more than 5 years before an FFTP showed an association of a similar magnitude, but the confidence limits were wider (HRR = 1.25; 95% CI, 1.01-1.55 and HRP = 1.30; 95% CI, 0.83-2.01). For both carrier groups, alcohol consumption was not associated with breast cancer risk. CONCLUSIONS: The finding that smoking during the prereproductive years increases breast cancer risk for mutation carriers warrants further investigation. IMPACT: This is the largest prospective study of BRCA mutation carriers to assess these important risk factors.

13.
J Physician Assist Educ ; 30(4): 207-213, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31664008

RESUMO

Opioid addiction has become a national epidemic. Morbidity and mortality from prescription and synthetic opioid use and abuse have increased at an alarming rate in recent years. Ensuring that physician assistant (PA) graduates have the knowledge to become safe prescribers of medications, including opiates, is a goal of PA training programs. Achieving that goal requires fostering PA student competence regarding current issues in pain control, drug use and misuse, polypharmacy, diversion, self-medication, and substance use disorder. We present a public health approach to addressing that need. Our approach involved developing consensus among the 9 PA programs in Massachusetts concerning the adoption and implementation of statewide, graduate core competencies for the prevention and management of prescription drug misuse. The process implemented in Massachusetts could be used as a model in other states and might be relevant to addressing other public health crises. We present the adopted competencies as well as individual PA programs' curricular approaches.


Assuntos
Analgésicos Opioides/uso terapêutico , Competência Clínica , Prescrições de Medicamentos/normas , Assistentes Médicos/normas , Humanos , Massachusetts , Assistentes Médicos/educação
14.
Neurol Ther ; 8(2): 251-271, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586303

RESUMO

INTRODUCTION: Although fatigue is a well-studied concept in neurological disease, cognitive fatigability (CF) is less understood. While most studies measure fatigue using subjective self-report, fewer have measured CF objectively. Given the negative impact of CF on quality-of-life, there is a need for targeted interventions. The objective of this review was to determine which procedural, behavioural and pharmacological treatments for objectively measured CF are available to people living with neurological conditions. METHODS: In accordance with the PRISMA guidelines, systematic searches for randomized control trials (RCTs), case-controlled studies and case reports/series were conducted across the Ovid Medline, PsycInfo, EMBASE and Cochrane Library databases. English-language articles published between 1980 and February 2019 were considered for eligibility. Included were those that objectively measured CF in individuals with neurological disease/disorder/dysfunction between the ages of 18 and 65 years. Studies were reviewed using a modified Cochrane Data Extraction Template. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review process was facilitated using Covidence software (www.covidence.org). Two authors reviewed articles independently, with a third resolving conflicts regarding article inclusion. RESULTS: The search identified 450 records. After duplicates were removed and remaining titles/abstracts were screened for eligibility, 28 full-text articles were assessed, and two studies were included in the qualitative synthesis. Studies were a priori divided into those with pharmacological, procedural or behavioural interventions. Two studies met eligibility criteria; both of these included participants with multiple sclerosis. One study utilized a procedural intervention (i.e. transcranial direct current stimulation), while the other utilized a pharmacological intervention (i.e. fampridine-SR). Studies were evaluated for risk of bias, and evidence from both eligible studies was discussed. CONCLUSION: Despite the positive results of the procedural intervention, the paucity of eligible studies and the nascent nature of the field suggests that more studies are required before firm conclusions can be drawn regarding the amenability of CF to treatment. TRIAL REGISTRATION: The review was registered with PROSPERO (CRD42019118706).

15.
Evol Appl ; 12(7): 1305-1317, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31417616

RESUMO

Understanding the extent to which captivity generates maladaptation in wild species can inform species recovery programs and elucidate wild population responses to novel environmental change. Although rarely quantified, effective population size (N e ) and genetic diversity should influence the magnitude of plastic and genetic changes manifested in captivity that reduce wild fitness. Sexually dimorphic traits might also mediate consequences of captivity. To evaluate these relationships, we generated >600 full- and half-sibling families from nine wild brook trout populations, reared them for one generation under common, captive environmental conditions and contrasted several fitness-related traits in wild versus captive lines. We found substantial variation in lifetime success (lifetime survival and reproductive success) and life history traits among wild populations after just one captive generation (fourteen- and threefold ranges across populations, respectively). Populations with lower heterozygosity showed lower captive lifetime success, suggesting that captivity generates maladaptation within one generation. Greater male-biased mortality in captivity occurred in populations having disproportionately higher growth rates in males than females. Wild population N e and allelic diversity had little or no influence on captive trait expression and lifetime success. Our results have four conservation implications: (i) Trait values and lifetime success were highly variable across populations following one generation of captivity. (ii) Maladaptation induced by captive breeding might be particularly intense for the very populations practitioners are most interested in conserving, such as those with low heterozygosity. (iii) Maladaptive sex differences in captivity might be associated with population-dependent growth costs of reproduction. (iv) Heterozygosity can be a good indicator of short-term, intraspecific responses to novel environmental change.

16.
Int J MS Care ; 21(6): 243-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31889928

RESUMO

Background: People with multiple sclerosis (MS) are at increased risk for cognitive impairment, mental health concerns, and psychosocial issues, which can negatively affect disease outcomes and quality of life. Current MS care guidelines recommend integrated interdisciplinary services to address these concerns; however, issues can be overlooked during routine care. To date, there is inadequate research on how often these issues are identified and addressed during routine MS care. Methods: One hundred medical records were randomly selected and reviewed (55 relapsing-remitting MS, 17 secondary progressive MS, 8 primary progressive MS, and 20 other or subtype not indicated). All visits to, and contacts with (ie, telephone, e-mail), an MS clinic over 1 year were included in the analysis to determine the proportion of patients presenting with cognitive, mental health, and psychosocial concerns and the proportion of patients offered associated services. Results: Of the 25 patients with at least one identified concern, treatment recommendations occurred for 13 (52%). Rates of identification of cognitive, mental health, and psychosocial concerns in standard clinical practice were significantly lower than the identified prevalence in epidemiologic studies. Demographic factors had no bearing on who was offered treatment. Patients with concerns access MS clinic services more often than those without. Conclusions: Discrepancies between reported and expected frequencies may be due to overreliance on patient self-disclosure and concerns by the health care team that inadequate resources are available to address issues. An interdisciplinary team model may help address these issues.

17.
Arch Clin Neuropsychol ; 34(1): 31-38, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29471423

RESUMO

Objective: Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The present study examined the interrelatedness of disease severity, fatigue, depression, and sleep quality in order to evaluate their predictive roles of CF in MS. Four theoretical models examining these variables were assessed. Methods: Fifty-eight individuals with a diagnosis of MS were recruited. CF was measured by examining last third versus first third performance on the Paced Auditory Serial Addition Test (PASAT). The PASAT and self-report measures of fatigue, depression, and sleep quality were administered. Path analysis was used to evaluate each of the models. Results: CF was correlated only with depression (r = .362, p = .006) and sleep quality (r = .433, p = .001). Sleep quality was the greatest significant independent predictor of CF (ß = .433, t(1,55) = 3.53, p < .001), accounting for 17.3% of the total variance. The best fitting model showed sleep quality as the largest contributor to CF; however, depression played a smaller predictive role. Furthermore, depression emerged as the strongest predictor of sleep quality and fatigue. Disease severity weakly predicted depression. Conclusions: Sleep quality is the most significant predictor of CF in MS. As such, sleep quality may be a treatable cause of CF. Sleep quality itself, however, accounted for only 17.3% of the variance in CF suggesting that other variables which were not formally assessed in this sample (e.g., anxiety, etc.) may also play a predictive role. Follow-up studies should evaluate how results may differ with a larger sample size.


Assuntos
Cognição/fisiologia , Fadiga Mental/complicações , Esclerose Múltipla/complicações , Ansiedade/complicações , Ansiedade/psicologia , Depressão/complicações , Depressão/psicologia , Seguimentos , Humanos , Fadiga Mental/psicologia , Modelos Teóricos , Esclerose Múltipla/psicologia , Testes Neuropsicológicos
18.
Can J Neurol Sci ; 45(5): 580-582, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30234464

RESUMO

Multiple sclerosis (MS) is a chronic, progressive, autoimmune, neurodegenerative disorder that can interfere with physical and psychological functioning, negatively affecting health-related quality of life (HRQoL). Fostering mindfulness may mitigate the negative consequences of MS on HRQoL. The relationship between mindfulness, mood and MS-related quality of life was investigated. In total, 52 individuals with MS completed questionnaires to examine the relationship between trait mindfulness and wellness. Higher levels of trait mindfulness were associated with better HRQoL, lower depression and anxiety, lower fatigue impact and fewer perceived cognitive deficits. Mindfulness interventions have the potential to enhance wellness in those living with MS.


Assuntos
Conscientização , Atenção Plena , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Qualidade de Vida/psicologia , Adulto , Transtornos Cognitivos/etiologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Dor/etiologia , Inquéritos e Questionários
19.
Int J MS Care ; 20(4): 173-179, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30150901

RESUMO

Background: Up to 70% of people with multiple sclerosis (MS) experience cognitive impairment. Some remain cognitively intact despite advanced disease. Cognitive reserve (CR) theory postulates that individuals with higher levels of intellectual enrichment can tolerate more pathology than others before exhibiting cognitive impairment. Methods: Thirty-two individuals with early-phase relapsing-remitting MS with mild physical disability and disease duration less than 10 years and 32 controls were recruited. At baseline and after 3 years, participants completed neuropsychological tests evaluating several cognitive domains. The CR was assessed via a cognitive reserve index (CRI) using educational levels and North American Adult Reading Test scores. Change in cognition was assessed using a reliable change index. Results: At baseline, people with MS performed worse than controls on visual memory. There were no significant group differences on information processing speed, learning, language, and executive functions. Most cognitive domains showed no change over time, and CRI was not a significant predictor in the regression model. Conclusions: People with MS performed worse on memory tasks at baseline compared with controls. Cognitive change differed between people with MS and controls in executive functions. Although people with MS and controls improved over time, beyond practice effects, people with MS improved less than controls. Overall, no cognitive deterioration was noted over time, and CR did not predict change in cognition. Sample homogeneity in terms of disease stage and CR may explain these findings.

20.
Regul Toxicol Pharmacol ; 97: 24-32, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29885342

RESUMO

Medical device biocompatibility testing is used to evaluate the risk of adverse effects on tissues from exposure to leachates/extracts. A battery of tests is typically recommended in accordance with regulatory standards to determine if the device is biocompatible. In vitro cytotoxicity, a key element of the standards, is a required endpoint for all types of medical devices. Each validated cytotoxicity method has different methodology and acceptance criteria that could influence the selection of a specific test. In addition, some guidances are more specific than others as to the recommended test methods. For example, the International Organization for Standardization (ISO1) cites preference for quantitative methods (e.g., tetrazolium (MTT/XTT), neutral red (NR), or colony formation assays (CFA)) over qualitative methods (e.g., elution, agar overlay/diffusion, or direct), while a recent ISO standard for contact lens/lens care solutions specifically requires a qualitative direct test. Qualitative methods are described in United States Pharmacopeia (USP) while quantitative CFAs are listed in Japan guidance. The aim of this review is to compare the methodologies such as test article preparation, test conditions, and criteria for six cytotoxicity methods recommended in regulatory standards in order to inform decisions on which method(s) to select during the medical device safety evaluation.


Assuntos
Materiais Biocompatíveis/farmacologia , Segurança de Equipamentos , Teste de Materiais , Animais , Sobrevivência Celular/efeitos dos fármacos , Humanos
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