Trajectories of Symbol Digit Modalities Test performance in individuals with multiple sclerosis.

BACKGROUND: Although cognitive problems have been identified in people with multiple sclerosis (PwMS), few studies have investigated the long-term change in cognitive functioning. OBJECTIVE: To identify trajectories of change in cognitive functioning for PwMS. METHODS: Participants enrolled in the quality-of-life subgroup from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) were eligible for our analysis. In 2006, participants in this group began to complete the Symbol Digit Modalities Test (SDMT) annually. Latent trajectory models were used to identify groups of participants with similar longitudinal change in SDMT scores. Linear and quadratic trajectory models were fit, and the models were compared. Latent trajectory models were also fit adjusting for baseline age and disease duration as well as using normalized SDMT scores. The groups identified across the approaches were compared. RESULTS: We found that classes with higher-than-average baseline values improved, classes with average baseline values remained relatively constant, and classes with lower baseline values experienced cognitive worsening. Similar results were observed in the alternative latent trajectory models accounting for other variables. CONCLUSION: Our models show that subjects with higher SDMT scores at baseline showed improvement, while subjects with lower SDMT scores at baseline showed worsening. Baseline age and disease duration were also associated with SDMT performance.

Phylogeography and population genetics of the cryptic bonnethead shark Sphyrna aff. tiburo in Brazil and the Caribbean inferred from mtDNA markers.

Resolving the identity, phylogeny and distribution of cryptic species within species complexes is an essential precursor to management. The bonnethead shark, Sphyrna tiburo, is a small coastal shark distributed in the Western Atlantic from North Carolina (U.S.A.) to southern Brazil. Genetic analyses based on mitochondrial markers revealed that bonnethead sharks comprise a species complex with at least two lineages in the Northwestern Atlantic and the Caribbean (S. tiburo and Sphyrna aff. tiburo, respectively). The phylogeographic and phylogenetic analysis of two mitochondrial markers [control region (mtCR) and cytochrome oxidase I (COI)] showed that bonnethead sharks from southeastern Brazil correspond to S. aff. tiburo, extending the distribution of this cryptic species >5000 km. Bonnethead shark populations are only managed in the U.S.A. and in the 2000s were considered to be regionally extinct or collapsed in southeast Brazil. The results indicate that there is significant genetic differentiation between S. aff. tiburo from Brazil and other populations from the Caribbean (ΦST  = 0.9053, P < 0.000), which means that collapsed populations in the former are unlikely to be replenished from Caribbean immigration. The species identity of bonnethead sharks in the Southwest Atlantic and their relationship to North Atlantic and Caribbean populations still remains unresolved. Taxonomic revision and further sampling are required to reevaluate the status of the bonnethead shark complex through its distribution range.

Food allergies are associated with increased disease activity in multiple sclerosis.

OBJECTIVE: The association between allergy and multiple sclerosis (MS) is still unclear. In our study, we assessed the association between a self-reported history of allergic conditions with MS clinical and MRI disease activity. METHODS: A subset of 1349 patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) study completed a self-administered questionnaire on environmental, food and drug allergies. Patients were distributed among four allergy groups: (1) environmental, (2) food, (3) drug, (4) no known allergies (NKA). Clinical (number of attacks, expanded disability status scale (EDSS), MS severity score (MSSS)) and radiological variables (presence of gadolinium-enhancing lesions and lesion count), and their associations with the different allergy groups or those with NKA, were assessed. RESULTS: The food allergy group had a 1.38 times higher rate for cumulative number of attacks compared with the NKA group (P=0.0062); this difference remained significant in the adjusted analysis (relapse rate ratio 1.27, P=0.0305). The food allergy group showed more than twice the likelihood (OR 2.53, P=0.0096) of having gadolinium-enhancing lesions on MRI. The environmental and drug allergy groups did not show significant differences when compared with the NKA group. The EDSS and MSSS were not affected by any type of allergy. CONCLUSIONS: MS patients with food allergy had more relapses and a higher likelihood of gadolinium-enhancing lesions compared with patients with no known allergy. Future prospective studies are needed to confirm our findings and investigate underlying biological mechanisms, which may unveil new therapeutic and preventative strategies for MS.

Assessment of computer adaptive testing version of the Neuro-QOL for people with multiple sclerosis.

BACKGROUND: To date, the computerized adaptive testing (CAT) version of the Neuro-quality of life (QOL) has not been assessed in a large sample of people with multiple sclerosis (MS). OBJECTIVE: The aim of this study was to assess the associations between the CAT version of Neuro-QOL and other clinical and patient-reported outcome measures. METHODS: Subjects (n = 364) enrolled in SysteMS completed the CAT version of the Neuro-QOL and the 36-Item Short Form Survey (SF-36) within 4 weeks of a clinical exam that included the Multiple Sclerosis Functional Composite-4 (MSFC-4). The correlations between the Neuro-QOL domains and the MSFC-4 subscores and the SF-36 scores were calculated. The changes over time in the Neuro-QOL and other measures were also examined. RESULTS: The lower extremity functioning score of the Neuro-QOL showed the highest correlations with MSFC-4 components including Timed 25-Foot Walk, 9-Hole Peg Test, and cognitive score. The expected domains of the Neuro-QOL showed high correlations with the SF-36 subscores, and some Neuro-QOL domains were associated with many SF-36 subscores. There was limited longitudinal change on the Neuro-QOL domains over 12 months, and the change was not associated with change on other measures. CONCLUSION: The CAT version of the Neuro-QOL shows many of the expected associations with clinical and patient-reported outcome measures.

The Role of NRAMP1/SLC11A1 Gene Variant D543N (1730G/A) in the Genetic Susceptibility to Develop Rheumatoid Arthritis in the Mexican Mestizo population.

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease whose cause has not been fully elucidated. However, genetic factors seem to have an important role in its pathogenesis. OBJECTIVE: We analyzed the possible association between rheumatoid arthritis and variants of the SLC11A1 gene, which encodes for NRAMP1, a protein involved in the activation of phagocytes and synthesis of proinflammatory cytokines. METHODS: In a case-control study in a Mexican Mestizo population, blood samples from 188 patients with rheumatoid arthritis and 133 healthy individuals were obtained to determine the frequency of SLC11A1 gene variants INT4 (469+14G/C or rs3731865), D543N (1730G/A or rs17235409) and 3'UTR (1729+55del4 or rs17235416) by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found similar frequencies of INT4 and 3'UTR polymorphisms in patients and controls (p = 0.18 and 0.89, respectively). In contrast, a significantly lower frequency of the D543N polymorphism was observed in patients with rheumatoid arthritis compared to controls (p corrected = 0.016; OR: 0.48; 95% CI: 0.28-0.80). CONCLUSION: Our data suggest that the D543N variant of SLC11A1 gene has a protective effect in the development of rheumatoid arthritis, an interesting finding that has not been previously reported in any population.

Assessing the ecological effects of human impacts on coral reefs in Bocas del Toro, Panama.

Environmental and biological reef monitoring was conducted in Almirante Bay (Bahía Almirante) in Bocas del Toro, Panama, to assess impacts from anthropogenic developments. An integrated monitoring investigated how seasonal temperature stress, turbidity, eutrophication and physical impacts threatened reef health and biodiversity throughout the region. Environmental parameters such as total suspended solids [TSS], carbon isotopes (δ(13)C), C/N ratios, chlorophyll a, irradiance, secchi depth, size fractions of the sediments and isotope composition of dissolved inorganic carbon [DIC] of the water were measured throughout the years 2010 and 2011 and were analysed in order to identify different impact sources. Compared to data from Collin et al. (Smithsonian Contributions to the Marine Sciences 38:324-334, 2009) chlorophyll a has doubled at sites close to the city and the port Almirante (from 0.46-0.49 to 0.78-0.97 µg l(-1)) and suspension load increased, visible by a decrease in secchi depth values. Visibility decreased from 9-13 m down to 4 m at the bay inlet Boca del Drago, which is strongly exposed to river run off and dredging for the shipping traffic. Eutrophication and turbidity levels seemed to be the determining factor for the loss of hard coral diversity, most significant at chlorophyll a levels higher than 0.5 µg l(-1) and TSS levels higher than 4.7 mg l(-1). Hard coral cover within the bay has also declined, at some sites down to <10 % with extremely low diversities (7 hard coral species). The hard coral species Porites furcata dominated the reefs in highly impacted areas and showed a strong recovery after bleaching and a higher tolerance to turbidity and eutrophication compared to other hard coral species in the bay. Serious overfishing was detected in the region by a lack of adult and carnivorous fish species, such as grunts, snappers and groupers. Study sites less impacted by anthropogenic activities and/or those with local protection showed a higher hard coral cover and fish abundance; however, an overall loss of hard coral diversity was observed.

Characterizing Bacillus globigii as a Bacillus anthracis surrogate for wastewater treatment studies and bioaerosol emissions.

This study characterized Bacillus globigii (BG) as a Bacillus anthracis Sterne (BAS) surrogate for wastewater treatment-related studies of UV inactivation, adsorption onto powdered activated carbon (PAC), and bioaerosol emission. The inactivation of BG was faster than that of BAS in DI water (pseudo first-order rate constants of 0.065 and 0.016 min-1 respectively) and in PBS solution (0.030 and 0.005 min-1 respectively). BG was also removed more quickly than BAS by PAC adsorption in DI (0.07 and 0.05 min-1 respectively) and in PBS (0.09 and 0.04 min-1 respectively). In DI, BG aggregated more (P < 0.05) than BAS when the pH was 7 or greater but there were no statistically significant differences in NaCl solution. Spore aggregation was also studied with extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) models. Less than 1% of all spores were released as bioaerosols, and there was no significant difference (P > 0.05) in emission between BG and BAS. To the author's knowledge, this study is the first to demonstrate that BG is a suitable surrogate for BAS for bioaerosol emissions, but a poor surrogate for both UV inactivation and PAC adsorption. These results can be used to understand the ability of BAS to act as a surrogate for BA Ames because of its genetic and morphological similarities with BAS.

Plasmid Carrying bla CTX-M-15, bla PER-1, and bla TEM-1 Genes in Citrobacter spp. From Regional Hospital in Mexico.

INTRODUCTION: Citrobacter spp. is an opportunistic bacteria that have been recognized as significant pathogens in patients with underlying diseases or immunocompromised status. The aim of this study was to identify extended-spectrum ß-lactamases in clinical isolates of Citrobacter spp. METHODS: This cross-sectional study was conducted at Hospital Central "Dr. Ignacio Morones Prieto" in San Luis Potosi, Mexico. Nineteen isolates of Citrobacter spp. were obtained from clinical specimens between April to December 2015. Four isolates were resistant to third-generation cephalosporins. The presence of genes encoding ESBL (bla CTX-M-15, bla TEM-1, bla VEB-1, bla SHV, and bla PER-1) was analyzed by PCR. For this purpose, plasmid DNA was extracted and horizontally transferred to recipient E. coli Top 10. RESULTS: bla CTX-M-15 and bla VEB-1 genes were detected in Citrobacter freundii and Citrobacter sedlakii, whereas bla PER-1 gene was identified in 1 isolate of Citrobacter freundii. In contrast, bla SHV gene was not detected in any isolate. One strain carried bla CTX-M-15, bla TEM-1, bla VEB-1, and bla PER-1 genes, most in a 275-kb plasmid. CONCLUSION: This study shows the presence of different types of ESBL in clinical isolates of Citrobacter freundii and Citrobacter sedlakii, which confer resistance to broad-spectrum ß-lactams. The plasmid identified in this study harboring ESBL genes could play an important role in the dissemination of antibiotic resistance.

Altered adipokine levels are associated with dimethyl fumarate treatment in multiple sclerosis patients.

BACKGROUND: Obesity is linked to increased risk of multiple sclerosis (MS) and worsening disease severity. Recent experimental and clinical data indicates that adipokines are involved in regulating immune response and serve as cross talk between immune and neural system. Dimethyl fumarate (DMF) is an oral MS medication with unknown mechanism of action. It upregulates the nuclear factor E2-related factor 2 (Nrf2) pathway, a pathway for adipocyte differentiation. To determine a possible relationship between treatment with dimethyl fumarate, serum adipokine profiles and treatment response in patients with MS, we conducted an observational cohort study and measured serum adipokine and Vitamin D levels before and after treatment with DMF and examined their association with treatment response. METHODS: We identified patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study who were treated with dimethyl fumarate and had available serum samples. Longitudinal pre-treatment and on-treatment samples were available in 23 patients. Cross-sectional on-treatment samples were available in 91 patients, who were classified into DMF responders and non-responders based on radiologic and clinical relapse activity or disability progression. We measured serum leptin, adiponectin, resistin, ghrelin, fatty acid binding protein-4 (FABP-4) and-5 (FABP-5), vitamins D2 and D3. Statistical analysis was performed with paired t-tests, Wilcoxon signed-rank and Mann-Whitney U tests. RESULTS: After treatment with DMF, serum adiponectin levels significantly increased, whereas FABP-4 levels significantly decreased compared to baseline levels, without a statistically significant change in the patients' BMI. Ghrelin levels were insignificantly lower post-treatment. FABP-4 levels were significantly higher in DMF responders compared to non-responders. This effect was sex-specific, with higher FABP4 levels associated with treatment response in males, but not females. CONCLUSION: DMF treatment is associated with significant changes in serum adipokine levels, primarily adiponectin and FABP-4. Sex may affect the association between FABP-4 and treatment response.

Obesity is associated with the Optic Neuritis severity in Male patients with Multiple Sclerosis.

BACKGROUND: Obesity is an important modifiable risk factor of MS; a deeper biological understanding of this association is needed. OBJECTIVE: To evaluate the determinants of acute optic neuritis (AON) severity and recovery in multiple sclerosis (MS). METHODS: We included 61 patients with MS with recorded AON severity and recovery according to visual acuity outcomes before, at, and, after the relapse. We measured body mass index (BMI) and the serum concentration of estrogen, leptin, testosterone, sex hormone-binding globulin, and vitamin D. We tested the association between BMI and serum hormones and AON severity and recovery with logistic regressions. RESULTS: In males, moderate/severe AON was associated with higher BMI (31.26 kg/m2 vs 25.73 kg/m2, logistic regression, p= 0.03), higher serum estrogen levels (32.24 nmol/L vs 23.06 nmol/L, logistic regression, p=0.04), and higher serum leptin levels (12.29 ng/mL vs mild AON: 4.1 ng/mL, logistic regression, p=0.06) than mild AON. These observations were not seen in female patients. We did not find an association with BMI or hormone levels and AON recovery. CONCLUSION: BMI, serum leptin, and serum estrogen were associated with AON severity in male patients but not in female patients. No association of these factors and AON recovery was observed.

Comparison of health-related quality of life across treatment groups in individuals with multiple sclerosis.

BACKGROUND: Outcome measures typically used to evaluate disease modifying therapies (DMTs) provide important information regarding their effects on disease activity, but they do not capture the full impact of living with multiple sclerosis (MS). Patient reported outcome measures (PROs) are increasingly being used to capture an individual's subjective experience of disease. We compared DMTs across a wide range of PRO outcomes in individuals with MS. METHODS: Subjects enrolled in SysteMS completed the computer adaptive testing version of the Neuro-QoL within four weeks of a clinical neurological exam. Neuro-QoL measures included the following 11 health-related quality of life (HRQOL) domains: Ability to participate in Social Roles and Activities, Anxiety, Cognitive Function, Depression, Emotional and Behavioral Dyscontrol, Fatigue, Lower Extremity Function (mobility), Positive Affect and Wellbeing, Satisfaction with Social Roles and Activities, Stigma, and Upper Extremity Function (fine motor). Treatments were grouped based on the three main modes of delivery: injectable, oral and infusion. The three treatment groups were compared using linear regression adjusting for two sets of covariates (set 1: age, sex, disease duration and EDSS; set 2: age, sex, disease duration, EDSS and treatment duration). We also compared the individual treatments using linear regression. RESULTS: After adjusting for the first set of clinical and demographic features of MS, there was a difference between treatment groups for Upper Extremity Function and Stigma. Subjects using injectable treatments reported better functioning in terms of Upper Extremity Function and Stigma than subjects using infusion treatments. In addition, subjects using injectable treatments reported better Upper Extremity Function than subjects treated with oral DMTs. When all individual treatments were compared, interferon-treated subjects reported significantly better functioning in terms of Stigma than natalizumab treated subjects. When further adjusting for time on treatment, the group differences were attenuated and no longer statistically significant. CONCLUSION: We examined differences between MS treatment groups across a wide range of HRQOL outcomes. The results suggest that overall there are few differences between treatments on the physical, cognitive and emotional dimensions of well-being.

Temporal association of sNfL and gad-enhancing lesions in multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is an autoimmune demyelinating disorder, which is characterized by relapses and remissions. Serum neurofilament light chain (sNfL) is an emerging biomarker of disease activity but its clinical use is still limited. In this study, we aim to characterize the temporal association between sNfL and new clinical relapses and new gadolinium-enhancing (Gd+) lesions. METHODS: Annual sNfL levels were measured with a single-molecule array (SIMOA) assay in 94 patients with MS enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) study. We used a multivariable linear mixed-effects model to test the temporal association of sNfL with clinical relapses and/or new Gd+ lesions. We adjusted this model for age, disease duration, sex, and disease-modifying therapies (DMTs) use. RESULTS: In the 3 months after a Gd+ lesion, we observed an average 35% elevation in sNfL (P < 0.0001) compared to remission samples. We also observed an average 32.3% elevation in sNfL at the time of or prior to a Gd+ lesion (P = 0.002) compared to remission. We observed a significant elevation in sNfL after a clinical relapse only when associated with a Gd+ lesion. INTERPRETATION: Our findings support sNfL as a marker of clinical relapses and Gd+ lesions. sNfL peaks in a 3-month window around Gd+ lesions. sNfL shows promise as a biomarker of neurological inflammation and possibly of simultaneous Gd+ lesions during a clinical relapse.

Conservation genetics of the bonnethead shark Sphyrna tiburo in Bocas del Toro, Panama: Preliminary evidence of a unique stock.

The bonnethead shark, Sphyrna tiburo, is a small elasmobranch distributed in the Eastern Pacific from southern California to Ecuador, and along the Western Atlantic, with preferences for continental margins of North, Central and South America, the Gulf of Mexico, and the Caribbean. Recent studies have suggested that it could be under a process of cryptic speciation, with the possibility to find different species in similar geographic locations. Here we assessed the population structure and genetic diversity of this highly philopatric and non-dispersive species in the Bocas del Toro Archipelago, Panama. Fragments of the mitochondrial genes cytochrome oxidase I and control region, were used to test the genetic structure of adult and juvenile S. tiburo in this area, and were compared with other locations of the Western Atlantic and Belize. We found significant genetic differentiation between Caribbean bonnethead sharks from Bocas del Toro and Belize, when compared to bonnetheads from other locations of the Western Atlantic. These results also suggest that Bocas del Toro could constitute a different genetic population unit for this species, whereby bonnethead sharks in this area could belong to a unique stock. The information obtained in this study could improve our understanding of the population dynamics of the bonnethead shark throughout its distribution range, and may be used as a baseline for future conservation initiatives for coastal sharks in Central America, a poorly studied an often overlooked region for shark conservation and research.

Discontinuation of disease-modifying therapy for patients with relapsing-remitting multiple sclerosis: Effect on clinical and MRI outcomes.

BACKGROUND: Disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) have been shown to reduce relapses and new MRI lesions. However, few studies have assessed the impact of discontinuing DMT after a period of disease inactivity. OBJECTIVE: To investigate the impact of DMT discontinuation on clinical and radiological outcomes in RRMS patients. METHODS: 69 RRMS patients who discontinued DMT after a period of disease inactivity were identified from the Comprehensive Longitudinal Investigation of MS study at the Brigham and Women's Hospital, based on the following inclusion criteria: age 18 or older; treated with DMT ≥2 years; no clinical and radiological relapse ≥2 years until the discontinuation; not restarting DMT for ≥6 months after discontinuation. Patients matched by age, gender, treatment, treatment duration, disease duration and Expanded Disability Status Scale score who remained on DMT were identified. Univariate and multivariable Cox proportional hazard models with robust standard errors to account for the paired data were used to test the differences based on DMT discontinuation with the outcome measures: time to clinical relapse, MRI event, disability progression, and disease activity (either clinical relapse or MRI event). RESULTS: Based on the 69 pairs of patients, discontinuation was not associated with time to clinical relapse (HR = 0.87, 95% CI = 0.44-1.72, p = 0.69), MRI event (HR = 0.95, 95% CI = 0.57 to 1.59, p = 0.84), disability progression (HR = 1.24, 95% CI = 0.61 to 2.53, p = 0.55) and disease activity (HR = 0.89, 95% CI = 0.56 to 1.42, p = 0.62). When we performed subgroup analysis to compare the impact of DMT discontinuation between older (age > 45) and younger (age ≤ 45) patients, we found a significant difference in the association between young and old for time to MRI event (p = 0.012) and time to new disease activity (p = 0.0005). CONCLUSIONS: This study found that patients who discontinued treatment after a period of disease inactivity had a similar time to next event compared to subjects who remained on first-generation DMTs. In our cohort, we found that discontinuation after age 45 was associated with a stable disease course, while patients younger than age 45 who discontinued treatment were more likely to experience a new clinical relapse or MRI event.

Cross-sectional study of smoking exposure: no differential effect on OCT metrics in a cohort of MS patients.

BACKGROUND: Optical coherence tomography (OCT) provides quantitative measures of retinal layer thickness. Cigarette smoking is a risk factor for multiple sclerosis (MS) onset and disease severity: its effects on OCT metrics have not been assessed. OBJECTIVE: The objective of this study was to assess the effect of smoking history on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform (GCIP) of MS patients by OCT. METHODS: 112 MS patients were recruited from the Brigham and Women's Hospital. Spectralis OCT scans were acquired to measure GCIP, peripapillary RNFL, and total macular volume. Multivariable linear mixed effects regression model assessed RNFL and GCIP change with fixed effects for smoking history while adjusting for optic neuritis eye status, age, disease duration, sex, baseline EDSS, and disease modifying therapies (DMTs). RESULTS: Smoking histories were available for 102 patients: 46 (45.10%) had a history of smoking cigarettes and 56 (54.90%) never smoked. No statistically significant differences were found between ever-smokers and never-smokers with respect to GCIP, RNFL, and macular volume. CONCLUSION: Our study shows no significant difference in retinal thickness between ever-smokers and never-smokers. If confirmed, this result suggests mechanistic differences between the retina and other central nervous system (CNS) compartments in response to smoking and should be noted when considering OCT as a surrogate measure of CNS activity.

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis.

Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.

Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis.

OBJECTIVE: To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS). METHODS: We identified patients in our center's Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study enrolled within 5 years of disease onset, and with annual blood samples up to 10 years (n = 122). Serum NfL was measured using a single molecule array (SIMOA) assay. An automated pipeline quantified brain T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) from year 10 high-resolution 3T MRI scans. Correlations between averaged annual NfL and 10-year clinical/MRI outcomes were assessed using Spearman's correlation, univariate, and multivariate linear regression models. RESULTS: Averaged annual NfL values were negatively associated with year 10 BPF, which included averaged year 1-5 NfL values (unadjusted P < 0.01; adjusted analysis P < 0.01), and averaged values through year 10. Linear regression analyses of averaged annual NfL values showed multiple associations with T2LV, specifically averaged year 1-5 NfL (unadjusted P < 0.01; adjusted analysis P < 0.01). Approximately 15-20% of the BPF variance and T2LV could be predicted from early averaged annual NfL levels. Also, averaged annual NfL levels with fatigue score worsening between years 1 and 10 showed statistically significant associations. However, averaged NfL measurements were not associated with year 10 EDSS, SDMT or T25FW in this cohort. INTERPRETATION: Serum NfL measured during the first few years after the clinical onset of MS contributed to the prediction of 10-year MRI brain lesion load and atrophy.

Soluble Fms-Like Tyrosine Kinase-1 Alters Cellular Metabolism and Mitochondrial Bioenergetics in Preeclampsia.

Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1). sFlt-1 effects are mediated in part by decreasing VEGF signaling. The direct effects of sFlt-1 on cellular metabolism and bioenergetics in preeclampsia, have not been established. The goal of this study was to evaluate whether sFlt-1 causes mitochondrial dysfunction leading to disruption of normal functioning in endothelial and placental cells in preeclampsia. Endothelial cells (ECs) and first-trimester trophoblast (HTR-8/SVneo) were treated with serum from preeclamptic women rich in sFlt-1 or with the recombinant protein. sFlt-1, dose-dependently inhibited ECs respiration and acidification rates indicating a metabolic phenotype switch enhancing glycolytic flux. HTR-8/SVneo displayed a strong basal glycolytic metabolism, remaining less sensitive to sFlt-1-induced mitochondrial impairment. Moreover, results obtained in ECs exposed to serum from preeclamptic subjects demonstrated that increased sFlt-1 leads to metabolic perturbations accountable for mitochondrial dysfunction observed in preeclampsia. sFlt-1 exacerbated mitochondrial reactive oxygen species (ROS) formation and mitochondrial membrane potential dissipation in ECs and trophoblasts exposed to serum from preeclamptic women. Forcing oxidative metabolism by culturing cells in galactose media, further sensitized cells to sFlt-1. This approach let us establish that sFlt-1 targets mitochondrial function in ECs. Effects of sFlt-1 on HTR-8/SVneo cells metabolism were amplified in galactose, demonstrating that sFlt-1 only target cells that rely mainly on oxidative metabolism. Together, our results establish the early metabolic perturbations induced by sFlt-1 and the resulting endothelial and mitochondrial dysfunction in preeclampsia.

Seguridad alimentaria y fortificación de alimentos a base de pulpa de café en tiempos pandémicos

Introducción: la pandemia de COVID-19 originó pérdidas humanas, tensiones en la atención médica, la economía y otros sistemas sociales. Objetivo: recopilar información sobre seguridad alimentaria y fortificación de alimentos a base de pulpa de café considerando que una buena nutrición contrarresta las infecciones. Metodología: se analizó literatura en las bases SciELO y SCOPUS restringiendo términos de búsqueda a: seguridad alimentaria, COVID-19, tecnología de bloques o blockchain, suministro alimenticio, micronutrientes, regulación, fortificación con hierro con énfasis en productos a base de pulpa de café. Resultados: en tiempos de pandemia y otros desastres, uno de los factores que afectan la respuesta de un huésped al virus es la nutrición, la seguridad alimentaria es importante especialmente en países con altas tasas de desnutrición y anemia, por ende, es fundamental la fortificación de alimentos comunes para contribuir en garantizar la adecuación nutricional como parte de las respuestas de los gobiernos, especialmente en áreas rurales y urbanas empobrecidas, planteándose sistemas de suministro de alimentos con la tecnología de bloques o blockchain. Conclusión: la fortificación de productos alimenticios a base de pulpa de café y el suministro que aplique tecnología de bloques podría ser una estrategia de respuesta a las consecuencias de la pandemia

SUMMARY Introduction: The COVID-19 pandemic caused human losses, tensions in medical care, the economy and other social systems. Objective: To collect information on food safety and fortification of foods based on coffee pulp, considering that good nutrition counteracts infections. Methodology: Literature in SciELO and SCOPUS bases was analyzed, restricting search terms to food safety, COVID-19, block chain technology, food supply, micronutrients, regulation, iron fortification with emphasis on coffee pulp-based products. Results: In times of pandemic and other disasters, one of the factors that affect the response of a host to the virus is nutrition. The importance of food security is recognized with proposals especially in countries with high rates of malnutrition and anemia, for the fortification of common foods to contribute to guaranteeing nutritional adequacy as part of the governments' responses, especially in impoverished rural and urban areas, considering food supply systems with block or Block Chain technology. Conclusion: The fortification of food products based on coffee pulp and their supply using block chain could be a response strategy to the consequences of the pandemic.

Introdução: a pandemia de COVID-19 causou perdas humanas, tensões na assistência médica, na economia e em outros sistemas sociais. Objetivo: coletar informações sobre segurança alimentar e fortificação de alimentos à base de polpa de café, considerando que uma boa nutrição combate infecções. Metodologia: a literatura foi analisada nas bases de dados SciELO e SCOPUS, restringindo os termos de busca a: segurança alimentar, COVID-19, tecnologia de bloco ou blockchain, abastecimento de alimentos, micronutrientes, regulação, fortificação de ferro com ênfase em produtos à base de polpa de café. Resultados: em tempos de pandemia e outros desastres, um dos fatores que afeta a resposta de um hospedeiro ao vírus é a nutrição, a segurança alimentar é importante principalmente em países com altos índices de desnutrição e anemia, portanto, a fortificação é essencial dos alimentos comuns para ajudar a garantir a adequação nutricional como parte das respostas governamentais, especialmente em áreas rurais e urbanas empobrecidas, considerando sistemas de abastecimento de alimentos com tecnologia block ou blockchain. Conclusão: a fortificação de produtos alimentícios à base de polpa de café e abastecimento aplicando tecnologia de blocos pode ser uma estratégia de resposta às consequências da pandemia.