The search for the genetic foundation of multiple sclerosis (MS) severity remains elusive. It is, in fact, controversial whether MS severity is a stable feature that predicts future disability progression. If MS severity is not stable, it is unlikely that genotype decisively determines disability progression. An alternative explanation tested here is that the apparent instability of MS severity is caused by inaccuracies of its current measurement. We applied statistical learning techniques to a 902 patient-years longitudinal cohort of MS patients, divided into training (n = 133) and validation (n = 68) sub-cohorts, to test four hypotheses: (1) there is intra-individual stability in the rate of accumulation of MS-related disability, which is also influenced by extrinsic factors. (2) Previous results from observational studies are negatively affected by the insensitive nature of the Expanded Disability Status Scale (EDSS). The EDSS-based MS Severity Score (MSSS) is further disadvantaged by the inability to reliably measure MS onset and, consequently, disease duration (DD). (3) Replacing EDSS with a sensitive scale, i.e., Combinatorial Weight-Adjusted Disability Score (CombiWISE), and substituting age for DD will significantly improve predictions of future accumulation of disability. (4) Adjusting measured disability for the efficacy of administered therapies and other relevant external features will further strengthen predictions of future MS course. The result is a MS disease severity scale (MS-DSS) derived by conceptual advancements of MSSS and a statistical learning method called gradient boosting machines (GBM). MS-DSS greatly outperforms MSSS and the recently developed Age Related MS Severity Score in predicting future disability progression. In an independent validation cohort, MS-DSS measured at the first clinic visit correlated significantly with subsequent therapy-adjusted progression slopes (r = 0.5448, p = 1.56e−06) measured by CombiWISE. To facilitate widespread use of MS-DSS, we developed a free, interactive web application that calculates all aspects of MS-DSS and its contributing scales from user-provided raw data. MS-DSS represents a much-needed tool for genotype-phenotype correlations, for identifying biological processes that underlie MS progression, and for aiding therapeutic decisions.

Evidence is presented for the existence of a soluble heterotetramer containing the low and middle molecular weight neurofilament (NF) proteins, NF-L and NF-M, and one containing the low and high molecular weight proteins, NF-L and NF-H, and for their role in filament assembly. When a mixture of either pair of proteins was renatured in 2 M urea, 20 mM Tris, pH 7.2, a new band representing a complex was observed in native gel electrophoresis. No new band was observed with a mixture of NF-M and NF-H. Two-dimensional gel electrophoresis showed that treatment of the complexes with SDS caused them to dissociate into their constituent polypeptide chains. Native neurofilaments dissociated in 2 M urea into a mixture of LM and LH complexes. Titration of NF-L with NF-M indicated that complex formation was complete at an approximately equimolar ratio of the two proteins. The LM complex had a sedimentation coefficient, s20,w, of 4.4 S, consistent with a tetrameric structure. Dialysis of a solution of the LM complex against 50 mM 4-morpholineethanesulfonic acid, 0.17 M NaCl, pH 6.25, led to the formation of 10-nm filaments in good yield. These results suggest that NF protein heterooligomers are intermediates in NF assembly and disassembly.

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Vietnam’s forests have experienced a notable transformation over the past 20 years from net deforestation to reforestation and expanding forests. Continued reforestation that aims to achieve further economic and environmental benefits remains a national priority and strategy. We explore the current status of plantation forests and highlight possible means to facilitate their expansion in the uplands of Vietnam. We employ mixed method triangulation to empirically explore plantation forests and their economic role in household livelihood, to quantify trade-offs between plantation forests and shifting cultivation, and to assess the constraints on plantation forest expansion in Nghe An province, north-central Vietnam. Results show that forest in the study area expanded by 406,000 ha (71.1%) between 1990 and 2016. Plantation forests increased by nearly 500% (from 32,000 ha to 190,000 ha), while natural forests expanded by 48.1% (from 538,000 ha to 797,000 ha). Plantation forests contributed an average of 35.1 percent of total household income in wealthier households and 27.9 percent of income in poor households. Switching from shifting cultivation to plantation forests would increase total household income and average carbon stock but decrease food provision. Total Economic Value would be higher for plantation forest scenarios if increased carbon stocks in plantations can be monetized. This carbon income might drive conversion of shifting cultivation to plantation forests. Constraints on further expansion of plantation forest are low external cooperation, education, market stability, and agroforestry extension services. Our empirical results inform national plantation forest development, sustainable upland livelihood development, and climate change mitigation programs to ultimately facilitate forest transition and improve the resilience and sustainability of socio-ecological systems.

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Background Arthritis and joint pain are highly prevalent in agricultural (ag) workers. Many ag operations are sustained by a small number of workers, and the disability of even one worker thus contributes to economic hardship. This study investigated associations between joint health in Montana ag workers and economic well-being and work capacity. Methods This observational mixed-methods study utilized quantitative survey data and qualitative focus group data. 299 ranchers and farmers in 9 Montana counties completed either an online or paper survey that included participant demographics, joint symptoms, history of arthritis and arthritis type, financial status, work capacity, and the need to rely on others to complete one’s work. The Western Ontario and McMaster Universities arthritis index (WOMAC) survey was completed by those with hip or knee pain. Data were entered into REDCap v8.9.2 for analysis with SAS 9.4, using logistic and linear regression models to detect associations between covariables and to calculate odds ratios and confidence intervals. Focus groups were held with ranchers in two Montana counties, discussing similar topics, and the themes expressed were identified. Results 87.6% of survey respondents reported joint pain, 47.8% a diagnosis of arthritis, and 22.4% osteoarthritis (OA). A 10-point increase in WOMAC was significantly associated with lower work capacity (OR 2.00; 95% CI [1.58, 2.55], p < 0.01), worse financial condition (OR 1.23; 95% CI [1.01,1.48], p = 0.04), and increased reliance on others (OR 1.82; 95% CI [1.32, 2.55], p < 0.01). An arthritis diagnosis was associated with worsening work capacity (OR 4.66; 95% CI [2.71, 8.01], p < 0.01) and increased odds of relying on others (OR 3.23; 95% CI [1.56, 6.66], p < 0.01). A diagnosis of OA was significantly associated with decreased work capacity (OR 3.47; 95% CI [1.97, 6.11], p < 0.01). Unadjusted for age and BMI, we found a significant association between years spent working in agriculture and joint health, which became non-significant after adjusting for age and BMI. Focus group themes included decreased productivity with increased joint symptoms and a tendency for ranchers to avoid interaction with the health care system. Conclusion Poor joint health is associated with economic risk on Montana ranches and farms.

Evidence indicates that stigma impedes an individual’s chance of seeking professional help for a mental health crisis. Commonly reported aggregate-level results for stigma-reduction efforts obfuscate how much stigma reduction is needed to incur a practically meaningful change within an individual, defined here as an attitudinal shift and openness towards seeking mental health for oneself and/or support for others. When basing conclusions and recommendations about stigma-reducing interventions on aggregate scales, it is unclear how much stigma reduction is needed to incur meaningful change within an individual. We explored the impact of reductions in stigma of help-seeking scores in response to an online suicide prevention video among young adults in the United States, using online surveys to collect qualitative and quantitative data. We compared mean changes in the stigma scores from pre- to post-test (video exposure) of 371 young U.S. adults using standard t-tests and individual level analysis. A separate thematic analysis of free-text responses was also conducted from a smaller, randomly-selected subgroup, capturing individuals’ attitudes towards help-seeking for mental health problems. Great attention was given to participants to ensure that they were in a campus setting where counseling services were available. Four main themes emerged: (1) small changes in stigma scores were associated with individual reports of meaningful reductions in their attitudes towards professional counseling; (2) increased empathy towards victims of suicide and other mental health problems sometimes indicated increased empathy for victims of suicide and decreased openness in professional help; (3) empathy towards victims sometimes took the form of increased scores and grief or sadness, possibly thwarting the potential for help-seeking; and (4) self-reports of decreased stigma were not always associated with increased openness towards help-seeking. Results also indicated that small stigma score charges, not meeting statistical significance, were often associated with increased openness towards seeking help. These findings, discovered using mixed-methods, contribute to the body of literature regarding stigma towards suicide and help-seeking by demonstrating deficits in the aggregate-only analysis of stigma-reducing interventions specifically aimed at suicide prevention. Such individuation in stigma experiences indicates that public education on how to reduce the stigma of help-seeking for suicide prevention needs to consider individual-level analyses for improving target populations. Recommendations for future research include additional studies prior to releasing suicide prevention videos to public forums where they may be seen by individuals without access to help.

Summary Chronic low-grade inflammation is a subclinical condition directly and indirectly linked to the development of a wide range of diseases responsible for the vast majority of morbidity. To examine mechanisms coupled to chronic disease, a group of overweight and obese human subjects without known inflammatory diseases participated in a high-fat meal challenge as an acute inflammation stimulus. Analysis of serum metabolites grouped by baseline cytokine levels revealed that single samples had little power in differentiating groups. However, an analysis that incorporated temporal response separated inflammatory response phenotypes and allowed us to create a metabolic signature of inflammation which revealed metabolic components that are crucial to a cytokine-mediated inflammation response. The use of temporal response, rather than a single time point, improved metabolomic prediction of high postprandial inflammation responses and led to the development of a dynamic biosignature as a potential tool for stratifying risk to a wide range of diseases.