Tight control of disease activity fails to improve body composition or physical function in rheumatoid arthritis patients.

OBJECTIVE: RA typically features rheumatoid cachexia [loss of muscle mass (MM) and excessive total fat mass (TFM), especially trunk FM], which contributes to physical disability. Since rheumatoid cachexia is driven by inflammation, it would be anticipated that the success of tight control of disease activity, such as treat-to-target (T2T), in attenuating inflammation would benefit body composition and physical function. This aim of this cross-sectional study was to assess the impact of T2T on body composition and objectively assessed function in RA patients. METHODS: A total of 82 RA patients exclusively treated by T2T, were compared with 85 matched sedentary healthy controls (HCs). Body composition was estimated by DXA, with appendicular lean mass the surrogate measure of total MM. Physical function was assessed by knee extensor strength, handgrip strength, 30 s sit-to-stands, 8' up and go, and 50' walk (tests which reflect the ability to perform activities of daily living). RESULTS: Although generally well treated (mean DAS28 = 2.8, with 49% in remission), RA patients had ∼10% proportionally less appendicular lean mass and were considerably fatter (by ∼27%), particularly in the trunk (∼32%), than HCs. All measures of function were 24-34% poorer in the RA patients relative to HC. CONCLUSIONS: Despite marked improvements in disease control (most patients achieving or approaching remission), the relative loss of MM and increased adiposity in RA patients compared with matched HCs was similar to that observed pre-T2T. Additionally, performance of objective function tests was unchanged from that reported by our group for pre-T2T RA patients. Thus T2T, even in responsive RA patients, did not attenuate rheumatoid cachexia or improve objectively assessed function.

Trends in substance abuse treatment 1998-2008: increasing older adult first-time admissions for illicit drugs.

OBJECTIVES: To see whether the percentage of older adults entering substance abuse treatment for their first time was increasing and whether there were changes in the use patterns leading to the treatment episode, particularly an increase in illicit drugs. SETTING: The Treatment Episode Data Sets publicly available from the Substance Abuse Mental Health Services Administration from 1998 to 2008. PARTICIPANTS: Young adults age 30-54 years as a comparison group (N = 3,547,733) and those age 55 years or older (N = 258,542) with a first-time admission for a publicly funded substance abuse treatment. MEASUREMENTS: Demographic and substance use history variables at admission. RESULT: The proportion of older adults going for substance abuse treatment for the first time is increasing relative to younger adults. The pattern of drug use is also changing, with an increasing illicit drug involvement (cocaine and heroin) in older adult admissions. CONCLUSIONS: We know little of these long-time users, their current medical state, cognitive abilities, and psychiatric symptoms after such a long exposure time. Previous studies on heroin and cocaine exposure focused on individuals identified much earlier in life, and the aging long-term users might represent a relatively large but unknown population.

Remission from substance dependence in U.S. Whites, African Americans, and Latinos.

The authors investigated remission from any type of substance dependence in Latinos, African Americans, and Whites using the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a national sample of community adults. Analyses focused on the 4,520 participants who indicated prior-to-last-year dependence on either alcohol or drugs. Outcome was categorized as current substance dependence or abuse, current use, or abstinence. Whites reported greater likelihood of substance dependence, and African Americans and Latinos were just as likely to remit as Whites once social support and age are controlled. The outcome variable "time to remission" produced a similar pattern of results.

Effectiveness of interventions aiming at reducing sedentary behaviour in a non-surgical population with overweight or obesity: A systematic review and meta-analysis.

AIM: This systematic review and meta-analyses of randomised controlled trials (RCTs) investigated the effectiveness of interventions to reduce sedentary behaviour amongst people with overweight or obesity. Secondarily, it aimed to investigate the effectiveness of these interventions on body mass index (BMI), time spent in moderate-to-vigorous physical activity (MVPA) and health-related quality of life (HRQoL). METHODS: A search of six databases (CENTRAL, PubMed, Embase, PEDro, CINAHL and PsycINFO) was conducted from inception to July 2018. RCTs in which sedentary behaviour was measured by accelerometry or inclinometry, with participants of any age with overweight or obesity were included. Subgroup analyses were undertaken comparing studies that included adults versus children and studies with an active component (e.g., treadmill desk, physically active breaks) versus no active component to their intervention. RESULTS: Nine studies (n=1859) were included. Compared to the control group, the interventions significantly reduced time spent in sedentary behaviour (standardised mean difference [95% confidence interval] -0.33 [-0.59 to -0.08] overall; -0.53 [-0.95 to -0.11] in adults). Subgroup analyses demonstrated that only interventions that included active components reduced time spent in sedentary behaviour (-0.54 [-0.88 to -0.20]) and increased time spent in MVPA (1.29 [0.02 to 2.56]). Subgroup analyses demonstrated that interventions only reduced BMI in studies of children (-0.09 [-0.18 to -0.00]) and in those with no active component (-0.09 [-0.18 to -0.01]). There were insufficient data to investigate the effectiveness of these interventions on HRQoL. CONCLUSIONS: This novel systematic review and meta-analyses suggests interventions aiming to effectively reduce objectively-measured sedentary behaviour need to specifically include an active component.

The 8-foot up and go test is the best way to assess physical function in the rheumatoid arthritis clinic.

OBJECTIVES: RA is characterized by poor physical function, which compromises patients' quality of life and outcome. Clinical assessment of function is usually performed using self-reported questionnaires, such as the Multi-Dimensional HAQ (MDHAQ) and the Short Form-36 (physical component) (SF36-PC). However, such subjective measures may not accurately reflect real functional status. This study aimed to determine: (i) which clinically practicable objective test best represents overall physical function; and (ii) the extent to which self-reported subjective functional measures reflect objectively assessed function. METHODS: Objective [isometric knee extensor strength, handgrip strength, sit-to-stands in 30 s, 8-foot up and go (8'UG), 50-foot walk (50'W) and estimated aerobic capacity (V̇O2max)] and subjective (MDHAQ and SF36-PC) measures of function were correlated with one another to determine the best overall test of functional status in 82 well-controlled RA patients (DAS28 (s.d.) = 2.8 (1.0)). RESULTS: In rank order of size, averaged correlations (r) to the other outcome measures were as follows: 8'UG: 0.650; 50'W: 0.636; isometric knee extensor strength: 0.502; handgrip strength: 0.449; sit-to-stands in 30 s: 0.432; and estimated V̇O2max: 0.358. The MDHAQ was weakly (0.361) and the SF36-PC moderately correlated (0.415) with objective measures. CONCLUSION: Our results show that the most appropriate measure of objective physical function in RA patients is the 8'UG, followed by the 50'W. We found discordance between objectively and subjectively measured function. In clinical practice, an objective measure that is simple and quick to perform, such as the 8'UG, is advocated for assessing real functional status.

Genome sequence of the dissimilatory metal ion-reducing bacterium Shewanella oneidensis.

Shewanella oneidensis is an important model organism for bioremediation studies because of its diverse respiratory capabilities, conferred in part by multicomponent, branched electron transport systems. Here we report the sequencing of the S. oneidensis genome, which consists of a 4,969,803-base pair circular chromosome with 4,758 predicted protein-encoding open reading frames (CDS) and a 161,613-base pair plasmid with 173 CDSs. We identified the first Shewanella lambda-like phage, providing a potential tool for further genome engineering. Genome analysis revealed 39 c-type cytochromes, including 32 previously unidentified in S. oneidensis, and a novel periplasmic [Fe] hydrogenase, which are integral members of the electron transport system. This genome sequence represents a critical step in the elucidation of the pathways for reduction (and bioremediation) of pollutants such as uranium (U) and chromium (Cr), and offers a starting point for defining this organism's complex electron transport systems and metal ion-reducing capabilities.

Cytochrome c release from rat brain mitochondria is proportional to the mitochondrial functional deficit: implications for apoptosis and neurodegenerative disease.

Apoptosis may be initiated in neurons via mitochondrial release of the respiratory protein, cytochrome c. The mechanism of cytochrome c release has been studied extensively, but little is known about its dynamics. It has been claimed that release is all-or-none, however, this is not consistent with accumulating evidence of cytosolic mechanisms for 'buffering' cytochrome c. This study has attempted to model an underlying disease pathology, rather than inducing apoptosis directly. The model adopted was diminished activity of the mitochondrial respiratory chain complex I, a recognized feature of Parkinson's disease. Titration of rat brain mitochondrial respiratory function, with the specific complex I inhibitor rotenone, caused proportional release of cytochrome c from isolated synaptic and non-synaptic mitochondria. The mechanism of release was mediated, at least in part, by the mitochondrial outer membrane component Bak and voltage-dependent anion channel rather than non-specific membrane rupture. Furthermore, preliminary data were obtained demonstrating that in primary cortical neurons, titration with rotenone induced cytochrome c release that was subthreshold for the induction of apoptosis. Implications for the therapy of neurodegenerative diseases are discussed.