Muscle MiR-27a is Decreased During Diabetes and is Regulated by Calcineurin Signaling

Please refer to the pdf version of the abstract located adjacent to the title

Using a System Identification Approach to Investigate Subtask Control during Human Locomotion

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Here we apply a control theoretic view of movement to the behavior of human locomotion with the goal of using perturbations to learn about subtask control. Controlling one’s speed and maintaining upright posture are two critical subtasks, or underlying functions, of human locomotion. How the nervous system simultaneously controls these two subtasks was investigated in this study. Continuous visual and mechanical perturbations were applied concurrently to subjects (n=20) as probes to investigate these two subtasks during treadmill walking. Novel application of harmonic transfer function (HTF) analysis to human motor behavior was used, and these HTFs were converted to the time-domain based representation of phase-dependent impulse response functions (_IRFs). These _IRFs were used to identify the mapping from perturbation inputs to kinematic and electromyographic (EMG) outputs throughout the phases of the gait cycle. Mechanical perturbations caused an initial, passive change in trunk orientation and, at some phases of stimulus presentation, a corrective trunk EMG and orientation response. Visual perturbations elicited a trunk EMG response prior to a trunk orientation response, which was subsequently followed by an anterior-posterior displacement response. This finding supports the notion that there is a temporal hierarchy of functional subtasks during locomotion in which the control of upper-body posture precedes other subtasks. Moreover, the novel analysis we apply has the potential to probe a broad range of rhythmic behaviors to better understand their neural control

Subconcussive Head Impact Results in a Unique Circulating Exosomal MicroRNA Signature

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Human bipedal instability in tree canopy environments is reduced by “light touch” fingertip support

Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However “light touch”, a sensorimotor feedback strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor’s ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Zastosowanie sekukinumabu w leczeniu chorych na łuszczycowe zapalenie stawów — stanowisko ekspertów Polskiego Towarzystwa Reumatologicznego i Polskiego Towarzystwa Dermatologicznego

Sekukinumab jest lekiem biologicznym, ludzkim monoklonalnym przeciwciałem skierowanym przeciwko interleukinie 17A stosowanym w leczeniu chorych na łuszczycowe zapalenie stawów. Lek może być stosowany po nieskuteczności metotreksatu lub leków biologicznych a u chorych na postać osiową choroby jako pierwszy lek, po nieskuteczności niesteroidowych leków przeciwzapalnych. Ze względu na mechanizm działania odmienny od dotychczas stosowanych leków, znaczącą skuteczność i duże bezpieczeństwo stosowania wprowadzenie sekukinumabu do leczenia chorych na łuszczycowe zapalenie stawów istotnie poszerzy możliwości dostępnej farmakoterapii tej choroby.  

Baseline new bone formation does not predict bone loss in ankylosing spondylitis as assessed by quantitative computed tomography (QCT) - 10-year follow-up

<p>Abstract</p> <p>Background</p> <p>To evaluate the relationship between bone loss and new bone formation in ankylosing spondylitis (AS) using 10-year X-ray, dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) follow-up.</p> <p>Methods</p> <p>Fifteen AS patients free from medical conditions and drugs affecting bone metabolism underwent X-ray, DXA and QCT in 1999 and 2009.</p> <p>Results</p> <p>In spine QCT a statistically significant (p = 0,001) decrease of trabecular bone mineral content (BMC) was observed (change ± SD: 18.0 ± 7.3 mg/cm³). In contrast, spine DXA revealed a significant increase of bone mineral density (change ± SD: -0.15 ± 0.14 g/cm²). The mean BMC, both at baseline and follow-up was significantly lower (p = 0.02 and p = 0.005, respectively) in advanced radiological group as compared to early radiological group. However, in multiple regression model after adjustment for baseline BMC, the baseline radiological scoring did not influence the progression of bone loss as assessed with QCT (p = 0.22, p for BMC*X-ray syndesmophyte scoring interaction = 0.65, p for ANOVA-based X-ray syndesmophyte scoring*time interaction = 0.39). Baseline BMC was the only significant determinant of 10-year BMC change, to date the longest QCT follow-up data in AS.</p> <p>Conclusions</p> <p>In AS patients who were not using antiosteoporotic therapy spine trabecular bone density evaluated by QCT decreased over 10-year follow-up and was not related to baseline radiological severity of spine involvement.</p

Sekukinumab w leczeniu pacjentów z osiową spondyloatropatią — stanowisko ekspertów Polskiego Towarzystwa Reumatologicznego

Zesztywniające zapalenie stawów kręgosłupa (ZZSK) to przewlekła, autozapalna choroba reumatologiczna charakteryzująca się przewlekłym procesem zapalnym, uszkodzeniem strukturalnym stawów krzyżowo-biodrowych w badaniu radiograficznym oraz wzmożoną osteogenezą w szkielecie osiowym. Aktualne wytyczne dotyczące leczenia systemowego w ZZSK obejmują niesteroidowe leki przeciwzapalne oraz inhibitory czynnika martwicy nowotworu alfa (TNF-alpha). Inhibitory TNF stanowią bardzo skuteczną opcję terapeutyczną u pacjentów z osiową spondyloatropatią, ale część chorych nie odpowiada na stosowane leczenie lub występują u nich objawy niepożądane. W ostatnich latach zainteresowania skupiły się nad rolą IL-17 w patogenezie spondyloatropatii jako potencjalnego celu terapii. Sekukinumab jest w pełni ludzkim przeciwciałem monoklonalnym przeciwko IL-17A, którego skuteczność w leczeniu pacjentów z ZZSK potwierdzono w badaniach klinicznych. W dwóch badaniach 3 fazy sekukinumab zmniejszał aktywność choroby w stopniu porównywalnym z inhibitorami TNF z jednoczesnym dobrym profilem bezpieczeństwa. Leczenie sekukinumabem prowadziło także do istotnej poprawy jakości życia uwarunkowanej stanem zdrowia oraz do zmniejszenia stopnia niesprawności i zmęczenia u pacjentów z aktywnym ZZSK. Wyniki 2-letniej obserwacji sugerują ponadto, że terapia sekukinumabem zmniejsza progresję zmian radiograficznych w kręgosłupie, co wymaga potwierdzenia w kontrolowanym badaniu w dłuższym horyzoncie czasowym. Sekukinumab jest pierwszym lekiem biologicznym innym niż inhibitory TNF zarejestrowanym do leczenie pacjentów z ZZSK w Stanach Zjednoczonych i Unii Europejskiej

Apremilast w leczeniu łuszczycowego zapalenia stawów — stanowisko ekspertów Polskiego Towarzystwa Reumatologicznego i Polskiego Towarzystwa Dermatologicznego

Apremilast jest inhibitorem fosfodiesterazy 4 stosowanym w leczeniu chorych na łuszczycowe zapalenie stawów. Zespół ekspertów Polskiego Towarzystwa Reumatologicznego (PTR) i Polskiego Towarzystwa Dermatologicznego (PTD) uważa, że apremilast może stanowić dodatkową opcję terapeutyczną w aktualnym schemacie postępowania terapeutycznego po stwierdzeniu nieskuteczności klasycznych syntetycznych leków modyfikujących przebieg choroby lub ich nietolerancji