The effect of support surface and footwear condition on postural sway and lower limb muscle action of the older women

Background: Diminished somatosensory function is a critical age-related change which is related to postural instability in the older population. Footwear is a cost-effective way to modulate the postural stability by altering sensorimotor inputs via mechanoreceptors on the plantar surface of the feet. Compared to insoles with indentions in the entire surface, we innovatively developed a textured insole with site-specific nodulous protrudous. This study thus aimed to investigate the immediate effect of the nodulous insole and supporting surface condition on static postural stability and lower limb muscle activation for healthy older women. Methods: This is a single-session study with repeated measurements. Twenty-three healthy older women stood on the firm (i.e., concrete floor) and foam surfaces with their eyes open in the three footwear conditions, namely barefoot, plain shoes and shoes with an innovative textured insole, for 30 seconds. Static postural sway and muscle activation of biceps femoris (BF), vastus lateralis (VL), tibialis anterior (TA), and lateral gastrocnemius (LG) of the dominant leg were measured during each testing condition. Results: Compared to a firm surface, standing on the foam could significantly increase the body sway and lower limb muscle activation (p<0.05). When standing on the foam, compared to barefoot, wearing footwear significantly decreased the VL and TA muscle activation and minimize the postural sway in medial-lateral and anterior-posterior direction, while the influence is larger for the shoes with nodulous insloe compared to the plain shoes. No significant differences between the footwear conditions for static stability and muscle activation were observed on firm surface condition. Conclusions:For older women, footwear could improve the postural stability in the unstable surface, particularly the footwear with nodulous insole, with the underlying mechanism as enhancing the mechanoreceptors on the plantar surface of the feet

Presurgery exercise-based conditioning interventions (prehabilitation) in adults undergoing lower limb surgery for peripheral arterial disease (Review)

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Lower limb peripheral arterial disease (PAD) is a type of cardiovascular disease where the blood vessels that carry the blood to the legs are hardened and narrowed. The most severe manifestation of PAD is critical limb ischaemia (CLI). This condition results in symptoms of intractable rest pain, non-healing wounds and ulceration, gangrene or both. PAD affects more than 200 million people worldwide and approximately 3% to 5% of people aged over 40 have PAD, rising to 18% in people over 70 years of age. Between 5% to 10% of symptomatic PAD patients will progress to CLI over a five-year period and the five year cumulative incidence rate for asymptomatic patients with PAD deteriorating to intermittent claudication is 7%, with 21% of these progressing to CLI. Treatment options include angioplasty, bypass or amputation of the limb, when life or limb is threatened. People with CLI have a high risk of mortality and morbidity. The mortality rates during a surgical admission are approximately 5%. Within one year of surgery, the mortality rate rises to 22%. Postoperative complications are as high as 30% and readmission rates vary between 7% to 18% in people with CLI. Despite recent advances in surgical technology, anaesthesia and perioperative care, a proportion of surgical patients have a suboptimal recovery. Presurgery conditioning (prehabilitation) is a multimodal conditioning intervention carried out prior to surgery using a combination of exercise, with or without nutritional or psychological interventions, or both. The use of prehabilitation is gaining momentum, particularly in elderly patients undergoing surgery and patients undergoing colorectal cancer surgery, as a means of optimising fitness to improve the prognosis for people undergoing the physiological stress of surgery. People with PAD are characterised by poor mobility and physical function and have a lower level of fitness as a result of disease progression. Therefore, prehabilitation may be an opportunity to improve their recovery following surgery. However, as multimodal prehabilitation requires considerable resources, it is important to assess whether it is superior to usual care. This review aimed to compare prehabilitation with usual care (defined as a preoperative assessment, including blood and urine tests). The key outcomes were postoperative complications, mortality and readmissions within 30 days of the surgical procedure, and one-year survival rates. Objectives: To assess the effectiveness of prehabilitation (preoperative exercise, either alone or in combination with nutritional or psychological interventions, or both) on postoperative outcomes in adults with PAD undergoing open lower limb surgery. Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 25 September 2019. Selection criteria: We considered all published and unpublished randomised controlled trials (RCTs) comparing presurgery interventions and usual care. Primary outcomes were postoperative complications, mortality and readmission to hospital within 30 days of the surgical procedure. Data collection and analysis: Two review authors independently reviewed all records identified by the searches conducted by the Cochrane Vascular Information Specialist. We planned to undertake data collection and analysis in accordance with recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions. Main results: We found no RCTs that met the inclusion criteria for this review. Authors' conclusions: We found no RCTs conducted to determine the effects of prehabilitation on mortality or other postoperative outcomes when compared to usual care for patients with PAD. As a consequence, we were unable to provide any evidence to guide the treatment of patients with PAD undergoing surgery. To perform a randomised controlled trial of presurgery conditioning would be challenging but trials are warranted to provide solid evidence on this topic

Presurgery conditioning interventions (prehabilitation) in adults undergoing lower limb surgery for peripheral arterial disease

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To assess the effectiveness of prehabilitation (preoperative exercise, either alone or in combination with nutritional or psychological interventions or both) on postoperative outcomes in adults with PAD undergoing open lower limb surgery

Micropatterned Cell–Cell Interactions Enable Functional Encapsulation of Primary Hepatocytes in Hydrogel Microtissues

Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell–cell interactions and cell–matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into three-dimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell–cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug–drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms.National Institutes of Health (U.S.) (Grant UH2 EB017103)National Institutes of Health (U.S.) (Grant R01 EB008396)National Institutes of Health (U.S.) (Grant R01 DK85713)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)American Gastroenterological Association (Research Scholar Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship (1122374

Childhood sleep health and epigenetic age acceleration in late adolescence: Cross-sectional and longitudinal analyses

Aim: Investigate if childhood measures of sleep health are associated with epigenetic age acceleration in late adolescence. Methods: Parent-reported sleep trajectories from age 5 to 17, self-reported sleep problems at age 17, and six measures of epigenetic age acceleration at age 17 were studied in 1192 young Australians from the Raine Study Gen2. Results: There was no evidence for a relationship between the parent-reported sleep trajectories and epigenetic age acceleration (p ≥ 0.17). There was a positive cross-sectional relationship between self-reported sleep problem score and intrinsic epigenetic age acceleration at age 17 (b = 0.14, p = 0.04), which was attenuated after controlling for depressive symptom score at the same age (b = 0.08, p = 0.34). Follow-up analyses suggested this finding may represent greater overtiredness and intrinsic epigenetic age acceleration in adolescents with higher depressive symptoms. Conclusion: There was no evidence for a relationship between self- or parent-reported sleep health and epigenetic age acceleration in late adolescence after adjusting for depressive symptoms. Mental health should be considered as a potential confounding variable in future research on sleep and epigenetic age acceleration, particularly if subjective measures of sleep are used

A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies.

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

ABC Efflux Transporters and Solute Carriers in the Early Developing Brain of a Marsupial Monodelphis domestica (South American Gray Short-Tailed Opossum)

This study used a marsupial Monodelphis domestica, which is born very immature and most of its development is postnatal without placental protection. RNA-sequencing (RNA-Seq) was used to identify the expression of influx and efflux transporters (ATP-binding cassettes [ABCs] and solute carriers [SLCs]) and metabolizing enzymes in brains of newborn to juvenile Monodelphis. Results were compared to published data in the developing eutherian rat. To test the functionality of these transporters at similar ages, the entry of paracetamol (acetaminophen) into the brain and cerebrospinal fluid (CSF) was measured using liquid scintillation counting following a single administration of the drug along with its radiolabelled tracer [3H]. Drug permeability studies found that in Monodelphis, brain entry of paracetamol was already restricted at P5; it decreased further in the first week of life and then remained stable until the oldest age group tested (P110). Transcriptomic analysis of Monodelphis brain showed that expression of transporters and their metabolizing enzymes in early postnatal (P) pups (P0, P5, and P8) was relatively similar, but by P109, many more transcripts were identified. When transcriptomes of newborn Monodelphis brain and E19 rat brain and placenta were compared, several transporters present in the rat placenta were also found in the newborn Monodelphis brain. These were absent from E19 rat brain but were present in the adult rat brain. These data indicate that despite its extreme immaturity, the newborn Monodelphis brain may compensate for the lack of placental protection during early brain development by upregulating protective mechanisms, which in eutherian animals are instead present in the placenta