This study aimed at evaluating the predictive ability of the Physical Resilience Instrument for Older Adults (PRIFOR) for the recovery of frailty, activity of daily living (ADL), and quality of life ...in older adults suffering from acute health stressors. The longitudinal study was adopted and patients aged 65 and older with Clinical Frailty Scale (CFS) scores between 4 and 6 were included. The PRIFOR was used to assess physical resilience at baseline. Katz ADL, CFS and EuroQoL 5-dimension Questionnaire (EQ 5D) scores were all assessed at baseline and one month after discharge. The mean age of the 192 participants was 76.29 ± 6.53 years, and 50.5% were female. After adjusting for the baseline condition, the PRIFOR was only significantly associated with the CFS (β=−0.183, p<0.001) at one month after discharge. Our study results provide evidence of the predictive capacity of the PRIFOR for recovery from frailty.
This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic ...circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.
Summary Objective Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been ...attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. Methods In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 μg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. Results Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. Conclusion This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and ‘cell-free’ therapeutic alternative to cell-based MSC therapy.
Seaweed and cellulose are promising natural polymers. This article reviews the basic information and recent developments of both seaweed and cellulose biopolymer materials as well as analyses the ...feasible formation of seaweed/cellulose composite films. Seaweed and cellulose both exhibit interesting film-forming properties. Nevertheless, seaweed has poor water vapour barrier and mechanical properties, whereas cellulose is neither meltable nor soluble in water or common organic solvents due to its highly crystalline structure. Therefore, modification of these hydrocolloids has been done to exploit their useful properties. Blending of biopolymers is a must recommended approach to improve the desired characteristics. From the review, seaweed is well compatible with cellulose, which possesses excellent mechanical strength and water resistance properties. Moreover, seaweed/cellulose composite films can prolong a product's shelf life while maintaining its biodegradability. Additionally, the films show potential in contributing to the bioeconomy. In order to widen seaweed and cellulose in biocomposite application across various industries, some of the viewpoints are highlighted to be focused for future developments and applications.
Abstract Objectives We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in ...rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. Methods The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies DLB, multiple system atrophy MSA). Results Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1–3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. Conclusions The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.
Background
In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys‐regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates ...microglia in the spinal dorsal horn (SDH). However, information on diabetes‐induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain.
Methods
Sixty‐six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration.
Results
All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up‐regulation of Nav1.3 and down‐regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ‐induced diabetes was mediated, in part, by phosphorylation of p‐38 mitogen‐activated protein kinase.
Conclusions
Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.
The term hydrocolloid generally refers to substances that form gels or provide viscous dispersion in the presence of water. Alginate, agar, and carrageenan are three commercially valuable ...hydrocolloids derived from certain brown and red seaweed and each has their distinct physicochemical properties (i.e. functional and bioactive). Various applications of these seaweed hydrocolloids as thickeners, stabilizers, coagulants and salves (in the wound and burn dressings) and materials to produce bio-medical impressions in the food, pharmaceutical, and biotechnology industries are highlighted in this review. Although the existing industrial methods of extraction for these seaweed hydrocolloids are well-established, still growing demand has exposed certain limitations of those methods, notably efficiency and product consistency. In order to achieve targeted hydrocolloids for specific purposes and functionalities, some novel and green extraction methods have also been proposed and discussed. Microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), supercritical fluid extraction (SFE), pressurized solvent extractions (PSE), reactive extrusion and photo-bleaching process are selectively presented as highly promising candidates that can avoid the use of chemicals and provide novel means of access to seaweed hydrocolloids with both economic and environmental benefits. However, this review does not provide the 'best' method or procedure as many are still under development. Hence, the review gives 'food for thought'as to new processes which might be adopted industrially and concluded that further research is required in order to contribute additional new knowledge and refinement to this field of study.
Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be ...overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1β (IL-1β) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E
(PGE
) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.
Summary
Background
The roles remain unclear of early on‐treatment quantitative serum HBsAg and hepatitis B virus (HBV) DNA levels in the prediction of a sustained response (SR) to peginterferon ...alfa‐2a therapy in HBeAg‐negative chronic hepatitis B (CHB) patients infected with genotype B or C.
Aims
To determine their roles in HBeAg‐negative CHB patients infected with genotype B or C.
Methods
Sixty‐one patients were treated with peginterferon alfa‐2a for 48 weeks. Serum HBsAg levels were quantified using the Abbott Architect HBsAg QT assay throughout treatment. Multiple regression analyses were performed to identify independent predictors of SR.
Results
Nineteen patients (31%) achieved SR with serum HBV DNA levels <312 copies/mL at 24 weeks post‐treatment. Serum HBsAg levels at 12 (OR 31.9; 95% CI 4.8–209.6; P = 0.0003) and 24 weeks of therapy (OR 8.8; 95% CI 2.0–38.0; P = 0.0035), and HBV DNA levels at baseline (OR 7.0; 95% CI 1.3–36.2; P = 0.0203), 12 (OR 7.9; 95% CI 1.2–48.4; P = 0.0249) and 24 weeks of therapy (OR 22.3; 95% CI 2.2–224.0; P = 0.0083) were early independent predictors of SR. A serum HBsAg cut‐off of 150 IU/mL at week 12 had an AUC, sensitivity, specificity and positive and negative predictive values of 0.75, 63%, 95%, 86% and 85% with respect to predicting SR respectively.
Conclusions
A quantitative serum HBsAg level at 12 weeks of therapy can be used for the early prediction of SR to peginterferon therapy in HBeAg‐negative CHB patients infected with genotype B or C.
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