To achieve enhanced biological response and controlled degradation of magnesium alloy, a modified biodegradable polymer coating called polycaprolactone (PCL) is fabricated by a thermal approach in ...which the heat treatment neither alters the chemical composition of the PCL membrane nor the rate of magnesium ion release, pH value, or weight loss, compared with the untreated sample. The changes in the crystallinity, hydrophilicity, and oxygen content of heat‐treated PCL coating not only improve the mechanical adhesion strength between the coating and magnesium substrate but also enhance the biological properties. Moreover, the thermally modified sample can lead to higher spreading and elongation of osteoblasts, due to the enhanced hydrophilicity and CO to CO functional group ratio. In the analyses of microcomputed tomography from one to four weeks postoperation, the total volume of new bone formation on the heat‐treated sample is 10%–35% and 70%–90% higher than that of the untreated and uncoated controls, respectively. Surprisingly, the indentation modulus of the newly formed bone adjacent to the heat‐treated sample is ≈20% higher than that of both controls. These promising results reveal the clinical potential of the modified PCL coating on magnesium alloy in orthopedic applications.
Schematic illustrating the effects of the change of the ratio between CO and CO before and after the heat treatment as well as release of Mg on osteoblast adhesion and bone formation: (a) Before the heat treatment, cell spreading of osteoblasts diminished and (b) after the heat treatment, cell spreading on the PCL membrane is enhanced.
Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to ...society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture-induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow-derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self-repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases.
Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest ...degeneration in rabbit and canine intervertebral discs. In this study, we have used the mouse model to investigate the mechanism of degeneration arrest. BMSC from Egfp transgenic mice were injected into the degenerated murine intervertebral discs induced by annular puncture. We found that BMSC could arrest the progressive degeneration of the discs with significant regeneration of the nucleus pulposus (NP). In the regeneration, expression of proteoglycan genes were upregulated and extracellular matrix (ECM) progressively accumulated in the NP after BMSC injection. Combined in situ hybridization and immunohistochemistry revealed that BMSC underwent chondrocytic differentiation in the regeneration process. Interestingly, BMSC-induced an increase of endogenous notochordal cells in NP and expression of chondrocytic markers. In this study, we have firstly shown that the BMSC could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells.
Abstract Background context Recent studies have demonstrated new therapeutic strategy using transplantation of mesenchymal stem cells (MSCs), especially bone marrow–derived MSCs (BM-MSCs), to ...preserve intervertebral disc (IVD) structure and functions. It is important to understand whether and how the MSCs survive and thrive in the hostile microenvironment of the degenerated IVD. Therefore, this review majorly examines how resident disc cells, hypoxia, low nutrition, acidic pH, mechanical loading, endogenous proteinases, and cytokines regulate the behavior of the exogenous MSCs. Purpose To review and summarize the effect of the microenvironment in biological characteristics of BM-MSCs for IVD regeneration; the presence of endogenous stem cells and the state of the art in the use of BM-MSCs to regenerate the IVD in vivo were also discussed. Study design Literature review. Methods MEDLINE electronic database was used to search for articles concerning stem/progenitor cell isolation from the IVD, regulation of the components of microenvironment for MSCs, and MSC-based therapy for IVD degeneration. The search was limited to English language. Results Stem cells are probably resident in the disc, but exogenous stem cells, especially BM-MSCs, are currently the most popular graft cells for IVD regeneration. The endogenous disc cells and the biochemical and biophysical components in the degenerating disc present a complicated microenvironment to regulate the transplanted BM-MSCs. Although MSCs regenerate the mildly degenerative disc effectively in the experimental and clinical trials, many underlying questions are in need of further investigation. Conclusions There has been a dramatic improvement in the understanding of potential MSC-based therapy for IVD regeneration. The use of MSCs for IVD degeneration is still at the stage of preclinical and Phase 1 studies. The effects of the disc microenvironment in MSCs survival and function should be closely studied for transferring MSC transplantation from bench to bedside successfully.
Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as ...definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5‐year‐old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.
Purpose
Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent ...segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model.
Methods
Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb’s method. The anatomy of the adjacent discs was observed histologically.
Results
DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved.
Conclusions
Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months.
Summary Background Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a ...proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding. Methods 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00365313. Findings Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8·9%) in the controls (95% CI difference, 4·1 to 13·7; p=0·0004). The median follow-up was 13 months (range 0·4–13·0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups. Interpretation Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.
•Living in an IDP camp is the common predictor of stress, depression and anxiety.•Separation from one's partner was predictive of depression and anxiety, but not stress.•Youthful age 18–29 years was ...a protective factor anxiety and stress.•Older adults aged ≥50 years were more likely to have depression, anxiety, and stress.
This study compares the psychological profile of Internally Displaced Persons (IDPs) and individuals living in host communities in the war-affected setting. We conducted a cross-sectional survey from October-November 2019. Subjects were recruited from six IDPs camps and the surrounding host communities within the metropolis of Maiduguri, Nigeria by convenience sampling. Data were collected using the Hausa version of Depression Anxiety Stress Scale-21, and analysed by logistic regression using adjusted odds ratio (AOR) at 95% Confidence Interval (CI). A total of 562 subjects were recruited. Living in IDP camp was the most significantly predictor of depression, anxiety, and stress. The common predictors were living in an IDP camp, and marital status (separated). Aged 18–29years was a protective factor compared to those ≥50years. Living in IDP camps, separated from partners, lack of education and pre-conflict employment were significant predictors of depression, anxiety and stress.
Abstract
We present the results of combined deep Keck/NIRC2,
HST
/WFC3 near-infrared, and
Herschel
far-infrared observations of an extremely star-forming dusty lensed galaxy identified from the
...Herschel
Astrophysical Terahertz Large Area Survey (
H
-ATLAS J133542.9+300401). The galaxy is gravitationally lensed by a massive
WISE
-identified galaxy cluster at
z
∼ 1. The lensed galaxy is spectroscopically confirmed at
z
= 2.685 from detection of
by GBT and from detection of
obtained with CARMA. We use the combined spectroscopic and imaging observations to construct a detailed model of the background dusty lensed submillimeter galaxy (SMG), which allows us to study the source plane properties of the target. The best-fit lens model provides magnifications of
μ
star
= 2.10 ± 0.11 and
μ
dust
= 2.02 ± 0.06 for the stellar and dust components, respectively. Multiband data yield a magnification-corrected star formation rate of 1900(±200)
M
⊙
yr
−1
and a stellar mass of
, consistent with a main sequence of star formation at
z
∼ 2.6. The CO observations yield a molecular gas mass of 8.3(±1.0) × 10
10
M
⊙
, similar to the most massive star-forming galaxies, which together with the high star formation efficiency, are responsible for the intense observed star formation rates. The lensed SMG has a very short gas depletion timescale of ∼40 Myr. The high stellar mass and small gas fractions observed indicate that the lensed SMG likely has already formed most of its stellar mass and could be a progenitor of the most massive elliptical galaxies found in the local universe.
Objective
Osteoarthritis (OA) of the hand can be a debilitating condition that hinders an individual's quality of life. With multiple joints within the hand that are commonly affected OA, an ...individual's ability to use their hand in everyday movements become more limited. The article aims to review literature on the aetiology and pathogenesis of OA, risk factors, characteristics of hand OA and the steps of diagnosis.
Key findings
The aetiology and pathogenesis of OA, in particular hand OA, is not fully understood. However, it is known that several factors play a role. Environmental factors, such as stress from mechanical loading, especially to vulnerable joints predispose individuals to developing OA. Extracellular matrix changes in protein levels have also been noted in individuals with OA. Linked to hand OA development are boney enlargements (Herbeden's and Bouchard's nodes). Several risk factors for OA include: age, obesity, gender, smoking, genetics, diet and occupation. Various diagnostic methods include a combination of using radiographic methods, clinical presentation, a number of developed measurements and scales.
Summary
With OA having several risk factors and various causes and contributing elements, it is important to elucidate the pathogenesis of OA and determine exactly how risk factors play a role in its development. Because of the contributions from several elements, diagnosis is best when it uses multiple methods. In turn, understanding OA and making better diagnoses could lead to improved management of the condition through both pharmacological and non‐pharmacological interventions.
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