Emerging materials and technologies for advancing bioresorbable surgical meshes.

Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.

Factors Associated with Mortality in Patients with Coronavirus Disease (COVID-19) in Babol, North of Iran.

BACKGROUND: The spectrum of the clinical features of coronavirus disease 2019 (COVID-19) spans from asymptomatic or mild disease to severe respiratory failure, while different factors are related to its mortality rate. This research aimed to determine the clinical and laboratory characteristics and the associated factors of mortality in patients with COVID-19. MATERIALS AND METHODS: Data were collected from hospitalized patients (May to June 2020), and COVID-19 was confirmed in patients by real-time polymerase chain reaction (PCR). The patient group was classified into survivor and deceased groups. The chi-square and the independent t-test with Statistical Package for the Social Sciences (SPSS) software program, version 18, were used for analysis. RESULTS: Mean age, hemoglobin, serum C-reactive protein (CRP), alkaline phosphatase (ALP), white blood cells, and level of procalcitonin in non-survivors were significantly higher than in survivors. Serum tumour necrosis factor-alpha (TNF-a) had a significant relationship with Ddimer (p = 0.0006). The risk of mortality in patients with serum CRP ≥ 100 mg/dl was significantly higher than those with CRP < 100 mg/dl (odds ratio (OR) = 4.8 (95% CI, 1.33-12.44, p = 0.01). CONCLUSION: COVID-19 has different clinical features and can be an asymptomatic, mild, or severe disease. Thus, findings about the disease and the consequent outcomes differ in patients. Further studies are needed to evaluate the clinical features and consequences of COVID-19 infection.

Silane-modified hydroxyapatite nanoparticles incorporated into polydioxanone/poly(lactide-co-caprolactone) creates a novel toughened nanocomposite with improved material properties and in vivo inflammatory responses.

The interface tissue between bone and soft tissues, such as tendon and ligament (TL), is highly prone to injury. Although different biomaterials have been developed for TL regeneration, few address the challenges of the TL-bone interface. Here, we aim to develop novel hybrid nanocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL), and hydroxyapatite (HA) nanoparticles suitable for TL-bone interface repair. Nanocomposites, containing 3-10% of both unmodified and chemically modified hydroxyapatite (mHA) with a silane coupling agent. We then explored biocompatibility through in vitro and in vivo studies using a subcutaneous mouse model. Through different characterisation tests, we found that mHA increases tensile properties, creates rougher surfaces, and reduces crystallinity and hydrophilicity. Morphological observations indicate that mHA nanoparticles are attracted by PDO rather than LCL phase, resulting in a higher degradation rate for mHA group. We found that adding the 5% of nanoparticles gives a balance between the properties. In vitro experiments show that osteoblasts' activities are more affected by increasing the nanoparticle content compared with fibroblasts. Animal studies indicate that both HA and mHA nanoparticles (10%) can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. In summary, this work highlights the potential of PDO/LCL/HA nanocomposites as an excellent biomaterial for TL-bone interface tissue engineering applications.

Distinct Clades of Protein Phosphatase 2A Regulatory B'/B56 Subunits Engage in Different Physiological Processes.

Protein phosphatase 2A (PP2A) is a strongly conserved and major protein phosphatase in all eukaryotes. The canonical PP2A complex consists of a catalytic (C), scaffolding (A), and regulatory (B) subunit. Plants have three groups of evolutionary distinct B subunits: B55, B' (B56), and B''. Here, the Arabidopsis B' group is reviewed and compared with other eukaryotes. Members of the B'α/B'ß clade are especially important for chromatid cohesion, and dephosphorylation of transcription factors that mediate brassinosteroid (BR) signaling in the nucleus. Other B' subunits interact with proteins at the cell membrane to dampen BR signaling or harness immune responses. The transition from vegetative to reproductive phase is influenced differentially by distinct B' subunits; B'α and B'ß being of little importance, whereas others (B'γ, B'ζ, B'η, B'θ, B'κ) promote transition to flowering. Interestingly, the latter B' subunits have three motifs in a conserved manner, i.e., two docking sites for protein phosphatase 1 (PP1), and a POLO consensus phosphorylation site between these motifs. This supports the view that a conserved PP1-PP2A dephosphorelay is important in a variety of signaling contexts throughout eukaryotes. A profound understanding of these regulators may help in designing future crops and understand environmental issues.

The prevalence and correlation of depression and anxiety with disease activity in rheumatoid arthritis.

Introduction: Depression and anxiety share similar symptoms with rheumatoid arthritis (RA) and these conditions are often not diagnosed or overlooked in RA. This study aimed to determine the prevalence of depression/anxiety in RA and their correlation with RA activity. Material and methods: Rheumatoid arthritis patients who presented at a rheumatology clinic were selected consecutively. The diagnosis of RA was confirmed by the ACR/EULAR criteria, disease activity was assessed by Disease Activity Score based on the 28-joint count (DAS28) and patients with DAS28 > 2.6 were considered to have active RA. The diagnosis of depression and anxiety was made by the Hospital Anxiety and Depression Scale (HADS). The Pearson test was used to determine the correlation between DAS28 and HADS scores. Results: Two-hundred patients (female, 82%) with a mean age of 53.5 ±10.1 years and mean disease duration of 6.6 ±6.8 years were studied. Depression was diagnosed in 27 (13.5%) patients and anxiety in 38 (19%) patients. The DAS28 score correlated positively with depression (r = 0.173, p = 0.014) and anxiety score (r = 0.229, p = 0.001). In multiple logistic regression analysis after adjustment for all covariates, age < 40 years and female sex were independently associated with RA activity in patients with depression, with OR = 4.21 (p = 0.002) and OR = 3.56 (p = 0.028) respectively. Conclusions: These findings indicate that depression and anxiety are prevalent in RA and correlate positively with active disease in particular in depressive female patients aged < 40 years.

Novel hybrid biocomposites for tendon grafts: The addition of silk to polydioxanone and poly(lactide-co-caprolactone) enhances material properties, in vitro and in vivo biocompatibility.

Biopolymers play a critical role as scaffolds used in tendon and ligament (TL) regeneration. Although advanced biopolymer materials have been proposed with optimised mechanical properties, biocompatibility, degradation, and processability, it is still challenging to find the right balance between these properties. Here, we aim to develop novel hybrid biocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL) and silk to produce high-performance grafts suitable for TL tissue repair. Biocomposites containing 1-15% of silk were studied through a range of characterisation techniques. We then explored biocompatibility through in vitro and in vivo studies using a mouse model. We found that adding up to 5% silk increases the tensile properties, degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the composites. Furthermore, addition of silk increases surface roughness and hydrophilicity. In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h, while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. Finally, we selected a promising biocomposite and created a prototype TL graft based on extruded fibres. We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament (ACL) repair applications.

Natural, synthetic and commercially-available biopolymers used to regenerate tendons and ligaments.

Tendon and ligament (TL) injuries affect millions of people annually. Biopolymers play a significant role in TL tissue repair, whether the treatment relies on tissue engineering strategies or using artificial tendon grafts. The biopolymer governs the mechanical properties, biocompatibility, degradation, and fabrication method of the TL scaffold. Many natural, synthetic and hybrid biopolymers have been studied in TL regeneration, often combined with therapeutic agents and minerals to engineer novel scaffold systems. However, most of the advanced biopolymers have not advanced to clinical use yet. Here, we aim to review recent biopolymers and discuss their features for TL tissue engineering. After introducing the properties of the native tissue, we discuss different types of natural, synthetic and hybrid biopolymers used in TL tissue engineering. Then, we review biopolymers used in commercial absorbable and non-absorbable TL grafts. Finally, we explain the challenges and future directions for the development of novel biopolymers in TL regenerative treatment.

Loss of LEUCINE CARBOXYL METHYLTRANSFERASE 1 interferes with metal homeostasis in Arabidopsis and enhances susceptibility to environmental stresses.

The biochemical function of LEUCINE CARBOXYL METHYLTRANSFERASE 1 (LCMT1) is to transfer a methyl group from the methyl donor S-adenosylmethionine (SAM) to the catalytic subunits of PROTEIN PHOSPHATASE 2A (PP2Ac), PP4 and PP6. This post-translational modification by LCMT1 is found throughout eukaryotes from yeast to animals and plants, indicating that its function is essential. However, Arabidopsis with knocked out LCMT1 still grows and develops almost normally, at least under optimal growth conditions. We therefore proposed that the presence of LCMT1 would be important under non-optimal growth conditions and favoured plant survival during evolution. To shed light on the physiological functions of plant LCMT1, phenotypes of the lcmt1 mutant and wild type Arabidopsis were compared under various conditions including exposure to heavy metals, variable chelator concentrations, and increased temperature. The lcmt1 mutant was found to be more susceptible to these environmental changes than wild type and resulted in poor growth of seedlings and rosette stage plants. Element analysis of rosette stage plants mainly showed a difference between the lcmt1 mutant and wild type regarding concentrations of sodium and boron, two-fold up or halved, respectively. In both lcmt1 and wild type, lack of EDTA in the growth medium resulted in enhanced concentration of copper, manganese, zinc and sulphur, and especially lcmt1 growth was hampered by these conditions. The altered phenotype in response to stress, the element and mRNA transcript analysis substantiate that LCMT1 has an important role in metal homeostasis and show that functional LCMT1 is necessary to prevent damages from heat, heavy metals or lack of chelator.

Accuracy of obesity indices alone or in combination for prediction of diabetes: A novel risk score by linear combination of general and abdominal measures of obesity.

Background: The predictive power of obesity measures varies according to the presence of coexistent measures. The present study aimed to determine the predictive power of combinations of obesity measures for diabetes by calculation of a linear risk score. Methods: Data from a population-based cross-sectional study of 994 representative samples of Iranian adults in Babol, Iran were analyzed. Measures of obesity including waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), and waist to hip ratio (WHR) were calculated, and diabetes was diagnosed by fasting blood sugar >126 mg/dl or taking antidiabetic medication. Multiple logistic regression model was used to develop a logit risk score based on BMI, WC, WHtR, and WHR. The ROC analysis was applied to determine the priority of every single index and combined logit score for the prediction of diabetes. Results: All four measures of general and abdominal obesity were predictors of diabetes individually in both sexes (P=0.0001). Calculation of risk score for a combination of all measures use full model improved predictive power. Adjustment for age resulted in further improvement in diagnostic power and combined novel risk score differentiated individuals with and without diabetes with an accuracy of 0.747 (95%CI: 0.690-0.808) in men and 0.789 (95%CI: 0.740, 0.837) in women. Conclusion: These findings indicate that the simultaneous calculation of age-adjusted risk score for all measures provides stronger diagnostic accuracy in both sexes. This issue suggests the calculation of combined risk scores for all obesity indices especially in a population at borderline risk.

Clinical, demographic, and laboratory characteristics of COVID -19 infection and risk of in-hospital mortality. A single center 4.

Background: Despite advances in preventive measures, COVID -19 spread and mortality is continuing due to delay in timely diagnosis. This problem is partly dependent on variations in disease characteristics, distribution of risk factors particularly comorbidities and demographic characteristics of patients. This study aimed to determine the clinical presentation and associated factors of mortality in patients hospitalized with COVID -19 infection. Methods: Patients were divided into survivor and deceased groups, and clinical and laboratory findings and factors associated with mortality between the two groups were compared by calculating odds ratio (OR) with 95% confidence interval (95% CI). Results: A total of 257 patients (female 45.1%) with a mean age of 59.8+15.7 years and a mean hospital stay of 4.89+3.57 days were studied. Diabetes, hypertension, cardiovascular disease and chronic renal disease (CRD) were found in 29.6%, 37.5%, 16.3% and 3.5% of all patients, respectively. Forty-one (16%) patients died. Factors such as age >50 years, coexisting CRD, serum creatinine > 2 mg/dl; SPO2 <70% lymphocytes < 20% during hospitalization were independently associated with mortality. The adjusted ORs (95% CI) were 10.08 (1.39-73); 4.51(1.15-17.61); 6 (1.14-31.5); 16.8(2.93-96.7); and 4.9(1.31-18.1), respectively. Most of the expected effective drugs were not associated with lower mortality. Conclusion: These results indicate a high in-hospital mortality rate in COVID -19 patients. Some mortality factors occurring during hospitalization were reversible and could be prevented by timely diagnosis and appropriate treatment.

The Technological Advancement to Engineer Next-Generation Stent-Grafts: Design, Material, and Fabrication Techniques.

Endovascular treatment of aortic disorders has gained wide acceptance due to reduced physiological burden to the patient compared to open surgery, and ongoing stent-graft evolution has made aortic repair an option for patients with more complex anatomies. To date, commercial stent-grafts are typically developed from established production techniques with simple design structures and limited material ranges. Despite the numerous updated versions of stent-grafts by manufacturers, the reoccurrence of device-related complications raises questions about whether the current manfacturing methods are technically able to eliminate these problems. The technology trend to produce efficient medical devices, including stent-grafts and all similar implants, should eventually change direction to advanced manufacturing techniques. It is expected that through recent advancements, especially the emergence of 4D-printing and smart materials, unprecedented features can be defined for cardiovascular medical implants, like shape change and remote battery-free self-monitoring. 4D-printing technology promises adaptive functionality, a highly desirable feature enabling printed cardiovascular implants to physically transform with time to perform a programmed task. This review provides a thorough assessment of the established technologies for existing stent-grafts and provides technical commentaries on known failure modes. They then discuss the future of advanced technologies and the efforts needed to produce next-generation endovascular implants.

Prevention of Osteoarthritis Progression by Statins, Targeting Metabolic and Inflammatory Aspects: A Review.

BACKGROUND AND PURPOSE: Several traditional risk factors of atherosclerosis such as age, obesity, and altered lipid metabolism are shared with osteoarthritis (OA). Metabolic abnormalities and atheromatous vascular disease are linked with systemic inflammation and progression of OA. Hence, treatment of OA with statins is expected to improve metabolic abnormalities and prevent OA progression. Many studies which have addressed this issue found inconsistent results. This review aims to elucidate the effect of statins in OA by summarizing the existing data. METHODS: Potential studies in English language published in Medline/PubMed, Scopus and Google Scholar since 2000 were searched by using keywords such as osteoarthritis, statins, progression, treatment, prevalence, synovitis, pain. Fourteen papers were found to be relevant and were summarised. RESULTS: Data regarding symptomatic effect of statins in OA are scarce and the results varied from no effect to a small improvement or even increased risk of pain in knee OA. However, most studies on the incidence and progression of OA found a significant decreased risk of incident OA, as well as reduced risk of radiographic progression in statin users vs. non-users. Factors such as patient adherence, duration of treatment, and higher cumulative statin doses were associated with greater efficacy. CONCLUSION: Existing data indicate a preventing effect of statin therapy on OA progression. However, unless a formal meta-analysis with weight analysis is made, a conclusion cannot be drawn.

Risk of COVID-19 infection in patients with rheumatic disease taking disease-modifying anti-rheumatic drugs.

BACKGROUND AND OBJECTIVE: Patients with rheumatic disease taking long-term disease-modifying anti-rheumatic drugs (DMARDs) are expected to have a higher risk of infection due to the alterations in cellular immunity associated with these medications. However, the potential risks associated with these drugs remain unclear. This study aimed to estimate the risk of COVID-19 infection in patients with rheumatic disease taking disease-modifying anti-rheumatic drugs. METHODS: Patients with autoimmune rheumatic disease taking DMARDs with or without long-term (> 6 months) HCQ treatment prior to the COVID-19 outbreak were selected consecutively. The diagnosis of COVID-19 was made based on the history of symptoms suggestive of the disease and/or serum IgG positivity. During statistical analysis, the risk of COVID-19 infection was calculated in rheumatic patients taking DMARDs versus controls, as well as in patients taking HCQ versus those who are not. The ORs and 95% CIs were also calculated. The participants in the control group were selected from individuals without RD. RESULTS: A total of 800 patients with RD and 449 controls were analyzed. COVID-19 infection was detected in 16.8% of rheumatic patients versus 17.6% of controls (OR 0.95; 95% CI 0.7-1.28). The proportions of COVID-19 infection in HCQ users versus non-users were 15.3% and 18.1%, respectively (OR 0.87; 95% CI 0.61-1.26). These results remained unchanged after adjusting for all covariates using logistic regression analysis. CONCLUSION: These findings indicate that rheumatic patients taking DMARDs are not at a higher risk of COVID-19 infection, and that HCQ therapy has no influence on the risk of COVID-19 infection. Key points • The risk of COVID-19 infection is not higher in patients with RD on DMARD therapy. • The prevalence of COVID-19 infection in HCQ users has not significant difference relative to non-users. • Significant percent of RD patients taking DMARDs had asymptomatic infection. • There was a positive association between leflunamide therapy and the risk of COVID-19 infection.

An amplified derepression controller with multisite inhibition and positive feedback.

How organisms are able to maintain robust homeostasis has in recent years received increased attention by the use of combined control engineering and kinetic concepts, which led to the discovery of robust controller motifs. While these motifs employ kinetic conditions showing integral feedback and homeostasis for step-wise perturbations, the motifs' performance differ significantly when exposing them to time dependent perturbations. One type of controller motifs which are able to handle exponentially and even hyperbolically growing perturbations are based on derepression. In these controllers the compensatory reaction, which neutralizes the perturbation, is derepressed, i.e. its reaction rate is increased by the decrease of an inhibitor acting on the compensatory flux. While controllers in this category can deal well with different time-dependent perturbations they have the disadvantage that they break down once the concentration of the regulatory inhibitor becomes too low and the compensatory flux has gained its maximum value. We wondered whether it would be possible to bypass this restriction, while still keeping the advantages of derepression kinetics. In this paper we show how the inclusion of multisite inhibition and the presence of positive feedback loops lead to an amplified controller which is still based on derepression kinetics but without showing the breakdown due to low inhibitor concentrations. By searching for the amplified feedback motif in natural systems, we found it as a part of the plant circadian clock where it is highly interlocked with other feedback loops.

A novel biocompatible polymeric blend for applications requiring high toughness and tailored degradation rate.

Finding the right balance in mechanical properties and degradation rate of biodegradable materials for biomedical applications is challenging, not only at the time of implantation but also during biodegradation. For instance, high elongation at break and toughness with a mid-term degradation rate are required for tendon scaffold or suture application, which cannot be found in each alpha polyester individually. Here, we hypothesise that blending semi-crystalline poly(p-dioxanone) (PDO) and poly(lactide-co-caprolactone) (LCL) in a specific composition will enhance the toughness while also enabling tailored degradation times. Hence, blends of PDO and LCL (PDO/LCL) were prepared in varying concentrations and formed into films by solvent casting. We thoroughly characterised the chemical, thermal, morphological, and mechanical properties of the new blends before and during hydrolytic degradation. Cellular performance was determined by seeding mouse fibroblasts onto the samples and culturing for 72 hours, before using proliferation assays and confocal imaging. We found that an increase in LCL content causes a decrease in hydrolytic degradation rate, as indicated by induced crystallinity, surface and bulk erosions, and tensile properties. Interestingly, the noncytotoxic blend containing 30% PDO and 70% LCL (PDO3LCL7) resulted in small PDO droplets uniformly dispersed within the LCL matrix and demonstrated a tailored degradation rate and toughening behaviour with a notable strain-hardening effect reaching 320% elongation at break; over 3 times the elongation of neat LCL. In summary, this work highlights the potential of PDO3LCL7 as a biomaterial for biomedical applications like tendon tissue engineering or high-performance absorbable sutures.

Biofabrication and Signaling Strategies for Tendon/Ligament Interfacial Tissue Engineering.

Tendons and ligaments (TL) have poor healing capability, and for serious injuries like tears or ruptures, surgical intervention employing autografts or allografts is usually required. Current tissue replacements are nonideal and can lead to future problems such as high retear rates, poor tissue integration, or heterotopic ossification. Alternatively, tissue engineering strategies are being pursued using biodegradable scaffolds. As tendons connect muscle and bone and ligaments attach bones, the interface of TL with other tissues represent complex structures, and this intricacy must be considered in tissue engineered approaches. In this paper, we review recent biofabrication and signaling strategies for biodegradable polymeric scaffolds for TL interfacial tissue engineering. First, we discuss biodegradable polymeric scaffolds based on the fabrication techniques as well as the target tissue application. Next, we consider the effect of signaling factors, including cell culture, growth factors, and biophysical stimulation. Then, we discuss human clinical studies on TL tissue healing using commercial synthetic scaffolds that have occurred over the past decade. Finally, we highlight the challenges and future directions for biodegradable scaffolds in the field of TL and interface tissue engineering.

Conjunctival polymerase chain reactions in COVID-19 patients and its correlation with clinical and paraclinical indexes.

BACKGROUND AND OBJECTIVES: This study aimed to detect SARS-CoV-2 in conjunctival samples of COVID-19 patients to investigate the transmission route of COVID-19 and its correlation with laboratory indexes. MATERIALS AND METHODS: In this cross-sectional study, 44 COVID-19 patients were tested for conjunctival PCR in Ayatollah Rouhani hospital of Babol, Iran, in January and February 2021. The conjunctival samples were collected using a conjunctival swab and suspended in a viral transport medium. After RNA extraction and cDNA synthesis, real-time PCR was performed to investigate the SARS-CoV-2 genome in samples. The ocular manifestations and laboratory indexes were evaluated for all patients. RESULTS: Among 44 COVID-19 patients, 6 samples (13.63%) were positive in terms of conjunctival PCR. The mean ± SD age of conjunctival PCR-positive patients was 76.17 ± 16.61-year-old, while conjunctival PCR-negative COVID-19 patients were aged 57.54 ± 13.61-year-old (p <0.05). D-dimer serum level is significantly higher in conjunctival PCR-positive COVID-19 patients (4001.00 ± 3043.36 µg/ml) compared to normal individuals (496.80 ± 805.92 µg/ml, p <0.01). CONCLUSION: Our study showed that the conjunctiva and tear contain the SARS-CoV-2 in COVID-19 patients as a possible transmission route.

A bio-inductive collagen scaffold that supports human primary tendon-derived cell growth for rotator cuff repair.

BACKGROUND: Rotator Cuff (RC) tendon tearing is a common clinical problem and there is a high incidence of revision surgery due to re-tearing. In an effort to improve patient outcome and reduce surgical revision, scaffolds have been widely used for augmentation of RC repairs. However, little is known about how scaffolds support tendon stem cell growth or facilitate tendon regeneration. The purpose of this study is to evaluate the structural and biological properties of a bioactive collagen scaffold (BCS) with the potential to promote tendon repair. Additionally, we conducted a pilot clinical study to assess the safety and feasibility of using the BCS for repair of RC tears. METHODS: A series of physical, ultrastructural, molecular and in vitro tests determined the biocompatibility and teno-inductive properties of this BCS. In addition, a prospective case study of 18 patients with RC tendon tears (>20 â€‹mm in diameter) was performed in an open-label, single-arm study, involving either mini-open or arthroscopic surgical RC repair with the BCS. Clinical assessment of RC repair status was undertaken by MRI-imaging at baseline, 6 and 12 months and patient evaluated questionnaires were taken at baseline as well as 3, 6 & 12 months. RESULTS: The BCS consists of highly purified type-I collagen, in bundles of varying diameter, arranged in a higher order tri-laminar structure. BCS have minimal immunogenicity, being cell and essentially DNA-free as well as uniformly negative for the porcine α-Gal protein. BCS seeded with human primary tendon-derived cells and exposed to 6% uniaxial loading conditions in vitro, supported increased levels of growth and proliferation as well as up-regulating expression of tenocyte differentiation marker genes including TNMD, Ten-C, Mohawk and Collagen-1α1. To test the safety and feasibility of using the BCS for augmentation of RC repairs, we followed the IDEAL framework and conducted a first, open-label single arm prospective case series study of 18 patients. One patient was withdrawn from the study at 3 months due to wound infection unrelated to the BCS. The remaining 17 cases showed that the BCS is safe to be implanted. The patients reported encouraging improvements in functional outcomes (ASES, OSS and Constant-Murley scores), as well as quality of life assessments (AQoL) and a reduction in VAS pain scores. MRI assessment at 12 months revealed complete healing in 64.8% patients (11/17), 3 partial thickness re-tears (17.6%) and 3 full thickness re-tears (17.6%). CONCLUSION: The BCS is composed of type-I collagen that is free of immunogenic proteins and supports tendon-derived cell growth under mechanical loading in vitro. This pilot study shows that it is safe and feasible to use BCS for RC argumentation and further controlled prospective studies are required to demonstrate its efficacy. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The results of this study indicate that this bioactive collagen scaffold has unique properties for supporting tendon growth and that it is non-immunogenic. The clinical study further confirms that the scaffold is a promising biological device for augment of human rotator cuff repairs.

Effectiveness and safety of routine calcium supplementation in postmenopausal women. A narrative review.

BACKGROUND: To determine whether routine administration of calcium supplementation is useful in postmenopausal women, while it is associated with an increased risk of cardiovascular complications. METHODS: A literature search was performed using Medline/PubMed, Scopus and Google Scholar by using relevant keywords. RESULTS: Calcium supplement exerts a small protective effect against bone loss which disappears after cessation. Antifracture effect of supplemental calcium is limited to older frail women or community-dwelling residents who are vitamin D deficient and have inadequate dietary calcium intake. The results of studies on the association between calcium supplementation and cardiovascular complications are contradictory and do not lead to a decisive conclusion CONCLUSION: Current data do not support routine calcium supplementation to all postmenopausal women for prevention of bone loss or bone fracture.

Multi-targeted trehalose-6-phosphate phosphatase I harbors a novel peroxisomal targeting signal 1 and is essential for flowering and development.

MAIN CONCLUSION: This work reveals information about new peroxisomal targeting signals type 1 and identifies trehalose-6-phosphate phosphatase I as multitargeted and is implicated in plant development, reproduction, and stress response. A putative, non-canonical peroxisomal targeting signal type 1 (PTS1) Pro-Arg-Met > was identified in the extreme C-terminus of trehalose-6-phosphate phosphatase (TPP)I. TPP catalyzes the final step of trehalose synthesis, and the enzyme was previously characterized to be nuclear only (Krasensky et al. in Antioxid Redox Signal 21(9):1289-1304, 2014). Here we show that the TPPI C-terminal decapeptide ending with Pro-Arg-Met > or Pro-Lys-Met > can indeed function as a PTS1. Upon transient expression in two plant expression systems, the free C- or N-terminal end led to the full-length TPPI targeting to peroxisomes and plastids, respectively. The nucleus and nucleolus targeting of the full-length TPPI was observed in both cases. The homozygous T-DNA insertion line of TPPI showed a pleiotropic phenotype including smaller leaves, shorter roots, delayed flowering, hypersensitivity to salt, and a sucrose dependent seedling development. Our results identify novel PTS1s, and TPPI as a protein multi-targeted to peroxisomes, plastids, nucleus, and nucleolus. Altogether our findings implicate an essential role for TPPI in development, reproduction, and cell signaling.