In vitro collagen biomarkers in mechanically stimulated human tendon cells: a systematic review.

OBJECTIVE: The aim of this study was to comprehensively examine and summarize the available in vitro evidence regarding the relationship between mechanical stimulation and biomarkers of collagen synthesis in human-derived tendon cells. METHODS: Systematic review with narrative analyses and risk of bias assessment guided by the Health Assessment and Translation tool. The electronic databases MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid) and COMPENDEX (Engineering Village) were systematically searched from inception to 3 August 2023. Inclusion criteria encompassed English language, original experimental, or quasi-experimental in vitro publications that subjected human tendon cells to mechanical stimulation, with collagen synthesis (total collagen, type I, III, V, XI, XII, and XIV) and related biomarkers (matrix metalloproteinases, transforming growth factor ß, scleraxis, basic fibroblast growth factor) as outcomes. RESULTS: Twenty-one publications were included. A pervasive definite high risk of bias was evident in all included studies. Owing to incomplete outcome reporting and heterogeneity in mechanical stimulation protocols, planned meta-analyses were unfeasible. Reviewed data suggested that human tendon cells respond to mechanical stimulation with increased synthesis of collagen (e.g., COL1A1, procollagen, total soluble collagen, etc.), scleraxis and several matrix metalloproteinases. Results also indicate that mechanical stimulation dose magnitude may influence synthesis in several biomarkers. CONCLUSIONS: A limited number of studies, unfortunately characterized by a definite high risk of bias, suggest that in vitro mechanical stimulation primarily increases type I collagen synthesis by human tendon cells. Findings from this systematic review provide researchers and clinicians with biological evidence concerning the possible beneficial influence of exercise and loading on cellular-level tendon adaptation.

Activation and Identification of a Griseusin Cluster in Streptomyces sp. CA-256286 by Employing Transcriptional Regulators and Multi-Omics Methods.

Streptomyces are well-known producers of a range of different secondary metabolites, including antibiotics and other bioactive compounds. Recently, it has been demonstrated that "silent" biosynthetic gene clusters (BGCs) can be activated by heterologously expressing transcriptional regulators from other BGCs. Here, we have activated a silent BGC in Streptomyces sp. CA-256286 by overexpression of a set of SARP family transcriptional regulators. The structure of the produced compound was elucidated by NMR and found to be an N-acetyl cysteine adduct of the pyranonaphtoquinone polyketide 3'-O-α-d-forosaminyl-(+)-griseusin A. Employing a combination of multi-omics and metabolic engineering techniques, we identified the responsible BGC. These methods include genome mining, proteomics and transcriptomics analyses, in combination with CRISPR induced gene inactivations and expression of the BGC in a heterologous host strain. This work demonstrates an easy-to-implement workflow of how silent BGCs can be activated, followed by the identification and characterization of the produced compound, the responsible BGC, and hints of its biosynthetic pathway.

Complete Genome Sequence of Streptomyces sp. Strain CA-256286.

Here, we report the sequencing, assembly, and annotation of the genome of Streptomyces sp. strain CA-256286. The genome consists of a linear 7,726,360-nucleotide chromosome and a linear 466,817-nucleotide putative plasmid. This strain is predicted to produce a range of novel secondary metabolites.

Diagnostic accuracy of ultrasound and MRI for Achilles tendon xanthoma in people with familial hypercholesterolemia: A systematic review.

BACKGROUND: Achilles tendon xanthoma (ATX) results from tendon thickening and subclinical inflammation triggered by hypercholesterolemia, and is associated with more severe coronary artery disease and a higher risk of cardiovascular events. The ability to detect ATX by clinical examination is limited, and diagnostic imaging, for instance, using ultrasonography or magnetic resonance imagine (MRI), may improve the identification of ATX. However, the accuracy of ultrasound (US) imaging or MRI in identifying ATX in people with familial hypercholesterolemia (FH) has not been systematically reviewed. OBJECTIVE: The objective of this study was to systematically review the accuracy of US imaging or MRI in diagnosing ATX in individuals with FH. METHODS: Searches in Medline, Embase, Cochrane Central, and Cochrane Database of Systematic Reviews on the Ovid platform from inception to April 15, 2018, were conducted to identify articles. Any study design that included US imaging or MRI of Achilles tendon xanthoma in people with FH, and that included a control group of non-FH participants with either normal or symptomatic Achilles tendons, was considered eligible. All of the included studies were reviewed according to the STAndards for the Reporting of Diagnostic accuracy (STARD) method. A qualitative synthesis of the included studies was undertaken. RESULTS: Fifteen studies with 699 patients with FH and 868 non-FH participants were included. Among the non-FH participants, 26 individuals had other documented Achilles tendon pathology (trauma or overuse). Evaluation with the STARD checklist suggested that the quality of evidence was low. US imaging and MRI may have acceptable sensitivity in detecting tendon thickening associated with ATX. There is a wide range in the suggested thickness thresholds and in the estimates of diagnostic accuracy. CONCLUSIONS: A small amount of low-quality evidence suggests that ultrasonography or MRI can improve clinicians' accuracy in identifying ATX in people with FH, thereby identifying those with more severe coronary artery disease.

Barriers and facilitators to employment for young adults with mental illness: a scoping review.

OBJECTIVES: The issue of gaining employment for those with mental illness is a growing global concern. For many in the young adult population, who are at a transitional age, employment is a central goal. In response, we conducted a scoping review to answer the question, 'What are the barriers and facilitators to employment for young adults with mental illness?' DESIGN: We conducted a scoping review in accordance to the Arksey and O'Malley framework. We performed a thorough search of Medline, EMBASE, CINAHL, ABI/INFORM, PsycINFO and Cochrane. We included studies that considered young adults aged 15-29 years of age with a mental health diagnosis, who were seeking employment or were included in an employment intervention. RESULTS: Our search resulted in 24 research articles that focused on employment for young adults with mental illness. Four main themes were extracted from the literature: (1) integrated health and social services, (2) age-exposure to employment supports, (3) self-awareness and autonomy and (4) sustained support over the career trajectory. CONCLUSIONS: Our review suggests that consistent youth-centred employment interventions, in addition to usual mental health treatment, can facilitate young adults with mental illness to achieve their employment goals. Aligning the mental health and employment priorities of young adults may result in improved health and social outcomes for this population while promoting greater engagement of young adults in care.

Improving access to competitive employment for service users in forensic psychiatric units.

Employment has been proven to be an effective recovery tool and therapeutic intervention for those with severe and enduring mental health conditions. Aside from monetary reward, employment is a means of structuring time and provides a sense of worth and achievement, which enhances self-esteem and confidence. A social identity is developed through employment, encouraging social support and increasing social networks. Securing employment can bring about improved quality of life and positive change in one's social circumstances; therefore it can reduce symptoms associated with mental illness and potentially prevent re-offending, as the individual develops a sense of independence, self-efficacy, and value. Barriers to employment exist for forensic mental health service users and therefore it is imperative that employment needs are addressed at the earliest possible stage in recovery. An evaluation of employment activities across two forensic mental health units revealed a lack of appropriate employment opportunities for service users, and those roles available were not implemented in line with recommended best practice. In response to this issue several enterprises were established to offer opportunities for service users to engage in meaningful employment and develop skills that a future employer would value. Each enterprise responds to a business need within the units to ensure sustainability of services. The enterprises are essentially micro-businesses with social objectives whose surpluses are reinvested for the purpose of increasing opportunities for service users. The enterprises are underpinned by the philosophy of the Individual Placement and Support (IPS) model; empirical evidence suggests that the IPS model is the most effective intervention, based on the 'place then train' philosophy. The model recommends a focus upon rapid job search to achieve competitive employment for those who want to work; opportunities sourced should be consistent with individual preference and benefits counselling offered. Support should be time unlimited and integrated with mental health treatment. A person-centred and strengths-based approach is also adopted to support people to build on their strengths, establish goals, and encourage motivation.