"Advancing the implementation of innovative analytical technologies in pharmaceutical manufacturing-Some regulatory considerations".

Analytical technologies and methods play a pivotal role in attribute understanding and control which are essential to the rapidly evolving field of pharmaceutical development and manufacturing. These technologies are advancing quickly, where innovations often involve both new scientific approaches and novel applications of established techniques. In many cases, the lack of harmonized global regulatory expectations presents challenges for the adoption of advanced technologies.

ICON 2023: International Scientific Tendinopathy Symposium Consensus - the core outcome set for Achilles tendinopathy (COS-AT) using a systematic review and a Delphi study of professional participants and patients.

To develop a core outcome set for Achilles tendinopathy (COS-AT) for use in clinical trials we performed a five-step process including (1) a systematic review of available outcome measurement instruments, (2) an online survey on truth and feasibility of the available measurement instruments, (3) an assessment of the methodological quality of the selected outcome measurement instruments, (4) an online survey on the outcome measurement instruments as COS and (5) a consensus in-person meeting. Both surveys were completed by healthcare professionals and patients. The Outcome Measures in Rheumatology guidelines with a 70% threshold for consensus were followed.

Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial.

Objectives: To investigate if daily treatment with glyceryl trinitrate (GTN) ointment, over 24 weeks combined with a 12-week eccentric exercise programme is more effective for chronic mid-portion Achilles tendinopathy than placebo ointment and eccentric exercise.

Methods: This was a single-site randomised double-blind placebo-controlled trial at an acute hospital, Dublin, Ireland. Patients with chronic mid-portion Achilles tendinopathy were randomised to either 24 weeks of daily GTN ointment or placebo ointment.

Pathways driving tendinopathy and enthesitis: siblings or distant cousins in musculoskeletal medicine?

Tendinopathy and enthesitis share clinical, anatomical, and molecular parallels. However, their relationship is complex, presenting challenges in diagnosis and treatment. The biomechanics underlying these pathologies, together with relative immune and stromal contributions to pathology, are characterised by crucial comparative elements.

Best Practices for Microbial Challenge In-Use Studies to Evaluate the Microbial Growth Potential of Parenteral Biological Products; Industry and Regulatory Considerations.

Microbial challenge in-use studies are performed to evaluate the potential for microbial proliferation in preservative-free single-dose biological products after first puncture and potential accidental contamination during dose preparation (e.g., reconstitution or dilution) and storage.

Structured content and data management-enhancing acceleration in drug development through efficiency in data exchange.

Innovation in pharmaceutical therapeutics is critical for the treatment of serious diseases with unmet medical need. To accelerate the approval of these innovative treatments, regulatory agencies throughout the world are increasingly adopting the use of expedited pathways and collaborative regulatory reviews. These pathways are primarily driven by promising clinical results but become challenging for Chemistry, Manufacturing, and Controls (CMC) information in regulatory submissions.

Frozen shoulder.

Frozen shoulder is a common debilitating disorder characterized by shoulder pain and progressive loss of shoulder movement. Frozen shoulder is frequently associated with other systemic conditions or occurs following periods of immobilization, and has a protracted clinical course, which can be frustrating for patients as well as health-care professionals. Frozen shoulder is characterized by fibroproliferative tissue fibrosis, whereby fibroblasts, producing predominantly type I and type III collagen, transform into myofibroblasts (a smooth muscle phenotype), which is accompanied by inflammation, neoangiogenesis and neoinnervation, resulting in shoulder capsular fibrotic contractures and the associated clinical stiffness.

Biopsychosocial approach to tendinopathy.

Tendinopathy describes a spectrum of changes that occur in damaged tendons, leading to pain and reduced function that remains extremely challenging for all clinicians. There is an increasing awareness of the influence that psychological and psychosocial components, such as self-efficacy and fear-avoidance, have on rehabilitation outcomes in musculoskeletal medicine. Although it is widely accepted that psychological/psychosocial factors exist in tendinopathy, there is currently a distinct lack of trials measuring how these factors affect clinical outcomes.

ICON 2020-International Scientific Tendinopathy Symposium Consensus: A Scoping Review of Psychological and Psychosocial Constructs and Outcome Measures Reported in Tendinopathy Clinical Trials.

Objective: To identify and describe the psychological and psychosocial constructs and outcome measures used in tendinopathy research.

Design: Scoping review.

Literature Search: We searched the PubMed, EMBASE, Scopus, Web of Science, PEDro, CINAHL, and APA PsychNet databases on July 10, 2021, for all published studies of tendinopathy populations measuring psychological and psychosocial factors.

Rapidly progressive crescentic diabetic nephropathy: two case reports.

Crescents are not a well recognised feature of diabetic nephropathy. We present two cases of patients presenting with a rapid decline in renal function and subacute onset of nephrotic syndrome. Glomerulonephritis screening was negative, and renal biopsy revealed non-necrotising cellular crescents and typical features of late-stage diabetic nephropathy.

The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review.

The physiological effects of physical exercise are ubiquitously reported as beneficial to the cardiovascular and musculoskeletal systems. Exercise is widely promoted by medical professionals to aid both physical and emotional wellbeing; however, mechanisms through which this is achieved are less well understood. Despite numerous beneficial attributes, certain types of exercise can inflict significant significant physiological stress.

Management of patellar tendinopathy: a systematic review and network meta-analysis of randomised studies.

Objectives: We performed a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) to provide insights into the effectiveness of available treatment modalities in patellar tendinopathy(PT).

Methods: Several databases were searched in May 2021 for RCTs assessing the effectiveness of any intervention compared with any other intervention, placebo or no treatment for pain and/or function in PT. The risk of bias and strength of evidence were assessed with the Cochrane Collaboration and GRADE (Grading of Recommendations, Assessment, Development and Evaluations)/GRADE-NMA tools.

ICON 2020-International Scientific Tendinopathy Symposium Consensus: A Systematic Review of Outcome Measures Reported in Clinical Trials of Achilles Tendinopathy.

Background: Nine core domains for tendinopathy have been identified. For Achilles tendinopathy there is large variation in outcome measures used, and how these fit into the core domains has not been investigated.

Objective: To identify all available outcome measures outcome measures used to assess the clinical phenotype of Achilles tendinopathy in prospective studies and to map the outcomes measures into predefined health-related core domains.

Primary membranous glomerulonephritis with negative serum PLA2R in haemophilia A successfully managed with rituximab - case report and review of the literature.

Background: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause a wide range of glomerular pathologies. In people with haemophilia, transfusion-associated infections with these viruses are common and definitive pathological diagnosis in this population is complicated by the difficulty of safely obtaining a renal biopsy. Membranous nephropathy (MN) is a common cause of adult onset nephrotic syndrome occurring in both primary and secondary forms.

Tendinopathy.

Tendinopathy describes a complex multifaceted pathology of the tendon, characterized by pain, decline in function and reduced exercise tolerance. The most common overuse tendinopathies involve the rotator cuff tendon, medial and lateral elbow epicondyles, patellar tendon, gluteal tendons and the Achilles tendon. The prominent histological and molecular features of tendinopathy include disorganization of collagen fibres, an increase in the microvasculature and sensory nerve innervation, dysregulated extracellular matrix homeostasis, increased immune cells and inflammatory mediators, and enhanced cellular apoptosis.

How does surgery compare to sham surgery or physiotherapy as a treatment for tendinopathy? A systematic review of randomised trials.

Purpose: To assess the effectiveness of surgery on all tendinopathies by comparing it to no treatment, sham surgery and exercise-based therapies for both mid-term (12 months) and long-term (> 12 months) outcomes.

Methods: Our literature search included EMBASE, Medline, CINAHL and Scopus. A combined assessment of internal validity, external validity and precision of each eligible study yielded its overall study quality.

Topical glyceryl trinitrate for the treatment of tendinopathies: a systematic review.

Objective: To produce a best evidence synthesis of the clinical effects of topical glyceryl trinitrate (GTN) in the treatment of tendinopathies.

Design: A systematic review of published randomised controlled trials (RCTs) of the use of GTN in patients with tendinopathy.

Data Sources: MEDLINE, Embase, Scopus and CINAHL from database inception to January 2018.

Fibrosis of the Choroid Plexus Filtration Membrane.

We report a previously undescribed inflammatory lesion consisting of deposition of activated complement (C3d and C9neo) in association with major histocompatibility complex type II (MHC2)-positive activated microglia in choroid plexus villi exhibiting classical fibrous thickening of the pericapillary filtration membrane. The proportion of villi affected ranged from 5% to 90% in 56 adult subjects with diseases of the CNS and 11 subjects with no preexisting disease of the CNS. In 3 of the 4 children studied, 2% or less of examined villi showed stromal thickening, complement deposition, and the presence of MHC2-positive microglia; in adults, the proportion of villi affected increased with age.

Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia.

Functional defects of the mitochondrial translation machinery, as a result of mutations in nuclear-encoded genes, have been associated with combined oxidative phosphorylation (OXPHOS) deficiencies. We report siblings with congenital sensorineural deafness and lactic acidemia in association with combined respiratory chain (RC) deficiencies of complexes I, III and IV observed in fibroblasts and liver. One of the siblings had a more severe phenotype showing progressive hepatic and renal failure.

Transmission of stability information through the N-domain of tropomyosin is interrupted by a stabilizing mutation (A109L) in the hydrophobic core of the stability control region (residues 97-118).

Tropomyosin (Tm) is an actin-binding, thin filament, two-stranded α-helical coiled-coil critical for muscle contraction and cytoskeletal function. We made the first identification of a stability control region (SCR), residues 97-118, in the Tm sequence that controls overall protein stability but is not required for folding. We also showed that the individual α-helical strands of the coiled-coil are stabilized by Leu-110, whereas the hydrophobic core is destabilized in the SCR by Ala residues at three consecutive d positions.

'Have you seen what is on Facebook?' The use of social networking software by healthcare professions students.

Objective: The use of social networking software has become ubiquitous in our society. The aim of this study was to explore the attitudes and experiences of healthcare professional students using Facebook at our school, to determine if there is a need for development of policy to assist students in this area.

Design: A mixed-methods approach was employed, using semistructured interviews to identify themes which were explored using an online survey.