Fresh Versus Frozen Meniscal Allograft Transplant: Revisit or Redundant? A Systematic Review.

BACKGROUND: Fresh-frozen allografts are the current standard in meniscal allograft transplant (MAT) surgery, due to their availability, ease of preservation, and affordability. However, fresh-frozen grafts are associated with several clinical challenges such as graft shrinkage and extrusion, among many others. PURPOSE: To present the current knowledge on the use of fresh meniscal allografts, presenting whether benefits associated with fresh grafts provide sufficient evidence to support their use in clinical practice. STUDY DESIGN: Systematic review; Level of evidence, 5. METHODS: A comprehensive search was conducted with keywords listed below. After an initial screening on title and abstract, full-text articles were assessed with the inclusion criteria. RESULTS: A total of 78 studies matched the inclusion criteria. Literature and preclinical studies indicated that fresh meniscal allografts are beneficial for maintaining mechanical properties, graft ultrastructure, and matrix metabolism due to the presence of viable cells. Therefore, fresh allografts may address common complications associated with fresh-frozen MAT. To overcome challenges associated with both fresh-frozen and fresh allografts, a group has studied treating fresh-frozen allografts with a cell-based injection therapy. CONCLUSION: Fresh meniscal allografts pose several challenges including limited availability, demanding preservation procedures, and high costs. Although the role of viable cells within meniscal allografts remains controversial, these cells may be vital for maintaining tissue properties.

Cellular Enhancement of Frozen Meniscus Allograft Combining Native Meniscus and Mesenchymal Stromal Cell Injections.

OBJECTIVE: This proof-of-concept study investigated an improved cell-based injection therapy combining mesenchymal stem cells (MSCs) and meniscus cells (MCs) to support superior meniscus allograft repopulation and early revival compared to injecting MSCs alone. DESIGN: In this controlled laboratory study, frozen meniscus allograft samples were injected vertically with a cell suspension containing different ratios of MSCs and MCs or control (lactated ringers) and cultured for 28 days. Samples were analyzed weekly for cell viability, migration, and metabolism using histological and biochemical assays. Tissue medium was analyzed for matrix metalloproteinase (MMP) expression using zymography. RESULTS: Cellular repopulation of frozen allografts injected with different cell suspensions was validated by immunohistochemistry. Significant higher DNA content was evidenced in grafts treated with suspensions of MCs or MC:MSC (1:4 ratio). Cell metabolic activity was significantly different between all treated groups and control group after 1 week. Allografts injected with MCs showed significantly more cell proliferation than injections with MSCs. MMP2 activity was detected in medium of all grafts cellularized with MCs with or without MSCs. Scanning electron microscopy (SEM) analysis showed resolution of the needle puncture, but not in the control group. Cell labeling of MCs upon injection of mixed MC:MSC suspensions revealed a gradual increase in the cell ratio. CONCLUSIONS: The findings of this study establish that injection of MCs with or without MSCs enhances the cellularity of meniscus allograft to support early graft revival and remodeling.

More than a gut feeling: What is the role of the gastrointestinal tract in female athlete health?

As with much of science, the female athlete is under researched, particularly in the area of gastrointestinal (GI) physiology. Gut function is of pivotal importance to athletes in that it supports digestion and absorption of nutrients, as well as providing a barrier between the external environment and the circulation. While sex-derived differences in GI structure and function have been well characterised at rest, there remains a paucity of data examining this during exercise. The wider impact of the GI system has begun to be realised and it is now widely acknowledged to play a role in more systemic bodily systems. In the current review, we discuss localised issues including the GI structure, function, and microbiome of male and females. We also discuss GI-related symptoms experienced by athletes, highlight the differences in incidence between males and females, and discuss contributing factors. We then move beyond the gut to discuss wider biological processes that have been shown to have both sex-related differences and that are impacted by the GI system. Some of these areas include immune function and risk of illness, sleep, hormones, bone health and the gut-brain-axis. The magnitude of such effects and relationships is currently unknown but there is enough mechanistic data for future studies to consider a more central role that the gastrointestinal tract may play in overall female athlete health. HighlightsThere are both clear similarities and differences in male-female gastrointestinal structure and function.Females typically reported a greater prevalence of gastrointestinal symptoms at rest, in particular during menstruation, but not during exercise.The links between female microbiome, oestrogen, and systemic physiological and biological processes are yet to be fully elucidated.Many of the male-female differences seen (e.g. in immune function) may be, at least in part, influenced by such GI related differences.

Trimester-specific reference intervals for haemoglobin A1c (HbA1c) in pregnancy.

BACKGROUND: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA(1c)). The correlation of HbA(1c) with clinical outcomes emphasises the need to measure HbA(1c) accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA(1c) assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA(1c) in non-diabetic Caucasian women. METHODS: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. RESULTS: The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol/mol (DCCT: 4.7%-5.7%). HbA(1c) was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. CONCLUSIONS: HbA(1c) trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.

ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation.

Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix stiffness to changes in fibroblast phenotype are incompletely understood. Here, we evaluated the effect of matrix stiffness on genome-wide chromatin accessibility in freshly isolated lung fibroblasts using ATAC-seq. We found higher matrix stiffness profoundly increased global chromatin accessibility relative to lower matrix stiffness, and these alterations were in close genomic proximity to known profibrotic gene programs. Motif analysis of these regulated genomic loci identified ZNF416 as a putative mediator of fibroblast stiffness responses. Genome occupancy analysis using ChIP-seq confirmed that ZNF416 occupies a broad range of genes implicated in fibroblast activation and tissue fibrosis, with relatively little overlap in genomic occupancy with other mechanoresponsive and profibrotic transcriptional regulators. Using loss- and gain-of-function studies, we demonstrated that ZNF416 plays a critical role in fibroblast proliferation, extracellular matrix synthesis, and contractile function. Together, these observations identify ZNF416 as novel mechano-activated transcriptional regulator of fibroblast biology.