Acceptability of using the Raising Awareness Tool for Endometriosis (RATE) in general practice: a mixed methods pilot study.

AIMS: The Raising Awareness Tool for Endometriosis (RATE) was developed to facilitate discussions with health providers regarding endometriosis-associated symptoms. We aim to evaluate the acceptability of the RATE by general practitioners (GP), including determining the prevalence of symptoms of women presenting to general practice and immediate management of symptoms. METHODS: A mixed-methods study was undertaken using a combination of quantitative and qualitative data in Western Australian General Practices from 2021 to 2022. A purposive sample of 12 GPs were included, who recruited women (18-50 years) on attendance for consultation over a one- to two-week period, followed by qualitative interviews exploring GPs' experiences with the tool. The quantitative and qualitative components were integrated during analysis of results. RESULTS: A total of 111 women completed the RATE (mean: 33, standard deviation: 8.6 years) prior to routine consultation. The tool was considered to be acceptable for use in general practice and aided discussions on symptoms and management. Overall, 68.5% of patients experienced pelvic pain or discomfort, with 22.4% rating that this interfered with quality of life. Of those with pelvic pain, 75% had associated chronic pain conditions, and 42.1% reported allodynia. The chronic pain questions provoked GP uncertainty. After symptoms were identified, GPs arranged individualised investigations and follow-up. CONCLUSIONS: The RATE was considered to be acceptable for use in the general practice setting. It identified symptoms and initiated discussions on possible diagnosis as well as management of endometriosis. Further GP education on identifying those women at most risk of developing chronic pain syndromes is needed.

Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion.

Therapies using mesenchymal stromal cells (MSCs) to treat immune and inflammatory conditions are now at an exciting stage of development, with many MSC-based products progressing to phase II and III clinical trials. However, a major bottleneck in the clinical translation of allogeneic MSC therapies is the variable immunomodulatory properties of MSC products due to differences in their tissue source, donor heterogeneity and processes involved in manufacturing and banking. This variable functionality of MSC products likely contributes to the substantial inconsistency observed in the clinical outcomes of phase III trials of MSC therapies; several trials have failed to reach the primary efficacy endpoint. In this review, we discuss various strategies to consistently maintain or enhance the immunomodulatory potency of MSCs during ex vivo expansion, which will enable the manufacture of allogeneic MSC banks that have high potency and low variability. Biophysical and biochemical priming strategies, the use of culture additives such as heparan sulfates, and genetic modification can substantially enhance the immunomodulatory properties of MSCs during in vitro expansion. Furthermore, robust donor screening, the use of biomarkers to select for potent MSC subpopulations, and rigorous quality testing to improve the release criteria for MSC banks have the potential to reduce batch-to-batch heterogeneity and enhance the clinical efficacy of the final MSC product. Machine learning approaches to develop predictive models of individual patient response can enable personalized therapies and potentially establish correlations between in vitro potency measurements and clinical outcomes in human trials.

Getting square pegs out through round holes: A survey of Australian and New Zealand Gynaecologists regarding specimen retrieval.

AIMS: To evaluate morcellation practices among Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). MATERIALS AND METHODS: RANZCOG Fellows were invited to complete an online survey. This anonymous, cross-sectional survey consisted of 29 questions regarding demographics and morcellation practices. RESULTS: Four hundred and thirty eight (19.04%) of 2300 RANZCOG Fellows responded, and of these 258 (11.22%) completed the entire survey; analysis was undertaken on data from the latter respondents. Respondents were broadly representative of all RANZCOG Fellows regarding gender, age, and location. Of the respondents, 53.10% considered themselves advanced laparoscopic surgeons. Of respondents who had worked as gynaecology consultants prior to 2014, 39.39% used uncontained power morcellation prior to 2014, compared to 17.58% since (a decrease of 44.63%). The most common reasons for utilising uncontained power morcellation less often were the 2014 Food and Drug Administration warnings (40.31%), risk of adverse outcomes (33.72%), and recommendations from colleges such as RANZCOG (27.13%). When undertaking an operation that required specimen extraction, the most common methods used were: employing an open approach from the get-go (utilised by respondents in 31.01% of such cases); contained manual morcellation (28.90%); and conversion to intra-operative laparotomy (10.10%). CONCLUSIONS: There has been a strong trend away from uncontained power morcellation since 2014, with a 36.00% increase in clinicians who never use uncontained power morcellation, and an 80.65% decrease in clinicians who always use this method of specimen extraction. The most common reason cited for employing uncontained power morcellation less often was the 2014 Food and Drug Administration's warnings.

Deficiency of Natriuretic Peptide Receptor 2 Promotes Bicuspid Aortic Valves, Aortic Valve Disease, Left Ventricular Dysfunction, and Ascending Aortic Dilatations in Mice.

RATIONALE: Aortic valve disease is a cell-mediated process without effective pharmacotherapy. CNP (C-type natriuretic peptide) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve health in vivo. OBJECTIVE: The aim of this study is to determine whether a deficient CNP signaling axis in mice causes accelerated progression of aortic valve disease. METHODS AND RESULTS: In cultured porcine valve interstitial cells, CNP inhibited pathological differentiation via the guanylate cyclase NPR2 (natriuretic peptide receptor 2) and not the G-protein-coupled clearance receptor NPR3 (natriuretic peptide receptor 3). We used Npr2+/- and Npr2+/-;Ldlr-/- mice and wild-type littermate controls to examine the valvular effects of deficient CNP/NPR2 signaling in vivo, in the context of both moderate and advanced aortic valve disease. Myofibrogenesis in cultured Npr2+/- fibroblasts was insensitive to CNP treatment, whereas aged Npr2+/- and Npr2+/-;Ldlr-/- mice developed cardiac dysfunction and ventricular fibrosis. Aortic valve function was significantly impaired in Npr2+/- and Npr2+/-;Ldlr-/- mice versus wild-type littermates, with increased valve thickening, myofibrogenesis, osteogenesis, proteoglycan synthesis, collagen accumulation, and calcification. 9.4% of mice heterozygous for Npr2 had congenital bicuspid aortic valves, with worse aortic valve function, fibrosis, and calcification than those Npr2+/- with typical tricuspid aortic valves or all wild-type littermate controls. Moreover, cGK (cGMP-dependent protein kinase) activity was downregulated in Npr2+/- valves, and CNP triggered synthesis of cGMP and activation of cGK1 (cGMP-dependent protein kinase 1) in cultured porcine valve interstitial cells. Finally, aged Npr2+/-;Ldlr-/- mice developed dilatation of the ascending aortic, with greater aneurysmal progression in Npr2+/- mice with bicuspid aortic valves than those with tricuspid valves. CONCLUSIONS: Our data establish CNP/NPR2 signaling as a novel regulator of aortic valve development and disease and elucidate the therapeutic potential of targeting this pathway to arrest disease progression.

Ignored Because It Is Benign - It Is Time to Treat Endometriosis as if It Were Cancer.

We are proposing a shift in mindset in the field of endometriosis, whereby care for patients with endometriosis mirrors that of patients with gynaecological cancer. To achieve this, we advocate for the recognition of complex benign gynaecology as a subspecialty. Since the establishment of gynaecological oncology as a subspecialty, outcomes for patients with ovarian cancer have improved, with their care managed by multidisciplinary teams in specialized units. Despite the marked difference in the primary treatment goal between these two conditions, they share common diagnostic and therapeutic challenges. We believe that care management by a multidisciplinary team of dedicated and specialized health care professionals will lead to improved outcomes, including improved quality of life, for people living with endometriosis.

Sub-confluent culture of human mesenchymal stromal cells on biodegradable polycaprolactone microcarriers enhances bone healing of rat calvarial defect.

In the current emerging trend of using human mesenchymal stromal cell (MSCs) for cell therapy, large quantities of cells are needed for clinical testing. Current methods of culturing cells, using tissue culture flasks or cell multilayer vessels, are proving to be ineffective in terms of cost, space and manpower. Therefore, alternatives such as large-scale industrialized production of MSCs in stirred tank bioreactors using microcarriers (MCs) are needed. Moreover, the development of biodegradable MCs for MSC expansion can streamline the bioprocess by eliminating the need for enzymatic cell harvesting and scaffold seeding for bone-healing therapies. Our previous studies described a process of making regulated density (1.06 g/cm3) porous polycaprolactone biodegradable MCs Light Polycarprolactone (LPCL) (MCs), which were used for expanding MSCs from various sources in stirred suspension culture. Here, we use human early MSCs (heMSCs) expanded on LPCL MCs for evaluation of their osteogenic differentiation potential in vitro as well as their use in vivo calvarial defect treatment in a rat model. In summary, (i) in vitro data show that LPCL MCs can be used to efficiently expand heMSCs in stirred cultures while maintaining surface marker expression; (ii) LPCL MCs can be used as scaffolds for cell transfer for transplantation in vivo; (iii) 50% sub-confluency, mid-logarithmic phase, on LPCL MCs (50% confluent) exhibited higher secretion levels of six cytokines (interleukin [IL]-6, IL-8, Vascular endothelial growth factor (VEGF), Monocyte Chemoattractant Protein-1 (MCP-1), growth-regulated oncogene-α (GRO-α) and stromal cell-derived factor-1α (SDF-1α)) as compared with 100% confluent, stationary phase cultures (100% confluent); (iv) these 50% confluent cultures demonstrated better in vitro osteogenic differentiation capacity as compared with 100% confluent cultures (higher levels of calcium deposition and at earlier stage); the improved bone differentiation capacity of these 50% confluent cultures was also demonstrated at the molecular level by higher expression of early osteoblast genes Runt-related transcription factor 2 (RUNX2), Alkaline phosphatase (ALP), collagen type I, osterix and osteocalcin); and (v) in vivo implantation of biodegradable LPCL MCs covered with 50% heMSCs into rats with calvarial defect demonstrated significantly better bone formation as compared with heMSCs obtained from monolayer cultures (5.1 ± 1.6 mm3 versus 1.3 ± 0.7 mm3). Moreover, the LPCL MCs covered with 50% heMSCs supported better in vivo bone formation compared with 100% confluent culture (2.1 ± 1.3 mm3). Taken together, our study highlights the potential of implanting 50% confluent MSCs propagated on LPCL MCs as optimal for bone regeneration. This methodology allows for the production of large numbers of MSCs in a three-dimensional (3D) stirred reactor, while supporting improved bone healing and eliminating the need for a 3D matrix support scaffold, as traditionally used in bone-healing treatments.

A virus capsid-like nanocompartment that stores iron and protects bacteria from oxidative stress.

Living cells compartmentalize materials and enzymatic reactions to increase metabolic efficiency. While eukaryotes use membrane-bound organelles, bacteria and archaea rely primarily on protein-bound nanocompartments. Encapsulins constitute a class of nanocompartments widespread in bacteria and archaea whose functions have hitherto been unclear. Here, we characterize the encapsulin nanocompartment from Myxococcus xanthus, which consists of a shell protein (EncA, 32.5 kDa) and three internal proteins (EncB, 17 kDa; EncC, 13 kDa; EncD, 11 kDa). Using cryo-electron microscopy, we determined that EncA self-assembles into an icosahedral shell 32 nm in diameter (26 nm internal diameter), built from 180 subunits with the fold first observed in bacteriophage HK97 capsid. The internal proteins, of which EncB and EncC have ferritin-like domains, attach to its inner surface. Native nanocompartments have dense iron-rich cores. Functionally, they resemble ferritins, cage-like iron storage proteins, but with a massively greater capacity (~30,000 iron atoms versus ~3,000 in ferritin). Physiological data reveal that few nanocompartments are assembled during vegetative growth, but they increase fivefold upon starvation, protecting cells from oxidative stress through iron sequestration.

Biodegradable poly-ε-caprolactone microcarriers for efficient production of human mesenchymal stromal cells and secreted cytokines in batch and fed-batch bioreactors.

Large numbers of human mesenchymal stromal cells (MSCs) used for a variety of applications in tissue engineering and cell therapy can be generated by scalable expansion in a bioreactor using microcarriers (MCs) systems. However, the enzymatic digestion process needed to detach cells from the growth surface can affect cell viability and potentially the potency and differentiation efficiency. Thus, the main aim of our study was to develop biocompatible and biodegradable MCs that can support high MSC yields while maintaining their differentiation capability and potency. After cell expansion, the cells that covered MCs can be directly implanted in vivo without the need for cell harvesting or use of scaffold. Poly-ε-caprolactone (PCL) is known as a biocompatible and biodegradable material. However, it cannot be used for generation of MCs because its high density (1.14 g/cm3) would exclude its applicability for suspension MCs in stirred reactors. In this article, we describe expansion and potency of MSCs propagated on low-density (1.06 g/cm3) porous PCL MCs coated with extracellular matrices (LPCLs) in suspended stirred reactors. Using these LPCLs, cell yields of about 4 × 104 cells/cm2 and 7- to 10-fold increases were obtained using four different MSC lines (bone marrow, cord blood, fetal and Wharton's jelly). These yields were comparable with those obtained using non-degradable MCs (Cytodex 3) and higher than two-dimensional monolayer (MNL) cultures. A fed-batch process, which demonstrated faster cell expansion (4.5 × 104 cells/cm2 in 5 days as compared with 7 days in batch culture) and about 70% reduction in growth media usage, was developed and scaled up from 100-mL spinner flask to 1-L controlled bioreactor. Surface marker expression, trilineage differentiation and clonogenic potential of the MSCs expanded on LPCL were not affected. Cytokine secretion kinetics, which occurred mostly during late logarithmic phase, was usually comparable with that obtained in Cytodex 3 cultures and higher than MNL cultures. In conclusion, biodegradable LPCL can be used to efficiently expand a variety of MSC lines in stirred scalable reactors in a cost-effective manner while maintaining surface markers expression, differentiation capability and high levels of cytokine secretion. This study is the first step in testing these cell-biodegradable porous MC aggregates for tissue engineering and cell therapy, such as bone and cartilage regeneration, or wound healing.

Tunable Volumetric Density and Porous Structure of Spherical Poly-ε-caprolactone Microcarriers, as Applied in Human Mesenchymal Stem Cell Expansion.

Polymeric microspheres may serve as microcarrier (MC) matrices, for the expansion of anchorage-dependent stem cells. They require surface properties that promote both initial cell adhesion and the subsequent spreading of cells, which is a prerequisite for successful expansion. When implemented in a three-dimensional culture environment, under agitation, their suspension under low shear rates depends on the MCs having a modest negative buoyancy, with a density of 1.02-1.05 g/cm3. Bioresorbable poly-ε-caprolactone (PCL), with a density of 1.14 g/cm3, requires a reduction in volumetric density, for the microspheres to achieve high cell viability and yields. Uniform-sized droplets, from solutions of PCL dissolved in dichloromethane (DCM), were generated by coaxial microfluidic geometry. Subsequent exposure to ethanol rapidly extracted the DCM solvent, solidifying the droplets and yielding monodisperse microspheres with a porous structure, which was demonstrated to have tunable porosity and a hollow inner core. The variation in process parameters, including the molecular weight of PCL, its concentration in DCM, and the ethanol concentration, served to effectively alter the diffusion flux between ethanol and DCM, resulting in a broad spectrum of volumetric densities of 1.04-1.11 g/cm3. The solidified microspheres are generally covered by a smooth thin skin, which provides a uniform cell culture surface and masks their internal porous structure. When coated with a cationic polyelectrolyte and extracellular matrix protein, monodisperse microspheres with a diameter of approximately 150 µm and densities ranging from 1.05-1.11 g/cm3 are capable of supporting the expansion of human mesenchymal stem cells (hMSCs). Validation of hMSC expansion was carried out with a positive control of commercial Cytodex 3 MCs and a negative control of uncoated low-density PCL MCs. Static culture conditions generated more than 70% cell attachment and similar yields of sixfold cell expansion on all coated MCs, with poor cell attachment and growth on the negative control. Under agitation, coated porous microspheres, with a low density of 1.05 g/cm3, achieved robust cell attachment and resulted in high cell yields of ninefold cell expansion, comparable with those generated by commercial Cytodex 3 MCs.

Evidence to justify retention of transvaginal mesh: comparison between laparoscopic sacral colpopexy and transvaginal Elevate™ mesh.

INTRODUCTION AND HYPOTHESIS: To determine if laparoscopic sacral colpopexy (LSC) offers better apical support with a lower exposure rate than transvaginal mesh surgery with Elevate™. METHODS: This was a retrospective cohort study comparing patients with apical prolapse (POP-Q point C ≥ -1) who underwent Elevate™ mesh repair (n = 146) with patients who underwent laparoscopic sacral colpopexy (n = 267). RESULTS: The sacral colpopexy group had a mean age of 59 years and a BMI of 25.7. Patients in the Elevate™ group were older, with a mean age of 63 and a BMI of 26.3. Most of the patients of both groups presented with pelvic organ prolapse stage III (LSC 73.8% and Elevate™ 87.0%) and their mean POP-Q point C were not significantly different (LSC 1.4 vs Elevate™ 1.2 cm). Operative time was longer in the LSC group (113 vs 91 min, p < 0.001), but estimated blood loss was lower (75 cm3 vs 137 cm3, p < 0.001). No difference in mesh exposure rate could be found between the two groups at one year (Elevate™ 0.7% vs LSC 2.6%, OR 0.26, 95% CI 0.03 to 2.10, p = 0.21). One-year objective cure rate, defined as no descent beyond the hymen, was 97.0% in the LSC group and 96.6% in the Elevate™ group (p = .81). The overall recurrence (objective, subjective recurrence or reoperation) was also not different between the groups (LSC 4.5% vs Elevate 4.8%, p = 0.89). CONCLUSION: Transvaginal Elevate™ mesh delivers comparable apical support with a low exposure rate similar to that of laparoscopic sacral colpopexy.

Integrated processes for expansion and differentiation of human pluripotent stem cells in suspended microcarriers cultures.

Current methods for human pluripotent stem cells (hPSC) expansion and differentiation can be limited in scalability and costly (due to their labor intensive nature). This can limit their use in cell therapy, drug screening and toxicity assays. One of the approaches that can overcome these limitations is microcarrier (MC) based cultures in which cells are expanded as cell/MC aggregates and then directly differentiated as embryoid bodies (EBs) in the same agitated reactor. This integrated process can be scaled up and eliminate the need for some culture manipulation used in common monolayer and EBs cultures. This review describes the principles of such microcarriers based integrated hPSC expansion and differentiation process, and parameters that can affect its efficiency (such as MC type and extracellular matrix proteins coatings, cell/MC aggregates size, and agitation). Finally examples of integrated process for generation cardiomyocytes (CM) and neural progenitor cells (NPC) as well as challenges to be solved are described.

Biodegradable ECM-coated PCL microcarriers support scalable human early MSC expansion and in vivo bone formation.

BACKGROUND AIMS: Human mesenchymal stromal cells or marrow stromal cells (MSCs) are of great interest for bone healing due to their multi-potency and trophic effects. However, traditional MSC expansion methods using 2-dimensional monolayer (MNL) flasks or cell stacks are limited by labor-intensive handling, lack of scalability, the need for enzymatic cell harvesting and the need for attachment to a scaffold before in vivo delivery. Here, we present a biodegradable microcarrier and MSC bioprocessing system that may overcome the abovementioned challenges. METHODS: We cultured human early MSCs (heMSCs) on biodegradable polycaprolactone microcarriers (PCL MCs) coated with extracellular matrix (ECM) and evaluated the in vitro osteogenic differentiation and in vivo bone formation capacity of ECM-coated PCL MC-bound heMSCs compared with conventional MNL-cultured cells. RESULTS: We found that heMSCs proliferate well on PCL MCs coated with a fibronectin, poly-l-lysine, and fibronectin (FN+PLL+FN) coating (cPCL MCs). During in vitro osteogenic induction, heMSCs cultured on cPCL MCs displayed a 68% increase in specific calcium deposition compared with cultures on MNL. In a mouse ectopic mineralization model, bone mass was equivalent for MNL-expanded and cPCL MC-bound heMSC implants but higher in both cases when compared with cell-free cPCL MC implants at 16 weeks post-implantation. In summary, compared with MNL cultures, biodegradable MC MSC cultures provide the benefits of large-scale expansion of cells and can be delivered in vivo, thereby eliminating the need for cell harvesting and use of scaffolds for cell delivery. These results highlight the promise of delivering heMSCs cultured on cPCL MCs for bone applications.

Fabrication of uniform-sized poly-ɛ-caprolactone microspheres and their applications in human embryonic stem cell culture.

The generation of liquefied poly-ɛ-caprolactone (PCL) droplets by means of a microfluidic device results in uniform-sized microspheres, which are validated as microcarriers for human embryonic stem cell culture. Formed droplet size and size distribution, as well as the resulting PCL microsphere size, are correlated with the viscosity and flow rate ratio of the dispersed (Q d) and continuous (Q c) phases. PCL in dichloromethane increases its viscosity with concentration and molecular weight. Higher viscosity and Q d/Q c lead to the formation of larger droplets, within two observed formation modes: dripping and jetting. At low viscosity of dispersed phase and Q d/Q c, the microfluidic device is operated in dripping mode, which generates droplets and microspheres with greater size uniformity. Solutions with lower molecular weight PCL have lower viscosity, resulting in a wider concentration range for the dripping mode. When coated with extracellular matrix (ECM) proteins, the fabricated PCL microspheres are demonstrated capable of supporting the expansion of human embryonic stem cells.

A rare disease in an atypical location-Kimura's Disease of the upper extremity.

Kimura's disease is a rare chronic inflammatory disorder predominantly affecting young Asian male patients, occurring mainly in the head and neck regions. Kimura's disease of the upper extremity is extremely rare, and previous case reports in the literature show similar imaging characteristics with consistent location at the medial epitrochlear region, predominantly with unilateral involvement. We present the first reported case of Kimura's disease affecting the anterolateral aspect of the upper arm, sparing the medial epitrochlear region, illustrating that with typical MR appearance and serology, the involvement of this rare disease in an atypical location still warrants consideration of this diagnosis. There was also bilateral asymmetrical involvement in our patient, suggesting the possibility of a propensity for Kimura's disease affecting the upper extremities to have bilateral involvement, which may necessitate imaging of the clinically asymptomatic contralateral limb in these patients for early lesion identification and treatment.

Are sexes affected differently by ketamine? An exploratory study in ketamine users.

One hundred primary ketamine users and 100 controls were recruited in Hong Kong between December 2009 and December 2011. Cognitive assessment included general intelligence, working, verbal, and visual memory, and executive functions. A Univariate General Linear Model was used to compare cognitive performance between the male and female ketamine users and controls. The female users appeared to have a higher risk of visual memory impairment than their male counterparts. Further studies are warranted to clarify the mechanism of the sex-specific effect of ketamine on cognitive functions.

Relating historical variables at first presentation with operative findings at laparoscopy for endometriosis.

OBJECTIVES: To determine the correlation between historical variables at presentation with the phenotype and location of biopsy proven endometriosis at laparoscopy. METHODS: Prospective observational study. Consecutive women had laparoscopic surgery following clinical suspicion of endometriosis. Standardised history and clinical examination were taken, and the presenting complaints were evaluated within four subsets of women: (i) primary laparoscopy for endometriosis (ii) previous laparoscopically confirmed endometriosis (iii) biopsy positive for endometriosis and (iv) all biopsies negative for endometriosis. Historical pain variables within the four subsets were compared with disease location and phenotype (superficial, deep infiltrating, endometriomata) at laparoscopy. A stringent P-value of 0.01 was used as the cut-off for significance. RESULTS: Overall 104 consecutive women were included: mean age 34.3 years, 66/104 (63.5%) had reoperation and 38/104 (36.5%) had primary laparoscopy. 89/104 (85.6%) were biopsy positive for endometriosis, and 11/104 (10.6%) were biopsy negative. Superficial endometriosis was most common phenotype. Site of pain did not correlate with ipsilateral location of disease. Significant correlations included as follows: dyspareunia and endometrioma (P = 0.0009) in women undergoing reoperation; dyspareunia and posterior compartment (P = 0.0086) and lateral compartment (P = 0.0004) disease in women with histology proven endometriosis; left iliac fossa pain and biopsy proven posterior compartment endometriosis (P = 0.0041). CONCLUSIONS: Although a history of dyspareunia in women with previous endometriosis was significantly correlated with endometrioma, site-specific locations of pain symptoms did not correlate with ipsilateral locations of endometriosis at laparoscopy. The phenotype - combined deep and superficial endometriosis - was associated with dyspareunia among women with previous history of endometriosis.

Challenges in diagnosing and managing endometriosis in general practice: A Western Australian qualitative study.

BACKGROUND AND OBJECTIVES: To reduce diagnostic delay for women with endometriosis-related symptoms, we need to understand general practitioners' (GPs) perspectives on the challenges they face in diagnosing and managing endometriosis. METHOD: Qualitative interviews were conducted with nine Western Australian GPs to explore their knowledge, experiences and challenges with the diagnosis and management of endometriosis. RESULTS: Three themes were identified as challenges: eliciting symptoms, with subthemes of multiple and complex symptoms, clinician experience and awareness, time constraints and screening opportunities; delivering patient-centred care, with subthemes of cultural factors and health literary, perceived gender biases and women's choices and priorities; and system and service, which included learning on the job, clearer diagnostic pathways, access to services and collaborative care models. DISCUSSION: GPs can be better supported in dealing with endometriosis through raising awareness and education; recognition of endometriosis as a complex chronic condition; and the development of pragmatic guidelines, with increased access to local centres for excellent and collaborative care.

The Effect of Upper Cervical Mobilization/Manipulation on Temporomandibular Joint Pain, Maximal Mouth Opening, and Pressure Pain Thresholds: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy of upper cervical joint mobilization and/or manipulation on reducing pain and improving maximal mouth opening (MMO) and pressure pain thresholds (PPTs) in adults with temporomandibular joint (TMJ) dysfunction compared with sham or other intervention. Data Sources: MEDLINE, CINAHL, EMBASE, and Cochrane Library from inception to June 3, 2022, were searched. Study Selection: Eight randomized controlled trials with 437 participants evaluating manual therapy (MT) vs sham and MT vs other intervention were included. Two reviewers independently extracted data and assessed risk of bias. Data Extraction: Two independent reviewers extracted information about origin, number of study participants, eligibility criteria, type of intervention, and outcome measures. Data Synthesis: Manual therapy was statistically significant in reducing pain compared with sham (mean difference [MD]: -1.93 points, 95% confidence interval [CI]: -3.61 to -0.24, P=.03), and other intervention (MD: -1.03 points, 95% CI: -1.73 to -0.33, P=.004), improved MMO compared with sham (MD: 2.11 mm, 95% CI: 0.26 to 3.96, P=.03), and other intervention (MD: 2.25 mm, 95% CI: 1.01 to 3.48, P<.001), but not statistically significant in improving PPT of masseter compared with sham (MD: 0.45 kg/cm2, 95% CI: -0.21 to 1.11, P=.18), and other intervention (MD: 0.42 kg/cm2, 95% CI: -0.19 to 1.03, P=.18), or the PPT of temporalis compared with sham (MD: 0.37 kg/cm2, 95% CI: -0.03 to 0.77, P=.07), and other intervention (MD: 0.43 kg/cm2, 95% CI: -0.60 to 1.45, P=.42). Conclusion: There appears to be limited benefit of upper cervical spine MT on TMJ dysfunction, but definitive conclusions cannot be made because of heterogeneity and imprecision of treatment effects.

Emerging Trends in Biodegradable Microcarriers for Therapeutic Applications.

Microcarriers (MCs) are adaptable therapeutic instruments that may be adjusted to specific therapeutic uses, making them an appealing alternative for regenerative medicine and drug delivery. MCs can be employed to expand therapeutic cells. MCs can be used as scaffolds for tissue engineering, as well as providing a 3D milieu that replicates the original extracellular matrix, facilitating cell proliferation and differentiation. Drugs, peptides, and other therapeutic compounds can be carried by MCs. The surface of the MCs can be altered, to improve medication loading and release, and to target specific tissues or cells. Allogeneic cell therapies in clinical trials require enormous volumes of stem cells, to assure adequate coverage for several recruitment locations, eliminate batch to batch variability, and reduce production costs. Commercially available microcarriers necessitate additional harvesting steps to extract cells and dissociation reagents, which reduces cell yield and quality. To circumvent such production challenges, biodegradable microcarriers have been developed. In this review, we have compiled key information relating to biodegradable MC platforms, for generating clinical-grade cells, that permit cell delivery at the target site without compromising quality or cell yields. Biodegradable MCs could also be employed as injectable scaffolds for defect filling, supplying biochemical signals for tissue repair and regeneration. Bioinks, coupled with biodegradable microcarriers with controlled rheological properties, might improve bioactive profiles, while also providing mechanical stability to 3D bioprinted tissue structures. Biodegradable materials used for microcarriers have the ability to solve in vitro disease modeling, and are advantageous to the biopharmaceutical drug industries, because they widen the spectrum of controllable biodegradation and may be employed in a variety of applications.