Fibrous Matrix Architecture-Dependent Activation of Fibroblasts with a Cancer-Associated Fibroblast-like Phenotype.

Cancer-associated fibroblasts (CAFs) are one of the most prevalent cell types within the tumor microenvironment (TME). While several physicochemical cues from the TME, including growth factors, cytokines, and ECM specificity, have been identified as essential factors for CAF activation, the precise mechanism of how the ECM architecture regulates CAF initiation remains elusive. Using a gelatin-based electrospun fiber mesh, we examined the effect of matrix fiber density on CAF activation induced by MCF-7 conditioned media (CM). A less dense (3D) gelatin mesh matrix facilitated better activation of dermal fibroblasts into a CAF-like phenotype in the CM than a highly dense (3D) gelatin mesh matrix. In addition, it was discovered that CAF activation on the less dense (LD) matrix is dependent on the cell size-related AKT/mTOR signaling cascade, accompanied by an increase in intracellular tension within the well-spread fibroblasts.

Retracted Rotator Cuff Repairs Heal With Disorganized Fibrogenesis Without Affecting Biomechanical Properties: A Comparative Animal Model Study.

PURPOSE: To determine the differences in the scar tissue formation during the healing of the repaired retracted cuff tear from that of the nonretracted tear. METHODS: Eighteen right rabbit shoulders received a 1-cm transverse cuff incision over the footprint to simulate "nonretracted cuff tears" before the transosseous repairs (group A). A 1-cm tendinous portion was excised from 18 left shoulders to create defects to simulate "retracted cuff tears" before repairing the defects (group B). At week 12 postrepair, 20 and 16 shoulders underwent histologic and biomechanical analyses, respectively. Eight shoulders were used as a control group for biomechanical analyses. RESULTS: All specimens showed good healing and continuity of the repaired tendons. At low magnification, fibrous tissue firmly held the tendon-to-bone junctions in group A; however, all specimens in group B showed medially retracted tendons with fibrous tissue continuity between the tendon stumps and footprints. At medium magnification, more irregular collagen fiber orientation was observed in group B. Polarized light microscopy showed fibrous tissue continuity with medially retracted tendons in group B. When we quantified collagen fiber orientation using ImageJ software, group B had inferior grayscale measurements when compared with group A (P = .001). At week 12, no statistical differences existed in mean loads-to-failure at the repair sites between the groups (P = .783). CONCLUSIONS: In the nonretracted cuff tears, fibrous tissue bound the tendon-to-bone junction with healing. After the healing of the retracted cuff tears, continuity of nontendinous tissue was observed adjacent to the medially retracted tendon, which comprised more disorganized immature fibrous tissue than that in the nonretracted cuff tears. CLINICAL RELEVANCE: Unlike the healing of nonretracted rotator cuff tear, repairing of the "retracted" tendon end of cuff tear still resulted in retraction of the tendon back to its original position but being held down with fibrous tissue to the footprint.

Physical analysis reveals distinct responses of human bronchial epithelial cells to guanidine and isothiazolinone biocides.

Changes in the physical state of the cells can serve as important indicators of stress responses because they are closely linked with the changes in the pathophysiological functions of the cells. Physical traits can be conveniently assessed by analyzing the morphological features and the stresses at the cell-matrix and cell-cell adhesions in both single-cell and monolayer model systems in 2D. In this study, we investigated the mechano-stress responses of human bronchial epithelial cells, BEAS-2B, to two functionally distinct groups of biocides identified during the humidifier disinfectant accident, namely, guanidine (PHMG) and isothiazolinone (CMIT/MIT). We analyzed the physical traits, including cell area, nuclear area, and nuclear shape. While the results showed inconsistent average responses to the biocides, the degree of dispersion in the data set, measured by standard deviation, was remarkably higher in CMIT/MIT treated cells for all traits. As mechano-stress endpoints, traction and intercellular stresses were also measured, and the cytoskeletal actin structures were analyzed using immunofluorescence. This study demonstrates the versatility of the real-time imaging-based biomechanical analysis, which will contribute to identifying the temporally sensitive cellular behaviors as well as the emergence of heterogeneity in response to exogenously imposed stress factors. This study will also shed light on a comparative understanding of less studied substance, CMIT/MIT, in relation to a more studied substance, PHMG, which will further contribute to more strategic planning for proper risk management of the ingredients involved in toxicological accidents.

Incidence of Cutibacterium acnes from shoulder arthroplasties in Asians: ethnic differences should be considered.

BACKGROUND: Most studies on Cutibacterium acnes in shoulder surgery have been conducted in the Western population, and studies on Asians are rare. We evaluated the incidence and risk factors of C acnes in shoulder arthroplasty in Asians. METHODS: We retrospectively analyzed 154 patients between January 2017 and May 2019 who underwent shoulder arthroplasty. Swabs were taken after skin preparation from the skin surface of the anterior acromion, axilla, and joint fluid to study the incidence of C acnes. Before skin preparation we also collected swabs from the anterior acromion, axilla, and thigh from 59 of the 154 patients. RESULTS: Eight of 154 patients after and 6 of 59 patients before skin preparation were positive for C acnes. C acnes were found in 2 patients at the anterior acromion and in 6 at the synovial joint after skin preparation and in 1 patient at the axilla, in 5 at the anterior acromion, and in 3 at the thigh before preparation. History of steroid injection and number of steroid injections were significantly associated with C acnes isolation (P = .039 and P = .006, respectively), whereas age, sex, body mass index, shoulder surgery history, hypertension, diabetes, and cerebrovascular disease were not, as were serum inflammatory markers, including white blood cell count, C-reactive protein level, and erythrocyte sedimentation rate. CONCLUSION: A total of 5.2% of the patients after skin preparation and 10.2% of patients before skin preparation were found to be positive for C acnes. The incidence of C acnes in patients who underwent shoulder arthroplasties in Asia was low and, thus, ethnic differences should be considered for C acnes. The history and number of steroid injections were associated with isolation of C acnes.

Neurologic deficit after reverse total shoulder arthroplasty: correlation with distalization.

BACKGROUND: Neurologic problems after reverse total shoulder arthroplasty (RTSA) have been reported, but there are a lack of studies regarding which nerve(s) are damaged and the outcomes for the patients who had neurologic complications after RTSA. The purpose of this study was to assess the prevalence and outcomes of neurologic deficit after RTSA and to evaluate the correlation between nonanatomic rearrangement of the shoulder joint and neurologic complications after RTSA. We hypothesized that the neurologic deficit was associated with excessive distalization or lateralization of the humerus after RTSA. METHODS: RTSA was performed on 182 consecutive shoulders with cuff tear arthropathy. Comparative analysis was performed on 34 shoulders with (group 1) and 148 shoulders without (group 2) neurologic deficit. RESULTS: The mean follow-up period in the study was 58.5 months (range: 24-124). The mean age was 71.5 ± 7.7 years in group 1 and 73.1 ± 7.2 years in group 2. Neurologic deficit after RTSA was found in 34 shoulders (19%). The mean postoperative acromiohumeral distance was 34.1 ± 11.0 mm in group 1 and 29.4 ± 7.6 mm in group 2 (P = .015). Significant differences in terms of postoperative distalization of the humerus were seen between group 1 (24.5 ± 9.4 mm) and group 2 (20.5 ± 8.3 mm) (P = .009). The most common forms of neurologic deficit after RTSA were axillary nerve (41.2%) and radial nerve (15%) injuries. Thirty shoulders (88%) had neuropraxia, and 4 shoulders (12%) had axonotmesis. By conservative treatment, all patients with neurologic complications achieved complete recovery without any additional surgery; the mean recovery period was 7.4 months (range: 2-38 months). CONCLUSION: Neurologic deficit occurred in 19% of patients who underwent RTSA, and it was significantly correlated with humeral distalization after surgery. Axillary nerve was mostly involved, and all patients with neurologic deficit achieved complete recovery without any additional surgery.

Prevalence of Vitamin D Deficiency and Its Association With Metabolic Disease in Korean Orthopedic Patients.

Vitamin D is considered essential for bone and muscle health, and some studies have demonstrated the positive effects of vitamin D on metabolic diseases and cancer. Nevertheless, a high prevalence of vitamin D deficiency has been reported in various populations, regardless of country or race. However, no studies regarding the prevalence of vitamin D deficiency in Korean orthopedic patients currently exist. This cross-sectional study included 272 male and 937 female patients aged 50 years and older who were consecutively admitted to the authors' orthopedic department. Vitamin D (25-hydroxy vitamin D), bone turnover markers (osteocalcin, c-telopeptide), and bone mineral density were measured. The prevalence of vitamin D deficiency and its association with other factors were evaluated. Mean patient age was 67.2 ± 8.9 years, and mean level of vitamin D was 16.1 ± 9.1 ng/mL. Overall, 91.2% of patients had deficient (<20 ng/mL; 70.6%) or insufficient (20-30 ng/mL; 20.6%) levels of vitamin D. Vitamin D level did not vary by age group or sex. The level of vitamin D was significantly associated with osteocalcin, c-telopeptide, calcium, alkaline phosphatase, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glucose (P<.01). Vitamin D level in Korean orthopedic patients of this region was extremely low, regardless of sex and age. Although vitamin D was not directly associated with bone mineral density, there were significant associations between vitamin D and other factors related to bone health and metabolic diseases.