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Background: Distal femoral varus osteotomy (DFVO) is an established surgical procedure for addressing valgus malalignment across various knee conditions. However, the effect of DFVO on stress distribution within the femorotibial joint has not been explored through in vivo studies. Purpose: To (1) explore the distribution pattern of subchondral bone density across the proximal tibia in nonarthritic knees without arthritis and in those of patients with valgus knees, (2) assess changes in the pattern of bone density distribution in patients with valgus knees before and after medial closing-wedge (MCW) DFVO, and (3) determine the correlation between leg alignment and changes in bone density distribution. Study Design: Cohort study; Level of evidence, 3. Methods: The authors retrospectively analyzed clinical and radiographic data from 14 patients (14 knees; mean age, 44 years; 3 men, 11 women) treated with MCW-DFVO for lateral compartment osteoarthritis (OA) due to valgus malalignment, alongside a control group of 18 patients (18 knees; mean age, 21 years; 4 men, 14 women) without OA. The distribution patterns of subchondral bone density distribution on the femorotibial articular surface of the tibia were examined both preoperatively and >1 year postoperatively using computed tomography osteoabsorptiometry. Quantitative analyses were conducted on the locations and percentages of the high-density areas (HDAs) on the articular surface. The mean time between surgery and the postoperative radiograph and computed tomography absorptiometry imaging was 13.6 months (range, 11-19 months). The mean length of clinical follow-up was 28.7 months (range, 14-62 months) after surgery. Results: The mean proportion of HDA in the lateral compartment relative to the total HDA (lateral ratio) was significantly greater in the preoperative OA group (58.8%) compared with the control group (41.1%) (P <.001). After MCW-DFVO, the mean lateral ratio in the OA group notably declined to 45.3% (P <.001). The lateral ratio exhibited a significant correlation with the hip-knee-ankle angle in both the control (r = 0.630; P =.011) and OA (r = 0.537; P =.047) groups. Moreover, the alteration in the lateral ratio after MCW-DFVO showed a significant relationship with changes in the hip-knee-ankle angle (r = 0.742; P =.002) and the mechanical lateral distal femoral angle (r = −0.752; P =.002). Within the lateral compartment, HDAs in the 3 lateral regions of the 4 lateral subregions diminished after MCW-DFVO, whereas in the medial compartment, HDAs in the 3 lateral subregions saw an increase. Conclusion: The mean lateral ratio was significantly greater in the preoperative OA group compared with the control group. MCW-DFVO resulted in a redistribution of HDA from the lateral to the medial compartment of the proximal tibial articular surface. The extent of alignment correction after MCW-DFVO was closely linked to the shifts in HDA distribution, reflecting changes in stress distribution. [ABSTRACT FROM AUTHOR]

Background: For glioma patients, the long-term advantages of dendritic cells (DCs) immunization remain unknown. It is extremely important to develop new treatment strategies that enhance the immunotherapy effect of DC-based vaccines. DCs exposed to glioma stem cells (GSCs) are considered promising vaccines against glioma. Methods: Glioma stem cells were isolated from mouse glioma GL261 cells (GCs). Both were subjected to severe (47°C) and mild (42°C) heat shock to induce immunogenic cell death (ICD). Membrane mobilization of calreticulin (CRT) and release of heat shock proteins (HSPs) were detected by flow cytometry. Dendritic cells were then exposed to heat-inactivated cells and co-culturing of T cells tested for immunotherapeutic efficacy in vitro. In vivo, we investigated the GSC targeting effect of the GSC-DC vaccine combined with CD47 blockade. Results: Heat shock induced ICD in GCs and GSCs, as indicated by significant release of calreticulin, HSP70, and HSP90. Heat shock condition ICD lysates induce maturation and activation-associated marker expression on monocyte-derived DCs. Accordingly, DCs pulsed with GCs and GSCs inactivated reduced colony formation, sphere formation, migration, and invasion of glioma and GSCs in vitro. Glioma stem cell-DC vaccine in combination with anti-CD47 antibody significantly enhanced survival in mice with glioma, induced production of interferon (IFN)-γ, and enhanced T-cell expansion in vivo. Of note, DCs pulsed with inactivated GSCs were more effective to control tumor growth than DCs pulsed with inactive GCs. Conclusions: Severe heat shock induces ICD in vitro. These data showed that administration of anti-CD47 antibody combined with GSC-DC vaccine may represent an effective immunotherapeutic strategy for cancer patients in clinical. [ABSTRACT FROM AUTHOR]

Background: Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear. Aims: This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways. Methods: A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays. Results: HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2. Conclusion: HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a prevalent and disabling disease that affects a significant proportion of the global population. Urine-derived stem cells (USCs) have shown great prospects in the treatment of OA, but there is no study that has compared them with traditional stem cells. Purpose: This study aimed to compare the therapeutic efficacy and mechanisms of USCs and adipose-derived stem cells (ADSCs) for OA treatment. Study Design: Controlled laboratory study. Methods: We compared the biological properties of USCs and ADSCs using CCK-8, colony formation, EdU, adhesion, and apoptosis assays. We evaluated the protective effects of USCs and ADSCs on IL-1β–treated OA chondrocytes by chemical staining, immunofluorescence, and Western blotting. We assessed the effects of USCs and ADSCs on chondrocyte autophagy by transmission electron microscopy, immunofluorescence, and Western blotting. We also compared the therapeutic efficacy of intra-articular injections of USCs and ADSCs by gross, histological, micro–computed tomography, and immunohistochemical analyses in an OA rat model induced by anterior cruciate ligament transection. Results: USCs showed higher proliferation, colony formation, DNA synthesis, adhesion, and anti-apoptotic abilities than ADSCs. Both USCs and ADSCs increased the expression of cartilage-specific proteins and decreased the expression of matrix degradation–related proteins and inflammatory factors in OA chondrocytes. USCs had a greater advantage in suppressing MMP-13 and inflammatory factors than ADSCs. Both USCs and ADSCs enhanced autophagy in OA chondrocytes, with USCs being more effective than ADSCs. The autophagy inhibitor 3-MA reduced the enhanced autophagy and protective effects of USCs and ADSCs on OA chondrocytes. Conclusion: To our knowledge, this is the first study to explore the efficacy of USCs in the treatment of knee OA and to compare them with ADSCs. Considering the superior properties of USCs in terms of noninvasive acquisition, a high cost-benefit ratio, and low ethical concerns, our study suggests that they may be a more promising therapeutic option than ADSCs for OA treatment under rigorous regulatory pathways. Clinical Relevance: USCs may be a superior cell source for stem cells to treat knee OA, and this study strengthens the evidence for the application of USCs. [ABSTRACT FROM AUTHOR]

Objectives: Exposure to benzo[α]pyrene (BaP) increases the incidence and severity of allergic rhinitis (AR), but the underlying mechanisms remain unclear. Thus, we investigated the in vivo effects of BaP exposure on mucus hypersecretion and tissue remodeling in a rat model of AR. Methods: Female Sprague–Dawley rats were randomly divided into 4 groups: a negative control group, a group of healthy rats exposed to BaP, a group of rats with ovalbumin (OVA)-induced AR, and a group of AR model rats exposed to BaP. Nasal symptoms and levels of OVA-specific serum immunoglobulin E (IgE) were measured in each individual rat. Moreover, examination of goblet cell hyperplasia and collagen deposition was carried out with periodic acid-Schiff (PAS) staining and Masson trichrome (MT) staining. Mucin 5AC (MUC5AC) expression was assessed by immunohistochemistry. Results: BaP significantly increased the number of sneezes, the number of nasal rubs and the levels of OVA-specific serum IgE in rats with AR. Statistically significant differences in goblet cell hyperplasia and collagen deposition were observed between the BaP-exposed AR model group and the AR model group. Immunohistochemical results showed that the nasal mucosa of AR model rats displayed markedly elevated MUC5AC expression after BaP exposure. Conclusion: Our data indicate that mucus hypersecretion and the development of nasal remodeling might be pathophysiologic mechanisms underlying increased susceptibility to AR after exposure to BaP. [ABSTRACT FROM AUTHOR]

Background: Acromioclavicular joint (ACJ) disruption occurs frequently in athletes engaged in contact sports. However, the current understanding of ACJ biomechanics during muscle-driven functional activities and the influence of different treatment approaches (eg, reconstruction surgery vs nonoperative methods) on ACJ kinematics and stability remains limited. The absence of precise in vivo biomechanical measurement modalities for scapular and clavicular kinematics contributes significantly to this lack of understanding. Purposes/Hypothesis: The purposes of this study were to determine whether dynamic stereo x-ray (DSX) imaging can be used to evaluate the in vivo kinematics of the ACJ and to provide preliminary comparative data on ACJ kinematics, range of motion, and isometric strength of surgically reconstructed or nonoperatively treated ACJ shoulders and their uninjured contralateral shoulders. It was hypothesized that ACJ kinematics could be measured successfully using DSX and that surgically and nonoperatively treated shoulders would show abnormal 3-dimensional (3-D) ACJ kinematics compared with the uninjured contralateral. Study Design: Controlled laboratory study. Methods: In this cross-sectional study, 11 participants who had undergone unilateral ACJ reconstruction surgery and 3 patients who received nonoperative treatment were enrolled. ACJ kinematics were assessed during active forward flexion, scaption, and abduction through high-speed DSX imaging, complemented by 3-D bone models obtained via computed tomography (CT) scans. To gauge kinematic differences, a 1-dimensional statistical parametric mapping method was employed, which compared outcomes in the index limb to those in the uninjured counterpart. In addition, the range of motion and isometric strength at various abduction angles were analyzed, employing a repeated-measures analysis of variance to compare the affected and uninjured sides. Results: Leveraging a combination of DSX imaging and patient-specific CT bone models, ACJ kinematics was measured successfully during movements along anatomic planes. Preliminary findings from this investigation revealed no detectable differences between the surgically reconstructed and uninjured sides in ACJ biomechanics, shoulder range of motion, and isometric strength outcomes. However, on average, the nonoperatively treated shoulders demonstrated increased internal rotation, upward rotation, and posterior tilting of the scapula relative to the clavicle (no statistical analyses were performed due to the small sample size). Conclusion: DSX imaging is a promising tool for evaluating potential in vivo kinematic abnormalities in the ACJ during muscle-driven activities, laying the groundwork for further investigations in both ACJ-reconstructed and nonreconstructed patients. This study furnished essential data for conducting power analyses and designing future studies with an adequate sample size to investigate the impact of different treatment approaches on shoulder girdle mechanics. Clinical Relevance: With its potential for accurately characterizing shoulder girdle kinematics post-ACJ injury, DSX imaging can offer valuable insights for future clinical studies, facilitating informed decisions regarding the short- and long-term impacts of treatment choices on shoulder health and function. [ABSTRACT FROM AUTHOR]

Background: The anterior cruciate ligament (ACL) is loaded under tension when the tibia translates anteriorly relative to the femur. The shape of the articular surfaces of the tibiofemoral joint may influence the amount of anterior tibial translation under compressive loading. Thus, a steep lateral tibial plateau and a shallow medial plateau are thought to be risk factors for ACL injury. Purpose/Hypothesis: The purpose of this study was to evaluate whether tibial plateau slope and depth influence peak ACL strain during a single-leg jump. We hypothesized that there would be a significant correlation between tibial plateau slope and depth with ACL strain. Study Design: Descriptive laboratory study. Methods: A total of 17 healthy participants (8 male, 9 female) were assessed using magnetic resonance imaging (MRI) and high-speed biplanar radiography to obtain peak ACL strain during a single-leg jump. Two orthopaedic surgeons used the sagittal plane MRI scans to measure the medial and lateral tibial plateau slopes and the medial tibial plateau depth. The intraclass correlation coefficient was used to assess measurement reliability, and the Spearman rank correlation was used to evaluate the relationship between measurements of tibial morphology and peak ACL strain during the single-leg jump. Results: The overall range of intraclass correlation coefficients for intra- and interrater reliability of the medial and lateral tibial plateau slopes and medial plateau depth was 0.59 to 0.97. No significant correlations were found between peak ACL strain and any of the slope or depth measurements. Conclusion: In this cohort of healthy participants, correlations between any of the tibial plateau measurements with peak ACL strain during a single-leg jump were not detected. These findings are consistent with prior work, suggesting that tibial plateau slope and depth may not be linked to risk for ACL rupture. However, it is possible that tibial plateau morphology may interact with other factors to increase ACL injury risk or that individuals with extreme slope angles may produce differing results. Clinical Relevance: This study enhances the knowledge of the loading mechanisms for the ACL and thus improves the understanding of risk factors for ACL injury. [ABSTRACT FROM AUTHOR]

Background: Tibial bone tunnel widening (TW) is a common postoperative phenomenon after anterior cruciate ligament reconstruction (ACLR). Purpose: To compare the physical, biomechanical, osteoinductive, and histological characteristics of 2 fabricated bioabsorbable interference screws: (1) a modified poly(l -lactide- co - d, l -lactide) and hydroxyapatite (mPLA/HA) screw and (2) a poly(l -lactide- co -glycolide) and β-tricalcium phosphate (PLGA/β-TCP) screw; and to evaluate the effect of the PLA/HA screw on ameliorating postoperative TW in a canine ACLR model. Study Design: Controlled laboratory study. Methods: In vitro, the physical and biomechanical properties of the mPLA/HA and PLGA/β-TCP screws were tested. The osteoinductive activity of the screws was studied by cell experiments. In vivo, ACLR was performed on 48 beagle dogs, divided into the mPLA/HA group and the PLGA/β-TCP group. The femoral and tibial ends of the graft were both fixed with screws. Six animals in each group were sacrificed after live computed tomography (CT) scanning at 1, 3, 6, and 12 months postoperatively. For six knee samples of each group, three knee samples underwent biomechanical testing, and 1 of them, along with the other 3 samples, underwent micro-CT and histological examination to evaluate tibial TW. Results: The mPLA/HA screw exhibited better particle dispersion, bending strength, desirable self-locking effect, and optimized degradation behavior both in vivo and in vitro. Histologically, the mPLA/HA screw had comparative osteoinductive activity. There was good screw-bone integration using the mPLA/HA screw, while most fibrous scar healing was in the PLGA/β-TCP group. There were significant differences between the mPLA/HA and PLGA/β-TCP groups in tibial bone tunnel diameter at the screw body (6 months postoperatively: 5.09 ± 0.44 vs 7.12 ± 0.67; 12 months postoperatively: 4.83 ± 0.27 vs 6.23 ± 0.56; P <.01 for both) and the screw tail (6 months postoperatively: 4.84 ± 0.28 vs 5.97 ± 0.73; 12 months postoperatively: 4.77 ± 0.29 vs 5.92 ± 0.56; P <.01 for both). Conclusion: Compared with the PLGA/β-TCP screw commonly used in clinics at present, the mPLA/HA screw had comparative biosafety and mechanical properties, satisfactory biomechanical properties, and osteoinductive activity in vivo and in vitro. It effectively ameliorated the postoperative tibial TW in a canine ACLR model and increased the quality of screw-bone integration. Clinical Relevance: The good mechanical and biological properties of the mPLA/HA screws may provide an option to reduce the incidence of complications after ACLR. [ABSTRACT FROM AUTHOR]

Aloe weloensis Sebsebe, a species used for therapeutic purposes in Ethiopia, exemplifies the plant's rich history of herbal use, traditional applications, and the need for further research. Aloe weloensis, a species of the Aloe genus, has gained attention for its potential pharmaceutical and therapeutic properties. This review examines the phytochemical composition, pharmacological effects, and pharmaceutical applications of Aloe weloensis. The methods involved a thorough review of published literature using reputable databases, focusing on English-language articles covering Aloe weloensis' phytochemistry, antioxidant, antibacterial, and antimalarial activities. Aloe weloensis leaf latex demonstrates diverse bioactive compounds, antioxidant activity (IC50: 10.25 μg/ml), significant antibacterial effects, and promising in vitro antimalarial activity (IC50: 9.14 μg/ml) on 3D7 strains of Plasmodium falciparum species. In vivo studies support its potential as an antimalarial remedy, showcasing its multifaceted pharmacological profile. Aloe weloensis presents promising pharmacological properties, including antioxidant, antibacterial, and antimalarial activities, supported by its rich phytochemical composition. The in vivo antimalarial results and mucilage's potential as a suspending agent highlight its significance in modern medicine, warranting further exploration. [ABSTRACT FROM AUTHOR]

This study aimed to understand parents' process of centering their child's interpersonal traumatic event in their lives post-disclosure. Specifically, how it informed their understanding of themselves, their lives, and the world. This phenomenon of centering a traumatic event in one's life is termed event centrality and has not been previously applied to qualitative research or this population. Participants were 17 primary caregivers (14 maternal caregivers and 3 paternal caregivers) of 27 victims of child interpersonal trauma (14 males and 13 females) located in Canada. The age of participants ranged from 35 to 75 years (average = 54.5 years) and majority self-identified as Caucasian (70.6%). Grounded theory was used to analyze the data. The resulting model was labeled Vicarious Event Centralization and Decentralization, indicating that parents center their child's interpersonal trauma across many areas of their lives, which orients them to focus on protecting and healing the child. After the child's functioning improves, parents are then able to reorient to life beyond the trauma, representing decentralization. The grounded theory consists of three phases: Centralization, Decentralization Gateway, and Decentralization. These results illustrate that parents' centralization of the trauma may be an adaptive mechanism that promotes child recovery, which in turn allows parents to begin to decentralize the trauma and move toward recovery. This study supports that parents are affected by their child's trauma in a myriad of ways and require unique services to address their needs. This study can help practitioners understand the post-trauma experience for parents and target areas likely to increase recovery. [ABSTRACT FROM AUTHOR]

Background: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region. Hypothesis: Local delivery of skeletal stem cell (SSC)–derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression. Study Design: Controlled laboratory study. Methods: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (GCON) and group treated with exosomes (GExosome). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms. Results: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro (P <.01). The GExosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the GCON at 8 weeks postoperatively (P <.05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the GCON, meniscal tissue in the GExosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the GCON than in the GExosome (P <.05). Compared with the GCON, the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family. Conclusion: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components. Clinical Relevance: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region. [ABSTRACT FROM AUTHOR]

Background: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. Purpose: To fabricate a tendon stem cell–derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. Study Design: Controlled laboratory study. Methods: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)–based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. Results: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. Conclusion: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. Clinical Relevance: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects. [ABSTRACT FROM AUTHOR]

Background: Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. Purpose/Hypothesis: The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. Study Design: Controlled laboratory study. Methods: A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. Results: The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. Conclusion: This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. Clinical Relevance: This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. Hypothesis: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. Study Design: Controlled laboratory study. Methods: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. Results: BMSCs labeled with 100 μg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. Conclusion: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. Clinical Relevance: This study provides an alternative strategy for improving TBI healing after RCR. [ABSTRACT FROM AUTHOR]

Objective: Postprandial hyperglycemia is considered an early sign of diabetes. Enzyme inhibitors, such as α-amylase and α-glucosidase inhibitors, are currently being studied as potential drugs for preventing postprandial hyperglycemia. Methods: In this study, we investigated the effects of four purified 7-hydroxycoumarine derivatives from Ferula assafoetida: umbelliprenin, farnesiferol A, farnesiferol C, and samarcandin. We evaluated cell toxicity using the MTT method and also examined glucose uptake and inhibition of α-amylase and α-glucosidase enzymes in vitro. Additionally, we conducted a molecular docking study to investigate the mechanism of enzyme inhibition. Results: The cell toxicity of the terpenoid coumarin derivatives (umbelliprenin, farnesiferol A, farnesiferol C, and samarcandin) on HepG2 cells was found to be approximately 28 to 37 µg/ml. The glucose uptake assay showed that these compounds (at a concentration of 25 µg/ml) were able to increase glucose consumption by HepG2 cells to a level comparable to that of the positive control (metformin at 50 µg/ml). Furthermore, umbelliprenin significantly inhibited the activity of α-amylase and α-glucosidase (by 35.07% and 4.98%, respectively). Molecular docking results indicated that umbelliprenin, with a farnesyl chain, had a more potent inhibitory effect. Conclusion: Our findings suggest that umbelliprenin may be a valuable compound for controlling postprandial hyperglycemia and diabetes. However, further in vivo studies and clinical trials are necessary to validate these effects. While this research offers potential for the development of more effective compounds with coumarin structures, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract- loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds. [ABSTRACT FROM AUTHOR]

Around 5% to 10% of hospitalized patients develop a hospital-acquired infection (HAI). Scrubs are a potential vector of HAIs. To compare the antimicrobial characteristics of scrubs with and without an antimicrobial fabric coating, as tested in the laboratory (in vitro) and hospital (in vivo) environments. Two protocols were conducted to address the purpose. The in vitro protocol was a laboratory study that involved observing the microbe growth after inoculating coated and uncoated scrub fabric swatches with S. aureus and then processing them in moist and dry environments. The in vivo protocol was a clinical trial that measured microbe growth on coated and uncoated scrubs prior to and following nursing staff completing a 12-hr shift on an acute care unit, as measured by colony forming units (CFUs). For high-humidity environments, the in vitro study indicated that swatches treated with an antimicrobial coating exhibited minimal microbe growth, while untreated swatches exhibited significant microbe growth. For low-humidity environments, coated and uncoated swatches were all found to exhibit minimal microbe growth. In the in vivo study, the CFUs increased on scrubs worn by nurses over a 12-hr shift with no significant difference in CFUs for coated and uncoated scrubs. For bacteria in a warm and moist environment, the antimicrobial coating was found to be important for inhibiting growth. For bacteria in a warm and dry environment, both coated and uncoated fabrics performed similarly as measured at 24 hr, with minimal bacterial growth observed. In a hospital environment, microbe growth was observed, but no significant difference was detected when comparing coated and uncoated scrubs. This may have been due to the short time between exposure and culturing the scrubs for analysis immediately at the end of the shift not allowing for enough time to kill or inhibit growth. Contact time between the bacteria and scrub fabric (coated or uncoated) in the in vivo study more directly correlated with the 0-hr observations for the in vitro study, suggesting that the ineffectiveness of the treated scrubs in the clinical results may be due in part to short residence times before collection. [ABSTRACT FROM AUTHOR]

Second-degree burns require greater care, as the damage is more extensive and worrisome and the use of a biomaterial can help in the cell repair process, with better planning, low cost, and better accessibility. Arnica has anti-inflammatory and analgesic properties in skin lesions treatments and laser therapy is another therapeutic alternative for burns. Evaluate the effects of arnica incorporated into PVA associated or not with low intensity laser on burns in rats. PVA and PVA with arnica (PVA+A) were obtained and characterized physicochemically. Through in vivo studies, the effects of PVA and PVA+A with or without the application of laser on the lesions allowed histological and immunohistochemical analyzes. PVA+A was biocompatible and with sustained release of the active, being a promising pharmacological tool and confirmed that laser therapy was effective in accelerating the healing process, due to its potential biomodulator, improving inflammatory aspects, promoting rapid healing in skin lesions. [ABSTRACT FROM AUTHOR]

Recently, more and more studies have shown that guanylate cyclase, an enzyme that synthesizes cyclic guanosine monophosphate (cGMP), plays an important role in bone metabolism. Vericiguat (VIT), a novel oral soluble guanylate cyclase stimulator, directly generates cyclic guanosine monophosphate and reduce the death incidence from cardio-vascular causes or hospitalization. Recent studies have shown beneficial effects of VIT in animal models of osteoporosis, but very little is currently known about the effects of VIT on bone defects in the osteoporotic states. Therefore, in this study, β-tricalcium phosphate (β-TCP) was used as a carrier to explore the effect of local VIT administration on the repair of femoral metaphyseal bone defects in ovariectomized (OVX) rats. When MC3T3-E1 was cultured in the presence of H2H2, VIT, similar to Melatonin (MT), therapy could increase the matrix mineralization and ALP, SOD2, SIRT1, and OPG expression, reduce ROS and Mito SOX production, RANKL expression, Promote the recovery of mitochondrial membrane potential. In the OVX rat model, VIT increases the osteogenic effect of β-TCP and better results were obtained at a dose of 5 mg. Local use of VIT can inhibit increased OC, BMP2 and RUNX2 expressions in bone tissue, while decreased SOST and TRAP expressions by RT-PCR and immunohistochemistry. Thereby, VIT stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff tears have been repaired using the transosseous method for decades. The direct suture (DS) technique has been widely used for rotator cuff tears; however, the retear rate is relatively high. Suture anchors are now used frequently for rotator cuff repair (RCR) in accordance with recent developments in materials. However, polyether ether ketone (PEEK) may still cause complications such as the formation of cysts and osteophytes. Some studies have developed the inlay suture (IS) technique for RCR. Purpose/Hypothesis: To compare how 3 different surgical techniques—namely, the DS, IS, and PEEK suture anchor (PSA)—affect tendon-bone healing after RCR. We hypothesized that the IS technique would lead to better tendon-to-bone healing and that the repaired structure would be similar to the normal enthesis. Study Design: Controlled laboratory study. Methods: Acute infraspinatus tendon tears were created in 36 six-month-old male rabbits, which were divided into 3 groups based on the technique used for RCR: DS, IS, and PSA. Animals were euthanized at 6 and 12 weeks postoperatively and underwent a histological assessment and imaging. The expression of related proteins was demonstrated by immunohistochemistry and immunofluorescence staining. Mechanical properties were evaluated by biomechanical testing. Results: At 12 weeks, regeneration of the enthesis was observed in the 3 groups. However, the DS group showed a lower type I collagen content than the PSA and IS groups, which was similar to the results for scleraxis. The DS group displayed a significantly inferior type II collagen expression and proteoglycan deposition after safranin O/fast green and sirius red staining. With regard to runt-related transcription factor 2 and alkaline phosphatase, the IS group showed upregulated expression levels compared with the other 2 groups. Conclusion: Compared with the DS technique, the PSA and IS techniques contributed to the improved maturation of tendons and fibrocartilage regeneration, while the IS technique particularly promoted osteogenesis at the enthesis. Clinical Relevance: The IS and PSA techniques may be more beneficial for tendon-bone healing after RCR. [ABSTRACT FROM AUTHOR]

Background: The labral suction seal has been shown to provide the majority of resistance in the initial phase of hip distraction. However, the effect of an unrepaired interportal capsulotomy and capsular repair on the initial phase of hip distractive stability in vivo is not well understood. Purpose: To investigate the effect of capsular repair on the initial phase of distractive stability of hip joints in patients with femoroacetabular impingement (FAI) syndrome. Study Design: Controlled laboratory study. Methods: Patients undergoing primary hip arthroscopy for FAI between March and August 2020 were prospectively enrolled. Total joint space was measured on fluoroscopic images at the medial and lateral edges of the sourcil at 12.5-lb (5.7-kg) axial traction intervals (up to 100 lb [45.4 kg]) in 3 capsular states: (1) native capsule, (2) interportal capsulotomy, and (3) capsular repair. Distraction on anteroposterior radiographs was calculated as the difference between total joint space at each traction interval and baseline joint space at 0 lb, normalized to millimeters. The native, capsulotomy, and capsular repair states were compared using Wilcoxon signed-rank and McNemar tests. Results: Included were 36 hips in 35 patients. The median force required to distract ≥3 mm was 75 lb (34.0 kg; 95% CI, 70-80 lb [31.8-36.3 kg]) in both the native and capsular repair states (P =.629), which was significantly greater than the median force required to distract ≥3 mm in the capsulotomy state (50 lb [22.7 kg]; 95% CI, 45-55 lb [20.4-24.9 kg]) (P <.001). The most rapid rates of change in joint space were observed at the traction interval at which hips first achieved ≥3 mm of distraction (n = 33 hips; 92%). Conclusion: The traction force at which hips distracted ≥3 mm was 75 lb (34.0 kg) in both the native capsular and capsular repair states. Significantly less traction force (50 lb [22.7 kg]) distracted hips ≥3 mm in the capsulotomy state. Complete capsular closure after interportal capsulotomy resulted in restoration of initial distractive stability relative to the unrepaired capsulotomy state at time zero after primary hip arthroscopy. Clinical Relevance: This study provides surgeons with an improved understanding of the additional stability to the hip joint from capsular repair after hip arthroscopy for FAI syndrome. [ABSTRACT FROM AUTHOR]

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p <.05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice. [ABSTRACT FROM AUTHOR]

Background: Restoration of osteochondral defects is critical, because osteoarthritis (OA) can arise. Hypothesis: Overexpression of insulin-like growth factor 1 (IGF-1) via recombinant adeno-associated viral (rAAV) vectors (rAAV-IGF-1) would improve osteochondral repair and reduce parameters of early perifocal OA in sheep after 6 months in vivo. Study Design: Controlled laboratory study. Methods: Osteochondral defects were created in the femoral trochlea of adult sheep and treated with rAAV-IGF-1 or rAAV- lacZ (control) (24 defects in 6 knees per group). After 6 months in vivo, osteochondral repair and perifocal OA were assessed by well-established macroscopic, histological, and immunohistochemical scoring systems as well as biochemical and micro–computed tomography evaluations. Results: Application of rAAV-IGF-1 led to prolonged (6 months) IGF-1 overexpression without adverse effects, maintaining a significantly superior overall cartilage repair, together with significantly improved defect filling, extracellular matrix staining, cellular morphology, and surface architecture compared with rAAV- lacZ. Expression of type II collagen significantly increased and that of type I collagen significantly decreased. Subchondral bone repair and tidemark formation were significantly improved, and subchondral bone plate thickness and subarticular spongiosa mineral density returned to normal. The OA parameters of perifocal structure, cell cloning, and matrix staining were significantly better preserved upon rAAV-IGF-1 compared with rAAV- lacZ. Novel mechanistic associations between parameters of osteochondral repair and OA were identified. Conclusion: Local rAAV-mediated IGF-1 overexpression enhanced osteochondral repair and ameliorated parameters of perifocal early OA. Clinical Relevance: IGF-1 gene therapy may be beneficial in repair of focal osteochondral defects and prevention of perifocal OA. [ABSTRACT FROM AUTHOR]

Background: Muscle edema formation and inflammatory processes are early manifestations of acute rotator cuff lesions in sheep. Histological analysis of affected muscles revealed edema formation, inflammatory changes, and muscle tissue disruption in MRs. Hypothesis: Edema contributes to inflammatory reactions and early muscle fiber degeneration before the onset of fatty infiltration. Study Design: Controlled laboratory study. Methods: Osteotomy of the greater tuberosity, including the insertion of the infraspinatus tendon, was performed on 14 sheep. These experimental animal models were divided into 2 groups: a nontrauma group with surgical muscle release alone (7 sheep) and a trauma group with standardized application of additional trauma to the musculotendinous unit (7 sheep). Excisional biopsy specimens of the infraspinatus muscle were taken at 0, 3, and 4 weeks. Results: Edema formation was histologically demonstrated in both groups and peaked at 3 weeks. At 3 weeks, signs of muscle fiber degeneration were observed. At 4 weeks, ingrowth of loose alveolar and fibrotic tissue between fibers was detected. Fatty tissue was absent. The diameter of muscle fibers increased in both groups, albeit to a lesser degree in the trauma group, and practically normalized at 4 weeks. Immunohistology revealed an increase in macrophage types 1 and 2, as well as inflammatory mediators such as prostaglandin E2 and nuclear factor kappa-light-chain-enhancer of activated B cells. Conclusion: Early muscle edema and concomitant inflammation precede muscle fiber degeneration and fibrosis. Edema formation results from tendon release alone and is only slightly intensified by additional trauma. Clinical Relevance: This study illustrates that early edema formation and inflammation elicit muscle fiber degeneration that precedes fatty infiltration. Should this phenomenon be applicable to human traumatic rotator cuff tears, then surgery should be performed as soon as possible, ideally within the first 21 days after injury. [ABSTRACT FROM AUTHOR]

Introduction: Adipose-derived stem cells (ADSCs) have been subject of several studies due to their abundance, ease of preparation, and application in bone regeneration. We aim to compare effectiveness of alveolar reconstruction utilizing human cancellous freeze-dried graft (HCG) and beta tricalcium phosphate (BTP), both seeded with human ADSC (hADSC) and autologous bone graft (ABG). Material and Methods: A 5 × 5 mm alveolar defect in 36 male Wistar rats were treated using: ABG (C), HCG–hADSC (H1), and BTP–hADSC (H2). At 1 and 8 weeks after surgery, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osterix (OSX), and bone morphogenetic protein 2 (BMP2; g/mL) were quantified using immunohistochemistry, while bone tissue volume (BV, mm3), bone tissue volume fraction (BF, percentage), and trabecular thickness of bone (TT, mm) were assessed using micro-computed tomography (CT). Results: One week after surgery, H2 was higher in RUNX2, OSX, ALP, and BMP2 than C (P <.05). Only RUNX2 and OSX were found to be higher in H1 than C, while ALP and BMP2 were higher in H2 than H1. Micro-CT revealed that H2 had a higher TT than C and C had a higher TT than H1 (P <.05). Eight weeks after surgery, both H2 and H1 was higher in RUNX2, OSX, ALP, and BMP2 than C (P <.05). RUNX2 and BMP2 were found to be higher in H1 than H2. Micro-CT revealed that H2 had higher BV and TT than C and H1 (P <.05). Conclusions: Exogenous hADSC strengthened the effectiveness of HCG and BTP to accelerate osteogenesis, osteoconduction, and osteoinduction. The latter was the most successful in bone formation, followed by HCG and ABG. [ABSTRACT FROM AUTHOR]

Diabetes is a prevalent medical condition that often leads to complications, including diabetic wounds that can have serious consequences such as infections, amputations, and death. In the current research, lodoxamide was loaded into electrospun polycaprolacton/gelatin scaffolds In order to improve wound healing in a rat model. Our developed dressings were characterized in vitro using various methods and then applied on a rat model of excisional wound. Study showed that the dressings were not toxic and promoted migration potential of skin-derived fibroblast cells. Wound healing study showed that lodoxamide-loaded dressings had markedly higher healing potential than other scaffolds and augmented collagen deposition and epithelialization. Gene expression studies showed that TNF-α, glutathione peroxidase, and superoxide dismutase genes were significantly downregulated by lodoxamide-loaded scaffolds. [ABSTRACT FROM AUTHOR]

Background: Hill-Sachs lesion (HSL) remplissage with Bankart repair (RMBR) provides a minimally invasive solution for treating HSLs and glenoid bone defects of <25%. The infraspinatus tendon is inserted into the HSL during the remplissage process, causing the infraspinatus to shift medially, leading to an unknown effect on glenohumeral alignment during the resting abduction–external rotation (ABER) and muscle-active states. Purpose/Hypothesis: The purpose of this study was to evaluate the possible check-rein effect and muscle-active control in stabilizing the glenohumeral joint after RMBR in vivo. We hypothesized that the check-rein effect and active control would stabilize the glenohumeral joint in the ABER position in patients after RMBR. Study Design: Controlled laboratory study. Methods: We included 42 participants—22 patients in group A who met the inclusion criteria after RMBR and 20 healthy participants in group B without shoulder laxity. Three-dimensional magnetic resonance imaging was performed to analyze the alignment relationship of the glenohumeral joint with and without muscular activity. Ultrasonic shear wave elastography was used to evaluate the elastic properties of the anterior capsule covered with the anterior bands of the inferior glenohumeral ligament. Results: Patients who underwent RMBR demonstrated more posterior (–1.81 ± 1.19 mm vs –0.76 ± 1.25 mm; P =.008) and inferior (–1.05 ± 0.62 mm vs –0.45 ± 0.48 mm; P =.001) shifts of the humeral head rotation center and less anterior capsular elasticity (70.07 ± 22.60 kPa vs 84.01 ± 14.08 kPa; P =.023) than healthy participants in the resting ABER state. More posterior (–3.17 ± 0.84 mm vs –1.81 ± 1.19 mm; P <.001) and less-inferior (–0.34 ± 0.56 mm vs –1.05 ± 0.62 mm; P <.001) shifts of the humeral head rotation center and less anterior capsular elasticity (36.57 ± 13.89 kPa vs 70.07 ± 22.60 kPa; P <.001) were observed in the operative shoulder during muscle-active ABER than in resting ABER states. Conclusion: The check-rein effect and muscle-active control act as stabilizing mechanisms in RMBR during the ABER position. Clinical Relevance: Stabilizing mechanisms in RMBR during the ABER position include the check-rein effect and muscle-active control. [ABSTRACT FROM AUTHOR]

Background: Knowledge of acromioclavicular (AC) joint kinematics and distance may provide insight into the biomechanical function and development of new treatment methods. However, accurate data on in vivo AC kinematics and distance between the clavicle and acromion remain unknown. Purpose/Hypothesis: The purpose of this study was to investigate 3-dimensional AC kinematics and distance during arm elevation in abduction, scaption, and forward flexion in a healthy population. It was hypothesized that AC kinematics and distance would vary with the elevation angle and plane of the arm. Study Design: Controlled laboratory study. Methods: A total of 19 shoulders of healthy participants were enrolled. AC kinematics and distance were investigated with a combined dual fluoroscopic imaging system and computed tomography. Rotation and translation of the AC joint were calculated. The AC distance was measured as the minimum distance between the medial border of the acromion and the articular surface of the distal clavicle (ASDC). The minimum distance point (MDP) ratio was defined as the length between the MDP and the posterior edge of the ASDC divided by the anterior-posterior length of the ASDC. AC kinematics and distance between different elevation planes and angles were compared. Results: Progressive internal rotation, upward rotation, and posterior tilt of the AC joint were observed in all elevation planes. The scapula rotated more upward relative to the clavicle in abduction than in scaption (P =.002) and flexion (P =.005). The arm elevation angle significantly affected translation of the AC joint. The acromion translated more laterally and more posteriorly in scaption than in abduction (P <.001). The AC distance decreased from the initial position to 75° in all planes and was significantly greater in flexion (P <.001). The MDP ratio significantly increased with the elevation angle (P <.001). Conclusion: Progressive rotation and significant translation of the AC joint were observed in different elevation planes. The AC distance decreased with the elevation angle from the initial position to 75°. The minimum distance between the ASDC and the medial border of the acromion moved anteriorly as the shoulder elevation angle increased. Clinical Relevance: These results could serve as benchmark data for future studies aiming to improve the surgical treatment of AC joint abnormalities to restore optimal function. [ABSTRACT FROM AUTHOR]

Background: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation–based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. Hypothesis: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. Study Design: Controlled laboratory study. Methods: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. Results: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P =.015) and migration (P =.001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P =.005) and interleukin-1α (P =.042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P =.003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P =.019) and fiber alignment (P <.001) of the repaired tendons. Conclusion: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. Clinical Relevance: The present study lays a foundation for future clinical applications of stem cell spheroid–based therapy for the management of tendon injuries. [ABSTRACT FROM AUTHOR]

Background: Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. Purpose/Hypothesis: The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. Study Design: Controlled laboratory study. Methods: A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. Results: Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. Conclusion: IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. Clinical Relevance: Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain. [ABSTRACT FROM AUTHOR]

Background: Total meniscectomy for treating massive meniscal tears may lead to joint instability, cartilage degeneration, and even progressive osteoarthritis. The meniscal substitution strategies for advancing reconstruction of the meniscus deserve further investigation. Hypothesis: A decellularized meniscal scaffold (DMS) modified with collagen affinity stromal cell–derived factor (C-SDF1α) may facilitate meniscal regeneration and protect cartilage from abrasion. Study Design: Controlled laboratory study. Methods: The authors first modified DMS with C-SDF1α to fabricate a new meniscal graft (DMS-CBD [collagen-binding domain]). Second, they performed in vitro studies to evaluate the release dynamics, biocompatibility, and differentiation inducibility (osteogenic, chondrogenic, and tenogenic differentiation) on human bone marrow mesenchymal stem cells. Using in vivo studies, they subjected rabbits that received medial meniscectomy to a transplantation procedure to implement their meniscal graft. At postoperative weeks 6 and 12, the meniscal regeneration outcomes and chondroprotective efficacy of the new meniscal graft were evaluated by macroscopic observation, histology, micromechanics, and immunohistochemistry tests. Results: In in vitro studies, the optimized DMS-CBD graft showed notable biocompatibility, releasing efficiency, and chondrogenic inducibility. In in vivo studies, the implanted DMS-CBD graft after total meniscectomy promoted the migration of cells and extracellular matrix deposition in transplantation and further facilitated meniscal regeneration and protected articular cartilage from degeneration. Conclusion: The new meniscal graft (DMS-CBD) accelerated extracellular matrix deposition and meniscal regeneration and protected articular cartilage from degeneration. Clinical Relevance: The results demonstrate that the DMS-CBD graft can serve as a potential meniscal substitution after meniscectomy. [ABSTRACT FROM AUTHOR]

Background: Distal tibial allograft (DTA) reconstruction for glenoid bone loss is nonanatomic, as it does not match the glenoid radius of curvature (ROC) in the anterior-posterior (AP) plane. The dorsal articular portion of the distal radius has not been previously described as an allograft reconstruction option for glenoid bone loss. Purpose: To evaluate distal radius fresh-frozen allograft (DRA) as a potential match for glenoid reconstruction. Study Design: Controlled laboratory study. Methods: Eighteen fresh-frozen human cadaveric specimens—including 6 shoulder, 6 wrist, and 6 tibia specimens—were used. The ROC and the graft length were measured in the superior-inferior (SI) plane. A 30% defect was created in all glenoid specimens, and both DTAs and DRAs were harvested to assess graft fit after fixation. Computed tomography analysis was used to assess bony ROC and bone mineral density (BMD). Results: The cadaveric specimens had a mean age of 77 years. The mean SI glenoid length was 39.7 mm compared with 36.8 mm for the DRA and 30 mm for the DTA. The ROC in the SI plane was 29 ± 5.3 mm for the glenoid, 37.8 ± 4.9 mm for the DRA, and 24 ± 3.7 mm for the DTA. In the AP plane, the ROC was 39.6 ± 6.6 mm for the glenoid, 30.4 ± 18.6 mm for the DRA, and 126.3 ± 9.5 mm for the DTA. On computed tomography analysis, the ROC in the SI plane was 30.4 ± 1.5 mm for the glenoid, 30.3 ± 5.6 mm for the DRA, and 24.5 ± 9.4 mm for the DTA. In the AP plane, the ROC was 30.8 ± 2 mm for the glenoid, 19.1 ± 2.3 mm for the DRA, and 46.7 ± 21.7 mm for the DTA. The BMD was 226.3 ± 79 Hounsfield units (HU) for the glenoid, 228.5 ± 94.7 HU for the DRA, 235 ± 96.2 HU for the coracoid process, and 235.1 ± 84.6 HU for the DTA. Conclusion: Compared with the DTA, the DRA had a greater mean graft length in the SI plane, providing utilization in cases of larger bony defects; the DRA has a more acute ROC in the AP plane (closer to that of the glenoid), providing a greater potential buttress to anterior humeral translation. Compared with currently utilized grafts, the DRA BMD was not significantly diminished. This study presents the DRA as a novel allograft reconstruction option in the setting of anterior glenoid bone loss; further biomechanical and clinical investigation is indicated. [ABSTRACT FROM AUTHOR]

Background: Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients. Purpose: To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model. Material and Methods: In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides. Results: There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score. Conclusion: The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses. [ABSTRACT FROM AUTHOR]

Acute oral toxicity (AOT) data inform the acute toxicity potential of a compound and guides occupational safety and transportation practices. AOT data enable the categorization of a chemical into the appropriate AOT Globally Harmonized System (GHS) category based on the severity of the hazard. AOT data are also utilized to identify compounds that are Dangerous Goods (DGs) and subsequent transportation guidance for shipping of these hazardous materials. Proper identification of DGs is challenging for novel compounds that lack data. It is not feasible to err on the side of caution for all compounds lacking AOT data and to designate them as DGs, as shipping a compound as a DG has cost, resource, and time implications. With the wealth of available historical AOT data, AOT testing approaches are evolving, and in silico AOT models are emerging as tools that can be utilized with confidence to assess the acute toxicity potential of de novo molecules. Such approaches align with the 3R principles, offering a reduction or even replacement of traditional in vivo testing methods and can also be leveraged for product stewardship purposes. Utilizing proprietary historical in vivo AOT data for 210 pharmaceutical compounds (PCs), we evaluated the performance of two established in silico AOT programs: the Leadscope AOT Model Suite and the Collaborative Acute Toxicity Modeling Suite. These models accurately identified 94% and 97% compounds that were not DGs (GHS categories 4, 5, and not classified (NC)) suggesting that the models are fit-for-purpose in identifying PCs with low acute oral toxicity potential (LD50 >300 mg/kg). Utilization of these models to identify compounds that are not DGs can enable them to be de-prioritized for in vivo testing. This manuscript provides a detailed evaluation and assessment of the two models and recommends the most suitable applications of such models. [ABSTRACT FROM AUTHOR]

Background: Fibroblast activation protein (FAP) has shown high expression in inflammatory responses and fibrosis. Hypothesis: We speculated that FAP could serve as a diagnostic and monitoring target in the tendon healing process. Study Design: Controlled laboratory study. Methods: A total of 72 Sprague-Dawley rats were randomly divided into a tendon crush group and a half-partial tendon laceration group. Four rats in each group were injected with radiotracers weekly for 4 weeks after surgery, with aluminum fluoride–labeled 1,4,7-triazacyclononane-N,N′,N″-triacetic acid–conjugated FAP inhibitor (Al18F-NODA-FAPI-04) administered on the first day of each week and 18F-fludeoxyglucose (18F-FDG) on the next day. Small animal positron emission tomography (PET) imaging was performed, and tendon tissue was collected for pathology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis each week after surgery. Results: One week after surgery, both radiotracers showed signal concentration at the lesion site, which was the highest radioactive uptake observed during 4 weeks postoperatively, consistent with the severity of the lesion. Consistent trends were observed for inflammatory cytokines during qRT-PCR analysis. Additionally, Al18F-NODA-FAPI-04 PET exhibited a more precise lesion pattern, attributed to its high specificity for naive fibroblasts when referring to histological findings. Over time, the uptake of both radiotracers at the injury site gradually decreased, with 18F-FDG experiencing a more rapid decrease than Al18F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al18F-NODA-FAPI-04 in the injured lesion almost reverted to the baseline levels, indicating a substantial decrease in naive fibroblasts and inflammatory cells and a reduction in inflammation and fibrosis, especially compared with the first week. Corresponding trends were also revealed in pathological and qRT-PCR results. Conclusion: Our findings suggest that inflammation is a prominent feature during the early stage of tendon injury. Al18F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity. [ABSTRACT FROM AUTHOR]

Background: Medial patellofemoral ligament (MPFL) reconstruction is associated with high complication rates because of graft overloading from incorrect graft positioning. To improve clinical outcomes, it is crucial to gain a better understanding of MPFL elongation patterns. Purpose: To assess MPFL length changes in healthy knees from 0° to 90° of dynamic flexion and their relationship with anatomic parameters of the patellofemoral joint. Study Design: Descriptive laboratory study. Methods: Dynamic computed tomography scans of an active flexion-extension-flexion movement in 115 knees from 63 healthy participants were evaluated to construct knee joint models. Using these models, the MPFL length was measured as the shortest wrapping path from the Schöttle point on the femur to 3 insertion points on the superomedial border of the patella (proximal, central, and distal). MPFL length changes (%) relative to the length in full extension were calculated, and their correlations with the tibial tuberosity–trochlear groove distance, Caton-Deschamps index, and lateral trochlear inclination were analyzed. Results: The proximal fiber was the longest in full extension and progressively decreased to a median length of −6.0% at 90° of flexion. The central fiber exhibited the most isometric pattern during knee flexion, showing a median maximal decrease of 2.8% relative to the full extension length and no evident elongation. The distal fiber first slightly decreased in length but increased at deeper flexion angles. The median overall length changes were 4.6, 4.7, and 5.7 mm for the proximal, central, and distal patellar insertion, respectively. These values were either not or very weakly correlated with the tibial tuberosity–trochlear groove distance, Caton-Deschamps index, and lateral trochlear inclination when the anatomic parameters were within the healthy range. Conclusion: The median MPFL length changed by approximately 5 mm between 0° and 90° of flexion. Proximally, the length continuously decreased, indicating slackening behavior. Distally, the length increased at deeper flexion angles, indicating tightening behavior. Clinical Relevance: In MPFL reconstruction techniques utilizing the Schöttle point to establish the femoral insertion, one should avoid distal patellar insertion, as it causes elongation of the ligament, which may increase the risk for complications due to overloading. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff repair is a common orthopaedic procedure, yet the rate of failure to heal after surgery is high. Repair site rupture is due to poor tendon-to-bone healing and lack of regeneration of the native fibrocartilaginous enthesis. During development, the enthesis is formed and mineralized by a pool of progenitors activated by hedgehog signaling. Furthermore, hedgehog signaling drives regenerative enthesis healing in young animals, in contrast to older animals, in which enthesis injuries heal via fibrovascular scar and without participation of hedgehog signaling. Hypothesis: Hedgehog activation improves tendon-to-bone healing in an animal model of rotator cuff repair. Study Design: Controlled laboratory study. Methods: A total of 78 adult Sprague-Dawley rats were used. Supraspinatus tendon injury and repair were completed bilaterally, with microsphere-encapsulated hedgehog agonist administered to right shoulders and control microspheres administered to left shoulders. Animals were sacrificed after 3, 14, 28, or 56 days. Gene expression and histological, biomechanical, and bone morphometric analyses were conducted. Results: At 3 days, hedgehog signaling pathway genes Gli1 (1.70; P =.029) and Smo (2.06; P =.0173), as well as Runx2 (1.69; P =.0386), a transcription factor of osteogenesis, were upregulated in treated relative to control repairs. At 14 days, transcription factors of tenogenesis, Scx (4.00; P =.041), and chondrogenesis, Sox9 (2.95; P =.010), and mineralized fibrocartilage genes Col2 (3.18; P =.031) and Colx (1.85; P =.006), were upregulated in treated relative to control repairs. Treatment promoted fibrocartilage formation at the healing interface by 28 days, with improvements in tendon-bone maturity, organization, and continuity. Treatment led to improved biomechanical properties. The material property strength (2.43 vs 1.89 N/m2; P =.046) and the structural property work to failure (29.01 vs 18.09 mJ; P =.030) were increased in treated relative to control repairs at 28 days and 56 days, respectively. Treatment had a marginal effect on bone morphometry underlying the repair. Trabecular thickness (0.08 vs 0.07 mm; P =.035) was increased at 28 days. Conclusion: Hedgehog agonist treatment activated hedgehog signaling at the tendon-to-bone repair site and prompted increased mineralized fibrocartilage production. This extracellular matrix production and mineralization resulted in improved biomechanical properties, demonstrating the therapeutic potential of hedgehog agonism for improving tendon-to-bone healing after rotator cuff repair. Clinical Relevance: This study demonstrates the therapeutic potential of hedgehog agonist treatment for improving tendon-to-bone healing after rotator cuff injury and repair. [ABSTRACT FROM AUTHOR]

Background: The inhibition of IKKβ by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. Purpose: To investigate the therapeutic effects of IKKβ inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. Study Design: Controlled laboratory study. Methods: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. Results: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P =.024), load to failure (P =.002), stiffness (P =.039), and elastic modulus (P =.048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P =.042) and 8 weeks (P =.009). Type I collagen expression (COL-I; P =.034) and the COL-I/collagen type III ratio (P =.015) increased while interleukin 6 expression decreased (P <.001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. Conclusion: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. Clinical Relevance: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Low-intensity pulsed ultrasound (LIPUS) irradiation has been shown to induce various responses in different cells. It has been shown that LIPUS activates extracellular signal–regulated kinase 1/2 (ERK1/2) through integrin. Purpose: To study the effects of LIPUS on myogenic regulatory factors and other related myogenesis elements in a volumetric skeletal muscle loss injury model. Study Design: Controlled laboratory study. Methods: C57BL/6J mice were subjected to full-thickness muscle defect injury of the quadriceps and treated with direct application of LIPUS 20 min/d or non-LIPUS treatment (control) for 3, 7, and 14 days. LIPUS was also applied to C2C12 cells in culture in the presence of low and high doses of lipopolysaccharides. The expression levels of myogenic regulatory factors and the expression levels of myokine-related and angiogenic-related proteins of the control and LIPUS groups were analyzed. Results: Muscle volume in the injury site was restored at day 14 with LIPUS treatment. Paired-box protein 7, myogenic factor 5, myogenin, and desmin expressions were significantly different between control and LIPUS groups at days 7 and 14. Myokine and angiogenic cytokine-related factors were significantly increased in the LIPUS group at day 3 and decreased with no significant difference between the groups by day 14. LIPUS induced different responses of myogenic regulatory factors in C2C12 cells with low and high doses of lipopolysaccharides. LIPUS promoted myogenesis through short-lived increase in interleukin-6 and heme oxygenase 1, together with activation of ERK1/2. Conclusion: LIPUS had a constant effect on the variables of tissue damage, from macrotrauma to microtrauma, leading to efficient muscle regeneration. Clinical Relevance: The focus of therapeutic strategies with LIPUS has been not only for microvascular regeneration but also for skeletal muscle and related local tissue recovery from acute or chronic damage. [ABSTRACT FROM AUTHOR]

Background: Stress ultrasonography (SUS) has provided clinicians with an alternative means of evaluating ulnar collateral ligament (UCL) injury by dynamically assessing ulnohumeral joint space gapping under applied valgus stress. However, 3 previous cadaveric studies have evaluated the biomechanical effect of partial UCL tears at different anatomic locations with conflicting results. Purpose/Hypothesis: The purpose of this study was to use in vivo data from patients with magnetic resonance (MR)–confirmed partial UCL tears to determine if anatomic partial tear location influenced the resultant stability of the elbow in terms of ulnohumeral joint gapping on SUS. It was hypothesized that no difference would be seen in the amount of ulnohumeral joint gapping based on MR-identified anatomic partial UCL tear location. Study Design: Cohort study; Level of evidence, 3. Methods: All patients diagnosed with elbow injury from 2015 to 2020 were screened to identify competitive baseball pitchers with a partial UCL tear who received an SUS. Partial UCL tear was diagnosed via surgeon and radiologist interpretation of elbow MR imaging (MRI) as well as confirmation at the time of surgery as documented in the operative report. Demographic, injury, and treatment data were collected from the clinic notes, MRI reports, and stress ultrasound reports. Ulnohumeral joint gapping on SUS was calculated as the difference between ulnohumeral joint gapping without valgus stress versus ulnohumeral joint gapping with valgus stress (delta) as performed by a musculoskeletal radiologist. Results: Overall, 60 male baseball pitchers (age, 19.2 ± 2.1 years), including 22 (37%) high school, 26 (43%) collegiate, and 12 (20%) professional pitchers, were evaluated. Regarding the location of partial UCL tears, 32 (53%) pitchers had proximal tears and 28 (47%) had distal tears. The mean delta value cohort was 2.1 ± 1.1 mm, and 34 pitchers (57%) had delta values >2.0 mm. Ulnohumeral joint gapping (high school [1.9 mm] vs collegiate [2.6 mm] vs professional [1.6 mm]; P =.004) and the percentage of pitchers with delta values >2.0 mm (45% vs 77% vs 33%; P =.017) differed based on level of competition. After controlling for age, body mass index, and level of competition in a multivariate linear regression, tear location was not related to ulnohumeral joint gapping (P =.499). Conclusion: No difference was observed in the amount of ulnohumeral joint gapping on SUS in symptomatic baseball pitchers with MR-identified partial UCL tears at differing anatomic locations. The findings of this study are contrary to previous cadaveric studies that have evaluated the effects of UCL tear characteristics on delta laxity. [ABSTRACT FROM AUTHOR]

Background: The incidence of rotator cuff tears is rapidly increasing, and operative techniques for rotator cuff repair have been developed. However, the rates of postoperative retear remain high. Purpose/Hypothesis: The purpose was to determine the effects of human dermal fibroblasts (HDFs) with hyaluronic acid (HA) on tendon-to-bone healing in a rabbit model of chronic rotator cuff tear injury. It was hypothesized that HA would enhance HDF proliferation and that a combination of HA and HDFs would produce a synergistic effect on the healing of repaired rotator cuff tendons of rabbits. Study Design: Controlled laboratory study. Methods: For in vitro study, HDFs were plated on a 24-well plate. After 1 day, 2 wells were designated as the test group and treated with 0.75% HA in phenol red–free Dulbecco's modified Eagle medium (DMEM). An other 2 wells served as control groups and were treated with the same volume of phenol red–free DMEM without HA. Each group was duplicated, resulting in a total of 4 wells, with 2 wells in each group for replication purposes. The cells were incubated for 24 hours, followed by 72-hour cultivation. Absorbance ratios at 96 and 24 hours were compared to evaluate cell proliferation. For the in vivo study, a total of 24 rabbits were randomly allocated to groups A, B, and C (n = 8 each). Supraspinatus tendons were detached bilaterally and left for 6 weeks to establish a chronic rotator tear model. Torn tendons were subsequently repaired using the following injections: group A, 0.5 × 106 HDFs with HA; group B, HA only; and group C, saline only. At 12 weeks after repair, biomechanical tests and histological evaluation were performed. Results: In vitro study showed that HDF proliferation significantly increased with HA (HDFs with HA vs HDFs without HA; 3.96 ± 0.09 vs 2.53 ± 0.15; P <.01). In vivo, group A showed significantly higher load-to-failure values than the other groups (53.8 ± 6.9 N/kg for group A, 30.6 ± 6.4 N/kg for group B, and 24.3 ± 7.6 N/kg for group C; P <.001). Histological evaluation confirmed that group A showed higher collagen fiber density and better collagen fiber continuity, tendon-to-bone interface maturation, and nuclear shape than the other groups (all P <.05). Conclusion: This controlled laboratory study verified the potential of the combination of HDFs and HA in enhancing healing in a chronic rotator cuff tear rabbit model. Clinical Relevance: A potential synergistic effect on rotator cuff tendon healing may be expected from a combination of HDFs and HA. [ABSTRACT FROM AUTHOR]

Background: Arthroscopic repair of large rotator cuff tendon tears is associated with high rates of retear. Construct failure often occurs at the suture-tendon interface. Patch augmentation can improve mechanical strength and healing at this interface. Purpose: To introduce a novel technique for suture-free attachment of an overlaid patch and evaluate its biomechanical strength and biological performance. Study Design: Descriptive and controlled laboratory studies. Methods: An established ovine model of partial infraspinatus tendon resection and immediate repair was used. After a nonwoven polyethylene terephthalate patch was overlaid to the resected tendon, a barbed microblade was used to draw fibers of the patch directly into the underlying tissue. In vivo histological assessment of healing was performed at 6 and 13 weeks after implantation. Ex vivo models were used to characterize primary repair strength of the suture-free patch fixation to tendon. Additional ex vivo testing assessed the potential of the technique for patch overlay augmentation of suture-based repair. Results: The in vivo study revealed no macroscopic evidence of adverse tissue reactions to the interlocked patch fibers. Histological testing indicated a normal host healing response with minimal fibrosis. Uniform and aligned tissue ingrowth to the core of the patch was observed from both the tendon and the bone interfaces to the patch. There was no evident retraction of the infraspinatus muscle, lengthening of the tendon, or tendon gap formation over 13 weeks. Ex vivo testing revealed that direct patch interlocking yielded tendon purchase equivalent to a Mason-Allen suture (150 ± 58 vs 154 ± 49 N, respectively; P =.25). In an overlay configuration, fiber interlocked patch augmentation increased Mason-Allen suture retention strength by 88% (from 221 ± 43 N to 417 ± 86 N; P <.01) with no detectable difference in repair stiffness. Conclusion: Testing in an ovine model of rotator cuff tendon repair suggested that surgical interlocking of a nonwoven medical textile can provide effective biomechanical performance, support functional tissue ingrowth, and help avoid musculotendinous retraction after surgical tendon repair. Clinical Relevance: The novel technique may facilitate patch augmentation of rotator cuff repairs. [ABSTRACT FROM AUTHOR]

Objective: Velopharyngeal dysfunction (VPD) associated with 22q11.2 deletion syndrome (22q11.2DS) has a complex etiology. This study had 3 aims: (1) assess differences in velopharyngeal and levator muscle configuration during rest versus sustained speech production (2) compare differences in velopharyngeal changes between children with and without 22q11.2DS (3) examine the relationship between adenoid thickness, pharyngeal depth, and velopharyngeal changes. Design: Cross-sectional. Methods: A total of 22 participants, 11 with 22q11.2DS and 11 controls with normal speech and velopharyngeal anatomy (ages 4-12 years), underwent nonsedated MRI at rest and during sustained /i/. Differences in velar and levator muscle contraction across the 2 different conditions were analyzed, using matched paired t -tests. Mean differences across participant groups were examined. Correlation analyses were also conducted. Results: When comparing differences between rest and sustained phoneme production (aim 1), significant (P <.05) differences were noted for all velar and levator muscle variables. For differences in velopharyngeal changes between children with and without 22q11.2DS (aim 2), VP ratio and effective VP ratio were noted to be significantly different. Pharyngeal depth and adenoid thickness were correlated with velar and levator muscle change measures and ratios (aim 3). Conclusion: Results from this study provide quantitative in vivo measurements of the contracted levator muscle and velum in young children with 22q11.2DS. Results demonstrated that VP ratio and EVP ratio are significantly different between children with and without 22q11.2DS and that pharyngeal depth is a strong clinical determinant of VPD in children with 22q11.2DS. [ABSTRACT FROM AUTHOR]

Fullerenes are carbon molecules that are found in nature in various forms. They are composed of hexagonal and pentagonal rings that create closed structures. Almost 4 decades ago, fullerenes were identified in the form of C60 and C70, and following the award of the Nobel Prize in Chemistry for this discovery in 1996, many laboratories started working on their water-soluble derivatives that could be used in different industries, including pharmaceutical industries. One of the first fullerene forms that was the focus of different research groups was fullerenol, C60(OH) n (n = 2-44). Both in-vitro and in-vivo studies have shown that polyhydroxylate fullerene derivatives can potentially be used as either antioxidative agents or cytostatics (depending on their co-administration, forms, and concentration/dose) in biological systems. The current review aimed to present a critical view of the potential applications and limitations of fullerenols in oncology, as understood from the past 2 decades of research. [ABSTRACT FROM AUTHOR]

PDE4 inhibitors exhibit anti-stress and antidepressant-like abilities by catalyzing the hydrolysis of cAMP, a primary regulator for intracellular communication in the brain. Herein, novel diarylpyrazole derivatives are synthesized and investigated for their ability to inhibit PDE4. In vitro studies indicate that most of the synthesized compounds show significant potency for the inhibition of PDE4. Specifically, N-(4-(3-(3,5-dimethoxyphenyl)-1H-pyrazol-5-yl)benzyl)-2-morpholinoethan-1-amine exhibits the most potent PDE4 inhibition, with an IC50 value of ca. 0.09 µM. It also produces antidepressant-like activities in sugar water consumption and in forced swimming tests in vivo. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment option for meniscus root tears is still challenging, and whether the meniscus root repair ultimately can arrest or delay osteoarthritic changes is still a concern. Purpose/Hypothesis: The purpose of this study was 2-fold: (1) to describe and compare histopathologic findings of 3 different therapeutic options for medial meniscus posterior root tear: nonoperative management, partial meniscectomy, and meniscus root repair; and (2) to test the hypothesis that meniscus root tears treated nonoperatively predispose to a lower risk of osteoarthritic progression compared with partial meniscectomy. Study Design: Controlled laboratory study. Methods: Posteromedial meniscus root tears were carried out in 39 New Zealand White rabbits. Animals were randomly assigned into 3 experimental groups: partial meniscectomy after root tear (PM; n = 13), root tears treated conservatively (CT; n = 13), and transtibial root repair (RR; n = 13). Contralateral limbs were used as healthy controls. The animals were euthanized at 16 weeks postoperatively; tissue samples of femoral and tibial articular cartilage were collected and processed for macro- and microscopic assessment to detect signs of early osteoarthritis (OA). Each sample was histopathologically assessed using the Osteoarthritis Research Society International grading and staging system. Results: Osteoarthritic changes were the hallmark in all 3 experimental groups. The RR group had the lowest scores for cartilage damage (mean, 2.5; range, 2-3), and the PM group exhibited higher and more severe signs of OA (mean, 16; range, 9-16) compared with the CT group (mean, 5; range, 4-6). The between-group comparison revealed significant differences, as the PM group showed a significantly higher rate of macro- and microscopic osteoarthritic changes compared with the RR (P <.001) and CT (P <.001) groups. The weightbearing area of the medial femoral condyle was the most severely affected, and tidemark disruption was evident in all tissue samples. Conclusion: Meniscus root repair cannot completely arrest the histopathologic progression of knee OA but leads to significantly less severe degenerative changes than partial meniscectomy and nonoperative treatment. Partial meniscectomy leads to the most severe osteoarthritic progression, while stable radial tears left in situ have lower progression compared with partial meniscectomy. Clinical Relevance: Histologic assessment is an essential tool and metric for guiding and understanding osteoarthritic features, providing insight into the disease development and progression. This study provides histopathologic evidence on osteoarthritic progression after medial meniscus posterior root repair. This knowledge can help to set more realistic expectations and can lead to the future development of augmented techniques. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a common disease that causes joint pain and disability. Stem cell therapy is emerging as a promising treatment for OA. Purpose: To evaluate the ability of peripheral blood–derived mesenchymal stem cells (PBMSCs) combined with donor-matched platelet-rich plasma (PRP) to treat OA in a rabbit model. Study Design: Controlled laboratory study. Methods: PBMSCs and donor-matched PRP were isolated and prepared from the same rabbit. PBMSCs were treated with serum-free medium, fetal bovine serum, and PRP; a series of PBMSC behaviors, including proliferation, migration, and adhesion, were compared among groups. The ability of PBMSCs or PRP alone and PBMSCs+PRP to protect chondrocytes against proinflammatory cytokine (interleukin 1β [IL-1β]) treatment was compared by analyzing reactive oxygen species (ROS)–scavenging ability and apoptosis. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate the expression of extracellular matrix (ECM) metabolism genes and proteins, and Western blotting was used to explore the potential mechanism of the corresponding signaling pathway. In vivo, the effect of PBMSCs+PRP on cartilage and inflammation of the synovium was observed in a surgery-induced OA rabbit model via gross observation, histological and immunohistochemical staining, and enzyme-linked immunosorbent assay. Results: Proliferation, migration, and adhesion ability were enhanced in PBMSCs treated with PRP. Moreover, compared with either PBMSCs or PRP alone, PBMSCs+PRP enhanced ROS-scavenging ability and inhibited apoptosis in IL-1β–treated chondrocytes. PBMSCs+PRP also reversed the IL-1β–induced degradation of collagen type 2 and aggrecan and increased expression of matrix metalloproteinase 13, and this effect was related to increased expression of ECM synthesis and decreased expression of degradation and inflammatory genes and proteins. Mechanistically, PBMSCs+PRP reduced the phosphorylation of inhibitor of nuclear factor-κBα (IκBα), which further inhibited the phosphorylation of downstream nuclear factor–κB (NF-κB) in the NF-κB signaling pathway. In vivo, compared with PBMSCs or PRP alone, intra-articular (IA) injection of PBMSCs+PRP enhanced cartilage regeneration and attenuated synovial inflammation in OA-induced rabbits. Conclusion: These results demonstrate that PRP could enhance biological activities, including viability, migration, and adhesion, in PBMSCs. PBMSCs+PRP could rescue ECM degeneration by inhibiting inflammatory signaling in IL-1β–treated OA chondrocytes. In addition, IA injection of PBMSCs+PRP effectively attenuated OA progression in a surgery-induced OA rabbit model. Clinical Relevance: PBMSCs+PRP may provide a promising treatment for knee OA, and this study can advance the related basic research. [ABSTRACT FROM AUTHOR]

Length change in the distal oblique band during forearm rotation was measured using four-dimensional CT in seven volunteers. There was no significant change in length, which provides more theoretical support for distal oblique band reinforcement for treatment of instability of the distal radioulnar joint. [ABSTRACT FROM AUTHOR]

Objective: Molecular hydrogen (H2) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H2 when inhaled immediately after impulse noise exposure. Methods: Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H2 inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H2 group), or to H2 inhalation (n = 5; the H2 group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H2 exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells. Results: Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H2 group; P <.05) but significantly less so in the Noise + H2 group (P <.05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H2 group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H2 group. The difference between the groups was significant in the basal region for OHCs (P =.003) and apical (P =.033) and basal (P =.048) regions for IHCs. Conclusions: Acute acoustic trauma can be reduced by H2 when inhaled immediately after impulse noise exposure. [ABSTRACT FROM AUTHOR]