A Dimeric Structural Scaffold for PRC2-PCL Targeting to CpG Island Chromatin.

Diverse accessory subunits are involved in the recruitment of polycomb repressive complex 2 (PRC2) to CpG island (CGI) chromatin. Here we report the crystal structure of a SUZ12-RBBP4 complex bound to fragments of the accessory subunits PHF19 and JARID2. Unexpectedly, this complex adopts a dimeric structural architecture, accounting for PRC2 self-association that has long been implicated. The intrinsic PRC2 dimer is formed via domain swapping involving RBBP4 and the unique C2 domain of SUZ12. MTF2 and PHF19 associate with PRC2 at around the dimer interface and stabilize the dimer. Conversely, AEBP2 binding results in a drastic movement of the C2 domain, disrupting the intrinsic PRC2 dimer. PRC2 dimerization enhances CGI DNA binding by PCLs in pairs in vitro, reminiscent of the widespread phenomenon of transcription factor dimerization in active transcription. Loss of PRC2 dimerization impairs histone H3K27 trimethylation (H3K27me3) on chromatin at developmental gene loci in mouse embryonic stem cells.

The proximal centriole-like structure maintains nucleus-centriole architecture in sperm.

Proper connection between the sperm head and tail is critical for sperm motility and fertilization. Head-tail linkage is mediated by the Head-Tail Coupling Apparatus (HTCA), which secures the axoneme (tail) to the nucleus (head). However, the molecular architecture of the HTCA is poorly understood. Here, we use Drosophila to investigate formation and remodeling of the HTCA throughout spermiogenesis by visualizing key components of this complex. Using structured illumination microscopy, we demonstrate that key HTCA proteins Spag4 and Yuri form a 'Centriole Cap' that surrounds the centriole (or Basal Body) as it invaginates into the surface of the nucleus. As development progresses, the centriole is laterally displaced to the side of the nucleus while the HTCA expands under the nucleus, forming what we term the 'Nuclear Shelf.' We next show that the proximal centriole-like (PCL) structure is positioned under the Nuclear Shelf, functioning as a critical stabilizer of centriole-nuclear attachment. Together, our data indicate that the HTCA is a complex, multi-point attachment site that simultaneously engages the PCL, the centriole, and the nucleus to ensure proper head-tail connection during late-stage spermiogenesis.

Alginate Improves the Chondrogenic Capacity of 3D PCL Scaffolds In Vitro: A Histological Approach.

Polycaprolactone (PCL) scaffolds have demonstrated an effectiveness in articular cartilage regeneration due to their biomechanical properties. On the other hand, alginate hydrogels generate a 3D environment with great chondrogenic potential. Our aim is to generate a mixed PCL/alginate scaffold that combines the chondrogenic properties of the two biomaterials. Porous PCL scaffolds were manufactured using a modified salt-leaching method and embedded in a culture medium or alginate in the presence or absence of chondrocytes. The chondrogenic capacity was studied in vitro. Type II collagen and aggrecan were measured by immunofluorescence, cell morphology by F-actin fluorescence staining and gene expression of COL1A1, COL2A1, ACAN, COL10A1, VEGF, RUNX1 and SOX6 by reverse transcription polymerase chain reaction (RT-PCR). The biocompatibility of the scaffolds was determined in vivo using athymic nude mice and assessed by histopathological and morphometric analysis. Alginate improved the chondrogenic potential of PCL in vitro by increasing the expression of type II collagen and aggrecan, as well as other markers related to chondrogenesis. All scaffolds showed good biocompatibility in the in vivo model. The presence of cells in the scaffolds induced an increase in vascularization of the PCL/alginate scaffolds. The results presented here reinforce the benefits of the combined use of PCL and alginate for the regeneration of articular cartilage.

Assessing the utility of the PC-PTSD-5 as a screening tool among a cancer survivor sample.

INTRODUCTION: Hematopoietic stem cell transplantation (HCT) is an intensive and invasive procedure used in cancer treatment that can lead to posttraumatic stress disorder (PTSD) symptoms. These symptoms are frequently overlooked in oncology and general health care settings. The suitability and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) within the cancer population remains uncertain. This study aims to evaluate its performance as a brief (five-item) case-finding screening alternative to the longer (20-item) PTSD Checklist for DSM-5 (PCL-5) in survivors who received an HCT 1 to 5 years ago. METHODS: A total of 817 cancer survivors completed the PC-PTSD-5 and PCL-5 during recruitment for a randomized clinical trial. Optimal cut scores for identifying probable PTSD and item performance were determined using indices correcting for chance and item response theory analyses. RESULTS: Of the HCT sample, 10.4% screened as positive for probable DSM-5 PTSD using the PCL-5. The PC-PTSD-5 exhibited strong internal consistency and significant associations with PCL-5 scores (total, r = .82; items, rs = .56-.61). A cutoff score of 2 provided optimal sensitivity for screening (κ[Se] = .95), whereas a cut score of 4 demonstrated the highest efficiency for detecting a probable DSM-5 PTSD diagnosis on the PCL-5 (κ[Eff] = .39). Item response theory analyses indicated that item 4 (numbing) of the PC-PTSD-5 yielded the most informative data, with other items potentially lacking incremental utility. CONCLUSION: Although not an instrument validation study, these findings offer efficient evidence for using the PC-PTSD-5 as a succinct screening tool among cancer survivors in a clinical context. TRIALS REGISTRATION: ClinicalTrials.gov, NCT04058795, registered 8/16/2019.

A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Guiding the Path to Healing: CuO2 -Laden Nanocomposite Membrane for Diabetic Wound Treatment.

Diabetic chronic wounds pose significant clinical challenges due to their characteristic features of impaired extracellular matrix (ECM) function, diminished angiogenesis, chronic inflammation, and increased susceptibility to infection. To tackle these challenges and provide a comprehensive therapeutic approach for diabetic wounds, the first coaxial electrospun nanocomposite membrane is developed that incorporates multifunctional copper peroxide nanoparticles (n-CuO2 ). The membrane's nanofiber possesses a unique "core/sheath" structure consisting of n-CuO2 +PVP (Polyvinylpyrrolidone)/PCL (Polycaprolactone) composite sheath and a PCL core. When exposed to the wound's moist environment, PVP within the sheath gradually disintegrates, releasing the embedded n-CuO2 . Under a weakly acidic microenvironment (typically diabetic and infected wounds), n-CuO2 decomposes to release H2 O2 and Cu2+ ions and subsequently produce ·OH through chemodynamic reactions. This enables the anti-bacterial activity mediated by reactive oxygen species (ROS), suppressing the inflammation while enhancing angiogenesis. At the same time, the dissolution of PVP unveils unique nano-grooved surface patterns on the nanofibers, providing desirable cell-guiding function required for accelerated skin regeneration. Through meticulous material selection and design, this study pioneers the development of functional nanocomposites for multi-modal wound therapy, which holds great promise in guiding the path to healing for diabetic wounds.

Bioengineered 3D ovarian model for long-term multiple development of preantral follicle: bridging the gap for poly(ε-caprolactone) (PCL)-based scaffold reproductive applications.

BACKGROUND: Assisted Reproductive Technologies (ARTs) have been validated in human and animal to solve reproductive problems such as infertility, aging, genetic selection/amplification and diseases. The persistent gap in ART biomedical applications lies in recapitulating the early stage of ovarian folliculogenesis, thus providing protocols to drive the large reserve of immature follicles towards the gonadotropin-dependent phase. Tissue engineering is becoming a concrete solution to potentially recapitulate ovarian structure, mostly relying on the use of autologous early follicles on natural or synthetic scaffolds. Based on these premises, the present study has been designed to validate the use of the ovarian bioinspired patterned electrospun fibrous scaffolds fabricated with poly(ε-caprolactone) (PCL) for multiple preantral (PA) follicle development. METHODS: PA follicles isolated from lamb ovaries were cultured on PCL scaffold adopting a validated single-follicle protocol (Ctrl) or simulating a multiple-follicle condition by reproducing an artificial ovary engrafted with 5 or 10 PA (AO5PA and AO10PA). The incubations were protracted for 14 and 18 days before assessing scaffold-based microenvironment suitability to assist in vitro folliculogenesis (ivF) and oogenesis at morphological and functional level. RESULTS: The ivF outcomes demonstrated that PCL-scaffolds generate an appropriate biomimetic ovarian microenvironment supporting the transition of multiple PA follicles towards early antral (EA) stage by supporting follicle growth and steroidogenic activation. PCL-multiple bioengineering ivF (AO10PA) performed in long term generated, in addition, the greatest percentage of highly specialized gametes by enhancing meiotic competence, large chromatin remodeling and parthenogenetic developmental competence. CONCLUSIONS: The study showcased the proof of concept for a next-generation ART use of PCL-patterned scaffold aimed to generate transplantable artificial ovary engrafted with autologous early-stage follicles or to advance ivF technologies holding a 3D bioinspired matrix promoting a physiological long-term multiple PA follicle protocol.

A new application of avocado oil to enrich the biological activities of polycaprolactone membranes for tissue engineering.

The metabolites synthesized by plants to protect themselves serves as natural antimicrobial agents used in biomaterials. In this study, avocado oil (AO), was incorporated as a plant source and natural antimicrobial agent into polycaprolactone (PCL) membranes. The effects of varying AO ratios (25, 50, and 100 wt%.-PCL@25AO, PCL@50AO, PCL@100AO) on PCL membrane morphology, chemical structure, wettability, antimicrobial activity, and cell viabilities were investigated. It was demonstrated that the AO acts as a pore-forming agent in solvent-casted membranes. Young's modulus of the membranes varied between 602.68 and 31.92 MPa and more flexible membranes were obtained with increasing AO content. Inhibition zones of AO were recorded between 7.86 and 13.97 mm against clinically relevant microbial strains including bacteria, yeast, and fungi. Antimicrobial activity of AO was retained in PCL membranes at all ratios. Resazurin assay indicated that PCL@25AO membranes were cytocompatible with mouse fibroblast cells (L929 cell line) on day 6 showing 72.4% cell viability with respect to neat PCL membranes. Viability results were supported by scanning electron microscopy images and DAPI staining. The overall results of this study highlight the potential of PCL@25AO membranes as a biomaterial with antimicrobial properties, cytocompatibility, and mechanical strength suitable for various biomedical applications.

Treatment of primary cardiac diffuse large B-cell lymphoma involving the coronary sinus with R-EPOCH: a case report and literature review.

Primary cardiac lymphomas (PCLs) are a rare clinical entity, in which treatment guidelines remain to be established. Rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) has been proposed, given that it involves a continuous infusion of anthracycline, reducing the risk of a cardiotoxicity and therefore the theoretical risk of perforation. However, the literature on this method of treatment is scarce. Herein, we present a unique case of a 75-year-old male, diagnosed with primary cardiac diffuse large B-cell lymphoma (DLBCL) with relatively unusual involvement of the coronary sinus, treated first with one cycle of R-EPOCH, followed by three cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) to reduce said risk. To our knowledge, this is one of two cases, in which a patient with PCL was treated this way.

Commitment of human mesenchymal stromal cells towards ACL fibroblast differentiation upon rAAV-mediated FGF-2 and TGF-ß overexpression using pNaSS-grafted PCL films.

Despite various clinical options, human anterior cruciate ligament (ACL) lesions do not fully heal. Biomaterial-guided gene therapy using recombinant adeno-associated virus (rAAV) vectors may improve the intrinsic mechanisms of ACL repair. Here, we examined whether poly(sodium styrene sulfonate)-grafted poly(ε-caprolactone) (pNaSS-grafted PCL) films can deliver rAAV vectors coding for the reparative basic fibroblast growth factor (FGF-2) and transforming growth factor beta (TGF-ß) in human mesenchymal stromal cells (hMSCs) as a source of implantable cells in ACL lesions. Efficient and sustained rAAV-mediated reporter (red fluorescent protein) and therapeutic (FGF-2 and TGF-ß) gene overexpression was achieved in the cells for at least 21 days in particular with pNaSS-grafted PCL films relative to all other conditions (up to 5.2-fold difference). Expression of FGF-2 and TGF-ß mediated by rAAV using PCL films increased the levels of cell proliferation, the DNA contents, and the deposition of proteoglycans and of type-I and -III collagen (up to 2.9-fold difference) over time in the cells with higher levels of transcription factor expression (Mohawk, Scleraxis) (up to 1.9-fold difference), without activation of inflammatory tumor necrosis alpha especially when using pNaSS-grafted PCL films compared with the controls. Overall, the effects mediated by TGF-ß were higher than those promoted by FGF-2, possibly due to higher levels of gene expression achieved upon rAAV gene transfer. This study shows the potential of using functionalized PCL films to apply rAAV vectors for ACL repair.

Microplastics Biodegradation by Estuarine and Landfill Microbiomes.

Plastic pollution poses a worldwide environmental challenge, affecting wildlife and human health. Assessing the biodegradation capabilities of natural microbiomes in environments contaminated with microplastics is crucial for mitigating the effects of plastic pollution. In this work, we evaluated the potential of landfill leachate (LL) and estuarine sediments (ES) to biodegrade polyethylene (PE), polyethylene terephthalate (PET), and polycaprolactone (PCL), under aerobic, anaerobic, thermophilic, and mesophilic conditions. PCL underwent extensive aerobic biodegradation with LL (99 ± 7%) and ES (78 ± 3%) within 50-60 days. Under anaerobic conditions, LL degraded 87 ± 19% of PCL in 60 days, whereas ES showed minimal biodegradation (3 ± 0.3%). PE and PET showed no notable degradation. Metataxonomics results (16S rRNA sequencing) revealed the presence of highly abundant thermophilic microorganisms assigned to Coprothermobacter sp. (6.8% and 28% relative abundance in anaerobic and aerobic incubations, respectively). Coprothermobacter spp. contain genes encoding two enzymes, an esterase and a thermostable monoacylglycerol lipase, that can potentially catalyze PCL hydrolysis. These results suggest that Coprothermobacter sp. may be pivotal in landfill leachate microbiomes for thermophilic PCL biodegradation across varying conditions. The anaerobic microbial community was dominated by hydrogenotrophic methanogens assigned to Methanothermobacter sp. (21%), pointing at possible syntrophic interactions with Coprothermobacter sp. (a H2-producer) during PCL biodegradation. In the aerobic experiments, fungi dominated the eukaryotic microbial community (e.g., Exophiala (41%), Penicillium (17%), and Mucor (18%)), suggesting that aerobic PCL biodegradation by LL involves collaboration between fungi and bacteria. Our findings bring insights on the microbial communities and microbial interactions mediating plastic biodegradation, offering valuable perspectives for plastic pollution mitigation.

Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO4H/CPs-SO4H-OH), 14 chlorinated benzene sulfates (CBs-SO4H), and 19 CP sulfite esters (CPs-SO3/CPs-S2O6), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph4PCl), respectively, were performed to determine the ionization forms ([M + Cl]- or [M - H]-) of CPs-S. The presence of fragment ions (SO4H-, SO3-, SO2Cl-, and HSO3-) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

Current Status on Management of Primary Plasma Cell Leukemia.

PURPOSEOF REVIEW: Plasma Cell Leukemia (PCL) is a very rare and highly aggressive form of plasma cell dyscrasia. This review seeks to evaluate the outcomes of PCL in the context of combination novel agent therapy and stem cell transplant (SCT) protocols. RECENT FINDINGS: The diagnostic criteria for PCL have now evolved to include patients with 5% circulating PC. While management remains challenging, the incorporation of novel agent-based induction regimen has significantly improved early mortality and reduced attrition of patients proceeding to SCT. In recent prospective clinical trials, patients with PCL demonstrated an overall response rates of 69% to 86%, with progression-free and overall survival ranging from 13.8 to 15.5 months and 24.8 to 36.3 months, respectively. B-cell lymphoma 2 (BCL2) inhibitors, such as venetoclax present a targeted intervention opportunity for patients with PCL with t(11;14). Dedicated clinical trials tailored to PCL are crucial, integrating newer therapies in the frontline setting to further optimize responses and enhance overall outcomes.

Adverse childhood events and self-harming behaviours among individuals in Ontario forensic system: the mediating role of psychopathy.

BACKGROUND: Adverse childhood events (ACEs), psychopathy, and self-harming behaviours are prevalent among individuals in the forensic psychiatry system. While existing literature suggests that ACEs, self-harm, and psychopathy are interrelated, little is known about the interplay of psychopathic traits in this relationship. The present study aimed to determine the mediating role of psychopathy in the relationship between ACEs and self-harming behaviours in forensic patients. METHODS: This was a retrospective study of patients under the Ontario Review Board (ORB) between 2014 and 2015. In the analysis, we included patients with complete data on ACEs, self-harming behaviours, and a Psychopathy Checklist-Revised (PCL-R) score - a measure of psychopathic traits and their severity conducted during the reporting period. Mediation analysis was based on the Baron and Kenny approach, and sensitivity analysis was performed based on the types of ACEs. RESULTS: ​​​The sample population (n = 593) was made up of adults, with a mean age of 41.21 (± 12.35) years and were predominantly males (92.37%). While there was a partial mediating effect of psychopathy on the relationship between ACEs and incidents of self-harming behaviours in the past year, the mediation was complete in the relationship between ACEs and a lifetime history of self-harming behaviours. Following sensitivity analysis based on the types of ACE, the mediating effects were more attributed to specific ACEs, especially having experienced child abuse or having an incarcerated household member before 18 years. CONCLUSION: Among forensic patients in Ontario, psychopathy mediates​ ​the relationship between experiencing ACEs and engaging in self-harming behaviours. Effective intervention to mitigate self-harming behaviours in this population should consider the potential role of psychopathy, especially among individuals who have experienced ACEs involving a history of child abuse and a family who was incarcerated.

Biocompatible PAMAM-PLGA-PCL Nanocarrier for Efficient Curcumin Delivery to Lung Cancer Cells: In Vitro Studies.

We developed a novel polylactic-co-glycolic acid (PLGA)-polyamidoamine G4 (PAMAM G4)-polycaprolactone (PCL) nanocarrier for efficient delivery of curcumin (Cur) to A549 lung cancer cells. The synthesized nanocarrier was characterized by applying analytical techniques, FT-IR, DLS, TEM, and TGA. Successful synthesis, nano-size diameter (40 to 80 nm), near neutral surface charge (8.0 mV), and high drug entrapment (11.5%) were measured for the nanocarrier. Controlled (about 5 folds within first 2 h) and pH-sensitive (2 to 3 folds faster within first hours) Cur release observed for PLGA-PAMAM-PCL-Cur. Cell viability test (MTT assay) indicated the high capability of nanocarrier in suppression of A549 cancer cells (21% viability after 24 h of treatment with 200 nM) while did not result in toxicity on MSC normal cells. The IC50 observed for 50 nM at 24 h of post-treatment in A549 cells. The qRT-PCR technique indicated inducing the expression of apoptotic genes (Caspase9 and Bax) by 6-8 folds and suppressing anti-apoptotic gene (Bcl2) by 7 folds. ROS considerably increased in cancer cells as well. This nanocarrier would be a promising drug delivery system against lung cancer.

No effect of dislocation status at arrival in emergency department on outcome of knee joint dislocations.

PURPOSE: Knee dislocation is a rare but severe injury of the lower extremities. The aim of this study was to report on the epidemiology, diagnostics and treatment of such injuries and to identify negative predictors of clinical outcomes. METHODS: This retrospective analysis included all knee dislocations treated at a Level I Trauma Centre in Germany between 2009 and 2021. Medical records were categorised, collected and analysed in a standardised manner. A follow-up visit 1 year after the injury focused on limitations in knee mobility. RESULTS: A total of 120 knee dislocations were included in the study. 29.3% of patients presented to the emergency department with a dislocated joint, and 17.5% (n = 21) had a neurovascular lesion. At follow-up 12 months after the injury, 65.8% of the patients reported limitations in the range of motion, and 11.7% (n = 14) reported severe limitations in daily activities. Site infections due to surgery occurred in 3.3% of patients. Increased body weight (r = 0.294; p < 0.001 and r = 0.259; p = 0.004), an increased body mass index above 25 kg/m2 (body mass index, r = 0.296; p < 0.001 and r = 0.264; p = 0.004) and deficits in peripheral perfusion as well as sensory and motor function (r = 0.231; p = 0.040 and r = -0.192; p = 0.036) were found to be negative predictive factors for clinical outcome. For posttraumatic neurovascular injury, lack of peripheral perfusion, insufficient sensory and motor function (r = -0.683; p < 0.0001), as well as a higher Schenck grade (r = 0.320; p = 0.037), were identified as independent risk factors. The status of dislocation at the site of the accident and on arrival at the emergency department had no impact on the outcome or neurovascular injury. CONCLUSION: Knee dislocation is a rare injury with a high rate of severe complications such as neurovascular lesions. In particular, the initial status of neurovascular structures and injury classification showed a relevant negative correlation with the posttraumatic status of nerves and vessels. In particular, patients with these characteristics need close monitoring to prevent negative long-term consequences. LEVEL OF EVIDENCE: Level III.

Decreased posterior tibial slope is a risk factor for primary posterior cruciate ligament rupture and posterior cruciate ligament reconstruction failure: A systematic review.

PURPOSE: To determine bony knee morphological factors associated with primary posterior cruciate ligament (PCL) rupture or PCL graft failure after PCL reconstruction. METHODS: Three databases, namely MEDLINE, PubMed and EMBASE, were searched on 30th May 2023. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data such as receiver operating characteristic curve parameters, as well as p-values for comparisons of values between patients with PCL pathology and control patients, were recorded. RESULTS: Nine studies comprising 1054 patients were included. Four studies reported that patients with PCL injury had flatter medial posterior tibial slopes (MTS) than controls, with mean values of 4.3 (range: 3.0-7.0) and 6.5 (range: 5.0-9.2) degrees, respectively. Two studies reported an MTS cutoff value ranging below 3.90-3.93° being a significant risk factor for primary PCL rupture or PCL graft failure. Two studies reported that shallow medial tibial depths were associated with primary PCL rupture, with mean values of 2.1 (range: 2.0-2.2) and 2.6 (range: 2.4-2.7) mm in PCL injury and control groups, respectively. Stenotic intercondylar notches and femoral condylar width were not consistently associated with PCL injuries. CONCLUSION: Decreased MTS is associated with primary PCL rupture and graft failure after PCL reconstruction with values below 3.93° being considered as a significant risk factor. Less common risk factors include shallow medial tibial depth, while femoral condylar width and parameters with regards to the intercondylar notch, such as notch width, notch width index and intercondylar notch volume, demonstrated conflicting associations with primary or secondary PCL injuries. LEVEL OF EVIDENCE: Level III.

Impact of sex and age on the lateralisation of the tibial tubercle in normal paediatric and adolescent populations.

PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.

The Modulation of Respiratory Epithelial Cell Differentiation by the Thickness of an Electrospun Poly-ε-Carprolactone Mesh Mimicking the Basement Membrane.

The topology of the basement membrane (BM) affects cell physiology and pathology, and BM thickening is associated with various chronic lung diseases. In addition, the topology of commercially available poly (ethylene terephthalate) (PET) membranes, which are used in preclinical in vitro models, differs from that of the human BM, which has a fibrous and elastic structure. In this study, we verified the effect of BM thickness on the differentiation of normal human bronchial epithelial (NHBE) cells. To evaluate whether the thickness of poly-ε-carprolactone (PCL) mesh affects the differentiation of NHBE cells, cells were grown on thin- (6-layer) and thick-layer (80-layer) meshes consisting of electrospun PCL nanofibers using an air-liquid interface (ALI) cell culture system. It was found that the NHBE cells formed a normal pseudostratified epithelium composed of ciliated, goblet, and basal cells on the thin-layer PCL mesh; however, goblet cell hyperplasia was observed on the thick-layer PCL mesh. Differentiated NHBE cells cultured on the thick-layer PCL mesh also demonstrated increased epithelial-mesenchymal transition (EMT) compared to those cultured on the thin-layer PCL mesh. In addition, expression of Sox9, nuclear factor (NF)-κB, and oxidative stress-related markers, which are also associated with goblet cell hyperplasia, was increased in the differentiated NHBE cells cultured on the thick-layer PCL mesh. Thus, the use of thick electrospun PCL mesh led to NHBE cells differentiating into hyperplastic goblet cells via EMT and the oxidative stress-related signaling pathway. Therefore, the topology of the BM, for example, thickness, may affect the differentiation direction of human bronchial epithelial cells.

PCL preservation or sacrifice does not influence clinical outcomes and survivorship at mid-term follow-up of a J-curve CR total knee replacement with a medial congruent liner and a functional coronal alignment.

BACKGROUND: In recent years, increasing interest has arisen for medial pivoting TKA implants, designed to mimic the physiological knee kinematics, maximizing the contact area on the medial compartment of the knee, increasing anterior-posterior stability, and contributing to a ball-in-socket effect that allows the posterior cruciate sacrifice without a post-CAM mechanism. The medial congruent liner works with a J-curve cruciate-retaining (CR) femur without a real ball-in-socket design. The aim of this study was to evaluate the clinical outcomes and survival of these implants, with or without PCL sparing, at a medium follow-up. METHODS: Between October 2016 and October 2018, 165 TKRs were performed in 161 patients (69.2% females and 30.8% males) and prospectively followed. Mean follow-up was 72 ± 12 months. All surgeries were performed using an extramedullary device and the same prosthetic implant. Patients were matched in two groups: in 80 patients, the PCL was preserved; in 85 patients, the PCL was sacrificed with a reduction of the tibial slope. RESULTS: The OKS and KSS improved in both groups. The difference between the two groups at the final follow-up was not statistically significant. Good-to-excellent clinical results according to the KSS were achieved in 93% of the knees in the PCP group and in 95% in the PCS group. At final follow-up, the Forgotten Joint Score (FJS) was 73.6 in the PCP group and 74.1 in the PCS group with no statistical difference between the two groups (P > 0.05). CONCLUSIONS: TKA with a medially congruent insert, showed promising results at mid-term follow-up, PCL preservation or sacrifice did not affect the clinical outcomes and survival. Further follow-up will be needed to evaluate these results at long term.