Local Repair Research Articles

A new limited-angle CT reconstruction algorithm based on the local anisotropic total variation restoration of continuity

A new limited-angle computed tomography(CT) reconstruction algorithm based on local detail information restoration in the CT image projection domain was proposed in this paper. The lost projection information could be repaired with the new algorithm called local anisotropic total variation repair method of sinogram (LATV). According to the continuity of local gradient in sinogram, local high frequency characteristics can be improved which are blurred by conventional TVM. A series of numerical reconstruction experiments were conducted to validate the new algorithm. The overall quality of images reconstructed by new algorithm was better than conventional TVM algorithm when quantitatively evaluated. Then, a local region with rich details was selected in order to evaluate the reconstruction effect of the internal details. From the perspective of three image quality evaluation parameters, it was shown that the local high frequency details were well repaired. Finally, the reconstruction quality was evaluated by actual CT experimental data. The new method also performed better than conventional method. Therefore, the new LATV algorithm proposed in this paper may be a new method suitable for limited-angle CT reconstruction problems.

A Solution for Knee Osteoarthritis with Adipose-Derived Autologous Stem Cells in Middle-Aged People

Background: Adipose tissue has achieved a great relevance as possible fount of mesenchymal stem cells for the healing of different articular pathologies including Knee Osteoarthritis (KOA). Stem cells derived from the Adipose Tissue (ADSCs) have a possibility to differentiate into chondrocyte, can reduce the immune response and can stimulate a local tissue repair, improving also the intra-articular Methods and Findings: Intra-articular injections of ADSCs with other conservative or surgical treatments can lead to an improving of all clinical and functional postoperative outcomes evaluated in middle-aged patients with KOA or chondral lesions. Moreover, some scores based on Magnetic Resonance Imaging (MRI) demonstrated an incremented quality of repaired cartilage in comparison with the pre-treatment. We observed no serious advent events. Conclusion: The use of ADSCs appeared to be out of danger, effective and it can be supposed an alternative procedure for the healing of chondral lesions and degenerative OA suitable for middle-aged athlete but no specific studies have been focus on this population and no long term follow-up data are available.

UNCOMMON PRESENTATION OF URETHRAL INJURY- A RARE CASE

Background: Urethroplasty is the surgical repair of an injury or defect within the walls of the urethra. Trauma, iatrogenic injury and infections are the most common causes of urethral injury/defect requiring repair. Urethroplasty is regarded as the go treatment for urethral strictures and offers better outcomes in terms of recurrence rates than dilatations and urethrotomies. It is probably the only useful modality of treatment for long and complex strictures though recurrence rates are higher for this difficult treatment group. Case: 32 years old male came to surgery opd with complaint of swelling over base of penile shaft since 6 months associated with dribbling of urine since 6 months, painful erection, burning micturition since 1week Patient had history of trauma 6 months back during intercourse following which he had swelling over penis and transient hematuria. For which he went to a local doctor and took symptomatic treatment. The swelling and dribbling persisted but did not seek any medical attention. On clinical examination 3x2cm swelling over ventral aspect at the base of penis at penoscrotal junction with Skin over the swelling appears normal and on palpation swelling was non tender, no local rise in temperature, no redness, no discharge, non-translucent Bilateral testis palpable in scrotum On Ultrasonography swelling s/o partial tear of corpora spongiosum at the root of penis on ventral aspect communicating with urethra with approximately 15 cc collection with internal echoes in it f/s/o fracture penis. Patient underwent urethroplasty with local flap repair using buckÂ’s fascia. Conclusion: Urethroplasty with local flap repair using buckÂ’s fascia also be considered in treatment of urethral injury .

Insight into Heart-Tailored Architectures of Hydrogel to Restore Cardiac Functions after Myocardial Infarction.

With permanent heart muscle injury or death, myocardial infarction (MI) is complicated by inflammatory, proliferation and remodeling phases from both the early ischemic period and subsequent infarct expansion. Though in situ re-establishment of blood flow to the infarct zone and delays of the ventricular remodeling process are current treatment options of MI, they fail to address massive loss of viable cardiomyocytes while transplanting stem cells to regenerate heart is hindered by their poor retention in the infarct bed. Equipped with heart-specific mimicry and extracellular matrix (ECM)-like functionality on the network structure, hydrogels leveraging tissue-matching biomechanics and biocompatibility can mechanically constrain the infarct and act as localized transport of bioactive ingredients to refresh the dysfunctional heart under the constant cyclic stress. Given diverse characteristics of hydrogel including conductivity, anisotropy, adhesiveness, biodegradability, self-healing and mechanical properties driving local cardiac repair, we aim to investigate and conclude the dynamic balance between ordered architectures of hydrogels and the post-MI pathological milieu. Additionally, our review summarizes advantages of heart-tailored architectures of hydrogels in cardiac repair following MI. Finally, we propose challenges and prospects in clinical translation of hydrogels to draw theoretical guidance on cardiac repair and regeneration after MI.

Elucidation of the etiological mechanisms underlying rare hereditary cilia/centrosome disorders using genome editing technology

Deep sequencing technology in forward genetics is a powerful tool to identify causal mutations underlying hereditary human diseases. To elucidate the etiological mechanisms, reverse genetics in human cultured cells is useful for generating disease models in vitro. However, the development of reverse genetics has been slow because of the lower efficacy of homologous recombination in almost all mammalian cultured cells. The history of reverse genetics in cultured cells began with the advent of genome editing technology, which could effectively modify the genome via artificial nuclease-induced local DNA repair activity. Bidirectional genetics based on deep sequencing technology and genome editing technology is now an essential approach for clarifying the pathophysiology of hereditary diseases. Here, we provide an overview of the validity of genome editing in cultured cells and its technical problems, discussing the example of centrosome/cilia-related disease models in cultured cells.

Evaluating and Improving Unified Debugging

Automated debugging techniques, including fault localization and program repair, have been studied for over a decade. However, the only existing connection between fault localization and program repair is that fault localization computes the potential buggy elements for program repair to patch. Recently, a pioneering work, ProFL, explored the idea of <i>unified debugging</i> to unify fault localization and program repair in the other direction for the first time to boost both areas. More specifically, ProFL utilizes the patch execution results from one state-of-the-art repair system, PraPR, to help improve state-of-the-art fault localization. In this way, ProFL not only improves fault localization for <i>manual repair</i> , but also extends the application scope of <i>automated repair</i> to all possible bugs (not only the small ratio of bugs that repair systems can automatically fix). However, ProFL only considers one program repair system (i.e., PraPR), and it is not clear how other existing program repair systems based on different designs contribute to unified debugging. In this work, we perform an extensive study of the unified debugging approach on 16 state-of-the-art program repair systems for the first time. Our initial experimental results on the widely studied Defects4J benchmark suite reveal various practical guidelines for unified debugging, such as (1) nearly all 16 studied repair systems positively contribute to unified debugging despite their varying repair capabilities, (2) repair systems targeting multi-edit patches can bring extraneous noise into unified debugging, (3) repair systems with more executed/plausible patches tend to perform better for unified debugging, (4) unified debugging effectiveness does not rely on the availability of correct patches from automated repair, and (5) we propose a new unified debugging technique, UniDebug++, which localizes over 20% more bugs within Top-1 than state-of-the-art unified debugging technique ProFL (evaluated against four Defects4J subjects). Furthermore, we conduct more comprehensive studies to extend the above experiments to make the following additional contributions: we (6) further perform an extensive study on 76.3% additional buggy versions from Defects4J (for Closure and Mockito) and confirm that UniDebug++ again outperforms ProFL by localizing 185 (out of 395 in total) bugs within Top-1, 14% more than ProFL, (7) investigate the impact of 33 SBFL formulae on unified debugging and observe that UniDebug++ consistently improves upon all formulae, e.g., 61% and 53% average improvement on MFR / MAR, (8) demonstrate that UniDebug++ can substantially boost state-of-the-art learning-based method-level fault localization techniques, (9) extend unified debugging to the statement level for first time and observe that UniDebug++ localizes 78 (out of 395 in total) bugs within Top-1 (22% more bugs than ProFL) and outperforms state-of-the-art learning-based fault localization techniques by 30%, and finally (10) propose a new technique, UniDebug+ <inline-formula><tex-math notation="LaTeX">$^\star$</tex-math></inline-formula> , based on detailed patch statistics, to improve upon UniDebug++, e.g., further localizing up to 9% more bugs within Top-1 than UniDebug++.

Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling

BackgroundGlucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs.ResultsIn this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs’ stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo.ConclusionsPL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.Graphical

P115RhoGEF activates RhoA to support tight junction maintenance and remodeling.

In vertebrates, epithelial cell-cell junctions must rapidly remodel to maintain barrier function as cells undergo dynamic shape-change events. Consequently, localized leaks sometimes arise within the tight junction (TJ) barrier, which are repaired by short-lived activations of RhoA, called "Rho flares." However, how RhoA is activated at leak sites remains unknown. Here we asked which guanine nucleotide exchange factor (GEF) localizes to TJs to initiate Rho activity at Rho flares. We find that p115RhoGEF locally activates Rho flares at sites of TJ loss. Knockdown of p115RhoGEF leads to diminished Rho flare intensity and impaired TJ remodeling. p115RhoGEF knockdown also decreases junctional active RhoA levels, thus compromising the apical actomyosin array and junctional complex. Furthermore, p115RhoGEF is necessary to promote local leak repair to maintain TJ barrier function. In all, our work demonstrates a central role for p115RhoGEF in activating junctional RhoA to preserve barrier function and direct local TJ remodeling.

Coronary artery involvement in type A aortic dissection: Fate of the coronaries.

Type A aortic dissection (TAAD) involves a tear in the intimal layer of the thoracic aorta proximal to the left subclavian artery, and hence, carries a high risk of mortality and morbidity and requires urgent intervention. This dissection can extend into the main coronary arteries. Coronary artery involvement in TAAD can either be due to retrograde extension of the dissection flap into the coronaries or compression and/or blockage of these vessels by the dissection flap, possibly causing myocardial ischemia. Due to the emergent nature of TAAD, coronary involvement is often missed during diagnosis, thereby delaying the required intervention. The main scope of this review is to summarize the literature on the incidence, mechanism, diagnosis, and treatment of coronary artery involvement in TAAD. A comprehensive literature search was performed using multiple electronic databases, including PubMed, Ovid, Scopus and Embase, to identify and extract relevant studies. Incidence of coronary artery involvement in TAAD was seldom reported in the literature, however, some studies have described patients diagnosed either preoperatively, intraoperatively following aortic clamping, or even during autopsy. Among the few studies that reported on this matter, the treatment choice for coronary involvement in TAAD was varied, with the majority revascularizing the coronary arteries using coronary artery bypass grafting or direct local repair of the vessels. It is well-established that coronary artery involvement in TAAD adds to the already high mortality and morbidity associated with this disease. Lastly, the right main coronary artery was often more implicated than the left. This review reiterates the significance of an accurate diagnosis and timely and effective interventions to improve prognosis. Finally, further large cohort studies and longer trials are needed to reach a definitive consensus on the best approach for coronary involvement in TAAD.

A quantitative 3D intravital look at the juxtaglomerular renin-cell-niche reveals an individual intra/extraglomerular feedback system.

The juxtaglomerular niche occupied by renin cells (RCN) plays an important role in glomerular repair but the precise temporal and spatial interrelations remain unclear. This study proposes the hypothesis of a local intra-extraglomerular regenerative feedback system and establishes a new quantifiable system for RCN responses in individual glomeruli in vivo. A strictly intraglomerular two-photon laser-induced injury model was established. Labeled renin cells (RC) in transgenic renin reporter mice were fate-traced in healthy and injured glomeruli over several days by intravital microscopy and quantified via new three-dimensional image processing algorithms based on ray tracing. RC in healthy glomeruli demonstrated dynamic extraglomerular protrusions. Upon intraglomerular injury the corresponding RCN first increased in volume and then increased in area of dynamic migration up to threefold compared to their RCN. RC started migration reaching the site of injury within 3 hours and acquired a mesangial cell phenotype without losing physical RCN-contact. During intraglomerular repair only the corresponding RCN responded via stimulated neogenesis, a process of de novo differentiation of RC to replenish the RCN. Repeated continuous intravital microscopy provides a state-of-the-art tool to prove and further study the local intraglomerular RCN repair feedback system in individual glomeruli in vivo in a quantifiable manner.

Outcomes of surgical treatment on type A acute aortic dissection accompanied with coronary artery involvement.

BackgroundCoronary artery (CA) involvement due to acute aortic dissection (AAD) is a catastrophic cardiovascular disease with high mortality. Two main surgery strategies, local coronary repair and coronary artery bypass grafting (CABG) can be applied to reestablish the blood flow in the aortic repair. This study was to evaluate the operative and long-term outcomes of type A AAD patients, who received aortic dissection repair plus CABG or local coronary repair.MethodWe reviewed our database and screened 148 type A AAD patients with CA involvement from January 2001 to December 2021. Local coronary repair or CABG was performed concomitantly on these enrolled patients.ResultsAt the time of aortic repair, there were 58 patients with concomitant CABG (Group I) and 90 patients with local coronary repair (Group II). The basal characteristics of these two groups had no difference, except for acute myocardial ischemia (AMI) and CA involvement type. 45 patients with AMI in Group I, but none in Group II (P < 0.001). There was a higher frequency of type B and C lesions of CA involvement in Group I than that in Group II (P < 0.001). There was no difference in surgical procedures and complications, except for postoperative acute kidney injury (AKI) (34.5% vs. 8.9%, P < 0.001). Hospital mortality in Group I was higher than that in Group II, but without statistical difference (20.7% vs. 11.1%, P = 0.155). No significant difference was obtained in long-term survival rate between the two groups (82.5 ± 4.8% vs. 81.2 ± 6.9%, P = 0.19).ConclusionCABG and local coronary repair suits different types of CA involvement, and their effects on perioperative results and long-term survival for type A AAD patients with CA involvement are equal.

Effects of replication domains on genome-wide UV-induced DNA damage and repair.

Nucleotide excision repair is the primary repair mechanism that removes UV-induced DNA lesions in placentals. Unrepaired UV-induced lesions could result in mutations during DNA replication. Although the mutagenesis of pyrimidine dimers is reasonably well understood, the direct effects of replication fork progression on nucleotide excision repair are yet to be clarified. Here, we applied Damage-seq and XR-seq techniques and generated replication maps in synchronized UV-treated HeLa cells. The results suggest that ongoing replication stimulates local repair in both early and late replication domains. Additionally, it was revealed that lesions on lagging strand templates are repaired slower in late replication domains, which is probably due to the imbalanced sequence context. Asymmetric relative repair is in line with the strand bias of melanoma mutations, suggesting a role of exogenous damage, repair, and replication in mutational strand asymmetry.

Recombinant PTH modification: A new strategy for a multifunctional CaP material to enhance bone regeneration

Bone regeneration requires the interaction of osteogenesis, osteolysis, and angiogenesis as well as an appropriate immune microenvironment. Recombinant human parathyroid hormone (PTH1-34) is approved for clinical anti-osteoporosis treatment because of its good osteogenic activity, osteoclastosis, and angiogenesis. However, the phenomenon of net bone resorption limits its use in local bone repair. Our group provides an effective strategy for multifunctional calcium phosphate (CaP) ceramics with modulating M1 macrophage pro-inflammatory effects, and bone regeneration. CaP ceramic scaffold is functionalized with parathyroid hormone related peptide-1 (PTHrP-1) for bone defect repair. First, peptide-functionalized true bone ceramic (TBC) scaffold exhibit limited M1 macrophage pro-inflammatory effects to improve the osteogenic microenvironment. Second, PTHrP-1 retains the osteogenic activity and angiogenic properties of PTH1-34 while downregulating osteoclast activity to induce favorable bone formation. Third, the peptide modified by tri-continuous aspartic acids (D3) and serine phosphorylation (PSer) has high affinity to the natural CaP matrix, achieving a slow release of PTHrP-1 in the TBC scaffold. Fourth, the carboxyl group of aspartate combined with calcium effectively promotes hydroxyapatite (HAP) nucleation and completes self-assembled mineralization. which is beneficial for bone regeneration. The results show that PTHrP-1-TBC is more suitable for bone regeneration than TBC scaffold and unmodified peptide alone.

Generation of cost-effective MXene@polydopamine-decorated chitosan nanofibrous wound dressing for promoting wound healing.

Herein, we designed and fabricated a MXene@polydopamine (MXene@PDA)-decorated chitosan non-woven fabric (M-CNF) hemostatic dressing with super hydrophilic properties for wound repair and regeneration. The M-CNF exhibit excellently wettability characteristics which can rapidly absorb water from blood. Moreover, M-CNF with 15mg/mL MXene@PDA (M-CNF-15) show better antibacterial performance, excellent blood-clotting performance, better blood cell and platelet adhesion ability than CNF, displaying both active and passive hemostatic mechanisms to accelerate blood clotting in mouse-liver injury model. In addition, the M-CNF-15 also shows better wound healed performance than Tegaderm™ film in a full-thickness skin defect model, and further demonstrating that the MXene@PDA can promote fibrinogen reformation the at the initial phases of the wound healing process. Therefore, this strategy for designing and manufacturing of multi-functional M-CNF wound dressing will have great potential for active local hemostasis and wound repair and regeneration.

Vanguard is a Glucose Deprivation-Responsive Long Non-Coding RNA Essential for Chromatin Remodeling-Reliant DNA Repair.

Glucose metabolism contributes to DNA damage response pathways by regulating chromatin remodeling, double‐strand break (DSB) repair, and redox homeostasis, although the underlying mechanisms are not fully established. Here, a previously uncharacterized long non‐coding RNA is revealed that is call Vanguard which acts to promote HMGB1‐dependent DNA repair in association with changes in global chromatin accessibility. Vanguard expression is maintained in cancer cells by SP1‐dependent transcription according to glucose availability and cellular adenosine triphosphate (ATP) levels. Vanguard promotes complex formation between HMGB1 and HDAC1, with the resulting deacetylation of HMGB1 serving to maintain its nuclear localization and DSB repair function. However, Vanguard downregulation under glucose limiting conditions promotes HMGB1 translocation from the nucleus, increasing DNA damage, and compromising cancer cell growth and viability. Moreover, Vanguard silencing increases the effectiveness of poly (ADP‐ribose) polymerase inhibitors against breast cancer cells with wild‐type breast cancer gene‐1 status, suggesting Vanguard as a potential therapeutic target.

CAQK, a peptide associating with extracellular matrix components targets sites of demyelinating injuries.

The destruction of the myelin sheath that encircles axons leads to impairments of nerve conduction and neuronal dysfunctions. A major demyelinating disorder is multiple sclerosis (MS), a progressively disabling disease in which immune cells attack the myelin. To date, there are no therapies to target selectively myelin lesions, repair the myelin or stop MS progression. Small peptides recognizing epitopes selectively exposed at sites of injury show promise for targeting therapeutics in various pathologies. Here we show the selective homing of the four amino acid peptide, cysteine-alanine-lysine glutamine (CAQK), to sites of demyelinating injuries in three different mouse models. Homing was assessed by administering fluorescein amine (FAM)-labeled peptides into the bloodstream of mice and analyzing sites of demyelination in comparison with healthy brain or spinal cord tissue. FAM-CAQK selectively targeted demyelinating areas in all three models and was absent from healthy tissue. At lesion sites, the peptide was primarily associated with the fibrous extracellular matrix (ECM) deposited in interstitial spaces proximal to reactive astrocytes. Association of FAM-CAQK was detected with tenascin-C although tenascin depositions made up only a minor portion of the examined lesion sites. In mice on a 6-week cuprizone diet, FAM-CAQK peptide crossed the nearly intact blood-brain barrier and homed to demyelinating fiber tracts. These results demonstrate the selective targeting of CAQK to demyelinating injuries under multiple conditions and confirm the previously reported association with the ECM. This work sets the stage for further developing CAQK peptide targeting for diagnostic and therapeutic applications aimed at localized myelin repair.

Mid-term Efficacy of Local Repair Using Modified Altemeier Technique for Stomal Prolapse: A Case Series.

Introduction: Stomal prolapse (SP) is characterized by full-thickness protrusion of the bowel through the stoma site. The surgical procedures for SP include local repair, abdominal wall fixation, and stoma relocation. However, previous reports were mostly case reports or case series with a small number of patients and lacked long-term results. A modified Altemeier technique (MAT) has been used for the local repair of SP in our institution, and this study aimed to evaluate its mid-term efficacy.Methods: We reviewed patients who underwent MAT for SP between August 2013 and December 2020. The variables included patient characteristics, type of stoma, indications of stoma creation, the time interval from stoma creation to prolapse, site of prolapse, reasons for SP surgery, perioperative variables, complications during SP surgery, and length of follow-up. Recurrence of SP was defined as the need for change in stoma care or re-protrusion of the stoma by more than 5 cm in length.Results: Ten patients were included in this study. The median age at the time of SP surgery was 71.5 years. The indications of stoma creation included unresectable or recurrent intra-abdominal malignancies in four patients, diverting ileostomy with rectal cancer surgery in two, transverse colon cancer in one, gastric and rectal cancer in one, rectovaginal fistula in one, and non-occlusive mesenteric ischemia in one. The median interval from stoma creation to prolapse was 2.5 months. Six patients underwent elective SP surgery, and four patients underwent emergency surgery for incarcerated prolapse. The median operative time was 75.5 min. Postoperative complications that included transient mucosal ischemia and subcutaneous abscess occurred in one patient. There were four recurrences (40%), and the median time interval from surgery to recurrence was 4.5 months. Two patients underwent repeated MAT, one of whom underwent stomal reversal with laparotomy for re-recurrence. The median follow-up duration was 19 months.Conclusion: MAT for SP is associated with a high recurrence rate in mid-term follow-up.

Clonal behaviour of myogenic precursor cells throughout the vertebrate lifespan.

ABSTRACTTo address questions of stem cell diversity during skeletal myogenesis, a Brainbow-like genetic cell lineage tracing method, dubbed Musclebow2, was derived by enhancer trapping in zebrafish. It is shown that, after initial formation of the primary myotome, at least 15 muscle precursor cells (mpcs) seed each somite, where they proliferate but contribute little to muscle growth prior to hatching. Thereafter, dermomyotome-derived mpc clones rapidly expand while some progeny undergo terminal differentiation, leading to stochastic clonal drift within the mpc pool. No evidence of cell-lineage-based clonal fate diversity was obtained. Neither fibre nor mpc death was observed in uninjured animals. Individual marked muscle fibres persist across much of the lifespan indicating low rates of nuclear turnover. In adulthood, early-marked mpc clones label stable blocks of tissue comprising a significant fraction of either epaxial or hypaxial somite. Fusion of cells from separate early-marked clones occurs in regions of clone overlap. Wounds are regenerated from several local mpcs; no evidence for specialised stem mpcs was obtained. In conclusion, our data indicate that most mpcs in muscle tissue contribute to local growth and repair and suggest that cellular turnover is low in the absence of trauma.

Knee osteochondritis dissecans-treatment technical aspects

Purpose and objectiveCurrent treatments of different stages of knee osteochondritis Dissecans (OCD) are depending on the age of the patients and the stability of the diseased osteochondral area. The purpose of this paper was to summarize the treatment alternatives in order to simplify the choice for the treating surgeon. Background and principle resultsOsteochondritis dissecans (OCD) of the knee is an idiopathic and local osteochondral abnormality that affects mainly children and adolescents with risk of loosening of osteochondral fragments. A good clinical result can be expected when the physes are still open, when the osteochondritis is small and when the osteochondritis can be assessed as stable by MRI. Unstable OCD lesions most often need to be treated operatively by different fixation methods and when the osteochondral cannot be refixated, different local chondral and osteochondral repairs are available to fill up the defect area to congruity Summary and major conclusionsThe final choice of which treatment to use is depending on fragment viability and forms. Viable fragments are refixated while poor quality fragments are removed followed by a local biological osteochondral repair. Such osteochondral resurfacing may be single bone marrow stimulation with or without scaffold augmentation or different cell seeded grafts.

Exceptional wide scope of bare nominals

One of the strongest arguments in favor of the kinds approach to bare nominals is that they always take narrow scope with respect to other scope bearing operators in the sentence (Carlson 1977; Chierchia 1998; Dayal 2011). The publications supporting the obligatory narrow scope of bare nominals in a wide range of typologically different languages vastly outnumber the ones that claim the opposite. In this paper, we survey the facts from the literature, work out how the kinds approach deals with them, and identify scrambled bare plurals as the ultimate challenge for the kinds approach. Dutch examples illustrate that scrambled bare plurals unambiguously take wide scope with respect to quantifiers and negation, while maintaining kind reference. The kinds approach proves unable to derive the wide scope reading of bare plurals under a surface-oriented composition of scrambled objects. Once we abandon the default kind shift, following Krifka (2004), and allow bare plurals to directly shift to an existential interpretation, we can easily derive the wide scope reading with a local type repair. We conclude that a flexible type shifting approach to bare nominals is preferred over a default kind shift for empirical reasons. EARLY ACCESS