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Failure of anterior cruciate ligament reconstruction (ACLR) is a common yet devastating complication due to inferior clinical outcomes associated with revision ACLR. Identifying the cause and associated risk factors for failure is the most important consideration during preoperative planning. Special attention to tunnel quality, concomitant injuries, and modifiable risk factors will help determine the optimal approach and staging for revision ACLR. Additional procedures including lateral extra-articular tenodesis and osteotomy may be considered for at-risk populations. The purpose of this review is to explore causes of ACLR failure, clinical indications and appropriate patient evaluation, and technical considerations when performing revision ACLR.

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Many membraneless organelles (MLOs) formed through phase separation play crucial roles in various cellular processes. Although these MLOs co-exist in cells, how they maintain their independence without coalescence or engulfment remains largely unknown. Here, we investigated the molecular mechanism by which paraspeckles with core–shell architecture scaffolded by NEAT1_2 long noncoding RNAs exist as distinct MLOs. We identified NEAT1 deletion mutants that assemble paraspeckles that are incorporated into nuclear speckles. Several paraspeckle proteins, including SFPQ, HNRNPF and BRG1, prevent this incorporation and thus contribute to the segregation of paraspeckles from nuclear speckles. Shell localization of these proteins in the paraspeckles, which is determined by NEAT1_2 long noncoding RNA domains, is required for this segregation process. Conversely, U2-related spliceosomal proteins are involved in internalizing the paraspeckles into nuclear speckles. This study shows that the paraspeckle shell composition dictates the independence of MLOs in the nucleus, providing insights into the importance of the shell in defining features and functions of MLOs.

The Ni-catalyzed cross-coupling of aryl halides and vinylzinc bromide for the synthesis of styrene derivatives was investigated. Of the catalysts surveyed, the combination of Ni(acac)2and Xantphos was found to be the most effective for this cross-coupling. This catalyst could be used in reactions with various aryl bromides and chlorides, including electron-rich aryl chlorides such as chloroanisoles.

There are no evidence-based reports on the proper duration of antimicrobial therapy following video-assisted thoracoscopic surgery debridement (VATS-D) in thoracic empyema (TE) or complicated parapneumonic effusion (PPE). This study aimed to investigate the optimal duration of antimicrobial therapy after VATS-D.

BackgroundMeningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence.MethodsWe retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects.ResultsPreoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003).ConclusionsAfter controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.

Background The use of mechanical thrombectomy (MT) for treatment of acute large vessel occlusion has recently increased. Prompt and timely guiding catheter (GC) induction is necessary to improve prognosis of MT and reduce the time for recanalization. However, difficulties in GC induction are encountered in some patients. This GC induction depends mainly on the aortic arch structure. Therefore, this study focused on assessing presence of tracheal shift on chest X-ray images as pre-treatment evaluation method for GC induction due to its wide availability as an indicator for status of the mediastinum.Methods: We retrospectively examined 33 patients who underwent MT at our facilities between April 2017 and March 2021. The patients were divided into two groups according to presence or absence of tracheal shift on chest X-ray images. Background characteristics and treatment courses in these two groups were compared.Results: Among 33 patients, tracheal shift was observed on the chest X-ray images of 14 patients. Furthermore, tracheal shift was positively correlated with the time of GC induction (32.9 min vs. 11.6 min, [p< 0.05]) and the female sex (p= 0.03). Additionally, tracheal shift exhibited correlations with multiple risk factors of atherosclerosis (p= 0.04).Conclusions: In patients with tracheal shift, GC induction could be expectedly difficult. Therefore, advanced disinfection of the right upper arm and affected side of the neck during MT in preparation for changing an approach route is required.

The helix-hairpin-helix (HhH) motif in prokaryote and eukaryote DNA binding proteins is involved in non-sequence-specific DNA binding. Several studies have examined various HhH binding interactions, but the effect of stereochemistry on non-sequence-specific DNA binding by HhH peptides remains unresolved. Here, we analyzed stereochemistry-specific interactions between DNA structures and HhH motif peptides derived from NAD+-dependent DNA ligase, which is a promising target for developing new antibiotics. We synthesized l- and d-forms of single HhH motif peptides and found that both the native l-HhH-N peptide and d-HhH-N peptide bind bubble DNA and the peptides were changed to α-helical structure. Moreover, the d-HhH-N peptide showed different interaction properties against single-stranded and double-stranded DNA when compared with the l-HhH-N peptide. This study provides insights into non-sequence-specific DNA binding of d-peptides for developing d-peptide drugs.The helix-hairpin-helix (HhH) motif plays a key role in non-sequence-specific DNA binding. d-peptides are composed of d-amino acids and attractive biomolecules for medical applications. In this study, we report the interactions between l/d-HhH-N peptides and different DNA structures. The interaction of the d-HhH-N peptide with DNA is dependent on the DNA structure and shows different binding properties than l-HhH-N peptide.

It is well-established that cervical lymph node metastasis is the most important prognostic factor in head and neck squamous cell carcinoma (HNSCC). Cancer cells invade the underlying stroma during metastasis by breaching the basement membrane.

Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation.

Background: Total ankle arthroplasty (TAA) has become one of the standard surgical treatments for patients with end-stage ankle osteoarthritis (OA). In recent years, TAA with total talar prosthesis (combined TAA) has been used for ankle OA patients with talar osteonecrosis, with severe talar collapse, or with subtalar joint OA. The purpose of this study was to investigate the functional and clinical outcomes of combined TAA, compared with conventional TAA.Methods: Forty-six ankles (44 patients, 32 women/12 men) that underwent conventional TAA with mean follow-up of 42 months, and 26 ankles (25 patients, 18 women/7 men) that underwent combined TAA with mean follow-up of 46 months were included. Clinical outcomes, which included ankle range of motion (ROM), the Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale, the Self-Administered Foot Evaluation Questionnaire (SAFE-Q), and complications were compared between the groups.Results: The preoperative ROM was significantly worse in combined TAA for both dorsiflexion and plantarflexion; however, in the final ROM, there was no significant difference between the groups. There was no significant difference in JSSF scale and SAFE-Q between the groups. Revision rate was 10.9% in conventional TAA and 0% in combined TAA.Conclusion: In this small series, at an average of 3.5 years, we found no significant difference in clinical results between conventional TAA and combined TAA; however, the revision rate was higher in conventional TAA.Level of Evidence: Level III, retrospective cohort study.

This study proposes to further exploit the potential of the carbon dioxide supercritical anti-solvent precipitation (SAS) process by using liquefied gas as a feed solvent in the SAS process. In this study, liquefied dimethyl ether (DME) is compared to conventional ethyl acetate as the feed solvent for β-carotene. DME is a gas in its standard state, and when it is made into a subcritical liquefied gas, it has a larger self-diffusion coefficient and saturated vapor pressure, and smaller viscosity and surface tension than liquid solvents. Because of these characteristics of liquefied DME, liquefied DME prevents primary particle agglomeration and DME residue. When ethyl acetate was used as the feed solvent, the conditions giving the smallest particles were 60 °C and 12 MPa, and 31 ± 5 nm primary particles of β-carotene were obtained. However, most of these were aggregated into secondary particles of several hundred nanometers. In the case of liquefied DME, the condition giving the smallest particles was 40 °C and 12 MPa, and primary particles of 58 ± 8 nm β-carotene were dispersed without aggregation. Furthermore, FT-IR analysis detected residual ethyl acetate in the aggregated β-carotene particles, whereas DME was not detected in the dispersed particles. Liquefied DME is likely to be a suitable solvent for the micronization of heat-sensitive substances using the SAS method without agglomeration. Combining various liquefied gases, not just DME, with the SAS process may create possibilities for applying the SAS process to target materials that are insoluble in conventional liquid solvents and for synthesizing even finer nanoparticles.

BackgroundEndovascular embolization using standalone coils is the preferred treatment option for ruptured cerebral aneurysms to avoid the use of dual antiplatelet therapy with stent coiling or endoluminal flow diversion devices. However, it has been reported that patients undergoing the standalone coiling approach are at risk for periprocedural thromboembolism. Therefore, this systematic review and meta-analysis was performed to clarify the risks and benefits of antiplatelet therapy (AT) during coiling procedures performed to treat ruptured aneurysms, including the incidence of early thromboembolic events, hemorrhagic and delayed ischemic events, as well as clinical outcomes.MethodsA comprehensive search of three databases was performed for articles from inception to June 2021. After fulfilling the inclusion criteria, five studies were included in this meta-analysis and 462 patients with aneurysmal subarachnoid hemorrhage (aSAH) were identified who underwent endovascular standalone coiling treatment. Aneurysm location, patient characteristics, and aSAH grades were comparable between the AT and non-AT groups.ResultsAT significantly decreased the incidence of thromboembolic events immediately after the coiling procedures compared with non-AT (OR 3.42; 95% CI 1.77 to 6.61, p<0.001). The incidences of hemorrhage, delayed ischemia, and clinical outcomes with or without AT were not significantly different between groups.ConclusionsAlthough this study showed no beneficial effect of AT on clinical outcomes, the results suggest that AT could be combined with standalone coiling to avoid thromboembolism during the perioperative period. A large prospective study and/or an additional meta-analysis would be required to further investigate how AT benefits standalone coil embolization in aSAH.

Pediatric brain tumor survivors who received proton beam therapy at the University of Tsukuba Hospital from 2004 to 2011 were retrospectively evaluated for cognitive function. Five patients were included. The median age of diagnosis was 5.4 years (range: 1.5 to 12.5 y) and the median follow-up time was 5.8 years (range: 3.1 to 8.1 y). IQ scores at follow-up were decreased in 2 of 5 patients; 1 underwent whole-brain irradiation and the other was examined just after surgical removal of recurrent tumors. Local proton beam therapy may preserve cognitive function in survivors of pediatric brain tumors.

According to the World Health Organization (WHO), 47 million people display mental health disorders Worldwide. In addition, epidemiological studies have shown that the extension of life expectancy and the increase in aged population will significantly impact the prevalence of several mental impairments. Although there are strategies for preventing and alleviating mental illnesses, such as pharmacological and psychological approaches, limited results have been observed. Thus, the search for new therapeutics for managing psychiatric disorders has explored multiple roads. In recent years, it has been demonstrated that physical activity and exercise promote health benefits. On the other hand, among the neurobiological systems that participate in the genesis and development of mental disruptions, the endocannabinoid system has been suggested as an active player. Supporting this hypothesis, data suggest that the elements comprising the endocannabinoid system, such as the CB1/CB2 cannabinoid receptors, endogenous ligands (N-arachidonoylethanolamine [anandamide, AEA] and 2- arachidonoylglycerol [2-AG]), transporters and the enzymes involved in the biosynthesis and degradation of the AEA and 2-AG, modulate mental diseases. In this review, we discuss that the endocannabinoid system might be considered as a modulator for the positive outcomes of exercise in the management of mental disorders. Clinically, this promising field might be exploited by targeting the elements of the endocannabinoid system aimed to increase the exercise benefits applied to patients with mental illnesses.

The peroxisome proliferator activated receptors (PPARs) are a superfamily of well-recognized ligand-binding nuclear receptors comprising three isoforms: PPARα, PPARγ, and PPARβ/δ. In response to endogenous lipid messengers, PPARs trigger the transcription of genes related to a wider spectrum of physiological phenomena, including fatty acid oxidation, inflammation, adipogenesis, among many others. Thus, the importance of PPARs as putative protective therapy in health issues has increased the interest of studying these nuclear receptors, including the management of neurodegenerative disorders, multiple sclerosis, and likely addiction. In recent years, several pieces of evidence from animal models have demonstrated the promising role of PPARs as a critical element for interventions in addictive behaviors by reducing the reinforcing properties of addictive substances such as alcohol. However, there is a lack of data in the scope and has so far been unexplored the function of PPARs in additional drugs such as cannabis, opioids, methamphetamine, or cocaine. A similar scenario has been found for the management of binge-type eating disorders. Thus, here we review recent advances in understanding the relevance of the PPAR controlling addiction.

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1or IDH2mutations. These tumors also had chromosome 19q13 deletion, including the CICgene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest thatIDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CICgene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

Background For patients who undergo endovascular treatment for acute ischemic stroke, the total time for treatment may increase during off-duty hours leading to worse outcomes. The present study compared endovascular treatment outcomes for on-duty and off-duty hours and examined factors that could be responsible for the prolonged treatment of patients in a multicenter registry.Methods The study group comprised 1571 patients listed in the multicenter stroke registry (K-NET) who had undergone endovascular treatment between January 2018 and June 2020. The modified Rankin Scale (mRS), evaluated at 90 days after stroke onset, was utilized as the primary outcome. Patients were divided into on-duty and off-duty patients based on admission time. Multivariate logistic regression analysis was used to identify the independent factors that increased the time from admission to puncture during the off-duty period.Results The mean mRS score at 90 days after stroke onset was 2.9, similar in both on-duty and off-duty patients, with no significant difference (p = 0.77); however, significant differences were observed in time from door-to-puncture (74.7 vs. 88.8, p< 0.01). Additionally, the mRS score at 90 days worsened significantly for door-to-puncture time >60 min in the off-duty period. Multivariate logistic regression analysis revealed that a low National Institute of Health Stroke Scale (NIHSS) score, high pre-mRS score, posterior circulation, and diabetes were independent indicators of door-to-puncture time >60 min during the off-duty period.Conclusion Door-to-puncture time >60 min during off-duty hours was associated with poor outcomes related to low NIHSS, high pre-mRS, posterior circulation, and diabetes.

Background: Cadaver biomechanical testing suggests that the morphology of articulating bones contributes to the stability of the joints and determines their kinematics; however, there are no studies examining the correlation between bone morphology and kinematics of the subtalar joint. The purpose of this study was to investigate the influence of talar and calcaneal morphology on subtalar kinematics during walking in healthy individuals.Methods: Forty ankles (20 healthy subjects, 10 women/10 men) were included. Participants walked at a self-selected pace while synchronized biplane radiographs of the hindfoot were acquired at 100 images per second during stance. Motion of the talus and calcaneus was tracked using a validated volumetric model-based tracking process, and subtalar kinematics were calculated. Talar and calcaneal morphology were evaluated using statistical shape modeling. Pearson correlation coefficients were used to assess the relationship between subtalar kinematics and the morphology features of the talus and calcaneus.Results: This study found that a shallower posterior facet of the talus was correlated with the subtalar joint being in more dorsiflexion, more inversion, and more internal rotation, and higher curvature in the posterior facet was correlated with more inversion and eversion range of motion during stance. In the calcaneus, a gentler slope of the middle facet was correlated with greater subtalar inversion.Conclusion: The morphology of the posterior facet of the talus was found to a primary factor driving multiplanar subtalar joint kinematics during the stance phase of gait.Clinical Relevance: This new knowledge relating form and function in the hindfoot may assist in identifying individuals susceptible to subtalar instability and in improving implant design to achieve desired kinematics after surgery.

Background:An aspiration catheter needs to attach to a thrombus in order to achieve first-pass recanalization by mechanical thrombectomy (MT) for acute ischemic stroke (AIS), particularly that using a direct aspiration first pass technique. The meniscus sign, which is defined as meniscoid contrast opacification indicating the proximal edge of a thrombus, has been suggested to contribute to successful recanalization. In some cases, the meniscus sign is not detected following an injection of contrast medium through a guiding catheter. To precisely identify the location of a thrombus, we use “the microcatheter contrast injection (MCI) technique,” which accurately shows the proximal edge of a thrombus. We herein introduce this novel technique and discuss its efficacy in MT. Methods:In cases without the meniscus sign, a microcatheter was advanced to the distal end of contrast opacification, and contrast medium was injected through the microcatheter to detect the meniscus sign. An aspiration catheter was then advanced to the thrombus indicated by the meniscus sign and slowly withdrawn under aspiration. Results:29 patients underwent MT for AIS using the MCI technique. Even in cases without the meniscus sign on initial angiography, the MCI technique accurately revealed the proximal edge of the thrombus. Moreover, middle cerebral artery occlusion due to atherosclerotic stenosis and displacement of the aspiration catheter and thrombus axis were detected using this technique. Conclusions:The MCI technique may effectively reveal the exact site of a thrombus and increase the success rate of first-pass recanalization.

Background This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2–3 using real-world data.Methods Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4–5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0–3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0–3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only.Results After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2–3). A 90-day mRS score of 0–3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2–3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0–3.Conclusion Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.

Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1and GLI3are highly expressed in SHH-activated medulloblastoma, whereas GLI3but not GLI1is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

Polymer particles are used in various consumer products, such as cosmetics and paints. However, large amounts of surfactants are used to synthesize polymer nanoparticles, which increase the environmental load. In this study, we propose a method for synthesizing polymer nanoparticles without using surfactants. In this method, the nanoparticles are polymerized inside the melamine foam (MF) used as a reaction field. A study of the distribution of particles in each area of the foam revealed that nanoparticles could be obtained with a relatively uniform size in the height direction. We successfully controlled the particle size by controlling the porosity of the MF by filling it with spherical glass beads of 50 μm diameter. As no surfactant is used, this polymerization method has a low environmental impact. Because the surface of the polymer nanoparticles is not contaminated by surfactants, they can be used in medical applications. Our study provides a new direction in the synthesis and application of polymer nanoparticles.

Hyalinizing clear cell carcinoma (HCCC) is a low-grade epithelial tumor classified as a subtype of salivary gland carcinoma. HCCC occurs most frequently on the palate and base of the tongue. Noteworthy, HCCC arising in the anterior of the tongue is quite rare and it has yet to be fully characterized in the clinical literature. Herein, we present a case of a 59‐year‐old man with HCCC on the anterior of the tongue. A present case was confirmed by a detection of EWSR1-ATF1fusion gene with a same breakpoint that previously reported in HCCC cases. To our knowledge, this report represents the rare case of HCCC arising in the anterior of the tongue in the literature.