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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.

Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown of high mobility group box-1 and S100b, both of which are RAGE ligands endogenously expressed in 3T3-L1 cells, also canceled RAGE-medicated adipocyte hypertrophy, implicating a fundamental role of ligands-RAGE ligation. Adipocyte hypertrophy induced by RAGE overexpression is associated with suppression of glucose transporter type 4 and adiponectin mRNA expression, attenuated insulin-stimulated glucose uptake, and insulin-stimulated signaling. Toll-like receptor (Tlr)2 mRNA, but not Tlr4 mRNA, is rapidly upregulated by RAGE overexpression, and inhibition of Tlr2 almost completely abrogates RAGE-mediated adipocyte hypertrophy. Finally, RAGE-v- mice exhibited significantly less body weight, epididymal fat weight, epididymal adipocyte size, higher serum adiponectin levels, and higher insulin sensitivity than wild-type mice. RAGE deficiency is associated with early suppression of Tlr2 mRNA expression in adipose tissues. Thus, RAGE appears to be involved in mouse adipocyte hypertrophy and insulin sensitivity, whereas Tlr2 regulation may partly play a role., Receptor for advanced glycation end products (RAGE), a pattern recognition receptor, is a multiligand cell-surface protein that was isolated from bovine lung in 1992 by the group of Schmidt and [...]

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 apolipoprotein e4 gene may be more prevalent among gout patients with high levels of fat in the blood, or hyperlipidemia, than in people with normal levels of fat in the blood. Researchers compared blood samples taken after fasting of 221 male gout patients with 141 men who did not have gout. They found that although the apolipoprotein (apo) E gene type was identified in similar numbers of people with gout and without, the apo E4/3 gene type was found more often in hyperlipidemic patients with gout. Gout patients with the apo E4/3 gene type had higher blood levels of triglyceride and cholesterol than did gout patients with the apo E3/3 gene type. This finding suggests that the apo e4 gene fragment may play a role in increasing blood levels of fat in gout patients.

Lipoprotein levels tend to be increased among gout patients, which is a risk factor for cardiovascular disease. Cardiovascular disease is more common among gout patients. Concentrations may be decreased by taking niceritorol without exacerbating the gout. Serum lipoprotein was measured among 175 men with gout and compared with values from 172 non-gouty men. Gout patients had an average lipoprotein value of 15.5 milligrams per decaliter versus 8.6 milligrams per decaliter among healthy control subjects. Gout patients were more likely to have values in the upper range and less likely to have values in the lower range. Fifteen gout patients with high lipoprotein concentrations were given moderate dosages of niceritorol, and blood serum evaluations one, three, and five months later showed reduced lipoprotein levels without an increase in serum uric acid. High doses of niceritorol have been shown to be effective but serum uric acid levels increase.

This article presents a case of lethal midline granuloma on the palate of a 44-year-old woman, which had been identified histologically as B-cell lymphoma with leukemic transformation in the terminal stages. At the first visit, physical and laboratory examinations showed no remarkable findings except for a necrotizing ulcer of the palate, and the biopsy specimens only showed massive inflammatory cell infiltration and necrosis of the granulation tissue. There was a short-term resolution after treatment with cyclophosphamide and prednisolone, but the disease reactivated and the necrotic ulcerative lesion progressively advanced into the nasal cavity. Specimens from the third biopsy exhibited histologic features that were consistent with malignant lymphoma of the diffuse, mixed B-cell type. Chemotherapy with the regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone was adopted but was interrupted after a short time because of bone marrow suppression. Subsequently, large numbers of enlarged abnormal lymphocytes with a few vacuoles in the cytoplasm appeared in the circulating blood, indicating leukemic transformation of the midline lymphoma. The patient died on the seventh day after the initiation of chemotherapy. In the presentation of this case, the authors mention clinically important matters regarding midline lethal lymphoma and briefly discuss the pathophysiology and pathogenesis. Cancer 1992; 70:2958-62.

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.

Aging is an inevitable process that involves changes across life in multiple neurochemical, neuroanatomical, hormonal systems, and many others. In addition, these biological modifications lead to an increase in age-related sickness such as cardiovascular diseases, osteoporosis, neurodegenerative disorders, and sleep disturbances, among others that affect activities of daily life. Demographic projections have demonstrated that aging will increase its worldwide rate in the coming years. The research on chronic diseases of the elderly is important to gain insights into this growing global burden. Novel therapeutic approaches aimed for treatment of age-related pathologies have included the endocannabinoid system as an effective tool since this biological system shows beneficial effects in preclinical models. However, and despite these advances, little has been addressed in the arena of the endocannabinoid system as an option for treating sleep disorders in aging since experimental evidence suggests that some elements of the endocannabinoid system modulate the sleep-wake cycle. This article addresses this less-studied field, focusing on the likely perspective of the implication of the endocannabinoid system in the regulation of sleep problems reported in the aged. We conclude that beneficial effects regarding the putative efficacy of the endocannabinoid system as therapeutic tools in aging is either inconclusive or still missing.

AimsTo compare the changes in the macular retinal nerve fibre layer (mRNFL), macular ganglion cell layer and inner plexiform layer (mGCIPL), and circumpapillary retinal nerve fibre layer (cpRNFL) in various stages of normal tension glaucoma (NTG) using spectral domain optical coherence tomography.MethodsEyes with NTG (n=218) were assigned into three groups based on initial mean deviation (MD) as follows: mild (MD>−6 dB), moderate (−6 dB≥MD≥−12 dB) and severe (−12 dB>MD>−20 dB). Annual rates of change in mRNFL, mGCIPL and cpRNFL thickness were calculated by linear regression analysis.ResultsAge, gender, spherical equivalent, and average intraocular pressure during follow-up were not significantly different among the three groups. There were significant differences in the mRNFL, mGCIPL and cpRNFL among the three groups at baseline (p<0.0001 in all sectors except for the mRNFL in the superonasal sector). The average thinning rates of the mRNFL, mGCIPL and cpRNFL were −0.38±0.32 µm/year, −0.62±0.46 µm/year and −0.86±0.83 µm/year, respectively. No significant difference in the rates of change in the mRNFL and mGCIPL were found among the groups in any sector. However, there was a significant difference in the rate of change in the cpRNFL among the groups (in all sectors: p<0.0001).ConclusionsChanges in the mRNFL and mGCIPL can reflect the progression of NTG even in its advanced stage. However, careful interpretation of changes in the cpRNFL in the advanced stage of glaucoma is warranted due to a potential floor effect.

The effects of allopurinol, a medication used to control production of uric acid in patients with gout, are chiefly due to oxypurinol, its major metabolite (breakdown product). After conversion of allopurinol to oxypurinol, the metabolite is excreted by the kidney without further reactions. The concentration of oxypurinol in blood must reach certain levels in order to be therapeutically effective, as is true for most drugs, and the blood level of oxypurinol is directly rated to the rate of removal of the drug from the blood by the kidneys. The kidney appears to handle oxypurinol similarly to uric acid, but this has not been well studied. Probenecid and benzbromarone are two drugs which are used to treat gout, as they increase kidney excretion of uric acid. These seem to inhibit kidney reabsorption (removal from urine back into the tissues and circulation) of uric acid at a distant portion of kidney tubules, after tubular secretion (secretion of solutes or salts back into the tubular fluid that becomes urine). The effects of these two drugs and that of pyrazinamide, an antitubercular drug which inhibits tubular secretion of uric acid, on renal (kidney) excretion of oxypurinol was studied in 15 healthy men. Pyrazinamide decreased renal clearance of oxypurinol by over half, but had no effect on the drug's blood levels. Probenecid increased renal clearance of oxypurinol by almost half, and benzbromarone had a similar effect. Neither of these last two drugs affected blood levels of oxypurinol. The results suggest that oxypurinol is indeed reabsorbed from urine into kidney tissues after secretion of solutes into the urine-containing tubule. The study suggests that in combination therapy using allopurinol and benzbromarone, the effects together may be less than would be expected from their single effects on uric acid metabolism. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background: Total ankle arthroplasty (TAA) has been developed to treat patients with end-stage ankle osteoarthritis (OA). However, there is often difficulty in treating complicated pathologies such as ankle OA with subtalar joint OA and severe talar collapse. Therefore, this study aimed to explore the short-term results and complications of TAA with total talar prosthesis, known as combined TAA, as the new techniques to treat such complicated pathology.Methods: We examined postoperative results including ankle range of motion, Japanese Society for Surgery of the Foot (JSSF) scale, and complications. There were 22 patients (15 women), with mean follow-up of 34.9 (range, 24–53 months), and the mean age was 72 (range, 62–80) years. The main indications for combined TAA included osteoarthritis (18 patients), rheumatoid arthritis (3 patients), and talar osteonecrosis with osteoarthritis (one patient).Results: The mean range of motion improved from 4.0 to 14.4 degrees in dorsiflexion and from 23.8 to 32.0 degrees in plantarflexion. The JSSF scale improved from 50.5 to 91.5 points. Prolonged wound healing occurred in 3 patients, and medial malleolus fracture occurred in 4 patients.Conclusion: Combined TAA was a reliable procedure for the treatment of not only ankle OA following avascular necrosis of talus but also of degeneration of both ankle and subtalar joints.Level of Evidence: Level IV, case series.

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A nanocomposite hydrogel of poly(vinyl alcohol) (PVA) and polystyrene (PS)-poly(N-vinylacetamide) (PNVA) colloid particles was prepared by repeated freezing and thawing. The polymer colloid was synthesized by soap-free emulsion polymerization, and its molecular weight was controlled by varying the initiator concentration. The biologically safe PNVA hydrogen-bonds with PVA to form a network. To prepare a hydrogel with higher mechanical strength, a composite of PVA with uniformly dispersed PS-PNVA particles was prepared. This gel was evaluated in terms of the swelling characteristics and mechanical properties, for its application to biomaterials.Polystyrene (PS)-poly(N-vinylacetamide) (PNVA) colloid was synthesized by soap-free emulsion polymerization, and then poly(vinyl alcohol) (PVA) gel was prepared by repeated freezing and thawing. The PNVA created hydrogen-bonds with PVA to form a double network in the gel. To prepare a homogeneous network hydrogel, a composite of PVA with uniformly dispersed PS-PNVA particles was prepared.

Background: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco’s mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. Methods: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. Results: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. Conclusion: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+signaling and CaMKK2 pathways. Graphical Abstract:

Small thrombosed varices (diameter, < 10 mm) in the oral cavity are known to be prevalent in the tongue, lips, and buccal mucosa of elderly individuals. No past reports have described varices larger than 10 mm, except in the tongue. We report a very rare case in which a large varix (20 × 20 × 15 mm) in the midline of the oral floor and including partially organizing thrombosis occurred 3 days before the first visit in an 82-year-old man. This case is the first report of large oral varix in a region other than the tongue. Large oral varix may occur not only on the tongue, but also in any area of the oral cavity.

We describe the synthesis of hollow porous silica particles by the soap-free emulsion polymerization of styrene with N-vinylacetamide to produce polymer cores, followed by sol-gel reactions with tetraethyl orthosilicate on the surfaces of the polymer particles to create silica shells. Removal of the polymer cores from the core-shell particles by heat treatment resulted in particles that were hollow and porous. The pore sizes of the silica particles are controllable by the solubility parameter of alcohol used in the sol-gel reaction.The pore sizes of hollow silica particles are controllable by adjusting the N-vinylacetamide concentration during polymerization, and the solubility parameter of the alcohol used in the sol-gel reaction.

In the current article, we provide in vitro efficacy evaluation of a unique accelerator-based neutron source, constructed at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation), for boron neutron capture therapy (BNCT), which is particularly effective in the case of invasive cancers. U251MG, CHO-K1 and V79 cells were incubated and irradiated in various concentrations of boric acid with epithermal neutrons for 2-3 h in a plexiglass phantom, using 2.0 MeV proton energy and 1.5-3.0 mA proton current, resulting in a neutron fluence of 2.16 × 1012 cm-2. The survival curves of cells loaded with boron were normalized to those irradiated without boron (to exclude the influence of the fast neutron and gamma dose components) and fit to the linear-quadratic (LQ) model. Colony formation assays showed the following cell survival rates (means ± SDs): CHO-K1: 0.348 ± 0.069 (10 ppm), 0.058 ± 0.017 (20 ppm), 0.018 ± 0.005 (40 ppm); V79: 0.476 ± 0.160 (10 ppm), 0.346 ± 0.053 (20 ppm), 0.078 ± 0.015 (40 ppm); and U251MG: 0.311 ± 0.061 (10 ppm), 0.131 ± 0.022 (20 ppm), 0.020 ± 0.010 (40 ppm). The difference between treated cells and controls was significant in all cases (P < 0.01) and confirmed that the neutron source and irradiation regimen were sufficient for control over cell colony formation. We believe our study will serve as a model for ongoing in vitro experiments on neutron capture therapy to advance in this area for further development of accelerator-based BNCT into the clinical phase.

Various halogenated mesoionic‐carbene (MIC)‐coordinated palladium complexes (denoted as TAPs and e‐TAPs) were prepared using triazolylidene precursors that were synthesized in only two steps via a click reaction. Among the prepared complexes, 2‐Bromophenyl group substituted e‐TAP (Br‐e‐TAP) showed optimal catalytic activity for the arylation of aldehydes with arylboronic compounds. Additionally, the Br‐e‐TAP catalyst assisted in synthesizing a wide range of functionalized diarylmethanols and arylmethanols in 29–95% yields with loadings of 0.2–0.6 mol% Pd. The halogenated mesoionic‐carbene‐coordinatedpalladium complexes (TAPs/e‐TAPs) were synthesized and acted as the catalyst for the arylation of aldehydes using arylboron compounds. Among them, 1‐(2‐bromophenyl)‐1,2,3‐triazolidene (η3‐allyl)palladium chloride (Br‐e‐TAP) promoted the arylation most efficiently.

Risk-benefit analysis results for the treatment of unruptured aneurysms smaller than 5 mm are controversial. This study aimed to identify the outcomes and complication associated with treating such unruptured aneurysms.