Effects of antipsychotics on intravenous sedation with midazolam and propofol during dental treatment for patients with intellectual disabilities.

BACKGROUND: Some patients with intellectual disabilities (ID) are prescribed antipsychotic drugs for symptomatic treatment of behavioural disorders. Nevertheless, it can still prove difficult to perform dental treatments safely for some patients with ID. In such cases, treatment under intravenous sedation (IVS) is one option. Sedative, hypnotic and α-blocking effects of antipsychotic drugs may cause adverse events, such as severe hypotension, among patients who take antipsychotic drugs regularly. This study aimed to investigate the effects of oral antipsychotic medication on cardiovascular function during IVS. Accordingly, we compared mean blood pressure (MBP) and heart rate (HR) between patients who regularly take antipsychotic drugs and patients who do not. METHODS: Thirty-seven patients with ID were enrolled in this study. All participants were outpatients of Special Care Dentistry of general hospital and received dental treatment under IVS performed with a combination of midazolam and propofol. Eighteen patients regularly took antipsychotics (medication group), and 19 patients were not currently taking antipsychotics (non-medication group). MBP, HR, dose, and effect-site concentration of intravenous sedative medications were measured at three points: 'before IVS', 'at optimal sedation', and 'during dental treatment'. RESULTS: The magnitude of reduction of MBP was significantly smaller in the medication group than in the non-medication group (P < 0.023). However, there were no differences in MBP, HR, dose, and effect-site concentration of midazolam and propofol between groups at any point. CONCLUSION: These results suggest that antipsychotic medication may not have clinically significant adverse effects on cardiovascular fluctuations during dental treatment under IVS for persons with ID.

Effects of age at estrogen replacement therapy initiation on trabecular bone score in Japanese adults with Turner syndrome.

The effects of the age at estrogen replacement therapy (ERT) initiation on bone quality in Turner syndrome were evaluated using trabecular bone score. Early puberty ERT positively correlated with increase in bone quality. Early initiation of ERT is necessary for the acquisition of bone quality as well as bone density. INTRODUCTION: Studies have reported associations between bone mineral density and estrogen replacement therapy (ERT) in Turner syndrome (TS) patients; however, few studies exist on the effect on bone quality. The aim of this study was to evaluate the effects of the age at ERT initiation on bone quality of Japanese TS patients, cross-sectionally and longitudinally. METHODS: Cross-sectionally, 95 TS patients were divided into three groups based on their age at initiation of ERT: A (12-14 years, 11 patients), B (15-17 years, 47 patients), and C (over 18 years, 37 patients). To assess bone quality, trabecular bone score (TBS) was used. The effects of age at initiation and duration of ERT on TBS were examined using multiple regression analysis. In the longitudinal study, 48 patients who underwent dual-energy X-ray absorptiometry multiple times were divided into three groups: D (12-14 years, 8 patients), E (15-17 years, 18 patients), and F (over 18 years, 22 patients). Each group was analyzed for the rate of change in TBS per year. RESULTS: Cross-sectionally, the TBS showed significant differences among the three groups (TBS A, 1.302; B, 1.299; C, 1.245) (p = 0.013); group C was significantly lower than B (p = 0.014); bone quality was degraded. Multiple regression analysis revealed that age at ERT initiation significantly affected the increase in TBS (p = 0.002). Longitudinally, the rate of change of TBS was not significantly different in the three groups (p = 0.73). CONCLUSION: Early initiation of ERT may have positive effects on bone quality in TS. Large prospective studies will be needed.

Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Development and validation of a model to predict the need for emergency front-of-neck airway procedures in trauma patients.

The present study aimed to develop and validate a model for predicting the need for emergency front-of neck airway (eFONA) procedures among trauma patients. This was a multicentre retrospective cohort study using data from the Japan Trauma Data Bank between January 2004 and December 2017. Only adult trauma patients were included. The cohort was divided into development and validation cohorts. A simple scoring system was developed to predict the necessity for emergency front-of neck airway procedures in the development cohort using a logistic regression model. The external validity and diagnostic ability of the scoring system was assessed in the validation cohort. In total, 198,182 out of 294,274 patients were included; emergency front-of-neck airway occurred in 467 patients (0.24%) they were divided into development (n = 100,120 with 0.22% undergoing emergency front-of neck airway) and validation (n = 98,062 with 0.25% undergoing emergency front-of neck airway) cohorts. The 'eFONA' prediction scoring system was developed in the development cohort, with a score of +1 for each of the following: Eye opening (no eye opening in response to any stimuli); Fall from height or motor bike; Oral-maxillofacial injury; Neck tracheal injury; and Airway management by paramedics. In the validation cohort, the C-statistic of the scoring system was 0.820. Setting the cut-off value at one for rule-out, the sensitivity and negative likelihood ratios were 0.86 and 0.22, respectively. Setting the cut-off value at two for rule-in, the specificity and positive likelihood ratios were 0.91 and 6.6, respectively. The present scoring system may assist in predicting the need for emergency front-of neck airway procedures among the general trauma population.

Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)-mediated hyaluronan degradation and skin wrinkling.

OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBID-mediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecular-weight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. CONCLUSION: Sanguisorba officinalis root extract showed an anti-HYBID-mediated HA degradation activity and anti-wrinkle activity on human facial skin, which is accompanied by the improvement in elasticity. Our study provides the possibility of a new strategy to inhibit HYBID-mediated HA degradation for anti-wrinkle care.

OBJECTIFS: l'acide hyaluronique (AH), un composant important de la matrice extracellulaire de la peau, assure de nombreuses activités biologiques, telles que l'hydratation qui contribue à la fermeté et l'élasticité de la peau. Nous avons rapporté que la réduction d'AH dans le derme papillaire et une surexpression de la protéine de liaison de l'AH impliquée dans la dépolymérisation de l'AH (HYBID, alias KIAA1199 ou CEMIP), une molécule clé de la dégradation de l'AH des fibroblastes cutanés, sont impliquées dans la formation des rides au niveau de la peau du visage chez les femmes d'origine japonaise et caucasienne. Cependant, peu ou aucune information n'est disponible concernant les substances qui inhibent la dégradation de l'AH provoquée par la protéine HYBID. MÉTHODES: l'inhibition de l'extrait de racine de la pimprenelle (Sanguisorba officinalis) et du ziyuglycoside I, l'un des composants de l'extrait de racine de Sanguisorba officinalis, sur la dégradation de l'AH provoquée par la protéine HYBID a été évaluée à l'aide d'une chromatographie par exclusion stérique de l'AH dépolymérisé par des transfectants stables de la protéine HYBID dans les cellules HEK293 (cellules HYBID/HEK293) ou les fibroblastes cutanés humains normaux (lignée cellulaire Detroit 551 et cellules des fibroblastes du derme humain chez l'adulte). L'expression de l'ARNm et de la protéine HYBID a été examinée par PCR quantitative en temps réel et par immuno-empreinte des fibroblastes cutanés traités avec de l'extrait de racine de Sanguisorba officinalis, et l'attribution des tailles des nouveaux échantillons produits de l'AH a été évaluée par préparation d'AH radiomarqué métaboliquement. Une étude en double aveugle, randomisée et contrôlée par placebo a été menée auprès des 21 femmes japonaises en bonne santé, qui ont été traitées localement avec la formulation élaborée à partir d'extraits de racine de Sanguisorba officinalis ou un placebo, sur chaque côté du visage, notamment sur la zone à pattes d'oie. RÉSULTATS: l'extrait de racine de Sanguisorba officinalis a permis d'arrêter la dégradation de l'AH provoquée par la protéine HYBID par les cellules HYBID/HEK293, mais ce n'était pas le cas du ziyuglycoside I. L'extrait de racine de Sanguisorba officinalis a également inhibé la dégradation de l'AH provoquée par la protéine HYBID des fibroblastes cutanés en diminuant l'expression de l'ARNm et des protéines HYBID. Bien que les fibroblastes cutanés témoins non traités aient produit de l'AH polydispersé, les cellules traitées aux extraits de racine de Sanguisorba officinalis ont produit uniquement de l'AH de haut poids moléculaire. Le traitement par lotion formulée à partir d'extraits de racine de Sanguisorba officinalis a amélioré de manière significative l'élasticité de la peau et réduit les scores de vieillissement du coin extérieur de la peau autour des yeux, par rapport à la formulation placebo. CONCLUSION: l'extrait de racine de Sanguisorba officinalis a démontré une action anti-dégradation de l'AH provoquée par la protéine HYBID et une activité antirides au niveau de la peau du visage humain, s'accompagnant d'une amélioration de l'élasticité. Notre étude fournit la possibilité d'une nouvelle stratégie pour inhiber la dégradation de l'AH provoquée par la protéine HYBID dans le cadre des soins antirides.

Reduction of hyaluronan and increased expression of HYBID (alias CEMIP and KIAA1199) correlate with clinical symptoms in photoaged skin.

BACKGROUND: Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing-dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive. OBJECTIVES: We examined the amount, size and tissue distribution of HA and expression levels of HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the degree of photoageing. METHODS: Photoageing-dependent changes of HA were investigated by studying skin biopsies isolated from photoprotected and photoexposed areas of the same donors, and the relationships between HA and photoageing symptoms such as skin wrinkling and sagging were examined. RESULTS: Skin biopsy specimens showed that the amount and size of HA are decreased in photoexposed skin compared with photoprotected skin, and this was accompanied by increased expression of HYBID and decreased expression of HAS1 and HAS2. Histologically, HA staining in the papillary dermis was decreased in photoexposed skin, showing reverse correlation with HYBID expression. HYBID expression in the photoexposed skin directly correlated with skin roughness and sagging parameters, and the reduced HA staining in the papillary dermis in the photoexposed skin positively correlated with these symptoms. CONCLUSIONS: These data demonstrate that imbalance between HYBID-mediated HA degradation and HAS-mediated HA synthesis may contribute to enhanced HA catabolism in photoaged skin, and suggest that HYBID-mediated HA reduction in the papillary dermis is related to skin wrinkling and sagging of photoaged skin.

Efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for lupus nephritis: a prospective, single-arm, single-centre, open label pilot study in Japan.

Background Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997). The treatment protocol was a starting dose of prednisolone of 0.6-1.0 mg/kg/day for 2 weeks and then tapered to a maintenance dose, intravenous cyclophosphamide (500 mg biweekly for 3 months) and tacrolimus (3.0 mg/day). Tacrolimus was continued as maintenance therapy. Complete remission was defined as a spot urine protein/creatinine ratio of < 0.5 g/gCr with no active urine casts and a serum creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with cyclophosphamide and prednisolone. Results At baseline, the mean patient age was 41.5 ± 14.6 years (male:female ratio 2:13), urine protein/creatinine ratio 3.9 ± 2.3 g/gCr and serum creatinine 84.6 ± 34.6 µmol/L. Lupus nephritis classifications included classes IV ( n = 8), III + V ( n = 1), IV + V ( n = 5) and unclassified ( n = 1). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of thrombotic microangiopathy. Conclusions Multitarget therapy with cyclophosphamide and tacrolimus can be a therapeutic option for lupus nephritis. Clinical trials registration Combination therapy of tacrolimus and intravenous cyclophosphamide for remission induction of lupus nephritis, UMIN: 000004893, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005830&language=E . Date of registration: 18 January 2011.

A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities.

Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules µm-2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules µm-2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1.

Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women.

BACKGROUND: Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women. METHODS: The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID. RESULTS: Among the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID-immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high-HYBID-expression group compared with the low-HYBID-expression group, respectively. CONCLUSION: Our data suggest that like Japanese women, HYBID-mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.

Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model.

Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin-KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D-ligand in allografts and demonstrated the significance of this using grafts expressing Rae-1, a murine NKG2D-ligand, which induced severe bronchiolitis obliterans in WT and Rag-1 KO recipients. This effect was ameliorated by injection of anti-NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.

Intermediate band solar cell with extreme broadband spectrum quantum efficiency.

We report, for the first time, about an intermediate band solar cell implemented with InAs/AlGaAs quantum dots whose photoresponse expands from 250 to ∼6000 nm. To our knowledge, this is the broadest quantum efficiency reported to date for a solar cell and demonstrates that the intermediate band solar cell is capable of producing photocurrent when illuminated with photons whose energy equals the energy of the lowest band gap. We show experimental evidence indicating that this result is in agreement with the theory of the intermediate band solar cell, according to which the generation recombination between the intermediate band and the valence band makes this photocurrent detectable.

From the era of genome analysis to the era of genomic drug discovery: a pioneering example of rheumatoid arthritis.

Although we have obtained comprehensive catalogs of genetic risk loci that are linked to human diseases, little is known regarding how to devise a systematic strategy to integrate genetic study results with diverse biological resources. Such strategies will be crucial for providing novel insights into disease biology and for aiding drug discovery as an ultimate goal. Here we describe the current progress in this field using a pioneering example of large-scale genetic association studies on rheumatoid arthritis (RA), an autoimmune disease characterized by inflammation and destruction of joints. Through functional and bioinformatic annotations of risk single nucleotide polymorphisms (SNPs) and genes from >100 RA risk loci identified by genome-wide association study (GWAS) meta-analysis, we found novel biological insights into RA pathogenicity. Further, by integrating RA genetic findings with the complete catalog of approved drugs for RA and other diseases, we provide empirical data to indicate that human genetic-based approaches may be useful for supporting 'genetics-driven genomic drug discovery' efforts in complex human traits and suggest that further development of integrative approaches should be undertaken.

Ethnic differences in GRHPR mutations in patients with primary hyperoxaluria type 2.

The objective of this study was to investigate ethnic differences in the glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene in patients with primary hyperoxaluria type 2 (PH2). GRHPR was genotyped in Japanese patients with PH2 and all GRHPR mutations described to date were reviewed in terms of geographic and ethnic association. We identified a novel mutation, a two-nucleotide deletion (c.248_249delTG) in exon 3 creating a premature 'stop' at codon 91. Also, we found that the c.864_865delTG mutation was associated with the rs35891798 single-nucleotide polymorphism. The allelic frequencies of the c.103delG, c.494G>A, c.403_404+2 delAAGT, and c.864_865delTG mutations in PH2 patients were 37.8%, 15.6%, 10.0%, and 10.0%, respectively. All patients with the c.103delG mutation were Caucasian. Patients with the c.494G>A mutation and 78% (7/9) of those with the c.403_404+2 delAAGT mutation were from the Indian subcontinent, whereas those with the c.864_865delTG mutation were Chinese or Japanese. Molecular analysis of GRHPR of four Japanese PH2 patients identified a novel mutation (c.248_249delTG in exon 3). Caucasians with PH2 should be screened for the c.103delG mutation; patients from the Indian subcontinent for c.494G>A; and patients of East Asian origin (particularly) for c.864_865delTG. The prevalence of the latter mutation in PH2 patients from East Asia was 75.0%.

Pathogenetic role of an autoimmune susceptibility locus derived from MRL/MpJ strain chromosome 1 in chronic pancreas inflammation.

We examined the role of Mag, an autoimmune susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune exocrinopathy. At nine to 12 months of age, strain-specific differences were observed in the pancreas of the animals. B- and T-cell-containing periductal/perivascular cell infiltrations in the pancreases of MRL/MpJ and B6.MRLc1 congenic C57BL/6-background Mag-carrying strains were more severe than were those of C57BL/6. Pancreatic periductal/perivascular cell infiltration was observed frequently in A/J, AKR/N, B6.MRLc1, C57BL/6, and MRL/MpJ, moderately in DBA/1 and DBA/2, and rarely in BALB/c and C3H/He strains. Females tended to have greater pancreatic periductal/perivascular cell infiltration than males. C57BL/6 mice possessed defined borders between cell infiltrations and acini, but borders were indistinct in MRL/MpJ and B6.MRLc1 mice. We attributed this to the invasion of inflammatory cells between each acinus and the disruption of acinar cells around cell infiltrations in the latter strains. No strain-specific differences were observed in the appearance of fibrotic lesions and high endothelial venules in the cell infiltrates. The levels of serum anti-dsDNA antibodies and amylase, and mRNA expression of tumor necrosis factor-α and Fc gamma receptor III (encoded on Mag) in the pancreases, were elevated in MRL/MpJ- and B6.MRLc1-strain mice relative to C57BL/6. These results emphasized the crucial roles of Mag in the molecular and genetic pathogenesis of autoimmune-mediated pancreatitis.

Intravenous thrombolysis for patients with reverse magnetic resonance angiography and diffusion-weighted imaging mismatch: SAMURAI and NCVC rt-PA Registries.

BACKGROUND AND PURPOSE: The characteristics of reverse magnetic resonance angiography and diffusion-weighted imaging (MRA-DWI) mismatch (RMM), defined as a large DWI lesion in the absence of major artery occlusion (MAO), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA). METHODS: Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI-ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI-ASPECTS cut-off value of <7. RMM was defined as DWI-ASPECTS <7 without MAO. Clinical characteristics, symptomatic intracerebral hemorrhage (sICH) and favorable functional outcome (modified Rankin Scale score 0-2) at 90 days were compared amongst the four groups. RESULTS: Of the 486 patients enrolled (167 women, median age 74 years, median initial National Institutes of Health Stroke Scale score 13), reverse MRA-DWI mismatch was observed in 24 (5%). Of the clinical characteristics, cardioembolism was the only factor that was independently associated with RMM [odds ratio (OR) 5.49, 95% confidence interval (CI) 1.25-24.1]. Multivariable analyses revealed that patients with RMM more commonly had sICH than those with DWI-ASPECTS ≥ 7 irrespective of the presence (OR 5.44, 95% CI 1.13-26.1) or absence (13.1, 2.07-83.3) of MAO, and they had a more favorable functional outcome than those with DWI-ASPECTS < 7 plus MAO (7.45, 2.39-23.2). CONCLUSION: RMM was observed in 5% of patients treated with rt-PA and associated with cardioembolism. Patients with RMM may benefit from thrombolysis compared with those with EIC with MAO, although increment in the rate of sICH is a concern.

Sweet potato resistance to Euscepes postfasciatus (Coleoptera: Curculionidae): larval performance adversely effected by adult's preference to tuber for food and oviposition.

The preferences of the West Indian sweet potato weevil, Euscepes postfasciatus (Fairmaire), to tubers of sweet potato, Ipomoea batatas (L.), for food and for oviposition were evaluated, and correlated to sweet potato's resistance to immatures. Adults (parent) were released in a plastic box containing tubers of sweet potato cultivars and maintained for 5 d, after which the adults on each tuber were counted. All adults were then removed and each tuber was maintained separately. New adults that emerged from the tubers were counted. Cultivars were grouped by cluster analyses using the number of parent adults on the tubers and the number of new adults emerging from the tubers, adjusted for the weight of each tuber. Cultivars were divided into five groups: average level of preference, preferred, preferred for oviposition but not for food, preferred for food but not for oviposition, and not preferred. New adults from the first two groups took less time to eclose than those from the other groups, and their body size was smaller. In a second experiment, one to five cultivars were selected from each group and inoculated each tuber with 10 weevil eggs on each cultivar. Although the proportion of eclosed adults was not significantly different between cultivars, the time to eclosion was shorter and body size was smaller on preferred cultivars. The selection of tubers by parent adults was not linearly related with larval development, and did not reduce the survival of the immatures.

Randomized Trial to Test a Chemo-Mechanical Antiplaque Regimen as Adjunct to Periodontal Therapy.

BACKGROUND: The control of dental biofilm regrowth after nonsurgical periodontal therapy is associated with better clinical outcomes. However, many patients have difficulty achieving optimal plaque control. Subjects with diabetes, in which immune and wound-healing responses are typically impaired, may benefit from intensive antiplaque control regimens after scaling and root planing (SRP). OBJECTIVES: This study aimed to evaluate the effects of an intensive, at-home, chemical, and mechanical antiplaque regimen as an adjunct to SRP for the treatment of moderate to severe periodontitis. A secondary objective was to compare responses in subjects with type 2 diabetes and nondiabetics. METHODS: This was a 6-mo, single-center, parallel-group, randomized trial. The test group received SRP and oral hygiene instructions, and subjects were instructed to use a 0.12% chlorhexidine gluconate mouthrinse twice a day for 3 mo and utilize rubber interproximal bristle cleaners twice a day for 6 mo. The control group received SRP and oral hygiene instructions. The main outcome was change in mean probing depth (PD) from baseline to 6 mo. Secondary outcomes included change in sites with deep PDs, mean clinical attachment level, bleeding on probing, plaque index, hemoglobin A1C, fasting blood glucose, C-reactive protein, and taste assessment. This study was registered at ClinicalTrials.gov as NCT04830969. RESULTS: In total, 114 subjects were randomized to either treatment. Eighty-six subjects completed the trial with no missing visits. Neither an intention-to-treat nor a per-protocol analysis showed statistically significant differences between treatment groups in mean PD at 6 mo. In a subgroup analysis, subjects with diabetes in the test group showed a statistically significant greater reduction in mean PD at 6 mo when compared to subjects with diabetes receiving the control treatment (Δ = 0.15, P = 0.04), while there were no differences within nondiabetics (Δ = 0.02, P = 0.75). CONCLUSION: Outcomes in subjects with diabetes may be improved by chemo-mechanical antiplaque measures after nonsurgical periodontal therapy. KNOWLEDGE TRANSFER STATEMENT: This study suggests diabetic subjects may benefit from an intensive, at-home, chemical, and mechanical antiplaque regimen to improve nonsurgical periodontal therapy outcomes.

Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma.

BACKGROUND: Bcl-xL has an important role in the control of cell death through its inhibition of apoptosis. The aim of this study was to investigate the clinicopathological significance of Bcl-xL in upper urinary tract urothelial carcinoma (UTUC) and the therapeutic effect of targeting Bcl-xL protein in urothelial carcinoma (UC) cells. METHODS: We evaluated the immunohistochemical expression of Bcl-xL in 175 UTUC patients to determine the clinical role of Bcl-xL expression in clinical outcome. We used bafilomycin A1 (BMA) as a specific inhibitor of Bcl-xL to examine the biological effects in UC cells in vitro and in vivo. RESULTS: Immunohistochemical analysis of Bcl-xL expression revealed that patients with a high Bcl-xL score had a significantly lower 5-year cancer-specific survival (CSS) rate (53.2%) than those with a low Bcl-xL score (77.2%) (P=0.0011). Multivariate analysis indicated that a high Bcl-xL score was an independent prognostic factor of CSS (P=0.023). BMA inhibited UMUC-3 cell proliferation in vitro by induction of apoptosis. Treatment with BMA significantly inhibited tumour growth in UMUC-3 tumours in this mouse xenograft model accompanied by an elevated apoptosis induction. CONCLUSION: Bcl-xL appears to be a significant molecular marker for the prognosis of UTUCs. Targeting Bcl-xL may be a promising therapeutic strategy for patients with UC.

The prognostic significance of vasohibin-1 expression in patients with prostate cancer.

BACKGROUND: We recently isolated vasohibin-1 (VASH1), a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells (ECs), and the status of VASH1 expression has been documented in various cancer angiogenesis. The aim of this study was to assess the prognostic value of VASH1 expression in prostate cancer (PCa). METHODS: In this study, we retrospectively analysed the clinical records and evaluated the VASH1 expression of tumour microvessels in 167 patients with PCa who underwent radical prostatectomy. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD) and the microvessels with activated ECs positive for VASH1 density. RESULTS: We found that the VASH1 expression was restricted to ECs in the tumour stroma. VASH1 density was significantly associated with pathological T stage, Gleason score and MVD. The 5-year PSA recurrence-free survival rate was 58.8% in patients with higher VASH1 density (≧12 per mm(2)) and 89.1% in patients with lower VASH1 density (<12 per mm(2)), respectively (P<0.001). Microvessel density was not an independent predictor of PSA recurrence. Multivariate analysis revealed that high VASH1 density was an independent prognostic indicator of PSA recurrence (P=0.007, HR=2.950). CONCLUSION: VASH1 density represents a clinically relevant predictor of patient prognosis and can be a new biomarker that would provide additional prognostic information in PCa.

Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.