Auditory brainstem responses in adults with autism spectrum disorder.

OBJECTIVE: To investigate possible differences in the auditory peripheral and brainstem functions between adults with autism spectrum disorder (ASD) and neurotypical (NT) adults. METHODS: Click-evoked auditory brainstem responses (ABRs) were obtained from 17 high-functioning ASD adults (aged 21-38 years) and 20 NT adults (aged 22-36 years). A relatively large number of stimulus presentations (6000) were adopted, and ABRs by horizontal and vertical electrode montages were evaluated, in order to allow precise evaluations of early ABR components. RESULTS: Waves I, II, III, and V were identified in the vertical electrode montage, and wave I and the summating potential (SP) in electrocochleograms were identified in the horizontal electrode montage. There were no significant group differences in the wave I, II, III, and V latencies or the interpeak latencies (IPLs) in the vertical electrode montage. In the horizontal montage, the ASD adults exhibited significantly shortened SP latencies compared with the NT adults, whereas there was no significant group difference in the wave I latency. CONCLUSION: The ASD adults may have the abnormalities of processing more in the peripheral auditory system than in the brainstem. SIGNIFICANCE: The current study suggests that the peripheral abnormality is associated with ASD.

Novel host immune evasion strategy of the endoparasitoid Drino inconspicuoides.

The tachinid fly Drino inconspicuoides (Diptera: Tachinidae) is an ovolarviparous endoparasitoid whose larvae develop in the host haemocoel and avoids the host immune system. In this study, we investigated the immune evasion mechanisms of this species during infestation in the host Mythimna separata (Lepidoptera: Noctuidae). We discovered a unique 'cloak' that surrounded D. inconspicuoides larvae that penetrated into the host and determined through genomic polymerase chain reaction analysis that this structure originated from the host rather than the tachinid. The 'cloak' contained both haemocytes and fat body cells from the host, with the haemocytes assembling around the larvae first and the fat body cells then covering the haemocyte layer, following which the two mixed. Living D. inconspicuoides larvae that were wrapped in the 'cloak' were not melanized whereas encapsulated dead larvae were melanized, suggesting that this structure contributes to the avoidance of host immune reactions.

Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, potentiates coagulation function in factor XI-deficient plasma in vitro.

Essentials Emicizumab mimics factor (F)VIIIa cofactor function, augments the intrinsic tenase activity. We assessed the emicizumab-driven hemostatic function in FXI-deficient plasmas. Emicizumab improved the coagulation potentials in severe FXI-deficient plasma. Emicizumab may provide a possibility for clinical application in patients with FXI deficiency. SUMMARY: Background Patients with factor (F)XI deficiency commonly present with markedly prolonged activated partial thromboplastin times (APTT), although bleeding phenotypes are heterogeneous. Emicizumab, a bispecific monoclonal antibody to FIX/FIXa and FX/FXa, mimics FVIIIa cofactor function on phospholipid (PL) surfaces. Antibody reactions were designed, therefore, to augment mechanisms during the propagation phase of blood coagulation. Aim To assess emicizumab-driven hemostatic function in FXI-deficient plasmas. Methods and Results Standard ellagic acid (Elg)/PL-based APTTs of different FXI-deficient plasmas (n = 13; FXI activity, < 1 IU dl-1 ) were markedly shortened dose dependently by the presence of emicizumab. To further analyze the effects of emicizumab, clot waveform analysis (CWA) in FXI-deficient plasmas with emicizumab, triggered by tissue factor (TF)/Elg demonstrated improvements in both clot times, reflecting the initiation phase, and coagulation velocity, which represents the propagation phase. Emicizumab also enhanced the TF/Elg-triggered thrombin generation in FXI-deficient plasmas dose-dependently although the degree of enhancement varied in individual cases. Thrombin generation with either FVII-deficient plasma or FIX-deficient plasma treated with anti-FXI antibody showed little or no increase by the co-presence of emicizumab, suggesting that the accelerated thrombin generation in FXI-deficient plasmas by emicizumab should depend on the FIXa-involved coagulation propagation initially triggered by FVIIa/TF. The ex vivo addition of emicizumab to whole blood from three patients with severe FXI deficiency demonstrated modest, dose-dependent improvements in Ca2+ -triggered thromboelastograms (NATEM mode). Conclusion Emicizumab appeared to improve coagulation function in severe FXI-deficient plasma, and might provide possibilities for clinical application in patients with FXI deficiency.

Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures.

Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction-diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

Rapid Bactericidal Action of Propolis against Porphyromonas gingivalis.

Propolis, a resinous substance produced by bees, is used as a folk medicine for treatment of periodontal diseases. However, its mode of the action and the compounds responsible for its activities remain obscure. In the present study, we comprehensively investigated the antibacterial activities of ethanol-extracted propolis (EEP) and EEP-derived compounds toward Porphyromonas gingivalis, a keystone pathogen for periodontal diseases. Broth microdilution and agar dilution assays were used to determine the minimum inhibitory concentrations of EEP against a range of oral bacterial species, of which P. gingivalis showed a higher level of sensitivity than oral commensals such as streptococci. Its antibacterial activity toward P. gingivalis was maintained even after extensive heat treatment, demonstrating a high level of thermostability. EEP also induced death of P. gingivalis cells by increasing membrane permeability within 30 min. Spatiotemporal analysis based on high-speed atomic force microscopy revealed that EEP immediately triggered development of aberrant membrane blebs, followed by bleb fusion events on the bacterial surface. Furthermore, we isolated artepillin C, baccharin, and ursolic acid from EEP as antibacterial compounds against P. gingivalis. Of those, artepillin C and baccharin showed bacteriostatic activities with membrane blebbing, while ursolic acid showed bactericidal activity with membrane rupture. In particular, ursolic acid demonstrated a greater ability to affect bacterial membrane potential with increased membrane permeability, probably because of its highly lipophilic nature as compared with other compounds. Taken together, these findings provide mechanistic insight into the antibacterial activities of EEP and its exquisite membrane-targeting antibacterial compounds and imply the applicability of narrow-spectrum therapeutics with EEP for treatment of periodontitis. In addition, the advanced technology utilized in the present study to visualize the nanometer-scale dynamics of microorganisms will contribute to expanding our understanding of the activities of antimicrobials and the mechanism of drug resistance in bacteria.

Photopatterning of fluorescent host-guest carriers through pore activation of metal-organic framework single crystals.

Encoded fluorescent particles are fabricated through the selective uptake of dyes in photopatterned metal-organic framework single crystals. The concept is based on spatially controlled photochemical cleavage of pore-blocking pendant groups. Because of the crystalline and porous nature of the host, this approach enables guest uptake that is tunable and can be triggered though controlled irradiation.

Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study.

In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.

Lymphoepithelioma-like carcinoma of the uterine cervix: a case report.

Lymphoepithelioma-like carcinoma (LELC) is a rare variant of carcinoma of the uterine cervix, of which Epstein-Barr virus (EBV) and/or human papilloma virus (HPV) may play an important role in the pathogenesis. The authors report a case of a patient with cervical LELC who was also examined for the presence of EBV and HPV. A 31-year-old Japanese female presented with irregular genital bleeding. The biopsy showed an invasive squamous cell carcinoma. Based on the clinical data, the patient was diagnosed as having squamous cervical carcinoma, and radical hysterectomy with ovarian conservation was performed. A diagnosis of cervical LELC was then made by histological methods. An additional examination revealed that the patient was infected with HPV types 16 and 71, but not infected with EBV.

Magnetic Behavior of Volborthite Cu_{3}V_{2}O_{7}(OH)_{2}·2H_{2}O Determined by Coupled Trimers Rather than Frustrated Chains.

Motivated by recent experiments on volborthite single crystals showing a wide 1/3-magnetization plateau, we perform microscopic modeling by means of density functional theory (DFT) with the single-crystal structural data as a starting point. Using DFT+U, we find four leading magnetic exchanges: antiferromagnetic J and J_{2}, as well as ferromagnetic J^{'} and J_{1}. Simulations of the derived spin Hamiltonian show good agreement with the experimental low-field magnetic susceptibility and high-field magnetization data. The 1/3-plateau phase pertains to polarized magnetic trimers formed by strong J bonds. An effective J→∞ model shows a tendency towards condensation of magnon bound states preceding the plateau phase.

Assessing the clinical severity of type 1 von Willebrand disease patients with a microchip flow-chamber system.

BACKGROUND: The clinical phenotype of von Willebrand disease (VWD) is heterogeneous, and von Willebrand factor ristocetin cofactor activity (VWF:RCo) does not always reflect clinical severity, especially in VWD type 1. We have reported the potential of a microchip flow-chamber system (Total-Thrombus Formation Analysis System [T-TAS®]) for assessing physiologic hemostasis in VWD. Aim To evaluate the relationship between T-TAS, bleeding score (BS) and laboratory test results in type 1 VWD patients. METHODS: Microchips coated with collagen (platelet chip [PL-chip]) or collagen/thromboplastin (AR-chip) were used to assess platelet thrombus formation (PTF) at high shear rates or fibrin-rich PTF at low shear rates, respectively, in whole blood from 50 patients. The times needed for the flow pressure to increase by 10 kPa and 30 kPa (T10 and T30 ) from baseline were calculated from flow pressure curves. BS was determined by the use of a standardized questionnaire. RESULTS: PL-T10 values correlated with BS (R(2) ~ 0.45) better than VWF:RCo (R(2) ~ 0.36), irrespective of the flow rate, whereas AR-T10 showed only a weak correlation with BS (R(2) ~ 0.18). Patients with PL-T10 > 10 min or AR-T10 > 30 min had lower VWF levels and higher BS than those with PL-T10 ≤ 10 min or AR-T10 ≤ 30 min, and the greatest differences were observed with PL-T10. Clinical severity appeared to correlate best with PL-T10 > 8 min. BS was significantly higher in patients with VWF:RCo of < 10 IU dL(-1) than in those with VWF:RCo of 10 IU dL(-1) to < 25 IU dL(-1) and 25-40 IU dL(-1). In patients with VWF:RCo of < 10 IU dL(-1) , BS was significantly higher in those with PL-T10 > 8 min than in those with PL-T10 ≤ 8 min. CONCLUSION: T-TAS could be a useful technique for discriminating and predicting BS in VWD type 1 patients.

Systematic monitoring of hemostatic management in hemophilia A patients with inhibitor in the perioperative period using rotational thromboelastometry.

BACKGROUND: The management of hemophilia A (HA) patients with inhibitors on bypassing therapy remains challenging. In particular, the monitoring of treatment is restricted by the limited reliability and lack of standardization of currently available methods to evaluate the physiological effects of various hemostatic agents. Accurate monitoring of these patients is particularly important in surgical situations. The recently developed comprehensive coagulation assays, including rotational thromboelastometry (ROTEM), may be useful in these circumstances. OBJECTIVE: We have attempted to establish a systematic monitoring protocol using ROTEM (NATEM triggered by CaCl2 ) to evaluate the choice and effectiveness of different bypassing agents in the perioperative period. METHODS AND RESULTS: The hemostatic effects of recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC) were determined using a three-step procedure (spike, preoperative and perioperative) in eight patients with HA inhibitor admitted for elective surgery and assessed for individually tailored therapy. The ROTEM parameters demonstrated similar improvement to approximately normal levels at each stage after treatment with rFVIIa. Results in the presence of aPCC showed a marked improvement in the spike data, although this appeared to be different from those in the preoperative and perioperative assessments. The information derived from the spike and preoperative findings provided a useful guide for establishing an effective dose of therapeutic material, and facilitated good hemostatic control during and after surgery in all cases. CONCLUSION: The findings suggest that this systematic analysis using ROTEM could provide a promising strategy for the use of bypassing therapy in HA patients with inhibitor.

Ambipolar organic field-effect transistors based on solution-processed single crystal microwires of a quinoidal oligothiophene derivative.

A simple and versatile solution-processing method based on molecular self-assembly is used to fabricate organic single crystal microwires of a low bandgap quinoidal oligothiophene derivative. Individual single crystal microwire transistors present well-balanced ambipolar behaviour with hole and electron mobilities as high as 0.4 and 0.5 cm(2) V(-1) s(-1), respectively.

Clinical relevance of Küttner tumour and IgG4-related dacryoadenitis and sialoadenitis.

OBJECTIVES: Küttner tumour (KT), so-called chronic sclerosing sialoadenitis, is characterised by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis independent of sialolith formation. However, recent studies have indicated that some patients with KT develop high serum levels of IgG4 and infiltration of IgG4-positive plasma cells, namely IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease. The aim of this study was to clarify the clinical and pathological associations between KT and IgG4-DS. MATERIALS AND METHODS: Fifty-four patients pathologically diagnosed with KT or chronic sialoadenitis were divided into two groups according to the presence or absence of sialolith (KT-S (+) or KT-S (-), respectively). RESULTS: There were no significant differences in the clinical findings, including the mean age, sex and disease duration, between the two groups. All patients in the KT-S (+) group showed unilateral swelling without infiltration of IgG4-positive plasma cells or a history of other IgG4-related diseases (IgG4-RD), while those in the KT-S (-) group showed bilateral swelling (37.5%), strong infiltration of IgG4-positive plasma cells (87.5%) and a history of other IgG4-RD (12.5%). CONCLUSIONS: These results suggest an association between the pathogeneses of KT-S (-) and IgG4-DS, but not KT-S (+).

Influence of balancing-side occlusal interference on smoothness of working-side condylar movement and intra-articular space in chewing efforts.

Response of temporomandibular joint (TMJ) articulation adapting to occlusal alteration has been sparsely known. For 10 healthy adults with acceptably good occlusion, an artificial occlusal interference (OI) was introduced to the lower molar on the balancing side of unilateral chewing. Subjects were asked to chew a gum on their preferred side. The chewing jaw movements with/without the OI were recorded using a video-based optoelectronic system. The mandibular movements were generated in each individual's TMJ model reconstructed by magnetic resonance images. The smoothness of local condylar point movements towards the normal direction of the condylar surface and interarticular space on the working side was measured. Overall, the smoothness of condylar point movements in the closing phase was impaired immediately after introduction of the OI. In the intercuspal phase, the OI increased the joint space. After about 60 chewing cycles, the movement smoothness and joint space began to recover. These findings suggest that OI on the balancing side induced irregular stress field translation on the working-side condylar surface followed by acute recovery process.

Saliva as a potential tool for diagnosis of dry mouth including Sjögren's syndrome.

OBJECTIVES: Recently, the use of saliva as a diagnostic tool has gained considerable attention because it is non-invasive and easy to perform repeatedly. In this study, we focused on soluble molecules in saliva to establish a new diagnostic method for xerostomia. MATERIALS AND METHODS: Saliva was obtained from 90 patients with Sjögren's syndrome (SS), 22 patients with xerostomia associated with neurogenic/neuropsychiatric disorders and drugs (XND), 30 patients with radiation-induced xerostomia (RX), and 36 healthy controls. Concentrations of helper T (Th) cytokines in saliva were measured by flow cytometric analysis. Concentrations of secretory IgA (SIgA) and chromogranin A (CgA) were measured by ELISA. RESULTS: Unstimulated and stimulated whole saliva from patients with SS, XND, and RX was significantly reduced compared with controls. Th1 and Th2 cytokines from SS patients were significantly higher than controls. Furthermore, Th2 cytokines were closely associated with strong lymphocytic accumulation in salivary glands from SS patients, while Th1 and Th17 cytokines were negatively associated. SIgA levels were not significantly different between all patient groups and controls. CgA levels from XND patients were significantly higher than controls. CONCLUSIONS: The measurement of cytokines, CgA, and SIgA in saliva is suggested to be useful for the diagnosis of xerostomia and also to reveal disease status.