IκB kinase β–induced phosphorylation of CARMA1 contributes to CARMA1–Bcl10–MALT1 complex formation in B cells

Protein kinase C (PKC) β has been reported (Shinohara, H., T. Yasuda, Y. Aiba, H. Sanjo, M. Hamadate, H. Watarai, H. Sakurai, and T. Kurosaki. 2005. J. Exp. Med. 202:1423–1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Immunity. 23:561–574) to play a crucial role in B cell receptor (BCR)–mediated IκB kinase (IKK) activation through phosphorylation of caspase recruitment domain 11, Bimp3 (CARMA1). However, it remains unclear whether this PKCβ-mediated phosphorylation accounts fully for the activation status of CARMA1, because involvement of other kinases, such as phosphoinositide 3-kinase–dependent kinase 1, has also been suggested. We show that PKCβ mediates phosphorylation of CARMA1 on Ser668, which in turn is essential for BCR-mediated CARMA1–Bcl10–mucosal-associated lymphoid tissue 1 (MALT1) association and subsequent IKK activation. Our analyses also demonstrate that the downstream kinase IKKβ contributes to facilitating formation of the complex CARMA1–Bcl10–MALT1 by mediating phosphorylation of CARMA1. Hence, our data suggest that PKCβ is crucial for initial activation of IKK. The activated IKKβ does not merely function as an effector enzyme but also modifies the upstream signaling complex through a feedback mechanism, thereby optimizing the strength and duration of the nuclear factor κB signal

Neuroprotective DAMPs member prothymosin alpha has additional beneficial actions against cerebral ischemia-induced vascular damages

AbstractProthymosin alpha (ProTα) suppresses stress-induced necrosis of cultured cortical neurons. As neuroprotection alone could not explain the long-lasting protective actions against cerebral ischemia by ProTα, we further examined whether ProTα, in addition to neuroprotective effects, has other anti-ischemic activities. When recombinant mouse ProTα (rmProTα) at 0.3 mg/kg was intravenously (i.v.) given 2 h after the start of tMCAO, all mice survived for more than 14 days. In evaluation of CD31- and tomato lectin-labeling as well as IgG and Evans blue leakage, rmProTα treatment (0.1 mg/kg) largely blocked ischemia-induced vascular damages. Therefore, rmProTα has novel beneficial effects against ischemia-induced brain damage through vascular mechanisms

Isolated gestational proteinuria preceding the diagnosis of preeclampsia : an observational study

Introduction. Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. Material and methods. This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. Results. IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2-18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. Conclusions. IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE

Psychiatric comorbidities in patients with Atypical Odontalgia

Objective: Atypical Odontalgia (AO) is a condition characterized by tooth pain with no apparent cause. Although psychiatric comorbidity seems to be very common, it has rarely been studied. To clarify the influence of psychiatric comorbidity on the clinical features in patients with AO, we retrospectively evaluated their examination records. Methods: Clinical features and psychiatric diagnoses of 383 patients with AO were investigated by reviewing patients' medical records and referral letters. Psychiatric diagnoses were categorized according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We also analyzed visual analogue scale (VAS), self-rating depression scale (SDS), and the short-form McGill pain questionnaire (SF-MPQ) scores. Results: Of the 383 patients with AO, 177 (46.2%) had comorbid psychiatric disorders. The most common were depressive disorders (15.4%) and anxiety disorders (10.1%). Serious psychotic disorders such as bipolar disorder (3.0%) and schizophrenia (1.8%) were rare. Dental trigger of AO was reported in 217 (56.7%) patients. There were no significant correlations between psychiatric comorbidities and most of the demographic features. Higher VAS and SDS scores, higher frequency of sleep disturbance, and higher ratings of “Fearful” and “Punishing-cruel” descriptors of the SF-MPQ were found in patients with psychiatric comorbidity. Conclusions: About half of AO patients had comorbid psychiatric disorders. Dental procedures are not necessarily causative factors of AO. In AO patients with comorbid psychiatric disorders, pain might have a larger emotional component than a sensory one. VAS, SDS, and SF-MPQ scores might aid in the noticing of underlying comorbid psychiatric disorders in AO patients

Saizu: A Very Big Loanword in Japanese

The tradition of student-centered active learning for development of critical thinking at Miyazaki International College provides valuable opportunities for discovery in the classroom. This brief paper outlines the results of one such student project in LL3141, Topics in Linguistics, taught by Debra J Occhi in fall semester of 2013. Students were inspired to undertake this research while reading and discussing Language Contact Meets Cognitive Linguistics: A Case of Getto-suru in Japanese (Horie & Occhi 2001). This paper reviews those findings, presents issues students found especially relevant about loanword behavior discussed in Olah (2007) and about English made in Japan (wasei eigo, discussed in Miller 1997), lists noun loanwords found in Japanese-English dictionaries, presents and analyzes instances of use of the loanword saizu (from English “size”)

Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study

Maeda M., Humber D., Hida E., et al. (2024) Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study. PLoS ONE 19(3.0): e0299510. doi.org/10.1371/journal.pone.0299510.The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181–0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [−5.49–4.12]; LVDd, −0.55 [−3.24–2.15]; LVDd index, −0.25 [−1.92–1.43]; LVDs, −0.03 [−3.84–3.90]; LVDs index, −0.04 [−2.38–2.30]; heart rate, 1.62 [−3.07–6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol

Lubiprostone Decreases the Small Bowel Transit Time by Capsule Endoscopy: An Exploratory, Randomised, Double-Blind, Placebo-Controlled 3-Way Crossover Study

The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117–407) minutes in the P-P regimen, 122.5 (27–282) minutes in the L-P regimen, and 110.5 (11–331) minutes in the P-L regimen (P=0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE