Authentic role of ATP signaling in micturition reflex

Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2 -/- and P2X3 -/- mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex

EGUIDE project and treatment guidelines

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Empirical Support for Probabilistic GLR Parsing

This paper discusses the effectiveness of a new probabilistic generalized LR model (PGLR) in word-based parsing (morphological and syntactic analysis) tasks, in which we have to consider the word segmentation and multiple part-of-speech problems. Parsing a sentence from the morphological level makes the task much more complex because of the increase of parse ambiguity stemming from word segmentation ambiguities and multiple corresponding sequences of parts-of-speech. The experiments show that the PGLR model yields the best results comparing with the existing Briscoe and Carroll model (B&amp;C) for GLR parsing, and &quot;two-level PCFG&quot;, on experimentation on the ATR Japanese corpus. 1 Introduction The PGLR model (Inui et al., 1997) has previously been proven better than the existing models, namely the model proposed by Briscoe and Carroll (1993) and the baseline model using a probabilistic context-free grammar (PCFG), in parsing strings of parts-of-speech (nonword -based parsing) (Sornlertlam..

Empirical Evaluation of Probabilistic GLR Parsing

This paper presents the results of experiments on probabilistic GLR (PGLR), a new probabilistic model proposed by (Inui et al., 1997). The model is formalized based on stack transition during parsing distinguishing it from the existing models proposed by Wright and Wrigley, and Briscoe and Carroll. Our model produces a remarkable improvement in syntactic parsing with probability. Associating probabilities directly to actions in an LR parsing table, and theoretically requiring only one probability for each action guarantee model trainability and potential applications to other related tasks. 1 Introduction Probabilistic techniques have been introduced to various kinds of natural language processing tasks, due to the increasing availability of text corpora. In syntactical parsing, probabilistic techniques are utilized to rank the potentially high numbers of parses generated for natural language (NL) applications. Several attempts have been made to prune meaningless parses and aid in th..

The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study

Introduction: Very little has been elucidated about sexual interest in female-to-male (FtM) transsexual persons. Aims: To investigate the sexual interest of FtM transsexual persons vs that of men using an eye-tracking system. Methods: The study included 15 men and 13 FtM transsexual subjects who viewed three sexual videos (clip 1: sexy clothed young woman kissing the region of the male genitals covered by underwear; clip 2: naked actor and actress kissing and touching each other; and clip 3: heterosexual intercourse between a naked actor and actress) in which several regions were designated for eye-gaze analysis in each frame. The designation of each region was not visible to the participants. Main Outcome Measures: Visual attention was measured across each designated region according to gaze duration. Results: For clip 1, there was a statistically significant sex difference in the viewing pattern between men and FtM transsexual subjects. Longest gaze time was for the eyes of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. For clip 2, there also was a statistically significant sex difference. Longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects, and there was a significant difference between regions with longest gaze time. The most apparent difference was in the gaze time for the body of the actor: the percentage of time spent gazing at the body of the actor was 8.35% in FtM transsexual subjects, whereas it was only 0.03% in men. For clip 3, there were no statistically significant differences in viewing patterns between men and FtM transsexual subjects, although longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. Conclusion: We suggest that the characteristics of sexual interest of FtM transsexual persons are not the same as those of biological men. Tsujimura A, Kiuchi H, Soda T, et al. The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study. Sex Med 2017;5:e169–e174