Female Veterans With Diagnoses of Both Chronic Pelvic Pain and Overactive Bladder; How Do They Compare to Women Diagnosed With Interstitial Cystitis?

OBJECTIVE: The objective of this study was to compare women with a known diagnosis of interstitial cystitis (IC) to a population that might be at risk for the diagnosis of IC, women with diagnoses of both chronic pelvic pain (CPP) and overactive bladder (OAB). METHODS: We conducted a retrospective study of data from the Veterans Affairs Corporate Data Warehouse. The cohort included all female veterans who had established care with a primary care provider from 1997 to present. International Classification of Diseases, Ninth Revision codes were used to identify women with a diagnosis of IC, CPP, and OAB. Demographic data and comorbidities were compared between groups. RESULTS: A total of 596,815 women were identified. Two thousand three hundred one women (0.4%) were diagnosed with IC; 4459 women (0.7%) were diagnosed with CPP and OAB. At baseline, women with OAB and CPP were more likely to identify as minority (P < 0.001). Anxiety (57.3% vs 49.5%), depression (39.0% vs 46.0%), and posttraumatic stress disorder (29.7 vs 26.4%) were all more common in the CPP and OAB group than in the IC group. In the multivariable model, women with CPP and OAB were more likely to identify as a minority, use tobacco, and carry a diagnosis of anxiety. CONCLUSIONS: There were more patients diagnosed with CPP and OAB compared with patients diagnosed with IC in this population of female veterans. Given the high rate of comorbid anxiety and depression in both groups, further study is warranted to determine whether these women are misdiagnosed.

Intrathecal IgG Synthesis and Persistent Inflammation Are Associated with White Matter Lesions in HIV-negative Patients with Cryptococcal Meningoencephalitis.

Objective Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in human immunodeficiency virus (HIV)-negative and HIV-positive populations. White matter lesions (WMLs) have been reported in both populations of CM patients; however, the mechanisms underlying WML formation remain unknown. We herein report the relationship between the intrathecal immune response and the development of WMLs in HIV-negative patients with CM. Methods Eleven consecutive HIV-negative patients with CM who presented at one of three emergency hospitals in Japan from April 2001 to March 2018 were enrolled. For all patients, we retrospectively assessed the relationships between clinical and laboratory information and the presence of WMLs. Results At presentation, 6 patients had WMLs on magnetic resonance imaging (MRI). The cerebrospinal fluid immunoglobulin G (CSF IgG) index was significantly higher in the patients with WMLs than in those without WMLs (mean, 1.34 vs. 0.70, p=0.017). The time from the symptom onset to initial neuroimaging was also significantly longer in the patients with WMLs than in those without WMLs (median, 31.5 vs. 7.0 days; p=0.008). The clinical outcome was comparable among the patients with and without WMLs. Conclusion In HIV-negative patients with CM, a persistent, aberrant immune response to Cryptococcus, such as intrathecal IgG synthesis, may induce WML formation.

A clinical predictive score for postoperative myasthenic crisis.

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis. METHODS: We studied 393 patients with MG who underwent thymectomy at 6 tertiary centers in Japan (275 patients for derivation and 118 for validation). Clinical characteristics, such as gender, age at onset and operation, body mass index, disease duration, MG subtype, severity, symptoms, preoperative therapy, operative data, and laboratory data, were reviewed retrospectively. A multivariate logistic regression with LASSO penalties was used to determine the factors associated with postoperative myasthenic crisis, and a score was assigned. Finally, the predictive score was evaluated using bootstrapping technique in the derivation and validation groups. RESULTS: Multivariate logistic regression identified 3 clinical factors for predicting postoperative myasthenic crisis risk: (1) vital capacity < 80%, (2) disease duration < 3 months, and (3) bulbar symptoms immediately before thymectomy. The postoperative myasthenic crisis predictive score, ranging from 0 to 6 points, had areas under the curve of 0.84 (0.66-0.96) in the derivation group and 0.80 (0.62-0.95) in the validation group. INTERPRETATION: A simple scoring system based on 3 preoperative clinical characteristics can predict the possibility of postoperative myasthenic crisis. Ann Neurol 2017;82:841-849.

Overstimulation of NMDA receptors impairs early brain development in vivo.

BACKGROUND: Brains of patients with schizophrenia show both neurodevelopmental and functional deficits that suggest aberrant glutamate neurotransmission. Evidence from both genetic and pharmacological studies suggests that glutamatergic dysfunction, particularly with involvement of NMDARs, plays a critical role in the pathophysiology of schizophrenia. However, how prenatal disturbance of NMDARs leads to schizophrenia-associated developmental defects is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Glutamate transporter GLAST/GLT1 double-knockout (DKO) mice carrying the NMDA receptor 1 subunit (NR1)-null mutation were generated. Bouin-fixed and paraffin-embedded embryonic day 16.5 coronal brain sections were stained with hematoxylin, anti-microtubule-associated protein 2 (MAP2), and anti-L1 antibodies to visualize cortical, hippocampal, and olfactory bulb laminar structure, subplate neurons, and axonal projections. NR1 deletion in DKO mice almost completely rescued multiple brain defects including cortical, hippocampal, and olfactory bulb disorganization and defective corticothalamic and thalamocortical axonal projections. CONCLUSIONS/SIGNIFICANCE: Excess glutamatergic signaling in the prenatal stage compromises early brain development via overstimulation of NMDARs.

Self-organization of feed-forward structure and entrainment in excitatory neural networks with spike-timing-dependent plasticity.

Spike-timing dependent plasticity (STDP) is an organizing principle of biological neural networks. While synchronous firing of neurons is considered to be an important functional block in the brain, how STDP shapes neural networks possibly toward synchrony is not entirely clear. We examine relations between STDP and synchronous firing in spontaneously firing neural populations. Using coupled heterogeneous phase oscillators placed on initial networks, we show numerically that STDP prunes some synapses and promotes formation of a feedforward network. Eventually a pacemaker, which is the neuron with the fastest inherent frequency in our numerical simulations, emerges at the root of the feedforward network. In each oscillatory cycle, a packet of neural activity is propagated from the pacemaker to downstream neurons along layers of the feedforward network. This event occurs above a clear-cut threshold value of the initial synaptic weight. Below the threshold, neurons are self-organized into separate clusters each of which is a feedforward network.

The N-terminal cleavage site of PrPSc from BSE differs from that of PrPSc from scrapie.

Heterogeneity in transmissible spongiform encephalopathy is thought to have derived from conformational variation in an abnormal isoform of the prion protein (PrPSc). To characterize PrPSc in bovine spongiform encephalopathy (BSE) and scrapie, we analyzed the newly generated N-terminus of PrPSc isoforms by digestion with proteinase K (PK). With a lower concentration of PK, the terminal amino acid of BSE PrPSc converged at N96. Under the same conditions, however, the terminal amino acid of scrapie PrPSc was G81 or G85. Furthermore, with an increase of PK concentration, the N-terminal amino acid was shifted and converged at G89. The results suggest that the PK cleavage site of BSE PrPSc is uniform and is different from the cleavage site of scrapie PrPSc.

Synthesis and Herbicidal Activity of Opened Hydantoin-ring Derivatives of Hydantocidin.

We synthesized three hydantocidin derivatives and evaluated their herbicidal activity in order to elucidate the role of the spirohydantoin system at the anomeric center of hydantocidin. With application to foliage at 1000 ppm, only α-ureidoamide 14 demonstrated activity, the remaining compounds being found to be inactive.