Low-Molecular-Weight Heparin Use in a Case of Noncardiogenic Multifocal Perinatal Thromboembolic Stroke

A full-term neonate suffered multifocal cerebral infarctions due to multiple large vessel thrombi. Thrombophilia and cardiovascular assessments were negative, but due to the severity of the lesions and the concern for expansion of the thrombi or future embolic events, treatment with low-molecular-weight heparin (LMWH) was initiated. No complications from treatment were experienced. We present this severe case in order to highlight difficult management decisions for newborns with multifocal perinatal thromboembolic stroke and to stress the need for further practice guidelines and research in this area

Feasibility of polyclonal avian immunoglobulins (IgY) as prophylaxis against human norovirus infection

Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.Instituto de VirologíaFil: Artman, Chad. Scaled Microbiomics; Estados UnidosFil: Idegwu, Nnebuefe. Scaled Microbiomics; Estados UnidosFil: Brumfield, Kyle D. College Park Campus. University of Maryland. Maryland Pathogen Research Institute; Estados UnidosFil: Brumfield, Kyle D. College Park Campus. University of Maryland. University of Maryland Institute for Advanced Computer Studies; Estados UnidosFil: Lai, Ken. University of Saskatchewan. Vaccine and Infectious Disease Organization; CanadáFil: Hauta, Shirley. University of Saskatchewan. Vaccine and Infectious Disease Organization; CanadáFil: Falzarano, Darryl. University of Saskatchewan. Vaccine and Infectious Disease Organization; CanadáFil: Falzarano, Darryl. University of Saskatchewan. Western College of Veterinary Medicine. Department of Veterinary Microbiology; CanadáFil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Geyer, James D. University of Alabama. College of Community Health Science. Institute for Rural Health Research; Estados UnidosFil: Goepp, Julius G. Scaled Microbiomics; Estados Unido

Co-occurring insomnia and obstructive sleep apnea

a b s t r a c t Study objectives: Prior research investigating co-occurring insomnia/obstructive sleep apnea (CIO) has mainly focused on comparing comorbid patients, obstructive sleep apnea (OSA), and insomnia (INS) to those with OSA alone. This approach is informative but omits the potentially interesting comparison of comorbid patients to those with INS alone. Our study used an incomplete factorial design, crossing OSA (present or absent) with INS (present or absent) to more clearly focus on the question, is comorbid INS an epiphenomenon of OSA or an independent disorder? Methods: Our study was an archival analysis from the database of a sleep center comparing consecutively diagnosed patients characterized as OSA or INS. A third group, CIO, was derived from the OSA group. Our study was conducted at an American Academy of Sleep Medicine-accredited sleep disorders center. We studied 299 patients, including 94 OSA, 97 INS, and 108 CIO. Patients ranged from ages 15 to 86 years. Results: Groups were compared on polysomnography (PSG), sleep pattern, sleep stages, sleep pathology, self-reported sleep concerns, and self-reported daytime functioning. From a consecutive group of OSA patients, we estimate the prevalence of CIO at 67.4%. Based mainly on multivariate analysis of covariance (MANCOVA) controlling for demographic differences between groups, we found few if any significant differences between CIO and INS alone or between CIO and OSA alone. Conclusions: The clinical presentation of CIO is indistinguishable from INS alone, both with respect to PSG findings and to self-reported sleep onset and sleep maintenance disturbance. We observed a weak relation between OSA severity and co-occurring INS. These data are consistent with the view that INS with co-occurring OSA is an independent, self-sustaining disorder. We hypothesized that in some unknown proportion of cases, OSA initially instigated the INS, but the INS was then perpetuated and reshaped by sleep concerns and self-defeating compensatory behaviors

Alternative splicing regulates stochastic NLRP3 activity

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3. exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus reveals unexpected regulatory roles of AS through differential utilization of LRRs modules in vertebrate innate immunity

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease

Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2

Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a \u3e 10% decline in left ventricular ejection fraction from baseline to a value \u3c 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function

Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope

The ANTARES telescope is well-suited for detecting astrophysical transient neutrino sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. The background due to atmospheric particles can be drastically reduced, and the point-source sensitivity improved, by selecting a narrow time window around possible neutrino production periods. Blazars, being radio-loud active galactic nuclei with their jets pointing almost directly towards the observer, are particularly attractive potential neutrino point sources, since they are among the most likely sources of the very high-energy cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions with the surrounding medium. Moreover, blazars generally show high time variability in their light curves at different wavelengths and on various time scales. This paper presents a time-dependent analysis applied to a selection of flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012. The results are compatible with fluctuations of the background. Upper limits on the neutrino fluence have been produced and compared to the measured gamma-ray spectral energy distribution.Comment: 27 pages, 16 figure

The Antares Collaboration : Contributions to the 34th International Cosmic Ray Conference (ICRC 2015, The Hague)

The ANTARES detector, completed in 2008, is the largest neutrino telescope in the Northern hemisphere. Located at a depth of 2.5 km in the Mediterranean Sea, 40 km off the Toulon shore, its main goal is the search for astrophysical high energy neutrinos. In this paper we collect the 21 contributions of the ANTARES collaboration to the 34th International Cosmic Ray Conference (ICRC 2015). The scientific output is very rich and the contributions included in these proceedings cover the main physics results, ranging from steady point sources, diffuse searches, multi-messenger analyses to exotic physics

The Melanin-Concentrating Hormone (MCH) System Modulates Behaviors Associated with Psychiatric Disorders

Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders