bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans
Authors: Reed Chrystal M. , Mosher Clayton P. , Chandravadia Nand , Chung Jeffrey M. , Mamelak Adam N. , Rutishauser Ueli 
Published: November 2019

Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.SIGNIFICANCE STATEMENTInterictal epileptiform discharges (IEDs) are thought to be a cause of memory deficits in chronic epilepsy patients, but the underlying mechanisms are not understood. Utilizing single-neuron recordings in epilepsy patients, we found that hippocampal IEDs transiently change firing of hippocampal neurons and disrupted selectively the retrieval, but not encoding, of declarative memories. The extent of the modulation of the individual firing of hippocampal neurons by an IED predicted the extent of reduction of subjective retrieval confidence. Together, these data reveal a specific kind of transient cognitive impairment caused by IEDs and link this impairment to the modulation of the activity of individual neurons. Understanding the mechanisms by which IEDs impact memory is critical for understanding memory impairments in epilepsy patients.
Motor Cortex Inputs at the Optimum Phase of Beta Cortical Oscillations Undergo More Rapid and Less Variable Corticospinal Propagation
Authors: Torrecillos Flavie , Falato Emma , Pogosyan Alek , West Timothy , Di Lazzaro Vincenzo , Brown Peter 
Published: November 2019

Brain oscillations involve rhythmic fluctuations of neuronal excitability and may play a crucial role in neural communication. The human corticomuscular system is characterized by beta activity and is readily probed by transcranial magnetic stimulation (TMS). TMS inputs arriving at the excitable phase of beta oscillations in the motor cortex are known to lead to muscle responses of greater amplitude. Here we explore two other possible manifestations of rhythmic excitability in the beta band; windows of reduced response variability and shortened latency. We delivered single-pulse TMS to the motor cortex of healthy human volunteers (10 females and 7 males) during electroencephalography recordings made at rest. TMS delivered at a particular phase of the beta oscillation benefited from not only stronger, but also less variable and more rapid transmission, as evidenced by the greater amplitude, lower coefficient of variation, and shorter latency of motor evoked potentials. Thus, inputs aligned to the optimal phase of the beta EEG in the motor cortex enjoy transmission amplitude gain, but may also benefit from less variability and shortened latencies at subsequent synapses. Neuronal phase may therefore impact corticospinal communication.SIGNIFICANCE STATEMENTBrain oscillations involve rhythmic fluctuations of neuronal excitability. Therefore, motor responses to transcranial magnetic stimulation are larger when a cortical input arrives at a particular phase of the beta activity in the motor cortex. Here, we demonstrate that inputs to corticospinal neurons which coincide with windows of higher excitability also benefit from more rapid and less variable corticospinal transmission. This shortening of latency and increased reproducibility may confer additional advantage to inputs at specific phases. Moreover, these benefits are conserved despite appreciable corticospinal conduction delays.
Attenuating Neurogenic Sympathetic Hyperreflexia Robustly Improves Antibacterial Immunity After Chronic Spinal Cord Injury
Authors: Mironets Eugene , Fischer Roman , Bracchi-Ricard Valerie , Saltos Tatiana M. , Truglio Thomas S. , O'Reilly Micaela L. , Swanson Kathryn A. , Bethea John R. , Tom Veronica J. 
Published: November 2019

Spinal cord injury (SCI) disrupts critical physiological systems, including the cardiovascular and immune system. Plasticity of spinal circuits below the injury results in abnormal, heightened sympathetic responses, such as extreme, sudden hypertension that hallmarks life-threatening autonomic dysreflexia. Moreover, such sympathetic hyperreflexia detrimentally impacts other effector organs, including the spleen, resulting in spinal cord injury-induced immunodeficiency. Consequently, infection is a leading cause of mortality after SCI. Unfortunately, there are no current treatments that prophylactically limit sympathetic hyperreflexia to prevent subsequent effector organ dysfunction. The cytokine soluble tumor necrosis factor α (sTNFα) is upregulated in the CNS within minutes after SCI and remains elevated. Here, we report that commencing intrathecal administration of XPro1595, an inhibitor of sTNFα, at a clinically feasible, postinjury time point (i.e., 3 d after complete SCI) sufficiently diminishes maladaptive plasticity within the spinal sympathetic reflex circuit. This results in less severe autonomic dysreflexia, a real-time gauge of sympathetic hyperreflexia, for months postinjury. Remarkably, delayed delivery of the sTNFα inhibitor prevents sympathetic hyperreflexia-associated splenic atrophy and loss of leukocytes to dramatically improve the endogenous ability of chronic SCI rats to fight off pneumonia, a common cause of hospitalization after injury. The improved immune function with XPro1595 correlates with less noradrenergic fiber sprouting and normalized norepinephrine levels in the spleen, indicating that heightened, central sTNFα signaling drives peripheral, norepinephrine-mediated organ dysfunction, a novel mechanism of action. Thus, our preclinical study supports intrathecally targeting sTNFα as a viable strategy to broadly attenuate sympathetic dysregulation, thereby improving cardiovascular regulation and immunity long after SCI.SIGNIFICANCE STATEMENTSpinal cord injury (SCI) significantly disrupts immunity, thus increasing susceptibility to infection, a leading cause of morbidity in those living with SCI. Here, we report that commencing intrathecal administration of an inhibitor of the proinflammatory cytokine soluble tumor necrosis factor α days after an injury sufficiently diminishes autonomic dysreflexia, a real time gauge of sympathetic hyperreflexia, to prevent associated splenic atrophy. This dramatically improves the endogenous ability of chronically injured rats to fight off pneumonia, a common cause of hospitalization. This preclinical study could have a significant impact for broadly improving quality of life of SCI individuals.
Intractable hypercalcaemia during pregnancy and the postpartum secondary to pathogenic variants in CYP24A1
Authors: Arnold Nirusha , O’Toole Victor , Huynh Tien , Smith Howard C , Luxford Catherine , Clifton-Bligh Roderick , Eastman Creswell J 
Published: November 2019

Summary
Parathyroid-independent hypercalcaemia of pregnancy, due to biallelic loss of function of the P450 enzyme CYP24A1, the principal inactivator of 1,25(OH)2D results in hypervitaminosis D, hypercalcaemia and hypercalciuria. We report two cases of this disorder, with intractable hypercalcaemia, one occurring during gestation and into the postpartum, and the other in the postpartum period. Case 1, a 47-year-old woman with a twin pregnancy conceived by embryo transfer, presented with hypercalcaemia at 23 weeks gestation with subnormal serum parathyroid hormone (PTH) and normal serum 25-OH D levels. She was admitted to hospital at 31 weeks gestation with pregnancy-induced hypertension, gestational diabetes and increasing hypercalcaemia. Caesarean section at 34 weeks gestation delivered two healthy females weighing 2.13 kg and 2.51 kg. At delivery, the patient’s serum calcium level was 2.90 mmol/L. Postpartum severe hypercalcaemia was treated successfully with Denosumab 60 mg SCI, given on two occasions. CYP24A1 testing revealed she was compound heterozygous for pathogenic variants c.427_429delGAA, (p.Glu143del) and c.1186C>T, (p.Arg396Trp). Case 2, a 36-year-old woman presented 4 days after the delivery of healthy twins with dyspnoea, bradycardia, severe headaches, hypertension and generalized tonic-clonic seizures after an uneventful pregnancy. She was hypercalcaemic with a suppressed PTH, normal 25(OH)D, and elevated 1,25(OH)2D levels. Her symptoms partially responded to i.v. saline and corticosteroids in the short term but bisphosphonates such as Pamidronate and Zoledronic acid did not result in sustained improvement. Denosumab 120 mg SCI successfully treated the hypercalcaemia which resolved completely 2 months post-partum. CYP24A1 testing revealed she was homozygous for the pathogenic variant c.427_429delGAA, (p.Glu143del).

Learning points:

Hypercalcaemia in pregnancy can be associated with considerable morbidity with few options available for management.

In non-PTH-related hypercalcaemia the diagnosis of CYP24A1 deficiency should be considered.

Making a definitive diagnosis of CYP24A1 deficiency by genetic testing delays the diagnosis, while the availability of serum 24,25-dihydroxyvitamin D (24,25(OH)2D) will expedite a diagnosis.

In pregnant women with CYP24A1 deficiency hypercalcaemia can worsen in the post-partum period and is more likely to occur with twin pregnancies but generally resolves within 2–3 months.

Therapeutic alternatives are limited in pregnancy and their effectiveness is short-lived and mostly ineffective. Denosumab used in both our patients after delivery was the most effective agent normalizing calcium and may have benefit as a long-term therapeutic agent in preventing complications in patients with CYP24A1 deficiency.
Las prácticas de evaluación de las matemáticas universitarias: Tensiones y desafíos desde la red conceptual en la que se inscriben
Authors: García-Oliveros Gloria , Salguero-Rivera Beatriz , Rodríguez-Díaz Oswaldo , Palomino-Bejarano Erminsul , Caicedo-Valencia Rafael 
Published: November 2019

Este artículo analiza, en el marco de un proyecto propedéutico de enseñanza de las matemáticas universitarias, aspectos en la transición de enfoques de la evaluación del rendimiento a la evaluación formativa. Se llevó a cabo un estudio cualitativo de corte exploratorio sobre el cambio en las prácticas de evaluación de profesores en los primeros cursos de matemáticas universitarias, localizadas en ambientes institucionales donde a los tipos de evaluación se les asigna fines integradores para orientar el proceso de aprendizaje. Los datos proceden de las entrevistas y exámenes realizados por 21 profesores universitarios que impartían los cursos Matemáticas Fundamentales para Ingeniería (MFI) y Fundamentos de Matemáticas para Economía y Administración (FMEA), en el primer semestre del 2018. Los resultados revelan el predominio de prácticas evaluadoras asentadas en la formulación de juicios cuantitativos para efectos de calificación, así como de prácticas evaluadoras asentadas sobre el rendimiento académico como certificación y en el que, la calificación visibiliza y garantiza con objetividad el grado del conocimiento matemático adquirido por el estudiante. Por último, se concluye que el desafío de configurar sistemas interactivos de evaluación entre los dos tipos existentes requiere la actualización de la competencia profesional en los profesores universitarios.
Measles Antibody Levels in Young Infants
Authors: Science Michelle , Savage Rachel , Severini Alberto , McLachlan Elizabeth , Hughes Stephanie L. , Arnold Callum , Richardson Susan , Crowcroft Natasha , Deeks Shelley , Halperin Scott , Brown Kevin , Hatchette Todd , Gubbay Jonathan , Mazzulli Tony , Bolotin Shelly 
Published: November 2019

BACKGROUND:Infants are often assumed to be immune to measles through maternal antibodies transferred during pregnancy and, in many countries, receive their first measles-containing vaccine at 12 to 15 months. Immunity may wane before this time in measles-eliminated settings, placing infants at risk for measles and complications. We investigated humoral immunity to measles in infants &lt;12 months of age in Ontario, Canada.METHODS:We selected sera collected at a tertiary pediatric hospital from infants &lt;12 months who were born at ≥37 weeks’ gestational age. We excluded infants with conditions that affect antibody levels. We selected ≤25 sera from 8 predetermined age bands and tested them for measles-neutralizing antibody using the plaque-reduction neutralization test. We calculated the proportion immune at each age band, and predictors of infant susceptibility were assessed by using multivariable logistic regression and Poisson regression.RESULTS:Of 196 infant sera, 56% (110 of 196) were from boys, and 35% (69 of 196) were from infants with underlying medical conditions. In the first month, 20% (5 of 25) of infants had antibodies below the protective threshold, which increased to 92% (22 of 24) by 3 months. By 6 months, all infants had titers below the protective threshold. In a multivariable analysis, infant age was the strongest predictor of susceptibility (odds ratio = 2.13 for each additional month increase; 95% confidence interval: 1.52–2.97).CONCLUSIONS:Most infants were susceptible to measles by 3 months of age in this elimination setting. Our findings inform important policy discussions relating to the timing of the first dose of measles-containing vaccine and infant postexposure prophylaxis recommendations.
Multidisciplinary Engagement Increases Medications in-Hand for Patients Hospitalized With Asthma
Authors: Parikh Kavita , Perry Karen , Pantor Candice , Gardner Catherine 
Published: November 2019

BACKGROUND:
Asthma exacerbations in children are a leading cause of missed school days and health care use. Patients discharged from the hospital often do not fill discharge prescriptions and are at risk for future exacerbations.

METHODS:
A multidisciplinary team aimed to increase the percentage of patients discharged from the hospital after an asthma exacerbation with their medications in-hand from 15% to 80%. Tools from the model of improvement were used to establish a process map, key driver diagram, and iterative plan-do-study-act cycles. Statistical process control charts were used to track the proportion of patients discharged with their medications in-hand as the primary outcome. Initiating multidisciplinary daily discharge huddles on the unit was the key intervention that facilitated change in the system.

RESULTS:
During the study period, the percentage of patients with asthma who received their medications in-hand increased from 15% to &gt;80% for all eligible children and &gt;90% for children with public insurance. Children had a median age of 6.7 years, 47% were female, and 83.8% identified as non-Hispanic African American. Through iterative meetings and mapping with the multidisciplinary team, a process map for bedside delivery and a key driver diagram were created. Balancing measures, specifically length of stay and discharge medications forgotten at the hospital, remained constant.

CONCLUSIONS:
Improvements in increasing medication possession at the time of discharge for children hospitalized with asthma were facilitated by multidisciplinary engagement. Standardizing discharge initiatives may play a key role in improving discharge transitions for children with asthma.
The Alchemy of Connection: A Fundamental Ingredient When Supporting Breastfeeding Dyads
Authors: Lopez-Bassols Indira , Garibaldi Jose Alberto 
Published: November 2019

BackgroundEvery encounter in lactation care should aim to set the ground for an emerging human connection between the lactation consultant (LC) and the breastfeeding mother. Cultivating connection is as important as adequate clinical competencies and effective communication skills.MethodsThe article proposes a hermeneutics of care that articulates elements that enhance the understanding between the LC and the circumstances and realities of the breastfeeding dyad in the context of diagnosis, management, and healing. These elements can be best described by Martin Buber's (2013) I–Thou approach, which we use to enter into a relationship.ResultsWhen the LC has the courage and humility to convey her full presence for that mother and her circumstances, connection has been primed. The quality and depth of the LC– breastfeeding mother relationship, in turn, enhances diagnosis and healing options, particularly in chronic cases.ConclusionsThe “alchemy of connection” opens the ground for a relation of mutual trust between the LC and the mother and her world, which supports better breastfeeding care.
Diet Pill and Laxative Use for Weight Control and Subsequent Incident Eating Disorder in US Young Women: 2001–2016
Authors: Levinson Jordan A. , Sarda Vishnudas , Sonneville Kendrin , Calzo Jerel P. , Ambwani Suman , Austin S. Bryn 
Published: November 2019

Objectives. To investigate the prospective association of diet pill and laxative use for weight control with subsequent first eating disorder diagnosis in young women.Methods. We used longitudinal data from 10 058 US women spanning 2001 through 2016. We used multivariable logistic regression models, adjusting for age, race/ethnicity, and overweight status to estimate the association between weight-control behaviors and subsequent eating disorder diagnosis.Results. Among those who had not previously received an eating disorder diagnosis, women who reported diet pill (adjusted odds ratio [AOR] = 5.6; 95% confidence interval [CI] = 3.0, 10.5) or laxative (AOR = 6.0; 95% CI = 4.2, 8.7) use for weight control had higher odds of receiving a subsequent first eating disorder diagnosis within 1 to 3 years than those who did not report using these products.Conclusions. Use of diet pills or laxatives for weight loss can be dangerous and may be a warning sign that warrants counseling and evaluation for the presence of or risk of developing an eating disorder.Public Health Implications. Policymakers and public health professionals should develop and evaluate policy initiatives to reduce or prohibit access to diet pills and laxatives abused for weight control.
Optimization of the Gas-Extraction Process in a New Mud-Logging System
Authors: Marum Daniela Martins , Afonso Maria Diná , Ochoa Brian Bernardo 
Published: November 2019

SummaryAn advanced gas analysis heated system (AGAHS) analyzes the gas extracted from a water-based mud (WBM) to estimate the hydrocarbons contents in drilled rock formations. Operating conditions within the gas-extraction device (gas trap) such as the gas concentration in the mud, stirring velocity, mud-flow rate and temperature, and ditch-line flow rate and pressure are studied to maximize the gas-extraction efficiency in the gas trap. The operating conditions that most affect the gas-extraction efficiency are the stirring velocity and the mud-flow rate. The highest and most stable gas-extraction efficiencies are obtained at 1,680 rev/min and 1.0 L/min.
N-3-oxo-octanoyl-homoserine Lactone-Mediated Priming of Resistance to Pseudomonas syringae Requires the Salicylic Acid Signaling Pathway in Arabidopsis thaliana
Authors: Liu Fang , Zhao Qian , Jia Zhenhua , Song Cong , Huang Yali , Ma Hong , Song Shuishan 
Published: November 2019

Abstract
Background: Many Gram-negative bacteria use N-acyl-homoserine lactones (AHLs) to communicate each other and to coordinate their collective behaviors. Recently, accumulating evidence shows that host plants are able to sense and respond to bacterial AHLs. Once primed, plants are in an altered state that enables plant cells to more quickly and/or strongly respond to subsequent pathogen infection or abiotic stress. Results: In this study, we report that pretreatment with N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL) confers resistance against the pathogenic bacterium Pseudomonas syringae pv. tomato DC3000 (PstDC3000) in Arabidopsis. Pretreatment with 3OC8-HSL and subsequent pathogen invasion triggered an augmented burst of hydrogen peroxide, salicylic acid accumulation, and fortified expression of the pathogenesis-related genes PR1 and PR5. Upon PstDC3000 challenge, plants treated with 3OC8-HSL showed increased activities of defense-related enzymes including peroxidase, catalase, phenylalanine ammonialyase, and superoxide dismutase. In addition, the 3OC8-HSL-primed resistance to PstDC3000 in wild-type plants was impaired in plants expressing the bacterial NahG gene and in the npr1 mutant. Moreover, the expression levels of isochorismate synthases (ICS1), a critical salicylic acid biosynthesis enzyme, and two regulators of its expression, SARD1 and CBP60g, were potentiated by 3OC8-HSL pretreatment followed by pathogen inoculation. Conclusions: Our data indicate that 3OC8-HSL primes the Arabidopsis defense response upon hemibiotrophic bacterial infection and that 3OC8-HSL-primed resistance is dependent on the SA signaling pathway. These findings may help establish a novel strategy for the control of plant disease.