bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron Level and Myelin Content in the Ventral Striatum Predict Memory Performance in the Aging Brain
Authors: Steiger Tineke K. , Weiskopf Nikolaus , Bunzeck Nico 
Published: March 2016

Age-related memory impairments have been associated with structural changes in the dopaminergic system, but the underlying mechanisms remain unclear. Recent work indicates that iron accumulation might be of particular relevance. As iron accumulates, a degeneration of myelin sheaths has been observed in the elderly, but the relationship between both and their impact on memory performance in healthy elderly humans remain important open questions. To address this issue, we combined an established behavioral paradigm to test memory performance [verbal learning memory test (VLMT)] with state of the art quantitative magnetic resonance imaging techniques allowing us to quantify the degree of myelination and iron accumulation via markers of tissue microstructure in a group of young (18–32 years) and healthy elderly humans (55–79 years). As expected, we observed a decrease in gray matter volume and myelin, and an increase of iron in the elderly relative to the young subjects within widespread brain regions, including the basal ganglia. Furthermore, higher levels of iron within the ventral striatum were accompanied by a negative correlation between myelin and iron specific for the elderly participants. Importantly, both markers of iron and myelin (and their ratio) predicted the performance of the elderly in the VLMT. This suggests that ventral striatum iron accumulation is linked to demyelination and impairments in declarative memory. Together, our data provide novel insights into underlying microstructural mechanisms of memory decline in the elderly.SIGNIFICANCE STATEMENTMemory decline in healthy elderly is a common phenomenon, but the underlying neural mechanisms remain unclear. We used a novel approach that allowed us to combine behavior and whole-brain measures of iron, myelin, and gray matter in the participant's individual subspace to analyze structure–structure and structure–behavior interactions. We were able to show, that age-related high levels of iron are accompanied by a negative correlation of iron and myelin in the ventral striatum, which predicted individual memory performance. As such, our findings provide unprecedented insights into the basic mechanisms of memory decline in the elderly.
Promoter-Specific Effects of DREADD Modulation on Hippocampal Synaptic Plasticity and Memory Formation
Authors: López Alberto J. , Kramár Enikö , Matheos Dina P. , White André O. , Kwapis Janine , Vogel-Ciernia Annie , Sakata Keith , Espinoza Monica , Wood Marcelo A. 
Published: March 2016

Designer receptors exclusively activated by designer drug (DREADDs) are a novel tool with the potential to bidirectionally drive cellular, circuit, and ultimately, behavioral changes. We used DREADDs to evaluate memory formation in a hippocampus-dependent task in mice and effects on synaptic physiology in the dorsal hippocampus. We expressed neuron-specific (hSyn promoter) DREADDs that were either excitatory (HM3D) or inhibitory (HM4D) in the dorsal hippocampus. As predicted, hSyn–HM3D was able to transform a subthreshold learning event into long-term memory (LTM), and hSyn–HM4D completely impaired LTM formation. Surprisingly, the opposite was observed during experiments examining the effects on hippocampal long-term potentiation (LTP). hSyn–HM3D impaired LTP and hSyn–HM4D facilitated LTP. Follow-up experiments indicated that the hSyn–HM3D-mediated depression of fEPSP appears to be driven by presynaptic activation of inhibitory currents, whereas the hSyn–HM4D-mediated increase of fEPSP is induced by a reduction in GABAAreceptor function. To determine whether these observations were promoter specific, we next examined the effects of using the CaMKIIα promoter that limits expression to forebrain excitatory neurons. CaMKIIα–HM3D in the dorsal hippocampus led to the transformation of a subthreshold learning event into LTM, whereas CaMKIIα–HM4D blocked LTM formation. Consistent with these findings, baseline synaptic transmission and LTP was increased in CaMKIIα–HM3D hippocampal slices, whereas slices from CaMKIIα–HM4D mice produced expected decreases in baseline synaptic transmission and LTP. Together, these experiments further demonstrate DREADDs as being a robust and reliable means of modulating neuronal function to manipulate long-term changes in behavior, while providing evidence for specific dissociations between LTM and LTP.SIGNIFICANCE STATEMENTThis study evaluates the efficacy of designer receptors exclusively activated by designer drug (DREADDs) as a means of bidirectionally modulating the hippocampus in not only a hippocampus-dependent task but also in hippocampal synaptic plasticity. This is the first study to evaluate the effects of DREADD-mediated inhibition and excitation in hippocampal long-term potentiation. More specifically, this study evaluates the effect of promoter-specific expression of DREADD viruses in a heterogenic cell population, which revealed surprising effects of different promoters. With chemogenetics becoming a more ubiquitous tool throughout studies investigating circuit-specific function, these data are of broad interest to the neuroscientific community because we have shown that promoter-specific effects can drastically alter synaptic function within a specific region, without parallel changes at the level of behavior.
Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington's Disease Model Mice
Authors: Jiang Ruotian , Diaz-Castro Blanca , Looger Loren L. , Khakh Baljit S. 
Published: March 2016

Astrocytes tile the entire CNS, but their functions within neural circuits in health and disease remain incompletely understood. We used genetically encoded Ca2+and glutamate indicators to explore the rules for astrocyte engagement in the corticostriatal circuit of adult wild-type (WT) and Huntington's disease (HD) model mice at ages not accompanied by overt astrogliosis (at approximately postnatal days 70–80). WT striatal astrocytes displayed extensive spontaneous Ca2+signals, but did not respond to cortical stimulation, implying that astrocytes were largely disengaged from cortical input in healthy tissue. In contrast, in HD model mice, spontaneous Ca2+signals were significantly reduced in frequency, duration, and amplitude, but astrocytes responded robustly to cortical stimulation with evoked Ca2+signals. These action-potential-dependent astrocyte Ca2+signals were mediated by neuronal glutamate release during cortical stimulation, accompanied by prolonged extracellular glutamate levels near astrocytes and tightly gated by Glt1 glutamate transporters. Moreover, dysfunctional Ca2+and glutamate signaling that was observed in HD model mice was largely, but not completely, rescued by astrocyte specific restoration of Kir4.1, emphasizing the important contributions of K+homeostatic mechanisms that are known to be reduced in HD model mice. Overall, our data show that astrocyte engagement in the corticostriatal circuit is markedly altered in HD. Such prodromal astrocyte dysfunctions may represent novel therapeutic targets in HD and other brain disorders.SIGNIFICANCE STATEMENTWe report how early-onset astrocyte dysfunction without detectable astrogliosis drives disease-related processes in a mouse model of Huntington's disease (HD). The cellular mechanisms involve astrocyte homeostasis and signaling mediated by Kir4.1, Glt1, and Ca2+. The data show that the rules for astrocyte engagement in a neuronal circuit are fundamentally altered in a brain disease caused by a known molecular defect and that fixing early homeostasis dysfunction remedies additional cellular deficits. Overall, our data suggest that key aspects of altered striatal function associated with HD may be triggered, at least in part, by dysfunctional astrocytes, thereby providing details of an emerging striatal microcircuit mechanism in HD. Such prodromal changes in astrocytes may represent novel therapeutic targets.
Agonist-Specific Recruitment of Arrestin Isoforms Differentially Modify Delta Opioid Receptor Function
Authors: Pradhan Amynah A. , Perroy Julie , Walwyn Wendy M. , Smith Monique L. , Vicente-Sanchez Ana , Segura Laura , Bana Alia , Kieffer Brigitte L. , Evans Christopher J. 
Published: March 2016

Ligand-specific recruitment of arrestins facilitates functional selectivity of G-protein-coupled receptor signaling. Here, we describe agonist-selective recruitment of different arrestin isoforms to the delta opioid receptor in mice. A high-internalizing delta opioid receptor agonist (SNC80) preferentially recruited arrestin 2 and, in arrestin 2 knock-outs (KOs), we observed a significant increase in the potency of SNC80 to inhibit mechanical hyperalgesia and decreased acute tolerance. In contrast, the low-internalizing delta agonists (ARM390, JNJ20788560) preferentially recruited arrestin 3 with unaltered behavioral effects in arrestin 2 KOs. Surprisingly, arrestin 3 KO revealed an acute tolerance to these low-internalizing agonists, an effect never observed in wild-type animals. Furthermore, we examined delta opioid receptor–Ca2+channel coupling in dorsal root ganglia desensitized by ARM390 and the rate of resensitization was correspondingly decreased in arrestin 3 KOs. Live-cell imaging in HEK293 cells revealed that delta opioid receptors are in pre-engaged complexes with arrestin 3 at the cell membrane and that ARM390 strengthens this membrane interaction. The disruption of these complexes in arrestin 3 KOs likely accounts for the altered responses to low-internalizing agonists. Together, our results show agonist-selective recruitment of arrestin isoforms and reveal a novel endogenous role of arrestin 3 as a facilitator of resensitization and an inhibitor of tolerance mechanisms.SIGNIFICANCE STATEMENTAgonists that bind to the same receptor can produce highly distinct signaling events and arrestins are a major mediator of this ligand bias. Here, we demonstrate that delta opioid receptor agonists differentially recruit arrestin isoforms. We found that the high-internalizing agonist SNC80 preferentially recruits arrestin 2 and knock-out (KO) of this protein results in increased efficacy of SNC80. In contrast, low-internalizing agonists (ARM390 and JNJ20788560) preferentially recruit arrestin 3 and, surprisingly, KO of arrestin 3 produces acute tolerance and impaired receptor resensitization to these agonists. Arrestin 3 is in pre-engaged complexes with the delta opioid receptor at the cell membrane and low-internalizing agonists promote this interaction. This study reveals a novel role for arrestin 3 as a facilitator of receptor resensitization.
Effect of age and social connection on perceived anxiety over radiation exposure among decontamination workers in Fukushima Prefecture, Japan
Authors: Hidaka Tomoo , Kakamu Takeyasu , Hayakawa Takehito , Kumagai Tomohiro , Jinnouchi Takanobu , Sato Sei , Tsuji Masayoshi , Nakano Shinichi , Koyama Kikuo , Fukushima Tetsuhito 
Published: March 2016

ObjectivesTo reveal the effect of age and other factors on perceived anxiety over radiation exposure among decontamination workers in Fukushima Prefecture, Japan.MethodsAsurvey questionnaire was sent to 1505 workers, with questions regarding age, presence of a written employment contract, previous residence, radiation passbook ownership, presence of close persons for consultation, knowledge of how to access public assistance, and a four‐point scale of radiation‐related anxiety (1 = “ Very much, ” 2 = “ Somewhat,” 3=“A little bit,” and 4=“None”). The relationships between the degree of anxiety and variables were analyzed using the chi‐square test and residual analysis.ResultsIn all, 512 participants responded to the questionnaire. The mean age of participants was 46.2 years (SD: 13.1, range: 18‐77). Of them, 50, 233, 168, and 61 workers chose “Very much,” “Somewhat,” “A little bit,” and “None, ” respectively, on the anxiety scale. Chi‐square test showed that participants aged 61 years and over had higher degrees of anxiety (p<0.001). Ordinal logistic regression showed that the degree of anxiety increased if they did not have a written contract (p =0.042) or persons to consult (p=0.034) and if they routinely checked the dose rate (p=0.046).ConclusionsDecontamination workers who do not have a written contract or who are in socially isolated situations have greater anxiety over radiation exposure. Thus, it is important to both create supportive human relationships for consultation and enhance labor management in individual companies.
Effects of occupational illness on labor productivity: A socioeconomic aspect of informal sector workers in urban Bangladesh
Authors: Sarker Abdur Razzaque , Sultana Marufa , Mahumud Rashidul Alam , Ahmed Sayem , Ahmed Mohammad Wahid , Hoque Mohammad Enamul , Islam Ziaul , Gazi Rukhsana , Khan Jahangir A.M. 
Published: March 2016

ObjectivesThe informal sector is the dominant area of employment and the economy for any developing country including Bangladesh. The cost of productivity loss due to absence from work or presenteeism with illness has rarely been examined in the Bangladesh context. This current study, therefore, attempted to examine the impact of ill health of informal sector workers on labor productivity, future earning, and healthcare‐related expenditure.MethodologyA cross‐sectional survey was conducted among three occupational groups of informal workers (rickshaw pullers, shopkeepers and restaurant workers) that were generally found in all urban areas in Bangladesh. A total of 557 informal workers were surveyed for this study.ResultsMost of the respondents (57%) reported that they had been affected by some type of illness for the last six months. The overall average healthcare expenditure of informal workers was US $48.34, while restaurant workers expended more (US$53.61) . Self reported sickness absenteeism was highest (50.37days) in the case of shop keepers, followed by rickshaw pullers (49.31 days), in the last six months. Considering the income loss due to illness in the past six months, the rickshaw pullers were exposed to the highest income loss (US$197.15), followed by the shop keepers (US$151.39).ConclusionsAlthough the informal sector contributes the most to the economy of Bangladesh, the workers in this sector have hardly any financial protection. This study provides critical clues to providing financial and social protection to informal sector workers in Bangladesh.
Current prevalence rate of latex allergy: Why it remains a problem?
Authors: Wu Miaozong , McIntosh James , Liu Jian 
Published: March 2016

ObjectivesThis article aims to review the current prevalence rate of latex allergy among healthcare workers, susceptible patients, and the general public, and to investigate why latex is still a ubiquitous occupational health hazard.MethodsScientific publications on PubMed, particularly those published within the last five years, and current regulations from agencies such as Food and Drug Administration (FDA) were reviewed. Consumer and commercial products that may contain latex were also surveyed.ResultsApproximately 12 million tons of natural rubber latex is produced annually and is widely used to manufacture millions of consumer and commercial products. Only limited number of latexderived products have been approved and regulated by government agencies, such as FDA, whereas the majority of finished products do not label whether they contain latex. Owing to millions of unidentifiable products containing latex and many routes for exposure to latex, preventing contact with latex allergens and reducing the prevalence of latex allergy are more difficult than expected. Reported data suggest that the average prevalence of latex allergy worldwide remains 9.7%, 7.2%, and 4.3% among healthcare workers, susceptible patients, and general population, respectively.ConclusionsLatex‐derived products are ubiquitous, and latex allergy remains a highly prevalent health risk in many occupations and to the general population. Developing alternative materials and increasing the ability to identify and label latex‐derived products will be practicable approaches to effectively control the health risks associated with latex.
Rapid Recovery Pathway After Spinal Fusion for Idiopathic Scoliosis
Authors: Muhly Wallis T. , Sankar Wudbhav N. , Ryan Kelly , Norton Annette , Maxwell Lynne G. , DiMaggio Theresa , Farrell Sharon , Hughes Rachel , Gornitzky Alex , Keren Ron , McCloskey John J. , Flynn John M. 
Published: March 2016

BACKGROUND:
Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is associated with significant pain and prolonged hospitalization. There is evidence that early mobilization and multimodal analgesia can accelerate functional recovery and reduced length of stay (LOS). Using these principles, we implemented a quality improvement initiative to enable earlier functional recovery in our AIS–PSF population.

METHODS:
We designed and implemented a standardized rapid recovery pathway (RRP) with evidence-based management recommendations for children aged 10 to 21 years undergoing PSF for AIS. Our primary outcome, functional recovery, was assessed using statistical process control charts for LOS and average daily pain scores. Our process measures were medication adherence and order set utilization. The balancing measure was 30-day readmission rate.

RESULTS:
We included 322 patients from January 1, 2011 to June 30, 2015 with 134 (42%) serving as historical controls, 104 (32%) representing our transition population, and 84 (26%) serving as our RRP population. Baseline average LOS was 5.7 days and decreased to 4 days after RRP implementation. Average daily pain scores remained stable with improvement on postoperative day 0 (3.8 vs 4.9 days) and 1 (3.8 vs 5 days) after RRP implementation. In the second quarter of 2015, gabapentin (91%) and ketorolac (95%) use became routine and order set utilization was 100%. Readmission rates did not increase as a result of this pathway.

CONCLUSIONS:
Implementation of a standardized RRP with multimodal pain management and early mobilization strategies resulted in reduced LOS without an increase in reported pain scores or readmissions.
Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies
Authors: Yip Steven M. , Heng Daniel Y.C. , Tang Patricia A. 
Published: March 2016

Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI) on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2), and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.
Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist
Authors: Maus Marcela V. , Levine Bruce L. 
Published: March 2016

AbstractThe field of cancer immunotherapy has rapidly progressed in the past decade as several therapeutic modalities have entered into the clinic. One such immunotherapy that has shown promise in the treatment of cancer is the use of chimeric antigen receptor (CAR)-modified T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T-cell signaling and costimulatory domains that can be used to reprogram a patient’s T cells to specifically target tumor cells. CAR T-cell therapy has demonstrated sustained complete responses for some patients with advanced leukemia, and a number of CAR therapies are being evaluated in clinical studies. CAR T-cell therapy-associated toxicities, including cytokine release syndrome, macrophage activation syndrome, and tumor lysis syndrome, have been observed and effectively managed in the clinic. In patients with significant clinical responses, sustained B-cell aplasia has also been observed and is a marker of CAR T-cell persistence that might provide long-term disease control. Education on CAR T-cell therapy efficacy and safety management is critical for clinicians and patients who are considering this novel type of treatment. In the present report, the current landscape of CAR T-cell therapy, the effective management of patients undergoing treatment, and which patients are the most suitable candidates for current trials are discussed.
White Matter Injury in Premature Newborns
Authors: Gano Dawn 
Published: March 2016

AbstractPreterm newborns are highly susceptible to brain injury. White matter injury is among the dominant patterns of brain injury in preterm newborns. The purpose of this review is to discuss the pathogenesis, diagnosis, management, and prevention of white matter injury in premature newborns. The long-term outcome of white matter injury in children born prematurely is also addressed.
UN ENFOQUE ESTRATÉGICO PARA LA GESTIÓN DEL CONOCIMIENTO EN LA UNIVERSIDAD. LA EXPERIENCIA DE LA UNIVERSIDAD PERUANA DE CIENCIAS APLICADAS (UPC)
Authors: Morgan Rozas Milagros , Sulmont Haak Lea 
Published: March 2016

sociedad de la información a la sociedad del conocimiento. Para afrontar esta tarea, la Universidad Peruana de Ciencias Aplicadas (UPC) considera necesario gestionar y valorar los contenidos académicos producidos por sus docentes e investigadores, ya que reconoce que el compartir dichos contenidos es un mecanismo importante para la creación y difusión del conocimiento. La implementación de DELFOS (2005), el Gestor de Contenidos Digitales de la UPC, refleja un esfuerzo por mejorar la gestión del conocimiento mediante la integración de tecnologías. Del mismo modo, dicha implementación resulta importante en la medida en que testimonia un cambio cultural en la organización, en la que docentes y alumnos están aprendiendo a crear y a compartir el conocimiento. El presente trabajo, por tanto, plantea un análisis de la experiencia de gestión del conocimiento de la UPC desde tres frentes: organizacional, tecnológico y pedagógico.
DESERCIÓN UNIVERSITARIA EN ESTUDIANTES DE UNA UNIVERSIDAD PRIVADA DE IQUITOS
Authors: Mori Sánchez Maria del Pilar 
Published: March 2016

El problema de deserción universitaria es complejo e incluye diversas causas. En este artículo se busca describir las razones que explican el fenómeno de la deserción universitaria en una universidad privada de la ciudad de Iquitos. La muestra estuvo conformada por 88 jóvenes que abandonaron los estudios en aquella universidad; sus edades fluctuaron entre los 18 y 25 años de edad; de ellos, el 42% fueron mujeres y el 58% fueron varones. En el presente trabajo, se analizan los datos obtenidos de los grupos focales, de las entrevistas y de la sistematización de la documentación existente. Los resultados muestran que las características institucionales serían el primer factor de deserción, seguido de los intereses vocacionales, los académicos y, finalmente, los económicos.