bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autocrine IL-10 activation of the STAT3 pathway is required for pathological macrophage differentiation in polycystic kidney disease
Authors: Peda Jacqueline D. , Salah Sally M. , Wallace Darren P. , Fields Patrick E. , Grantham Connor J. , Fields Timothy A. , Swenson-Fields Katherine I. 
Published: August 2016

ABSTRACT
Polycystic kidney disease (PKD) is characterized by slow expansion of fluid-filled cysts derived from tubules within the kidney. Cystic expansion results in injury to surrounding parenchyma and leads to inflammation, scarring and ultimately loss of renal function. Macrophages are a key element in this process, promoting cyst epithelial cell proliferation, cyst expansion and disease progression. Previously, we have shown that the microenvironment established by cystic epithelial cells can ‘program’ macrophages, inducing M2-like macrophage polarization that is characterized by expression of markers that include Arg1 and Il10. Here, we functionally characterize these macrophages, demonstrating that their differentiation enhances their ability to promote cyst cell proliferation. This observation indicates a model of reciprocal pathological interactions between cysts and the innate immune system: cyst epithelial cells promote macrophage polarization to a phenotype that, in turn, is especially efficient in promoting cyst cell proliferation and cyst growth. To better understand the genesis of this macrophage phenotype, we examined the role of IL-10, a regulatory cytokine shown to be important for macrophage-stimulated tissue repair in other settings. Herein, we show that the acquisition of the pathological macrophage phenotype requires IL-10 secretion by the macrophages. Further, we demonstrate a requirement for IL-10-dependent autocrine activation of the STAT3 pathway. These data suggest that the IL-10 pathway in macrophages plays an essential role in the pathological relationship between cysts and the innate immune system in PKD, and thus could be a potential therapeutic target.
A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice
Authors: Coughlan Karen S. , Halang Luise , Woods Ina , Prehn Jochen H. M. 
Published: August 2016

ABSTRACT
Transgenic transactivation response DNA-binding protein 43 (TDP-43) mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS); however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43A315T mice. Similar to our recent results in SOD1G93A mice, TDP-43A315T mice fed a standard pellet diet showed increased 5′ adenosine monophosphate-activated protein kinase (AMPK) activation at postnatal day (P)80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43A315T mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC) at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43A315T model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS.
A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease
Authors: Wolf Heike , Damme Markus , Stroobants Stijn , D'Hooge Rudi , Beck Hans Christian , Hermans-Borgmeyer Irm , Lüllmann-Rauch Renate , Dierks Thomas , Lübke Torben 
Published: August 2016

ABSTRACT
Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.
A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses
Authors: Preininger Marcela K. , Jha Rajneesh , Maxwell Joshua T. , Wu Qingling , Singh Monalisa , Wang Bo , Dalal Aarti , Mceachin Zachary T. , Rossoll Wilfried , Hales Chadwick M. , Fischbach Peter S. , Wagner Mary B. , Xu Chunhui 
Published: August 2016

ABSTRACT
Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs. An individual with CPVT harboring a novel mutation in the type 2 cardiac ryanodine receptor (RyR2) was identified whose persistent ventricular arrhythmias during β-blockade with nadolol were abolished during flecainide treatment. iPSC-CMs generated from this patient and two control individuals expressed comparable levels of excitation-contraction genes, but assessment of the sarcoplasmic reticulum Ca2+ leak and load relationship revealed intracellular Ca2+ homeostasis was altered in the CPVT iPSC-CMs. β-adrenergic stimulation potentiated spontaneous Ca2+ waves and unduly frequent, large and prolonged Ca2+ sparks in CPVT compared with control iPSC-CMs, validating the disease phenotype. Pursuant to the patient's in vivo responses, nadolol treatment during β-adrenergic stimulation achieved negligible reduction of Ca2+ wave frequency and failed to rescue Ca2+ spark defects in CPVT iPSC-CMs. In contrast, flecainide reduced both frequency and amplitude of Ca2+ waves and restored the frequency, width and duration of Ca2+ sparks to baseline levels. By recapitulating the improved response of an individual with CPVT to flecainide compared with β-blocker therapy in vitro, these data provide new evidence that iPSC-CMs can capture basic components of patient-specific drug responses.
Neurosteroids are reduced in diabetic neuropathy and may be associated with the development of neuropathic pain
Authors: Humble Stephen R. 
Published: August 2016

Introduction: Peripheral and central sensitisation are implicated in the development of neuropathic pain. Hypersensitivity of pain pathway neurons has been described in animal models of diabetic neuropathy, which is postulated to be related to an imbalance between inhibitory and excitatory signals within the spinal cord. GABAergic neurons within the pain pathway are vital for the transmission of painful stimuli to higher centres. A developmental change in the rate of exponential decay of GABAergic synaptic events has been observed in other types of neurons and this may be associated with fluctuations in endogenous neurosteroid tone. Methods: The whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from wild type mice between the ages of 6 and 80 days in the spinal cord, the nucleus reticularis of the thalamus and the cerebral cortex. Recordings were also obtained from mice with diabetic neuropathy (ob/ob and db/db) between the ages of 60 and 80 days. Behavioural experiments were performed to examine mechanical and thermal nociception. Results: Electrophysiological recordings from cortical pain pathway neurons from mature type-2 diabetic mice revealed that the endogenous neurosteroid tone is reduced compared to control. However, selected neurosteroid compounds had a more pronounced effect on the GABAA receptors of these diabetic mice. ob/ob mice exhibit mechanical hyperalgesia and allodynia, which was reduced by neurosteroids applied exogenously. Conclusions: The reduced endogenous neurosteroid tone in ob/ob mice may be linked to their hypersensitivity. Neurosteroids may exert analgesic effects in pathological pain states by attempting to restore the physiological GABAergic inhibitory tone.
Paramedics and medicines: legal considerations
Authors: England Ed 
Published: August 2016

This article will cover: The relevant legislation relating to medicines and ambulance services The restrictions that apply to different organisations or individuals regarding the possession of medicines Regulations on the administration and supply of medicines Patient Group Directions and Patient Specific Directions. The law in relation to the possession of medicines, administration to patients and the supply of medicines is separate. This article also provides guidance to ambulance services and ambulance clinicians on available options to ensure good patient access to medicines in England. The laws described also apply in Scotland and Wales but there are some different national processes. The law both enables and restricts access to medicines. However, it does require interpretation and a pharmacist can help with this. Where interpretation is contentious then organisations may obtain a legal opinion. Legal opinions can also differ, and can only be resolved in court.
Three dimensional measurement of minimum joint space width in the knee from stereo radiographs using statistical shape models
Authors: van IJsseldijk E. A. , Valstar E. R. , Stoel B. C. , Nelissen R. G. H. H. , Baka N. , van’t Klooster R. , Kaptein B. L. 
Published: August 2016

Objectives An important measure for the diagnosis and monitoring of knee osteoarthritis is the minimum joint space width (mJSW). This requires accurate alignment of the x-ray beam with the tibial plateau, which may not be accomplished in practice. We investigate the feasibility of a new mJSW measurement method from stereo radiographs using 3D statistical shape models (SSM) and evaluate its sensitivity to changes in the mJSW and its robustness to variations in patient positioning and bone geometry. Materials and Methods A validation study was performed using five cadaver specimens. The actual mJSW was varied and images were acquired with variation in the cadaver positioning. For comparison purposes, the mJSW was also assessed from plain radiographs. To study the influence of SSM model accuracy, the 3D mJSW measurement was repeated with models from the actual bones, obtained from CT scans. Results The SSM-based measurement method was more robust (consistent output for a wide range of input data/consistent output under varying measurement circumstances) than the conventional 2D method, showing that the 3D reconstruction indeed reduces the influence of patient positioning. However, the SSM-based method showed comparable sensitivity to changes in the mJSW with respect to the conventional method. The CT-based measurement was more accurate than the SSM-based measurement (smallest detectable differences 0.55 mm versus 0. 82 mm, respectively). Conclusion The proposed measurement method is not a substitute for the conventional 2D measurement due to limitations in the SSM model accuracy. However, further improvement of the model accuracy and optimisation technique can be obtained. Combined with the promising options for applications using quantitative information on bone morphology, SSM based 3D reconstructions of natural knees are attractive for further development. Cite this article: E. A. van IJsseldijk, E. R. Valstar, B. C. Stoel, R. G. H. H. Nelissen, N. Baka, R. van’t Klooster, B. L. Kaptein. Three dimensional measurement of minimum joint space width in the knee from stereo radiographs using statistical shape models. Bone Joint Res 2016;320–327. DOI: 10.1302/2046-3758.58.2000626.
Un/Paid Labor: Medicaid Home and Community Based Services Waivers That Pay Family as Personal Care Providers
Authors: Friedman Carli , Rizzolo Mary C. 
Published: August 2016

AbstractThe United States long-term services and supports system is built on largely unpaid (informal) labor. There are a number of benefits to allowing family caregivers to serve as paid personal care providers including better health and satisfaction outcomes, expanded workforces, and cost effectiveness. The purpose of this study was to examine how Medicaid HCBS Section 1915(c) waivers for people with intellectual and developmental disabilities allocate personal care services to pay family caregivers. Our analysis revealed about two thirds of waivers in fiscal year (FY) 2014 allowed for family caregivers to potentially be paid for personal care services. This amounted to up to $2.71 billion of projected spending, which is slightly more than half of all personal care service expenditures in FY 2014.
Smith-Magenis Syndrome and Social Security Administration's Compassionate Allowances Initiative: An Evaluative Review of the Literature
Authors: Burke Shanna L. , Maramaldi Peter 
Published: August 2016

Abstract
The Social Security Administration (SSA) launched the Compassionate Allowances List (CAL) in 2008. This created a mechanism for expediting review and delivery of disability benefits, while decreasing application backlog. This study hypothesized that developmental disorders, such as Smith-Magenis syndrome, may meet criterion for inclusion. An evaluative review of the literature was undertaken to determine if the expedited review criterion was met. Ten databases were searched and articles meeting pre-defined criteria were coded according to the SSA definition of disability to determine if severity indices screen in or screen out certain severity levels or exclude Smith-Magenis syndrome entirely in relation to the CAL program. It was strongly recommended that Smith-Magenis syndrome receive consideration for inclusion in the CAL.
Use of an Intravascular Warming Catheter during Off-Pump Coronary Artery Bypass Surgery in a Patient with Severe Cold Hemagglutinin Disease
Authors: Tholpady Ashok , Bracey Arthur W. , Baker Kelty R. , Reul Ross M. , Chen Alice J. 
Published: August 2016

Cold hemagglutinin disease with broad thermal amplitude and high titers presents challenges in treating cardiac-surgery patients. Careful planning is needed to prevent the activation of cold agglutinins and the agglutination of red blood cells as the patient's temperature drops during surgery.
We describe our approach to mitigating cold agglutinin formation in a 77-year-old man with severe cold hemagglutinin disease who underwent off-pump coronary artery bypass surgery without the use of preoperative plasmapheresis. This experience shows that the use of an intravascular warming catheter can maintain normothermia and prevent the activation and subsequent formation of cold agglutinins.
To our knowledge, this is the first reported use of this technique in a patient with cold hemagglutinin disease. The chief feature in this approach is the use of optimal thermal maintenance—rather than the more usual decrease in cold-agglutinin content by means of therapeutic plasma exchange.
The perplexities of ZC3H12A self-mRNA regulation
Authors: Wawro Mateusz , Kochan Jakub , Kasza Aneta 
Published: August 2016

The mechanisms regulating transcripts turnover are key processes in the regulation of gene expression. The list of proteins involved in mRNAs degradation is still growing, however, the details of RNase-mRNAs interaction are not fully understood. ZC3H12A is a recently discovered inflammation-related RNase engaged in the control of proinflammatory cytokines transcripts turnover. ZC3H12A regulates also its own transcript half-live. We studied the details of this regulation. Our results confirm the importance of the 3’UTR in ZC3H12A-dependent ZC3H12A mRNA degradations. We compared mouse and human stem‑loop structures present in this region and discovered that human conserved stem-loop structure is not sufficient for ZC3H12A-dependent degradation. However, this structure is important for ZC3H12A mRNA post-transcriptional regulation. Our studies emphasize the importance of surroundings of the identified stem-loop structure for its biological activity. Removing of this region together with stem-loop structure greatly inhibits ZC3H12A regulation of the investigated 3’-untranslated region (3’UTR).
O AMAZONISMO ACRIANO E OS POVOS INDÍGENAS: REVISITANDO A HISTÓRIA DO ACRE
Authors: Pimenta José 
Published: August 2016

Este artigo reflete sobre o lugar atribuído aos povos indígenas na história oficial do Acre. A partir da ideia de amazonismo, discuto o imaginário ocidental sobre a Amazônia e seus primeiros habitantes, enfatizando sua profunda ambiguidade. Mostro como esse imaginário serviu de guia à conquista do Acre durante o auge da economia extrativista da borrachae como os povos indígenas da região foram inicialmente marginalizados e excluídos da história para exaltar o heroísmo dos colonizadores, só adquirindo visibilidade após sua organização como atores políticos a partir da década de 1970 num novo contexto de colonização da região.Por fim, analiso a situação contemporânea que, apesar de mais favorável aos índios, reinventa uma história idílica e continua reproduzindo os estereótipos ocidentais sobre essas populações.Palavras-Chave: Amazônia, Acre, povos indígenas.
ARQUEOLOGIA DE CONTRATO, COLONIALISMO INTERNO E POVOS INDÍGENAS NO BRASIL
Authors: Oliveira Jorge Eremites de 
Published: August 2016

No presente artigo, o autor analisa as relações entre Arqueologia de Contrato, colonialismo interno e povos indígenas no Brasil desde a década de 1990 até o tempo presente. A discussão está baseada em estudos desenvolvidos na região Centro-Oeste, especialmente no estado de Mato Grosso do Sul. Nesta parte do país ocorrem várias formas de violação dos direitos de povos originários, como a usurpação de territórios tradicionais. Em um contexto assim, a Arqueologia de Contrato tem sido utilizada para o licenciamento socioambiental de empreendimentos que afetam o território e a dinâmica da vida de muitas comunidades indígenas. Além disso, tem sido recorrida no Judiciário para a produção de estudos inconsistentes, do tipo junk science, em defesa dos interesses de setores que são contrários à regularização de territórios indígenas nesta parte da América do Sul.Palavras-chave: Arqueologia do colonialismo; arqueologia de contratono Brasil; direitos indígenas; colonialismo interno; povos indígenas noBrasil.
CENAS DE LEITURA NO CINEMA E NA LITERATURA: UM ESTUDO COMPARATIVO ENTRE “DOM CASMURRO” E “DOM”
Authors: ALVES Marine Souto , GONÇALVES Cláudio do Carmo 
Published: August 2016

Considerando o leitor enquanto sujeito dotado de reações, desejos e vontades, o escritor/ autor busca seduzi-lo e convencê-lo, lançando mão de estratégias que estabeleçam a interatividade entre o narrador construído por este e o seu leitor potencial. Uma das várias dimensões da solidariedade da leitura é que se desenha a partir da representação de situações de leitura e do próprio leitor, recorte que estabelecemos para o presente estudo, cujo objetivo é analisar como as cenas do ato de ler são articuladas na literatura e no cinema. Para tanto, vale- se a investigação do romance “Dom Casmurro” (1899) e sua adaptação para o cinema “Dom” (2003). Tal análise fundamentar-se-á nas reflexões de Wolfgang Iser, Marisa Lajolo, Regina Zilberman, entre outros.PALAVRAS- CHAVE: leitura; literatura; cinema; cenas de leitura; leitor.
Use of Models as Non-destructive Method for Leaf Area Estimation in Horticultural Crops
Authors: Khan F. A. , Banday F. A. , Narayan S. , Khan F. U. , Bhat S. A. 
Published: August 2016

<div><p><em>Leaf area estimation is an important biometrical trait for evaluating leaf development and plant growth analysis in field study of horticultural as well as other species of crop plants. These measurements can be made either destructively and/or non-destructively by using a variety of sensitive instruments as well as models of leaf area estimation. Easy, accurate, cost-effective, and nondestructive methods of leaf area estimation are useful tool in physiological studies related to plant growth and development. The use of regression equations is a nondestructive, simple, quick, accurate, reliable and not expensive method of leaf area estimation. The usual procedure of this method involves measuring length (L), breadth (W) and/or dry mass (M) of a sample of leaves and then calculating the several possible regression coefficients or leaf factors to estimate the area of subsequent leaf samples. Computer programs such as Excel, SAS and SPSS may be used in this process. The paper thrashed out several leaf area estimation models of horticultural crops from the available literature and synthesized in tabular form for the use of researchers. Article also offered some advantages and disadvantages of leaf area estimation models used for analyzing the plant growth and development. </em></p></div>