bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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.
Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators
Authors: Qiu Jinsong , Zhou Bing , Thol Felicitas , Zhou Yu , Chen Liang , Shao Changwei , DeBoever Christopher , Hou Jiayi , Li Hairi , Chaturvedi Anuhar , Ganser Arnold , Bejar Rafael , Zhang Dong-Er , Fu Xiang-Dong , Heuser Michael
Published: August 2016

Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders with prevalent mutations in several splicing factors, but the splicing programs linked to specific mutations or MDS in general remain to be systematically defined. We applied RASL-seq, a sensitive and cost-effective platform, to interrogate 5502 annotated splicing events in 169 samples from MDS patients or healthy individuals. We found that splicing signatures associated with normal hematopoietic lineages are largely related to cell signaling and differentiation programs, whereas MDS-linked signatures are primarily involved in cell cycle control and DNA damage responses. Despite the shared roles of affected splicing factors in the 3′ splice site definition, mutations in U2AF1, SRSF2, and SF3B1 affect divergent splicing programs, and interestingly, the affected genes fall into converging cancer-related pathways. A risk score derived from 11 splicing events appears to be independently associated with an MDS prognosis and AML transformation, suggesting potential clinical relevance of altered splicing patterns in MDS.
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.
Synthesis, characterization and toxicity studies of pyridinecarboxaldehydes and L-tryptophan derived Schiff bases and corresponding copper (II) complexes
Authors: Malakyan Margarita , Babayan Nelly , Grigoryan Ruzanna , Sarkisyan Natalya , Tonoyan Vahan , Tadevosyan Davit , Matosyan Vladimir , Aroutiounian Rouben , Arakelyan Arsen
Published: August 2016

Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro. The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold.
ECG of the month
Authors: Regan Martin
Published: August 2016

Martin Regan presents an ECG for you to analyse
The mandate for change or the emperor's new clothing?
Authors: Peate Ian
Published: August 2016

In England, the Chief Allied Health Professions Officer has been encouraging allied health professionals to engage in sharing their views and having their say with regards to an emerging mandate for change. However, Ian Peate warns that engaging with these participants and failing to take into account current feeling within the NHS will amount to empty rhetoric.
What the ambulance service ought to be
Authors: Davis David
Published: August 2016

David Davis, founder and chairman of The Larrey Society, outlines Professor Douglas Chamberlain's future vision of the ambulance service, as outlined in the inaugural Larrey Lecture.
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

The 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

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.
Transcatheter Aortic Valve-in-Valve Replacement Instead of a 4th Sternotomy in a 21-Year-Old Woman with Aortic Homograft Failure
Authors: Díez José G. , Schechter Michael , Dougherty Kathryn G. , Preventza Ourania , Coselli Joseph S.
Published: August 2016

Transcatheter aortic valve replacement (TAVR) is a well-established method for replacing native aortic valves; however, it was conceived for elderly patients with aortic valve stenosis, and the lack of data on long-term durability has led practitioners to restrict the use of TAVR to patients who have short life expectancies. Here, we describe the case of a 21-year-old woman who had undergone 3 previous open aortic valve replacements and who presented with symptoms of recurrent valvular failure. Transthoracic echocardiograms and computed tomographic angiograms revealed a degenerating aortic root homograft with substantial calcification, moderate-to-severe aortic valve stenosis, and severe aortic valve regurgitation. Open surgical valve replacement posed substantial risk to our patient, so we decided to perform valve-in-valve TAVR with use of the Edwards Sapien XT Transcatheter Heart Valve. The patient's pulmonary artery pressure, valvular regurgitation, and symptoms improved substantially thereafter. We found that valve-in-valve TAVR into a failing aortic root homograft was less invasive than repeat surgical valve replacement in this young patient who had congenital vascular anomalies and a complex surgical history.
Coronary–Cameral Fistula Caused by Guidewire Trauma and Resolved by Coil Embolization
Authors: Banerjee Suvro , Patra Soumya
Published: August 2016

A 57-year-old woman presented with effort angina. A coronary angiogram revealed critical 2-vessel disease, for which she subsequently underwent percutaneous coronary intervention. During angioplasty, a coronary guidewire—inadvertently passed into the right ventricle through the septal branches of the posterior descending coronary artery—caused a coronary artery-to-right ventricular fistula. This fistula was successfully closed percutaneously by coil embolization. To our knowledge, this is the first report of a case in which a coronary artery-to-right ventricular fistula caused by a guidewire was managed successfully by coil embolization.
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.
Advanced Interventional Therapy for Radiation-Induced Cardiovascular Disease
Authors: Nieto Daisy C.
Published: August 2016

This report describes the case of a 61-year-old woman who presented with dyspnea, aortic stenosis, and coronary artery disease—typical side effects of radiation therapy for Hodgkin lymphoma. A poor candidate for surgery, she underwent successful high-risk percutaneous coronary intervention and subsequent transcatheter aortic valve replacement. This report highlights some of the cardiovascular-specific sequelae of radiation therapy for cancer treatment; in addition, possible directions for future investigations are discussed.
Parallel evaluation of multi-semi-joins
Authors: Daenen Jonny , Neven Frank , Tan Tony , Vansummeren Stijn
Published: August 2016

While services such as Amazon AWS make computing power abundantly available, adding more computing nodes can incur high costs in, for instance, pay-as-you-go plans while not always significantly improving the net running time (aka wall-clock time) of queries. In this work, we provide algorithms for parallel evaluation of SGF queries in MapReduce that optimize total time, while retaining low net time. Not only can SGF queries specify all semi-join reducers, but also more expressive queries involving disjunction and negation. Since SGF queries can be seen as Boolean combinations of (potentially nested) semi-joins, we introduce a novel multi-semi-join (MSJ) MapReduce operator that enables the evaluation of a set of semi-joins in one job. We use this operator to obtain parallel query plans for SGF queries that outvalue sequential plans w.r.t. net time and provide additional optimizations aimed at minimizing total time without severely affecting net time. Even though the latter optimizations are NP-hard, we present effective greedy algorithms. Our experiments, conducted using our own implementation Gumbo on top of Hadoop, confirm the usefulness of parallel query plans, and the effectiveness and scalability of our optimizations, all with a significant improvement over Pig and Hive.
META
Authors: Deng Dong , Li Guoliang , Wen He , Jagadish H. V. , Feng Jianhua
Published: August 2016

Autocompletion has been widely adopted in many computing systems because it can instantly provide users with results as users type in queries. Since the typing task is tedious and prone to error, especially on mobile devices, a recent trend is to tolerate errors in autocompletion. Existing error-tolerant autocompletion methods build a trie to index the data, utilize the trie index to compute the trie nodes that are similar to the query, called active nodes, and identify the leaf descendants of active nodes as the results. However these methods have two limitations. First, they involve many redundant computations to identify the active nodes. Second, they do not support top-
k
queries. To address these problems, we propose a matching-based framework, which computes the answers based on matching characters between queries and data. We design a compact tree index to maintain active nodes in order to avoid the redundant computations. We devise an incremental method to efficiently answer top-
k
queries. Experimental results on real datasets show that our method outperforms state-of-the-art approaches by 1--2 orders of magnitude.
Analysis of Family Structures Reveals Robustness or Sensitivity of Bursting Activity to Parameter Variations in a Half-Center Oscillator (HCO) Model
Authors: Doloc-Mihu Anca , Calabrese Ronald L.
Published: August 2016

The underlying mechanisms that support robustness in neuronal networks are as yet unknown. However, recent studies provide evidence that neuronal networks are robust to natural variations, modulation, and environmental perturbations of parameters, such as maximal conductances of intrinsic membrane and synaptic currents. Here we sought a method for assessing robustness, which might easily be applied to large brute-force databases of model instances. Starting with groups of instances with appropriate activity (e.g., tonic spiking), our method classifies instances into much smaller subgroups, called families, in which all members vary only by the one parameter that defines the family. By analyzing the structures of families, we developed measures of robustness for activity type. Then, we applied these measures to our previously developed model database, HCO-db, of a two-neuron half-center oscillator (HCO), a neuronal microcircuit from the leech heartbeat central pattern generator where the appropriate activity type is alternating bursting. In HCO-db, the maximal conductances of five intrinsic and two synaptic currents were varied over eight values (leak reversal potential also varied, five values). We focused on how variations of particular conductance parameters maintain normal alternating bursting activity while still allowing for functional modulation of period and spike frequency. We explored the trade-off between robustness of activity type and desirable change in activity characteristics when intrinsic conductances are altered and identified the hyperpolarization-activated (h) current as an ideal target for modulation. We also identified ensembles of model instances that closely approximate physiological activity and can be used in future modeling studies.
Dynamic Capabilities and Organizational Agility: Risk, Uncertainty, and Strategy in the Innovation Economy
Authors: Teece David , Peteraf Margaret , Leih Sohvi
Published: August 2016

“Organizational agility” is often treated as an immutable quality, implying that firms need to be in a constant state of transformation. However, this ignores that such transformations, while often essential, come at a cost. They are not always necessary, and may not even be possible. This article explores agility at a more fundamental level and relates it more specifically to dynamic capabilities. It demonstrates that it is first essential to understand deep uncertainty, which is ubiquitous in the innovation economy. Uncertainty is very different from risk, which can be managed using traditional tools and approaches. Strong dynamic capabilities are necessary for fostering the organizational agility necessary to address deep uncertainty, such as that generated by innovation and the associated dynamic competition. This article explores the mechanisms by which managers may calibrate the required level of organizational agility, deliver it cost effectively, and relate it to strategy.
How Do Firms Adapt to Discontinuous Change? Bridging the Dynamic Capabilities and Ambidexterity Perspectives
Authors: Birkinshaw Julian , Zimmermann Alexander , Raisch Sebastian
Published: August 2016

This article develops a conceptual integration of the dynamic capabilities and ambidexterity perspectives in order to understand how firms adapt to discontinuous change. Based on three illustrative case studies, it demonstrates that it is not possible to identify a universal set of dynamic capabilities. Rather, the distinct set of capabilities required depends on which of three modes of adaptation (structural separation, behavioral integration, or sequential alternation) has been prioritized. This article contributes a contingency perspective to dynamic capability research and offers guidance to managers about the alternative approaches they could take when seeking to adapt to environmental discontinuities.
Adapting to Fast-Changing Markets and Technologies
Authors: Day George S. , Schoemaker Paul J.H.
Published: August 2016

The dynamic capabilities framework identifies three components as critical for successful organizational adaptation: sensing, seizing and transforming. By contrasting two distinct business cases, a long-term biofuel investment by DuPont and Novartis's rapid deployment of digital technologies in marketing, this article assesses the managerial implications of each of these components. It develops an embryonic contingency model that illustrates why the relative importance of dynamic capabilities varies across firms. The article also highlights the critical role played by strategic leaders, who must selectively adapt and refine dynamic capabilities and also serve as a last line of defense in times of rapid change.
Generative Sensing: A Design Perspective on the Microfoundations of Sensing Capabilities
Authors: Dong Andy , Garbuio Massimo , Lovallo Dan
Published: August 2016

The ability to sense valuable strategic options and then to organize effectively and efficiently to embrace them is at the core of a company's dynamic capabilities. This article identifies and discusses a specific type of sensing that we call “generative sensing.” Companies and executives that display generative sensing capabilities proactively generate hypotheses about observed events and then test these hypotheses to generate new data in a recursive process. Borrowing from design cognition research, we discuss the two microfoundations of these capabilities—framing and abduction – and provide examples of how they are embedded in companies to enhance option generation.
AMPK-dependent regulation of GLP1 expression in L-like cells
Authors: Jiang Sushi , Zhai Hening , Li Danjie , Huang Jiana , Zhang Heng , Li Ziru , Zhang Weizhen , Xu Geyang
Published: August 2016

This study examined whether AMPK, an evolutionarily conserved sensor of cellular energy status, determines the production of glucagon-like peptide-1 (GLP1). A negative relation existed between phosphorylation of AMPKα and the expression and secretion of GLP1 during changes in energy status in STC-1 cells, an L-like cell line. High concentration of glucose (25 mmol/L) decreased AMPKα phosphorylation, whereas it stimulated the expression and secretion of GLP1 relative to 5.6 mmol/L glucose. Serum starvation upregulated AMPKα phosphorylation, whereas it reduced GLP1 production significantly. Stimulation of AMPK phosphorylation by AICAR and overexpression of wild-type AMPKα1, constitutively active AMPKα1 plasmids, or AMPKα1 lentivirus particles suppressed proglucagon mRNA and protein contents in STC-1 cells. Inactivation of AMPK by Compound C, AMPKα1 siRNA or kinase-inactive AMPKα1 mutant increased the expression and secretion of GLP1. Our results suggest that AMPKα1 may link energy supply with the production of GLP1 in L-like cells.
Ovarian tissue transport to expand access to fertility preservation: from animals to clinical practice
Authors: Duncan Francesca E , Zelinski Mary , Gunn Alexander H , Pahnke Jennifer E , O’Neill Conor L , Songsasen Nucharin , Woodruff Ryan I , Woodruff Teresa K
Published: August 2016

Primordial follicles dictate a female’s reproductive life span and therefore are central to fertility preservation for both endangered species and individuals with fertility-threatening conditions. Ovarian tissue containing primordial follicles can be cryopreserved and later thawed and transplanted back into individuals to restore both endocrine function and fertility. Importantly, increasing numbers of human live births have been reported following ovarian tissue cryopreservation and transplantation. A current limitation of this technology is patient access to sites that are approved or equipped to process and cryopreserve ovarian tissue – especially in larger countries or low resource settings. Here, we review empirical evidence from both animal models and human studies that suggest that ovarian tissue can be transported at cold temperatures for several hours while still maintaining the integrity and reproductive potential of the primordial follicles within the tissue. In fact, several human live births have been reported in European countries using tissue that was transported at cold temperatures for up to 20 h before cryopreservation and transplantation. Ovarian tissue transport, if implemented widely in clinical practice, could therefore expand both patient and provider access to emerging fertility preservation options.
The relationship between subjective well-being and empathy among Turkish medical students
Authors: Ozcakir Alis , Ediz Bulent , Bilgel Nazan
Published: August 2016

This article was migrated. The article was not marked as recommended. Background: Empathy as a part of humanistic medicine is an important component of medical education and could be taught throughout the years of medical study. In Turkey the national core medical curriculum is somewhat insufficient in terms of teaching empathy. In this study we wanted to measure empathy and to determine if there is a relationship between subjective well-being and empathy. Material & Methods: We used the Jefferson Scale of Empathy to measure empathy, Depression Anxiety and Stress Scales and the Oxford Happiness Questionnaire to measure the subjective well-being. Participants were first, third and sixth year (final-year) medical students. The total number of participants was 600 which represented 71.1% of the students of the corresponding medical school. Results: The mean empathy scores of Turkish students were found to be lower than of their counterparts in the Western countries. Female students had significantly higher scores than male students and there was a decline in empathy with increasing class-years. We found a significant positive relationship between happiness and empathy. Conclusions: Teaching empathy through the development of a new medical curriculum with a more humanistic approach should be a concern of medical schools in Turkey.
Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The Biologic Context
Authors: Leonhard Wouter N. , Happe Hester , Peters Dorien J.M.
Published: August 2016

Patients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys. However, the large intrafamilial variation in the progression rate of ADPKD suggests involvement of additional factors other than the type of mutation. The identification of these factors will increase our understanding of ADPKD and could ultimately help in the development of a clinically relevant therapy. Our review addresses the mechanisms by which various biologic processes influence cyst formation and cyst growth, thereby explaining an important part of the inter- and intrafamilial variability in ADPKD. Numerous studies from many laboratories provide compelling evidence for the influence on cyst formation by spatiotemporal gene inactivation, the genetic context, the metabolic status, the presence of existing cysts, and whether the kidneys were challenged by renal injury. Collectively, a solid basis is provided for the concept that the probability of cyst formation is determined by functional PKD protein levels and the biologic context. We model these findings in a graphic representation called the cystic probability landscape, providing a robust conceptual understanding of why cells sometimes do or do not form cysts.
International Portfolio Investment Holdings of Long-term Securities in the Enhanced Financial Accounts
Authors: Yook Youngsuk , Holmquist Elizabeth , Miller Max
Published: August 2016

This note and associated website provide new detail on international portfolio investment holdings of long-term securities, as part of the Enhanced Financial Accounts (EFA) initiative.
Dynamics of ultrastructural changes in the chorioretinal complex of rat eyes induced by high dose of methanol
Authors: Molchanyuk N.
Published: August 2016

The structure of chorioretinal complex (CRC) of rat eyes was studied by electron microscopy: choriocapillaris, retinal pigment epithelium (RPE) and retinal photoreceptor cells after 40 minutes, 1 hour and 10 minutes, on the first 1 st , 3 rd , 7 th and 14 th days after a single intraperitoneal injection of methanol in a dose of 7.0 g/kg of body weight. It was shown that the primary and significant destructive changes in the structures of the studied complex were observed in the RPE cells, which are characterized by alteration of mitochondria and tubules of smooth endoplasmic reticulum, equation of basal folds and local destruction of the apical microvilli. The destructive processes in the cells were growing in the dynamics of CRC structures research. In parallel, the features of compensatory-regenerative processes in these cells were detected.
Advances in chemistry of chromone aminomethyl derivatives
Authors: Mrug Galyna , Frasinyuk Mykhaylo
Published: August 2016

Chromones play an important role in the design and discovery of new pharmacologically active compounds. A large volume of reports dedicated to synthesis and study of properties of nitrogen-containing chromone derivatives show important role of chromone alkaloid-like compounds. The present review covers achievements in the field of synthesis of chromone aminomethyl derivatives as one of perspective scaffolds.
Avaliação da educação infantil: aportes de iniciativas estrangeiras
Authors: Sousa Sandra Zákia , Pimenta Cláudia Oliveira
Published: August 2016

Com base em pesquisa documental, são caracterizadas iniciativas estrangeiras de avaliação e de credenciamento de instituições de educação infantil quanto aos seus propósitos e sua operacionalização. São ainda reunidos resultados de estudos de pesquisadores brasileiros que têm recorrido às iniciativas de outros países para analisar a qualidade da educação infantil em contextos nacionais. Foram selecionadas proposições que se mostram potencialmente capazes de iluminar delineamentos a serem assumidos no Brasil, no âmbito da gestão pública, no que tange à avaliação dessa etapa da educação básica, vindo a dar concretude ao que prevê o Plano Nacional de Educação e ao dever do Estado de garantir educação de qualidade para todos.
Antimicrobial Activity of Lysozyme against Oral Pathogens
Authors: Jesse Joel T. , Suguna S. , Steffi S. R.
Published: August 2016

Saliva contains a number of antimicrobial substances which have their origin either in salivary glands or serum from which they may leak into the mouth via the gingival crevices. Saliva is believed to possess a substantial influence on the aggregates oral pathogens form in the mouth due to the antibodies as well as proteins whose antimicrobial properties do not depend on prior exposure to an antigen. One such enzyme is Lysozyme which is one of the most powerful natural antibacterial and antiviral compounds known to man. According to previous researches, it has been found out that lysozyme may bind and aggregate Gram-positive bacteria such as putative Gram-negative periodontopathic bacteria such as Capnocytophaga gingivalis. This particular study explores the natural phenomenon Lysozyme exhibits against oral microflora with noteworthy conclusions. Saliva samples were collected from the oral cavity of human, cow and dog. From these samples, lysozyme was isolated and purified. Furthermore, the quantity of the enzyme isolated was ascertained by Polyacrylamide Gel Electrophoresis. The quantified enzyme showed 32kDa for cow sample, 23kDa for dog sample and 23kDa for human sample. Finally the antimicrobial activity of the enzyme was determined by agar well diffusion method against Staphylococcus spp. and Enterococcus faecalis. Hence lysozyme in saliva is found to have the antibacterial activity against the pathogen due to the zone of inhibition observed and this proves that a tool to prevent dental decay is available and that there is potential to serve antimicrobial role in the specific application of medical industry.
Review on Ethnomedicinal uses of Memory Boosting Herb, Butterfly Pea, Clitoria ternatea
Authors: Kosai Piya , Sirisidthi Kanjana , Jiraungkoorskul Kanitta , Jiraungkoorskul Wannee
Published: August 2016

Clitoria ternatea (Family: Fabaceae) is one of the traditional medicinal plants used as “Shanka Pushpi” an Ayurvedic medicine used to boost or enhance neurological health. The plant contains alkaloid, flavonoid, taraxerol, taraxerone, triterpenoid and anthocyanin as active chemicals that bring about its biological effects. Its extracts possess a wide range of pharmacological activities including antibacterial, anti-diabetic, anti-diarrheal, anti-fungal, anti-helmintic, anti-inflammatory, antimicrobial, antioxidant, and antipyretic activities, hypolipidemia, immunomodulatory, and wound healing. This review is an attempt to compile information on various ethno medicinal uses of memory boosting herb, butterfly pea, Clitoria ternatea. Conclusion: It has a wide spectrum of neuro pharmacological benefits such as nootropic, anti-depressant, anti-stress, anxiolytic, and anticonvulsant activities.
Preclinical Evaluation of the Enceliacanescens Lam Extract: Medicinal Properties useful for Cancer Treatment
Authors: Cayún Juan P. , Zamorano Javier , Quiñones Luis , Varela Nelson M. , Squicciarini Valentina , Larenas Héctor D. , Cáceres Dante D.
Published: August 2016

Encelia canescens Lam (nv: mancapaqi, mataloba, matalobo, mucle, or “coronilla de fraile”) is a 30-80-cm high shrubby perennial plant that grows in the Atacama and Coquimbo regions of Chile up to 1,700 m above the sea. The present research was performed to examine the toxicological, antioxidant and antitumoural properties of aqueous and ethanol Encelia canescens Lam extracts. Our results revealed the presence of saponins, terpenes, flavonoids, coumarins and tannins. The total phenolic compound contents were 19±1.14 mg/g tannic acid in the aqueous extract and 23±1.60 mg/g tannic acid in the ethanol extract. The total flavonoid contents were 0.15±0.02 mg/g quercetinin the aqueous extract and 0.13±0.06 mg/g quercetinin the ethanol extract. Based on 2,2-diphenyl-1-picrylhydrazyl assays, the antioxidant capacities were 354±23 µmol trolox/100 g of the dry ethanol extract and 303±15 µmol trolox/100 g of the dry aqueous extract. Using 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, the antioxidant capacities were 2,354±568 µmol trolox/100 g of the dry ethanol extract and 1,856±453 µmol trolox/100 g of the aqueous extract. Neither of the extracts exhibited toxicity in the acute topical and oral toxicity tests on the rodents. Antiproliferative studies with cultures of SaOS-2 cells revealed substantial inhibitory effects of both extracts. Moreover, an in vivo antitumour assay revealed that the aqueous extractat a dose of 16 mg/kg x day and the lyophilized extract at a dose of 4 and 8 mg/kg x day efficiently increased the survival of mice with tumours, and the lyophilized extract was able to significantly reduce tumour size at adose of 8 mg/kg x day. Therefore, the results of the present study established that extracts of Encelia canescens Lam have antitumour activities. Considering the properties of Encelia canescens Lam revealed in this preclinical evaluation, clinical studies approved by the health authorities should be performed to examine the efficacy and safety of extracts of this plant in cancer patients.
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).
ESMOLEIROS DO DIVINO ESPÍRITO SANTO: RESSIGNIFICAÇÕES RELIGIOSAS NO CONTEXTO RIONEGRINO; PRODUÇÃO DE FARINHA NO BAIXO TOCANTINS: SABER E TRADIÇÃO
Authors: Sampaio Sully , Valente Thatiane Ferreira , Silva Gilmar Matta da
Published: August 2016

Sully Sampaio; Thatiane Ferreira Valente, Gilmar Matta da Silva
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.
MERCADORIAS E LIVRO: ENTRE FUMO DE RAPÉ E AGUARDENTE, NA BELÉM DO SÉCULO XIX
Authors: SALES Germana Araújo , NOBRE Izenete Garcia
Published: August 2016

Este trabalho objetiva apresentar aos leitores atuais um pouco da história do comércio de livros na Belém da segunda metade do século XIX, observando de que maneira os volumes eram comercializados, quais as principais obras divulgadas e como esse cenário se modificou e se ampliou até a fixação de livreiros na cidade.PALAVRAS- CHAVE: mercado livreiro, romances, história da leitura.
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.
A imagem da mulher no romance afro-brasileiro contemporâneo: Os casos de Conceição Evaristo e Ana Maria Gonçalves
Authors: JAECKEL Volker
Published: August 2016

Na presente comunicação abordaremos as obras de duas autoras contemporâneas de Minas Gerais, que tratam nos seus romances de épocas de rupturas, revoluções e transformações, no que se refere ao papel da mulher negra no Brasil. Trata-se de Becos de Memória (2006) e Ponciá Vicêncio (2003) de Conceição Evaristo, assim como, do romance histórico Um defeito de cor (2006) de Ana Maria Gonçalves. As duas autoras pertencem a uma geração de escritoras que apresenta aos seus leitores discursos sobre protagonistas femininas que sofreram durante um período de sua vida marginalização, perseguição, discriminação e opressão pela sociedade brasileira, por causa de sua origem étnica e social.Palavras-Chave: Romance afro-brasileiro, literatura de memória, história da mulher negra,
As redes femininas de oposição à ditadura civil-militar
Authors: RIBEIRO Maria Cláudia Badan
Published: August 2016

Este artigo pretende dar uma contribuição para se pensar a oposição política de mulheres ao regime militar no Brasil. Nosso objetivo foi mostrar a luta em seu interior, suas tensões e as formas como estas mulheres militantes se moveram sob este contexto para atuar, exigir e transgredir o muro de suas casas tecendo solidariedades e alianças. Suas lutas, compromissos e convicções políticas se forjaram na guerra e no enfrentamento às violências e arbitrariedades cometidas pelo governo repressor. PALAVRAS-CHAVE: Mulheres. Ditadura. Luta armada. Redes de apoio e solidariedade.