bluuebunny/crossref_metadata_2025 huggingface dataset:
The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia
Authors: Brumatti Gabriela , Ma Chunyan , Lalaoui Najoua , Nguyen Nhu-Y , Navarro Mario , Tanzer Maria C. , Richmond Jennifer , Ghisi Margherita , Salmon Jessica M. , Silke Natasha , Pomilio Giovanna , Glaser Stefan P. , de Valle Elisha , Gugasyan Raffi , Gurthridge Mark A. , Condon Stephen M. , Johnstone Ricky W. , Lock Richard , Salvesen Guy , Wei Andrew , Vaux David L. , Ekert Paul G. , Silke John
Published: May 2016

The combination of a SMAC mimetic and a caspase inhibitor kills AML cells by inducing necroptosis.
Double or nothing
Authors: Hulbert Monica L.
Published: May 2016

Two-drug targeted therapy could eliminate acute myeloid leukemia, even though the individual drugs are not effective.
Glycogen: Biosynthesis and Regulation
Authors: Preiss Jack
Published: May 2016

Glycogen accumulation occurs in
Escherichia coli
and
Salmonella enterica
serovar Typhimurium as well as in many other bacteria. Glycogen will be formed when there is an excess of carbon under conditions in which growth is limited because of the lack of a growth nutrient, e.g., a nitrogen source. This review describes the enzymatic reactions involved in glycogen synthesis and the allosteric regulation of the first enzyme, ADP-glucose pyrophosphorylase. The properties of the enzymes involved in glycogen synthesis, ADP-glucose pyrophosphorylase, glycogen synthase, and branching enzyme are also characterized. The data describing the genetic regulation of the glycogen synthesis are also presented. An alternate pathway for glycogen synthesis in mycobacteria is also described.
Human Meningitis-Associated
Escherichia coli
Authors: Kim Kwang Sik
Published: May 2016

Escherichia coli
is the most common Gram-negative bacillary organism causing meningitis, and
E. coli
meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of
E. coli
strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using
in vitro
and
in vivo
models of the blood-brain barrier have shown that
E. coli
meningitis follows a high degree of bacteremia and invasion of the blood-brain barrier.
E. coli
invasion of the blood-brain barrier, the essential step in the development of
E. coli
meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to
E. coli
invasion of the blood-brain barrier is shown to be efficient in preventing
E. coli
penetration into the brain. The basis for requiring a high degree of bacteremia for
E. coli
penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high degree of bacteremia and
E. coli
invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of
E. coli
meningitis.
Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice
Authors: Park Soyeong , Park Jung Wook , Pitot Henry C. , Lambert Paul F.
Published: May 2016

Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of
Bi-L E7
transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative.

IMPORTANCE
Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients.
One More Disguise in the Stealth Behavior of Streptococcus pyogenes
Authors: Fischetti Vincent A. , Dale James B.
Published: May 2016

The ability to hide in the animal kingdom is essential for survival; the same is true for bacteria.
Streptococcus pyogenes
is considered one of the more successful stealth bacteria in its production of a hyaluronic acid capsule that is chemically identical to the hyaluronic acid lining human joints. It has also acquired the capacity to enter eukaryotic cells to avoid the onslaught of the host’s immune defenses, as well as drugs. From this intracellular vantage point, it may remain dormant from days to weeks, only to cause disease again at a later time, perhaps causing a relapse in a drug-treated patient. We now learn that it is able to enter macrophages as well, enabling the
Streptococcus
to use this “Trojan horse” approach to be transported to distant sites in the body.
Ebola Virus Disease: Therapeutic and Potential Preventative Opportunities
Authors: Fisher Robert , Borio Luciana
Published: May 2016

The 2014 Ebola virus disease (EVD) epidemic in West Africa was unprecedented in its geographical distribution, scale, and toll on public health infrastructure. Standard public health measures were rapidly overwhelmed, and many projections on outbreak progression through the region were dire. At the beginning of the outbreak there were no treatments or vaccines that had been shown to be safe and effective for treating or preventing EVD, limiting health care providers to offer supportive care under extremely challenging circumstances and at great risk to themselves. Over time, however, drugs and vaccines in the development pipeline were prioritized based on all available research data and were moved forward for evaluation in clinical trials to demonstrate safety and efficacy. The armamentarium against EVD eventually included biologics such as monoclonal antibodies, convalescent plasma, and vaccines as well as small molecule therapeutics such as small interfering RNAs and nucleoside analogs. This article provides a high-level overview of the interventions and prophylactics considered for use in the outbreak and discusses the challenges faced when attempting to deploy investigational countermeasures in the midst of an evolving epidemic.
Bacterial Metabolism Shapes the Host–Pathogen Interface
Authors: Passalacqua Karla D. , Charbonneau Marie-Eve , O’Riordan Mary X.D.
Published: May 2016

Bacterial pathogens have evolved to exploit humans as a rich source of nutrients to support survival and replication. The pathways of bacterial metabolism that permit successful colonization are surprisingly varied and highlight remarkable metabolic flexibility. The constraints and immune pressures of distinct niches within the human body set the stage for understanding the mechanisms by which bacteria acquire critical nutrients. In this article we discuss how different bacterial pathogens carry out carbon and energy metabolism in the host and how they obtain or use key nutrients for replication and immune evasion.
Study on the safety and efficacy of miltefosine for the treatment of children and adolescents with post-kala-azar dermal leishmaniasis in Bangladesh, and an association of serum vitamin E and exposure to arsenic with post-kala-azar dermal leishmaniasis: an open clinical trial and case–control study protocol
Authors: Mondal D , Hasnain M G , Hossain M S , Ghosh D , Ghosh P , Hossain H , Baker J , Nath R , Haque R , Matlashewski G , Hamano S
Published: May 2016

Introduction

Post-kala-azar dermal leishmaniasis (PKDL) is a dermatological complication that occurs primarily among treated visceral leishmaniasis (VL) patients, and sporadically in a few without a history of VL. It mostly affects children and adolescents but is also common in adults. The conventional treatment with 120 intramuscular injections of sodium stibogluconate (SSG) is phasing out. Miltefosine (MF) is the only eventual alternative to SSG; however, its efficacy and safety profiles for treatment of children and adolescents with PKDL are lacking. In addition, risk factors for PKDL are poorly investigated. Host genetic, nutritional and environmental factors could be potential risk factors. As such, here we propose to evaluate the efficacy and safety of MF for 12 weeks at an allometric dose for children and adolescents with PKDL, and also to explore potential risk factors for PKDL.

Methods and analysis

A cross-sectional survey will look for suspected participants with PKDL among treated VL children and adolescents, a subsequent open clinical trial with MF at allometric dose, with a follow-up at 12 months. A case–control study will be carried out for PKDL risk factors. Assuming 95% cure rate, 95% CI and α=0.05, a sample size of 73 children with PKDL is needed. Considering an attrition rate of 10%, the final sample size is 80 children in each group. Descriptive and analytical analyses will be performed. Primary outcome is safety and cure rate of 12 weeks of treatment with MF.

Ethics and dissemination

International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) Ethical Review Committee (ERC) approved the protocol (PR#013045). Written informed consent will be taken from all participants and their guardians (in case of minor). A Data and Safety Monitoring Board (DSMB) of ICDDR,B ERC will monitor all study activities to ensure the safety of the participants.

Trial registration number

NCT02193022; Pre-results.
Does n-3 LCPUFA supplementation during pregnancy increase the IQ of children at school age? Follow-up of a randomised controlled trial
Authors: Gould Jacqueline F , Treyvaud Karli , Yelland Lisa N , Anderson Peter J , Smithers Lisa G , Gibson Robert A , McPhee Andrew J , Makrides Maria
Published: May 2016

Introduction

Despite recommendations that pregnant women increase their docosahexaenoic acid (DHA) intake to support fetal brain development, a recent systematic review found a lack of high-quality data to support the long-term effects of DHA supplementation on children's neurodevelopment.

Methods and analysis

We will assess child neurodevelopment at 7 years of age in follow-up of a multicentre double-blind randomised controlled trial of DHA supplementation in pregnancy. In 2010–2012, n=2399 Australian women with a singleton pregnancy <21 weeks’ gestation were randomised to receive 3 capsules daily containing a total dose of 800 mg DHA/day or a vegetable oil placebo until birth. N=726 children from Adelaide (all n=97 born preterm, random sample of n=630 born at term) were selected for neurodevelopmental follow-up and n=638 (preterm n=85) are still enrolled at 7 years of age. At the 7-year follow-up, a psychologist will assess the primary outcome, IQ, with the Wechsler Abbreviated Scale of Intelligence, Second Edition. Specific measures of executive functioning (Fruit Stroop and the Rey Complex Figure), attention (Test of Everyday Attention for Children), memory and learning (Rey Auditory Verbal Learning Test), language (Clinical Evaluation of Language Fundamentals, Fourth Edition) and basic educational skills (Wide Range Achievement Test, Fourth Edition) will also be administered. Caregivers will be asked to complete questionnaires measuring behaviour and executive functioning. Families, clinicians and research personnel are blinded to group assignment with the exception of families who requested unblinding prior to the follow-up. All analyses will be conducted according to the intention-to-treat principal.

Ethics and dissemination

All procedures will be approved by the relevant institutional ethics committees prior to start of the study. The results of this study will be disseminated in peer-reviewed journal publications and academic presentations.

Trial registration numbers

ACTRN12605000569606 and ACTRN12614000770662.
Paramedics' experiences of end-of-life care decision making with regard to nursing home residents: an exploration of influential issues and factors
Authors: Murphy-Jones Georgina , Timmons Stephen
Published: May 2016

Introduction

For a patient nearing the end of his or her life, transfer from a nursing home to the ED can be inappropriate, with potentially negative consequences, but transfer in these circumstances is, regrettably, all too common. There is a lack of published literature exploring how paramedics make decisions in end-of-life care situations. This study aims to explore how paramedics make decisions when asked to transport nursing home residents nearing the end of their lives.

Methods

Phenomenological influenced design with a pragmatic approach. Semi-structured face-to-face interviews were conducted with six paramedics in an English NHS Ambulance Trust and subsequent data collected by text message. Audio-recorded interviews were transcribed verbatim and analysed using a thematic approach.

Results

Three themes emerged in relation to the decision to transport patients from nursing homes to EDs in end-of-life care situations. Paramedics identified difficulties in understanding nursing home residents' wishes. When a patient no longer had the capacity for decision making, paramedics' reasoning processes were aligned to best interest decision making, weighing the risks and benefits of hospitalisation. Paramedics found it challenging to balance patients' best interests with pressure from others: nursing staff, patients' relatives and colleagues.

Conclusions

A range of factors influence paramedics' decisions to transport nursing home residents to EDs in end-of-life care situations. Decision making became a process of negotiation when the patient's perceived best interests conflicted with that of others, resulting in contrasting approaches by paramedics. This paper considers how paramedics might be better trained and supported in dealing with these situations, with the aim of providing dignified and appropriate care to patients as they reach the end of their lives.
Helicobacter pylori vacAtranscription is genetically-determined and stratifies the level of human gastric inflammation and atrophy
Authors: Sinnett Charlotte G , Letley Darren P , Narayanan Geetha L , Patel Sapna R , Hussein Nawfal R , Zaitoun Abed M , Robinson Karen , Atherton John C
Published: May 2016

Aims

Helicobacter pyloriinfection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxinvacA.Previously, we have described allelic variation invacAwhich determines toxin activity and disease risk. Here we aimed to quantifyvacAmRNA expression in the human stomach, define its genetic determinants and assess how well it predicts gastric pathology.

Methods

Gastric biopsies were donated by 39 patients withH. pyloriinfection attending for endoscopy at Queen's Medical Centre, Nottingham, UK. Total RNA was extracted, andvacAmRNA quantified by reverse transcriptase quantitative PCR. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system.H. pyloristrains were isolated from further biopsies, and the nucleotide sequence upstream ofvacAdetermined.

Results

vacAmRNA levels in human stomachs varied by two orders of magnitude independently ofvacAallelic type. AmongvacAi1-type (toxic) strains, increasedvacAexpression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005) and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem-loop structure within the 5′ untranslated region was significantly associated withvacAtranscript level and inflammation.

Conclusions

Increased gastricvacAexpression duringH. pyloriinfection is associated with inflammation and premalignant pathology. The +28 nucleotide within thevacA5′ stem-loop stratifies disease risk among toxicvacAi1-type strains.
Multicentric lymphoma in a pony presented as a case of metastatic strangles
Authors: Gustafsson Kajsa , Jahns Hanne , Lee Alison , Duggan Vivienne E
Published: May 2016

A four‐year‐old pony was presented for investigation of weight loss, pyrexia, multicentric lymph node enlargement and mucopurulent nasal discharge. The pony came from an area endemic for Streptococcus equi subspecies equi (strangles) hence metastatic strangles was suspected initially. Multiple enlarged non‐painful lymph nodes were also highly suggestive of multicentric lymphoma. Nasal discharge was negative by culture and PCR for Streptococcus equi subspecies equi while fine needle aspirate of three lymph nodes revealed a homogenous population of small lymphocytes with normal morphology. Based on the poor prognosis the pony was euthanased. During histopathology neoplastic cells were detected in various lymph nodes and in the spleen, Immunohistochemistry gave the final diagnosis; low‐grade diffuse small T cell multicentric lymphoma. Lymphoma has a broad range of presentations and is difficult to diagnose ante mortem but should be considered a differential diagnosis where generalised lymphadenopathy is detected, although this may be confounded by signs of upper airway infection.
Drift-filled hollows in Battersea: investigation of the structure and geology along the route of the Northern Line Extension, London
Authors: Toms Emma , Mason Philippa J. , Ghail Richard C.
Published: May 2016

Drift-filled hollows (DFHs) are a major subsurface hazard for engineering in London. They are characterized by a steeply inclined cone-shaped hollow into (sometimes through) the London Clay Formation, filled with unconsolidated fine- to coarse-grained drift and often covered by terrace gravels, making them difficult to identify at the surface. Their origin remains uncertain but most probably formed towards the end of glacial epochs by meltwater scouring, perhaps of collapsed pingos. Usually associated with tributaries to the Thames, DFHs are particularly prevalent in the Battersea area, through which the Northern Line Extension (NLE) is to be built. This study uses 283 public borehole records and site reports to build a 3D geological ground model of two known DFHs in the Battersea area to develop a more complete understanding of their origin. We show that DFHs are probably older than previously assumed, dating from the end-Anglian (Marine Isotope Stage (MIS) 12),
c.
300 kyr ago, before the deposition of the River Terrace Deposits. The two DFHs modelled fall into distinct types: a small shallow DFH that is probably a purely scour feature in origin, and a larger, deeper DFH that probably formed by the scouring of a perhaps fault-controlled pingo. It is unclear whether the faults controlled pingo formation passively by acting as a conduit for water, or in a more active sense by driving ground movements. Both DFHs represent a significant hazard for the NLE and require more detailed investigations to properly constrain their extent.
Numerical modelling of a forced gradient tracer test undertaken under non-ideal conditions
Authors: Heredia Javier , Moreno Luis , Sola Fernando , Vallejos Ángela , Pulido-Bosch Antonio , Durán Juan-José
Published: May 2016

Pumping and tracer tests are common methods for the characterization of the aquifers used for supplying desalination plants. A case study is presented from Almería in SE Spain in which the unexpected movement of fine sediment caused by continuous pumping and incomplete removal of the drilling mud in the boreholes makes it impossible to conduct and interpret a standard tracer test. A modified tracer test was therefore performed in the unconsolidated clastic aquifer at this site and then interpreted numerically using two conceptual models: (1) a homogeneous model representing an unaltered medium; (2) a heterogeneous model incorporating an alteration zone around the borehole. The heterogeneous model produced a better calibration with more realistic parameter values for the aquifer and silty material (permeability, specific storage, effective porosity, dispersivity). The aquifer was characterized as a poorly sorted detrital sedimentary deposit with a large quantity of silt in the matrix. The conclusion is that advective transport dominates almost all the tracer movement. However, dispersive and/or diffuse transport determine the tail length of the breakthrough curve.
On Battery Recovery Effect in Wireless Sensor Nodes
Authors: Narayanaswamy Swaminathan , Schlueter Steffen , Steinhorst Sebastian , Lukasiewycz Martin , Chakraborty Samarjit , Hoster Harry Ernst
Published: May 2016

With the perennial demand for longer runtime of battery-powered Wireless Sensor Nodes (WSNs), several techniques have been proposed to increase the battery runtime. One such class of techniques exploiting the
battery recovery effect
phenomenon claims that performing an intermittent discharge instead of a continuous discharge will increase the usable battery capacity. Several works in the areas of embedded systems and wireless sensor networks have assumed the existence of this recovery effect and proposed different power management techniques in the form of power supply architectures (multiple battery setup) and communication protocols (burst mode transmission) in order to exploit it. However, until now, a systematic experimental evaluation of the recovery effect has not been performed with real battery cells, using high-accuracy battery testers to confirm the existence of this recovery phenomenon. In this article, a systematic evaluation procedure is developed to verify the existence of this battery recovery effect. Using our evaluation procedure, we investigated Alkaline, Nickel-Metal Hydride (NiMH), and Lithium-Ion (Li-Ion) battery chemistries, which are commonly used as power supplies for Wireless Sensor Node (WSN) applications. Our experimental results do not show any evidence of the aforementioned recovery effect in these battery chemistries. In particular, our results show a significant deviation from the stochastic battery models, which were used by many power management techniques. Therefore, the existing power management approaches that rely on this recovery effect do not hold in practice. Instead of a battery recovery effect, our experimental results show the existence of the
rate capacity effect
, which is the reduction of usable battery capacity with higher discharge power, to be the dominant electrochemical phenomenon that should be considered for maximizing the runtime of WSN applications. We outline power management techniques that minimize the rate capacity effect in order to obtain a higher energy output from the battery.
Insights into the role of neuronal glucokinase
Authors: De Backer Ivan , Hussain Sufyan S. , Bloom Stephen R. , Gardiner James V.
Published: May 2016

Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested.
No insulating effect of obesity
Authors: Fischer Alexander W. , Csikasz Robert I. , von Essen Gabriella , Cannon Barbara , Nedergaard Jan
Published: May 2016

The development of obesity may be aggravated if obesity itself insulates against heat loss and thus diminishes the amount of food burnt for body temperature control. This would be particularly important under normal laboratory conditions where mice experience a chronic cold stress (at ≈20°C). We used Scholander plots (energy expenditure plotted against ambient temperature) to examine the insulation (thermal conductance) of mice, defined as the inverse of the slope of the Scholander curve at subthermoneutral temperatures. We verified the method by demonstrating that shaved mice possessed only half the insulation of nonshaved mice. We examined a series of obesity models [mice fed high-fat diets and kept at different temperatures, classical diet-induced obese mice, ob/ob mice, and obesity-prone (C57BL/6) vs. obesity-resistant (129S) mice]. We found that neither acclimation temperature nor any kind or degree of obesity affected the thermal insulation of the mice when analyzed at the whole mouse level or as energy expenditure per lean weight. Calculation per body weight erroneously implied increased insulation in obese mice. We conclude that, in contrast to what would be expected, obesity of any kind does not increase thermal insulation in mice, and therefore, it does not in itself aggravate the development of obesity. It may be discussed as to what degree of effect excess adipose tissue has on insulation in humans and especially whether significant metabolic effects are associated with insulation in humans.
Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema
Authors: Yu Jinyan , Ma Zhongsen , Shetty Sreerama , Ma Mengshi , Fu Jian
Published: May 2016

Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both α-tubulin and β-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-α induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-α-induced lung endothelial cell hyperpermeability, which was associated with increased α-tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-α-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced β-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of β-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and β-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of α-tubulin and β-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction.
Regional lung response to bronchodilator reversibility testing determined by electrical impedance tomography in chronic obstructive pulmonary disease
Authors: Vogt Barbara , Zhao Zhanqi , Zabel Peter , Weiler Norbert , Frerichs Inéz
Published: May 2016

Patients with obstructive lung diseases commonly undergo bronchodilator reversibility testing during examination of their pulmonary function by spirometry. A positive response is defined by an increase in forced expiratory volume in 1 s (FEV1). FEV1is a rather nonspecific criterion not allowing the regional effects of bronchodilator to be assessed. We employed the imaging technique of electrical impedance tomography (EIT) to visualize the spatial and temporal ventilation distribution in 35 patients with chronic obstructive pulmonary disease at baseline and 5, 10, and 20 min after bronchodilator inhalation. EIT scanning was performed during tidal breathing and forced full expiration maneuver in parallel with spirometry. Ventilation distribution was determined by EIT by calculating the image pixel values of FEV1, forced vital capacity (FVC), tidal volume, peak flow, and mean forced expiratory flow between 25 and 75% of FVC. The global inhomogeneity indexes of each measure and histograms of pixel FEV1/FVC values were then determined to assess the bronchodilator effect on spatial ventilation distribution. Temporal ventilation distribution was analyzed from pixel values of times needed to exhale 75 and 90% of pixel FVC. Based on spirometric FEV1, significant bronchodilator response was found in 17 patients. These patients exhibited higher postbronchodilator values of all regional EIT-derived lung function measures in contrast to nonresponders. Ventilation distribution was inhomogeneous in both groups. Significant improvements were noted for spatial distribution of pixel FEV1and tidal volume and temporal distribution in responders. By providing regional data, EIT might increase the diagnostic and prognostic information derived from reversibility testing.
Heat shock factor 1 induces crystallin-αB to protect against cisplatin nephrotoxicity
Authors: Lou Qiang , Hu Yanzhong , Ma Yuanfang , Dong Zheng
Published: May 2016

Cisplatin, a wildly used chemotherapy drug, induces nephrotoxicity that is characterized by renal tubular cell apoptosis. In response to toxicity, tubular cells can activate cytoprotective mechanisms, such as the heat shock response. However, the role and regulation of the heat shock response in cisplatin-induced nephrotoxicity remain largely unclear. In the present study, we demonstrated the induction of heat shock factor (Hsf)1 and the small heat shock protein crystallin-αB (CryAB) during cisplatin nephrotoxicity in mice. Consistently, cisplatin induced Hsf1 and CryAB in a cultured renal proximal tubular cells (RPTCs). RPTCs underwent apoptosis during cisplatin treatment, which was increased when Hsf1 was knocked down. Transfection or restoration of Hsf1 into Hsf1 knockdown cells suppressed cisplatin-induced apoptosis, further supporting a cytoprotective role of Hsf1 and its associated heat shock response. Moreover, Hsf1 knockdown increased Bax translocation to mitochondria and cytochrome c release into the cytosol. In RPTCs, Hsf1 knockdown led to a specific downregulation of CryAB. Transfection of CryAB into Hsf1 knockdown cells diminished their sensitivity to cisplatin-induced apoptosis, suggesting that CryAB may be a key mediator of the cytoprotective effect of Hsf1. Taken together, these results demonstrate a heat shock response in cisplatin nephrotoxicity that is mediated by Hsf1 and CryAB to protect tubular cells against apoptosis.
20-HETE and CYP4A2 ω-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats
Authors: Dalmasso Carolina , Maranon Rodrigo , Patil Chetan , Moulana Mohadetheh , Romero Damian G. , Reckelhoff Jane F.
Published: May 2016

In male rats, androgen supplements increase 20-hydroxyeicosatetraenoic acid (20-HETE) via cytochrome P-450 (CYP)4A ω-hydroxylase and cause an increase in blood pressure (BP). In the present study, we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague-Dawley rats (96 ± 2 vs. 108 ± 2 mmHg, P < 0.05) and was associated with increased renal microvascular CYP4A2 mRNA expression (15-fold), endogenous renal 20-HETE (5-fold), and ω-hydroxylase activity (3-fold). Chronic DHT also increased MAP in low salt-fed Dahl salt-resistant female rats (81 ± 4 vs. 95 ± 1 mmHg, P < 0.05) but had no effect on MAP in Dahl salt-sensitive female rats (154 ± 3 vs. 153 ± 3 mmHg), which are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2−/− and SS.5Bn (wild type) rats were treated with DHT. DHT increased MAP in SS.5Bn female rats (104 ± 1 vs. 128 ± 1 mmHg, P < 0.05) but had no effect in CYP4A2−/− female rats (118 ± 1 vs. 120 ± 1 mmHg). Renal microvascular 20-HETE was reduced in control CYP4A2−/− female rats and was increased with DHT in SS.5Bn female rats (6-fold) but not CYP4A2−/− female rats. ω-Hydroxylase activity was 40% lower in control CYP4A2−/− female rats than in SS.5Bn female rats, and DHT decreased ω-hydroxylase activity in SS.5Bn female rats (by 50%) but significantly increased ω-hydroxylase activity in CYP4A2−/− female rats (3-fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic female rats. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome.
Recommendations on Chronic Constipation (including Constipation Associated with Irritable Bowel Syndrome) Treatment
Authors: Paré Pierre , Bridges Ronald , Champion Malcolm , Ganguli Subhas C , Gray James R , Irvine E Jan , Plourde Victor , Poitras Pierre , Turnbull Geoffrey K , Moayyedi Paul , Flook Nigel , Collins Stephen M
Published: May 2016

While chronic constipation (CC) has a high prevalence in primary care, there are no existing treatment recommendations to guide health care professionals. To address this, a consensus group of 10 gastroenterologists was formed to develop treatment recommendations. Although constipation may occur as a result of organic disease, the present paper addresses only the management of primary CC or constipation associated with irritable bowel syndrome. The final consensus group was assembled and the recommendations were created following the exact process outlined by the Canadian Association of Gastroenterology for the following areas: epidemiology, quality of life and threshold for treatment; definitions and diagnostic criteria; lifestyle changes; bulking agents and stool softeners; osmotic agents; prokinetics; stimulant laxatives; suppositories; enemas; other drugs; biofeedback and behavioural approaches; surgery; and probiotics. A treatment algorithm was developed by the group for CC and constipation associated with irritable bowel syndrome. Where possible, an evidence-based approach and expert opinions were used to develop the statements in areas with insufficient evidence. The nature of the underlying pathophysiology for constipation is often unclear, and it can be tricky for physicians to decide on an appropriate treatment strategy for the individual patient. The myriad of treatment options available to Canadian physicians can be confusing; thus, the main aim of the recommendations and treatment algorithm is to optimize the approach in clinical care based on available evidence.
The Approach to Diagnosis and Treatment of Chronic Constipation: Suggestions for a General Practitioner
Authors: Pare Pierre
Published: May 2016

Chronic constipation is a frequent complaint. Symptoms of obstructive defecation (straining, hard and lumpy stools, or incomplete evacuation) are more frequent and bothersome than the frequency of bowel movements. Patient assessment is clinically based on the presence or absence of red flags. Commonly used therapies (eg, bulk-forming agents, stool softeners and stimulant laxatives) have only been evaluated in small studies of short duration. Polyethylene glycol was shown to be effective and safe in several rigorous trials with durations of more than one year. New drugs (prucalopride, lubiprostone and linaclotide) were shown to be effective and safe in well-designed and rigorous studies. Trials conducted in primary care patients are lacking for all therapies. Biofeedback and behavioural therapies are effective, but should be reserved for selected patients after proper diagnostic evaluation. A practical management algorithm is proposed using a multistep approach favouring early introduction of combined therapies and long-term step-down strategy to the lowest satisfactory regimen.
What is Chronic Constipation? Definition and Diagnosis
Authors: Gray James R
Published: May 2016

Although chronic constipation is a common complaint, there are no ideal biological markers for its diagnosis. Diagnosis rests on individual patient perception or clinical criteria developed by expert consensus. Investigation options are multiple but often not necessary. When selected, investigations are directed at confirming the absence of a primary underlying disease, differentiating or defining an alteration in colonic motility or identifying an anorectal evacuation disorder.
Epidemiology and Burden of Chronic Constipation
Authors: Sanchez Maria Ines Pinto , Bercik Premysl
Published: May 2016

Chronic constipation is an important component of clinical gastroenterology practice worldwide. Based on the definition, either selfreported or using Rome criteria, chronic constipation can affect from 2% to 27% of the population. Constipation is physically and mentally troublesome for many patients, and can significantly interfere with their daily living and well-being. Although only a proportion of patients with constipation seek medical care, most of them use prescribed or over-the-counter medication to improve their condition. The health care costs of constipation are significant as evidenced by the hundreds of million dollars spent yearly on laxatives alone. Because constipation is more common in older patients and life expectancy is increasing, an increase in the prevalence of constipation is expected in the years to come, with the associated impact on quality of life and socioeconomic burden.
Information Security of PHY Layer in Wireless Networks
Authors: Fang Weidong , Li Fengrong , Sun Yanzan , Shan Lianhai , Chen Shanji , Chen Chao , Li Meiju
Published: May 2016

Since the characteristics of wireless channel are open and broadcasting, wireless networks are very vulnerable to be attacked via eavesdropping, jamming, and interference. As traditional secure technologies are not suitable for PHY layer of wireless networks, physical-layer security issues become a focus of attention. In this paper, we firstly identify and summarize the threats and vulnerabilities in PHY layer of wireless networks. Then, we give a holistic overview of PHY layer secure schemes, which are divided into three categories: spatial domain-based, time domain-based, and frequency domain-based. Along the way, we analyze the pros and cons of current secure technologies in each category. In addition, we also conclude the techniques and methods used in these categories and point out the open research issues and directions in this area.
Differential Diagnosis of an Elderly Manic-Depressive Patient with Depersonalization and Other Symptoms
Authors: Ogata Shigehiro , Itohiya Yu , Sakamoto Yuri , Sato Yuki , Suyama Yudai , Atsuta Hidenori , Iwata Ken
Published: May 2016

The case study of an elderly man having persecutory delusions and bizarre complaints at the first psychiatric interview is reported. The patient complained: “I have no sense of time” and “I have no sense of money.” He refused nursing care. He had delusions centered on himself including that of his own death, which were difficult to diagnose but suggested the possibility of Cotard’s syndrome. We assumed that the man was depressed and treated him for depression. However, as a result of this treatment he became temporarily manic but finally recovered completely. After his recovery, we learnt the patient’s past history of hospitalization for psychiatric problems, and based on that history he was diagnosed as suffering from a bipolar I disorder. The lack of typical symptoms of depression and the remarkable depersonalization and derealization in this patient made it difficult to infer a depressive state. Nevertheless, being attentive to his strange feelings related to the flow of time would have helped us to make an accurate diagnosis earlier.
Efficient Photoelectrochemical Water Oxidation by Metal-Doped Bismuth Vanadate Photoanode with Iron Oxyhydroxide Electrocatalyst
Authors: Joo Eun Jin , Park Gisang , Gwak Ji Seon , Seo Jong Hyeok , Jang Kyu Yeon , Oh Kyung Hee , Nam Ki Min
Published: May 2016

Intensive attention has been currently focused on the discovery of semiconductor and proficient cocatalysts for eventual applications to the photoelectrochemical water splitting system. A W-Mo-doped BiVO4semiconductor was prepared by the surfactant-assisted thermal decomposition method on a fluorine-doped tin oxide conductive film. The W-Mo-doped BiVO4films showed a porous morphology with the grain sizes of about 270 nm. Because the hole diffusion length of BiVO4is about 100 nm, the W-Mo-doped BiVO4film in this study is an ideal candidate for the photoelectrochemical water oxidation. Iron oxyhydroxide (FeOOH) electrocatalyst was chemically deposited on the W-Mo-doped BiVO4to investigate the effect of the electrocatalyst on the semiconductor. The W-Mo-doped BiVO4/FeOOH composite electrode showed enhanced activity compared to the pristine W-Mo-doped BiVO4electrode for water oxidation reaction. The chemical deposition is a promising method for the deposition of FeOOH on semiconductor.
A Novel 3D Nonstationary Channel Model Based on the von Mises-Fisher Scattering Distribution
Authors: Bi Yuming , Zhang Jianhua , Zeng Ming , Liu Mengmeng , Xu Xiaodong
Published: May 2016

In the last decade, the nonstationary properties of channel models have attracted more and more attention for many scenarios, that is, vehicle-to-vehicle (V2V), mobile-to-mobile (M2M), and high-speed train (HST). However, little research has been done on the real-physical channel model. In this paper, we propose a generalized three-dimensional (3D) nonstationary channel model, in which the scatterers are assumed to be distributed around the transmitter (Tx) and receiver (Rx) on a two-sphere model. By employing the von Mises-Fisher distribution, the mean values of the azimuth angle of departure (AAoD) and elevation angle of departure (EAoD) and the azimuth angle of arrival (AAoA) and elevation angle of arrival (EAoA) are tracked by time-variant (TV) Brownian Markov (BM) motion paths, which ensure the nonstationarity of the proposed channel model. Moreover, the TV autocorrelation function (ACF) and Doppler power spectrum density (DPSD) of the proposed nonstationary channel model are calculated by using signal processing tools, for example, fast Fourier transform (FFT) and short-time Fourier transform (STFT). In addition, the simulation results show that the TV scatterer distribution results in a nonstationary nonisotropic channel model, and the proposed model can be employed to simulate the 3D nonstationary channel model.
The Impact of External Factors on the Epigenome:In Uteroand over Lifetime
Authors: Toraño Estela G. , García María G. , Fernández-Morera Juan Luis , Niño-García Pilar , Fernández Agustín F.
Published: May 2016

Epigenetic marks change during fetal development, adult life, and aging. Some changes play an important role in the establishment and regulation of gene programs, but others seem to occur without any apparent physiological role. An important future challenge in the field of epigenetics will be to describe how the environment affects both of these types of epigenetic change and to learn if interaction between them can determine healthy and disease phenotypes during lifetime. Here we discuss how chemical and physical environmental stressors, diet, life habits, and pharmacological treatments can affect the epigenome during lifetime and the possible impact of these epigenetic changes on pathophysiological processes.
Course Control of Underactuated Ship Based on Nonlinear Robust Neural Network Backstepping Method
Authors: Yuan Junjia , Meng Hao , Zhu Qidan , Zhou Jiajia
Published: May 2016

The problem of course control for underactuated surface ship is addressed in this paper. Firstly, neural networks are adopted to determine the parameters of the unknown part of ideal virtual backstepping control, even the weight values of neural network are updated by adaptive technique. Then uniform stability for the convergence of course tracking errors has been proven through Lyapunov stability theory. Finally, simulation experiments are carried out to illustrate the effectiveness of proposed control method.
Pulmonary Hemodynamics and Six-Minute Walk Test Outcomes in Patients with Interstitial Lung Disease
Authors: Nishiyama Osamu , Yamazaki Ryo , Sano Hiroyuki , Iwanaga Takashi , Higashimoto Yuji , Kume Hiroaki , Tohda Yuji
Published: May 2016

Background. Six-minute walk test (6MWT) has 3 measurement outcomes, which are walk distance, desaturation, and symptom. The aim of this study was to examine whether routinely measured right-heart catheter (RHC) data correlate with 6MWT outcomes in patients with interstitial lung disease (ILD).Methods. Between June 2010 and December 2012, consecutive patients with ILD who underwent evaluation, including pulmonary function test, hemodynamic studies with right-heart catheter, and 6MWT as routine general practice, were recruited. Correlates of 3 outcomes of 6MWT were examined to reveal significant predictors.Results. Forty-six patients consisting of 20 with idiopathic pulmonary fibrosis, 14 with collagen vascular disease associated ILD, and 12 with other idiopathic interstitial pneumonia were recruited (mean % predicted FVC:76.7±17.1%). Several physiological variables, including mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), were correlated with each 6MWT outcome. Stepwise multivariate regression analyses showed that % predicted FVC and % predicted DLco were independent predictors of walk distance (r2=0.35,p=0.0002). For SpO2at the end of 6MWT, % predicted DLco and PVR were selected as independent predictors (r2=0.46,p<0.0001). For dyspnea at the end of 6MWT, % predicted DLco was only one predictor (r2=0.18,p=0.005).Conclusion. Mean PAP had little impact on 6MWT outcomes in ILD patients who were nonselectively recruited, although PVR was one of predictors of desaturation.