bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal imaging for diagnosis and management of parasitic peritoneal myoma with myxoid degeneration after laparoscopic‐assisted myomectomy with electric power morcellation
Authors: Takeda Akihiro , Koike Wataru , Watanabe Kazuko
Published: March 2018

A 45‐year‐old multipara woman was referred due to the rapid enlargement of an asymptomatic pelvic mass that was detected during a regular check up. She had undergone laparoscopic‐assisted myomectomy 15 years previously. At the time, the uncontained extraction of an intraligamental myoma with electric power morcellation had been performed. Multimodal imaging revealed a heterogeneous mass in the vesicouterine pouch that was found to be supplied by the left gastro‐omental and superior vesical arteries. Although malignancy could not be completely denied, parasitic peritoneal myoma with myxoid degeneration was the most probable diagnosis. Single‐port laparoscopic excision of the peritoneal mass was performed along with laparoscopic‐assisted vaginal hysterectomy and bilateral salpingo‐oophorectomy. The excised peritoneal mass was placed into a retrieval bag and extracted through the vagina. The pathological diagnosis was a parasitic peritoneal myoma with myxoid degeneration. The postoperative course was uneventful, and there was no recurrence of parasitic myoma in the 1‐year follow up after surgery.
Global human papilloma virus vaccine implementation: An update
Authors: Sabeena Sasidharanpillai , Bhat Parvati V. , Kamath Veena , Arunkumar Govindakarnavar
Published: March 2018

Human papillomavirus (HPV) infections continue to be one of the most common sexually transmitted infections worldwide. The oncogenic potential of this virus was well established in anogenital malignancies and oropharyngeal cancers. Even though a fall in cervical cancer rates has been reported worldwide, the subsequent rise in HPV‐associated head and neck cancers among men and women have been reported from developed countries, necessitating the vaccination of adolescent boys as well. The objective of this narrative review is to provide an update on the current status of HPV vaccination worldwide. This will be helpful for clinicians in counseling parents and guardians as this vaccine mainly targets sexually naïve preadolescents. An electronic search of the databases was carried out to retrieve information concerning HPV vaccine implementation between July 2006 and 2017, with special emphasis on the current viewpoints, controversies and ethical issues. Globally, 74 countries have implemented the HPV vaccine in the national immunization schedule, and this vaccine is listed as an essential medicine by WHO. About 60% of the low‐ and lower–middle‐income countries have implemented the vaccine with financial assistance from Gavi and WHO. The HPV vaccine is a safe vaccine with no serious adverse effects as per the data available from developed nations as well as low/lower middle/upper middle‐income countries. However, long‐term follow‐up is essential to substantiate the impact of the vaccination programs in cancer prevention.
Clinical concentrations of peroxidases cause dysbiosis in in vitro oral biofilms
Authors: Herrero E.R. , Boon N. , Bernaerts K. , Slomka V. , Verspecht T. , Quirynen M. , Teughels W.
Published: March 2018

Background and Objective

Little is known about the initiation of dysbiosis in oral biofilms, a topic of prime importance for understanding the etiology of, and preventing, periodontitis. The aim of this study was to evaluate the effect of different concentrations of crevicular and salivary peroxidase and catalase on dysbiosis in multispecies biofilms in vitro.

Material and Methods

The spotting technique was used to identify the effect of different concentrations of myeloperoxidase, lactoperoxidase, erythrocyte catalase, and horseradish peroxidase in salivary and crevicular fluid on the inhibitory effect of commensals on pathobiont growth. Vitality–quantitative real‐time PCR was performed to quantify the dysbiotic effect of the peroxidases (adjusted to concentrations found in periodontal health, gingivitis, and periodontitis) on multispecies microbial communities.

Results

Agar plate and multispecies ecology experiments showed that production of hydrogen peroxide (H2O2) by commensal bacteria decreases pathobiont growth and colonization. Peroxidases at concentrations found in crevicular fluid and saliva neutralized this inhibitory effect. In multispecies communities, myeloperoxidase, at the crevicular fluid concentrations found in periodontitis, resulted in a 1‐3 Log increase in pathobionts when compared with the crevicular fluid concentrations found in periodontal health. The effect of salivary lactoperoxidase and salivary myeloperoxidase concentrations was, in general, similar to the effect of crevicular myeloperoxidase concentrations.

Conclusions

Commensal species suppress pathobionts by producing H2O2. Catalase and peroxidases, at clinically relevant concentrations, can neutralize this effect and thereby can contribute to dysbiosis by allowing the outgrowth of pathobionts.
Impact of veA on the development, aggressiveness, dissemination and secondary metabolism of Penicillium expansum
Authors: El Hajj Assaf Christelle , Snini Selma P. , Tadrist Souria , Bailly Sylviane , Naylies Claire , Oswald Isabelle P. , Lorber Sophie , Puel Olivier
Published: March 2018

Penicillium expansum, the causal agent of blue mould disease, produces the mycotoxins patulin and citrinin amongst other secondary metabolites. Secondary metabolism is associated with fungal development, which responds to numerous biotic and abiotic external triggers. The global transcription factor VeA plays a key role in the coordination of secondary metabolism and differentiation processes in many fungal species. The specific role of VeA in P. expansum remains unknown. A null mutant PeΔveA strain and a complemented PeΔveA:veA strain were generated in P. expansum and their pathogenicity on apples was studied. Like the wild‐type and the complemented strains, the null mutant PeΔveA strain was still able to sporulate and to colonize apples, but at a lower rate. However, it could not form coremia either in vitro or in vivo, thus limiting its dissemination from natural substrates. The impact of veA on the expression of genes encoding proteins involved in the production of patulin, citrinin and other secondary metabolites was evaluated. The disruption of veA drastically reduced the production of patulin and citrinin on synthetic media, associated with a marked down‐regulation of all genes involved in the biosynthesis of the two mycotoxins. Moreover, the null mutant PeΔveA strain was unable to produce patulin on apples. The analysis of gene expression revealed a global impact on secondary metabolism, as 15 of 35 backbone genes showed differential regulation on two different media. These findings support the hypothesis that VeA contributes to the pathogenicity of P. expansum and modulates its secondary metabolism.
Olive anthracnose: a yield‐ and oil quality‐degrading disease caused by several species of Colletotrichum that differ in virulence, host preference and geographical distribution
Authors: Talhinhas Pedro , Loureiro Andreia , Oliveira Helena
Published: March 2018

Olive anthracnose causes fruit rot leading to its drop or mummification, resulting in yield losses and the degradation of oil quality.

Taxonomy and distribution

The disease is caused by diverse species of Colletotrichum, mostly clustering in the C. acutatum species complex. Colletotrichum nymphaeae and C. godetiae are the prevalent species in the Northern Hemisphere, whereas C. acutatum sensu stricto is the most frequent species in the Southern Hemisphere, although it is recently and quickly emerging in the Northern Hemisphere. The disease has been reported from all continents, but it attains higher incidence and severity in the west of the Mediterranean Basin, where it is endemic in traditional orchards of susceptible cultivars.

Life cycle

The pathogens are able to survive on vegetative organs. On the fruit surface, infections remain quiescent until fruit maturity, when typical anthracnose symptoms develop. Under severe epidemics, defoliation and death of branches can also occur. Pathogen species differ in virulence, although this depends on the cultivar.

Control

The selection of resistant cultivars depends strongly on pathogen diversity and environmental conditions, posing added difficulties to breeding efforts. Chemical disease control is normally achieved with copper‐based fungicides, although this may be insufficient under highly favourable disease conditions and causes concern because of the presence of fungicide residues in the oil. In areas in which the incidence is high, farmers tend to anticipate harvest, with consequences in yield and oil characteristics.

Challenges

Olive production systems, harvest and post‐harvest processing have experienced profound changes in recent years, namely new training systems using specific cultivars, new harvest and processing techniques and new organoleptic market requests. Changes are also occurring in both the geographical distribution of pathogen populations and the taxonomic framework. In addition, stricter rules concerning pesticide use are likely to have a strong impact on control strategies. A detailed knowledge of pathogen diversity, population dynamics and host–pathogen interactions is basal for the deployment of durable and effective disease control strategies, whether based on resistance breeding, agronomic practices or biological or chemical control.
Spheroid formation and stemness preservation of human periodontal ligament cells on chitosan films
Authors: Yan X‐Z , van den Beucken JJJP , Yuan C , Jansen JA , Yang F
Published: March 2018

Objective

The therapeutic potential of periodontal ligament cells for periodontal regeneration gradually decreases when cultured as a monolayer in vitro. Three‐dimensional cell culture models provide an alternative to traditional monolayer cell culture. This study aimed to comparatively evaluate the influence of spheroid culture on periodontal ligament cells.

Materials and Methods

Chitosan films were used to culture three‐dimensional periodontal ligament cell spheroids. The proliferation, self‐renewal, and osteogenic capacity of periodontal ligament cells derived from spheroids were evaluated and compared with cells cultured on a monolayer.

Results

Viable spheroids of periodontal ligament cells were formed on chitosan films. Compared to monolayer cell culture, periodontal ligament cells exhibited decreased proliferation upon spheroid formation. In contrast, their expression of genes related to self‐renewal was significantly higher comparison with cells cultured in a monolayer. Moreover, the formation of periodontal ligament cell spheroids increased their colony‐forming unit ability and osteogenic differentiation capacity.

Conclusion

The results demonstrate the successful use of chitosan films for the culture of periodontal ligament cell spheroids. Compared to cells cultured in monolayer, periodontal ligament cells in spheroids did not proliferate, but exhibited higher self‐renewal gene expression, colony‐forming unit and osteogenic capacity.
Dynamics of post‐harvest pathogens Neofabraea spp. and Cadophora spp. in plant residues in Dutch apple and pear orchards
Authors: Köhl J. , Wenneker M. , Groenenboom‐de Haas B. H. , Anbergen R. , Goossen‐van de Geijn H. M. , Lombaers‐van der Plas C. H. , Pinto F. A. M. F. , Kastelein P.
Published: March 2018

Post‐harvest diseases of apple and pear cause significant losses. Neofabraea spp. and Cadophora spp. infect fruits during the growing season and remain quiescent until disease symptoms occur after several months in storage. Epidemiological knowledge of these diseases is limited. TaqMan PCR assays were developed for quantification of N. alba, N. perennans, C. malorum and C. luteo‐olivacea in environmental samples. Various host tissues, dead weeds and grasses, soil and applied composts were collected in 10 apple and 10 pear orchards in May 2012. Neofabraea alba was detected in 73% of samples from apple orchards and 48% from pear orchards. Neofabraea perennans was present in a few samples. Cadophora luteo‐olivacea was detected in 99% of samples from apple orchards and 93% from pear orchards, whilst C. malorum was not detected in any sample. In apple orchards, highest concentrations of N. alba were found in apple leaf litter, cankers and mummies, and of C. luteo‐olivacea in apple leaf litter, mummies and dead weeds. In pear orchards, N. alba and C. luteo‐olivacea were found in highest concentrations in pear leaf litter and in dead weeds. Substrate colonization varied considerably between orchards. The temporal dynamics of pathogens was followed in four apple orchards and four pear orchards. In apple orchards the colonization by pathogens decreased from April until August and increased from September until December. This pattern was less pronounced in pear. Knowledge on population dynamics is essential for the development of preventative measures to reduce risks of fruit infections during the growing season.
Cliticization and Abstract Case Assignment in Spanish
Authors: Romain Ian James
Published: March 2018

Building on recent work that argues in favor of a return to movement analyses for clitics (Uriagereka & Raposo 2005, Boeckx & Gallego, Roberts,; Gallego), this paper explains why object clitics need to engage in probe/goal relations with agreeing verbs to value their Case features. A Case‐based account within Phase Theory (cf. Chomsky,,) allows us to account for previously difficult to explain intervention and other displacement effects associated with these elements, and it also predicts clitic placement in a wide variety of ECM and causative constructions. Clitics in these constructions are sensitive to the timing and location of Case‐assigning mechanisms on the finite embedding verb, highlighting the importance of Case theory in deriving ‘raising to object’ phenomena in Spanish.
Blood product transfusion and wastage rates in obstetric hemorrhage
Authors: Yazer Mark H. , Dunbar Nancy M. , Cohn Claudia , Dillon Jessica , Eldib Howida , Jackson Bryon , Kaufman Richard , Murphy Michael F. , O'Brien Kerry , Raval Jay S. , Seheult Jansen , Staves Julie , Waters Jonathan H. ,   Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Published: March 2018

BACKGROUND

Bleeding emergencies can complicate pregnancies. Understanding the disposition of the products that are issued in this clinical setting can help inform inventory levels at hospitals where obstetric patients are seen.

STUDY DESIGN AND METHODS

Patients who had an obstetric hemorrhage of any etiology between January 2013 and June 2017, and whose resuscitation began with uncrossmatched red blood cells (RBCs) or emergency‐issued plasma or platelets (PLT), were included. The disposition of all blood products issued within 6 hours of the first uncrossmatched or emergency‐issued product was documented, as was basic patient demographic information.

RESULTS

In total, 301 women with an obstetric hemorrhage from seven academic institutions were identified. Their mean ± standard deviation age was 30.9 ± 6.1 years, 45.2% delivered by Cesarean section, and 40.5% delivered vaginally, while 12% did not deliver. The largest single etiology of hemorrhage was related to abnormal placentation. Of the 2280 issued RBC units, 55% were transfused, 43% were returned, and 2% were wasted. The rates of transfusion of the other blood products ranged from 58% for plasma units to 82% for cryoprecipitate. Seventeen percent of the issued cryoprecipitate units were wasted, the highest of any blood product. The rate of a patient receiving a transfusion when at least one blood product had been ordered ranged from 74% for PLTs to 91% for cryoprecipitate.

CONCLUSION

Although the rates of receiving a transfusion of at least one blood product when one is ordered was high, many of the issued units were returned, especially for RBCs.
Intraocular pressure reference intervals in eyes of clinically normal miniature donkeys (Equus africanusasinus)
Authors: Hibbs Carla D. , Barrett Paul M. , Dees D. Dustin
Published: March 2018

Purpose

To determine intraocular pressure (IOP) reference intervals in eyes of healthy miniature donkeys (Equus africanusasinus) via rebound and applanation tonometry.

Methods

Complete ophthalmic and physical examinations were performed by board‐certified veterinary ophthalmologists. Inclusion criteria for animals participating in this study were dictated by the American Society for Veterinary Clinical Pathology (ASVCP) reference interval guidelines. Intraocular pressure estimates (TonoVet®and TonoPenXL®) were obtained in both eyes. Forty animals (San Angelo group) received intramuscular xylazine hydrochloride 10% and auriculopalpebral (AP) nerve blocks prior to obtaining measurements. Twenty‐two animals (Austin group) received no sedation orAPblock. Statistical analysis followedASVCPreference interval guidelines. Analysis was performed using the softwaresasV9 (SASInstitute Inc., Cary,NC,USA).

Results

Fifty‐seven (114 eyes) healthy miniature donkeys were included in this study. The meanIOP± standard deviation (SD) was 25.75 ± 5.70 mm Hg for rebound tonometry with reference limits of 14.34 and 37.15. The meanIOP±SDwas 20.69 ± 5.06 mm Hg for applanation tonometry with reference limits of 12.82 and 33.38. No significant difference inIOPwas found between the Austin and San Angelo groups (P = .34). A significant difference was noted between rebound and applanationIOPestimates (P < .0001) with rebound tonometric values being higher.

Conclusions

Reference intervals forIOP's were established for this species. Intraocular pressure readings obtained by the rebound tonometer were significantly higher than with applanation. Sedation andAPblock did not affectIOPestimates.
Haemovigilance in China: experiences, challenges and strategies
Authors: Xie D. , Zhu Y.
Published: March 2018

Haemovigilance (HV) plays an essential role in ensuring the safety of donors and recipients with regard to blood transfusions. China now has annually survey on blood collection and supply, but no national reporting system of AR/AE related to blood transfusion. By 2013, the first guideline on HV in China was released by the Blood Quality Management Committee of Chinese Society of Blood Transfusion (CSBT) and revised in 2015. For blood establishments and hospitals looking for help with setting up new plans or further improving blood transfusion safety, the guideline provides ample information on definitions, methodology and documentation protocols. Based on the guideline, a series of education and promoting programmes was developed in Shanghai and other regions. With the integration of HV into the existing expert symposiums and education courses in the past few years, hundreds and thousands of clinicians and blood bank practitioners got training and the importance of HV were recognized widely, and the principles of nonpunitive principle and learning from errors. In 2017, the working party on haemovigilance of CSBT was set up, which is a milestone for the progress of HV in China. Through the working party, we can study the practices of antecedence countries and learning their experiences, by formulating policies, evaluating modes and mechanisms, compiling standards and guidelines, improving information management and standardization from one region to the other, to establish a national HV systems step by step in China.
Artemisinin based combination therapy for uncomplicated malaria management among children under five in Cameroon: a best practice implementation project
Authors: Okwen Patrick Mbah , Ngem Bedes , Chia Olivette Ndum , Cheabum Raphael , Moola Sandeep
Published: March 2018

Objective:

The aim of this evidence implementation project is to promote evidence-based practice in artemisinin-based combination therapy for managing uncomplicated malaria in children under five, thereby improving patient outcomes and resource utilization in the Bali Health District, Cameroon.

Introduction:

The burden of disease attributable to malaria has significantly improved in the last three years, however morbidity and mortality risks are still present, especially for children under five. In children with uncomplicated P. falciparum malaria, there is strong evidence to suggest that artemisinin-based combination therapy (ACT) is effective in treating malaria. The World Health Organization has strong recommendations with high-quality evidence guiding practice in the “test, treat and track” approach using microscopy, rapid diagnostics tests and ACTs.

Methods:

This evidence implementation project used the Joanna Briggs Institute Practical Application of Clinical Evidence System (JBI PACES) and Getting Research into Practice (GRiP) audit and feedback tool for promoting evidence-based healthcare involving three phases of activity.

Results:

We compared compliance with best practice recommendations at baseline against a follow-up compliance at four months, following implementation of strategies identified. Compliance rates improved overall by 31% (R: 20–42) for all criteria and sites, with differences noticed between sites. Nineteen barriers were identified, stratified into clinician, community health worker, patient and policy maker related barriers.

Conclusions:

Despite existing barriers to evidence implementation, getting research into practice is possible and does improve quality of care.
Effectiveness of non-pharmacological strategies for managing delirium in hospitalized postoperative adults: an umbrella review protocol
Authors: McNeil Joan , Denis Anne Marie , Michel Urick , Concert Catherine M.
Published: March 2018

Review question/objective:

The question of this review: What is the effectiveness of non-pharmacological strategies for the management of delirium in hospitalized adult postoperative patients?

The objective of this umbrella review is to determine the effectiveness of non-pharmacological strategies for the management of delirium in adult postoperative patients, 18 years and over, in an acute care hospitalized setting.

More specifically, the review aims to identify which non-pharmacological strategy/strategies, provided as a single strategy or combined as two or more strategies, is the most effective for management of delirium in hospitalized postoperative adult patients?
Dedicated education units as a clinical rotation for nursing students: a scoping review protocol
Authors: Harris Janet Y. , Keller Sheila , Hinton Elizabeth
Published: March 2018

Review question/objective:

The objective of this scoping review is to explore the existing literature regarding student nurse and nursing faculty perceived experiences and outcomes of dedicated education units, to examine and conceptually map the evidence, and to identify any gaps in the literature. The question of this review is:

What is known about student nurse and nursing faculty perceived experiences and outcomes with the use of a dedicated education unit as a clinical rotation?
Fibre sub‐type specific conduction reveals metabolic function in mouse sciatic nerve
Authors: Rich Laura R. , Brown Angus M.
Published: March 2018

Key points

We have developed an improved method that enables simultaneous recording of stimulus evoked compound action potentials from large myelinated A fibres and small unmyelinated C fibres in mouse sciatic nerves.

Investigations into the ability of fructose to support conduction in sciatic nerve revealed a novel glia‐to‐axon metabolic pathway in which fructose is converted in Schwann cells to lactate for subsequent shuttling to A fibres. The C fibres most likely directly take up and metabolise fructose.

These differences are indicative of fibre sub‐type specific metabolic profiles.

These results demonstrate that the physiological insights provided by the method can be applied to investigations of peripheral nerve, with a view to understanding the metabolic disruptions that underlie diabetic neuropathy.

The stimulus evoked compound action potential (CAP), recorded using suction electrodes, provides an index of the relative number of conducting axons within a nerve trunk. As such the CAP has been used to elucidate the diverse mechanisms of injury resulting from a variety of metabolic insults to central nervous white matter, whilst also providing a model with which to assess the benefits of clinically relevant neuroprotective strategies. In addition the technique lends itself to the study of metabolic cell‐to‐cell signalling that occurs between glial cells and neurones, and to exploring the ability of non‐glucose substrates to support axon conduction. Although peripheral nerves are sensitive to metabolic insult and are susceptible to diabetic neuropathy, there is a lack of fundamental information regarding peripheral nerve metabolism. A confounding factor in such studies is the extended duration demanded by the experimental protocol, requiring stable recording for periods of many hours. We describe a method that allows us to record simultaneously the stimulus evoked CAPs from A and C fibres from mouse sciatic nerve, and demonstrate its utility as applied to investigations into fibre sub‐type substrate use. Our results suggest that C fibres directly take up and metabolise fructose, whereas A fibre conduction is supported by fructose‐derived lactate, implying there exist unique metabolic profiles in neighbouring fibre sub‐types present within the same nerve trunk.
Rotation of endosomes demonstrates coordination of molecular motors during axonal transport
Authors: Kaplan Luke , Ierokomos Athena , Chowdary Praveen , Bryant Zev , Cui Bianxiao
Published: March 2018

Multipolarization microscopy shows tight linkage of the rotational dynamics of axonal endosomes to molecular motor activity.
Mechanisms of KCNQ1 channel dysfunction in long QT syndrome involving voltage sensor domain mutations
Authors: Huang Hui , Kuenze Georg , Smith Jarrod A. , Taylor Keenan C. , Duran Amanda M. , Hadziselimovic Arina , Meiler Jens , Vanoye Carlos G. , George Alfred L. , Sanders Charles R.
Published: March 2018

Long QT syndrome–associated mutations in KCNQ1 most often destabilize the protein, leading to mistrafficking and degradation.
Germany's new government makes big promises
Authors: Vogel Gretchen
Published: March 2018

Coalition says it will hike research spending to 3.5% of gross domestic product—but is that feasible?
Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection
Authors: Thaiss Christoph A. , Levy Maayan , Grosheva Inna , Zheng Danping , Soffer Eliran , Blacher Eran , Braverman Sofia , Tengeler Anouk C. , Barak Oren , Elazar Maya , Ben-Zeev Rotem , Lehavi-Regev Dana , Katz Meirav N. , Pevsner-Fischer Meirav , Gertler Arieh , Halpern Zamir , Harmelin Alon , Aamar Suhail , Serradas Patricia , Grosfeld Alexandra , Shapiro Hagit , Geiger Benjamin , Elinav Eran
Published: March 2018

Metabolic syndrome, leaky guts, and infection

Metabolic syndrome often accompanies obesity and hyperglycemia and is associated with a breakdown in the integrity of the intestinal barrier and increased risk of systemic infection. Thaiss
et al.
found that mice with systemic infection of a
Salmonella
analog,
Citrobacter rodentium
, also exhibited hyperglycemia. Deletion of the glucose transporter GLUT2 altered sensitivity to chemically induced epithelial permeability and protected mice from pathogen invasion. The authors also found a correlation in humans between glycated hemoglobin (an indicator of hyperglycemia) and serum levels of pathogen recognition receptor ligands.

Science
, this issue p.
1376
Response to Comment on “The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain)”
Authors: Rosas Antonio , Ríos Luis , Estalrrich Almudena , Liversidge Helen , García-Tabernero Antonio , Huguet Rosa , Cardoso Hugo , Bastir Markus , Lalueza-Fox Carles , de la Rasilla Marco , Dean Christopher
Published: March 2018

The comment by DeSilva challenges our suggestion that brain growth of the El Sidrón J1 Neandertal was still incomplete at 7.7 years of age. Evidence suggests that endocranial volume is likely to represent less than 90% adult size at El Sidrón as well as Neandertal male plus Krapina samples, in line with further evidence from endocranial surface histology and dural sinus groove size.
Diverging roads to the heart
Authors: Kelly Robert G. , Sperling Silke R.
Published: March 2018

Cardiovascular lineage decisions in the mouse embryo are explored at single-cell resolution
Intestinal barriers protect against disease
Authors: Citi Sandra
Published: March 2018

Leaky cell-cell junctions contribute to inflammatory and autoimmune diseases
Refining cell therapy
Authors: Roybal Kole T.
Published: March 2018

Synthetic Notch receptors expand the therapeutic potential of engineered T cells
The healing power of painful memories
Authors: Naik Shruti
Published: March 2018

Epidermal stem cells “remember” inflammation, accelerating subsequent wound repair
Health security's blind spot
Authors: Berkley Seth
Published: March 2018

The severity of this year's influenza virus is a reminder of the daunting task facing the global health community as it struggles to prevent infectious diseases from sparking deadly epidemics. Today, yellow fever and cholera continue to spread in Africa, while Brazil is in the midst of a major yellow fever outbreak. It was only recently that Zika virus and Ebola virus epidemics were in the headlines. The world needs to harness every resource and tool in the battle to catch outbreaks before they catch us. Prevention is always the first line of defense, and nations must maintain vigilant surveillance—and yet, effective and affordable, quick and definitive diagnostics are absent in the countries where they are most needed. This represents one of our most serious global health security blind spots.
A DNA Vaccine Expressing Consensus Hemagglutinin-Esterase Fusion Protein Protected Guinea Pigs from Infection by Two Lineages of Influenza D Virus
Authors: Wan Yanmin , Kang Guobin , Sreenivasan Chithra , Daharsh Lance , Zhang Junfeng , Fan Wenjin , Wang Dan , Moriyama Hideaki , Li Feng , Li Qingsheng
Published: March 2018

Two lineages of influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex, one of the most commonly diagnosed causes of morbidity and mortality within the cattle industry. Furthermore, IDV can infect other economically important domestic livestock, including pigs, and has the potential to infect humans, which necessitates the need for an efficacious vaccine. In this study, we designed a DNA vaccine expressing consensus hemagglutinin-esterase fusion (HEF) protein (FluD-Vax) and tested its protective efficacy against two lineages of IDV (D/OK and D/660) in guinea pigs. Animals that received FluD-Vax (
n
= 12) developed appreciable titers of neutralizing antibodies against IDV lineage representatives, D/OK and D/660. Importantly, vaccinated animals were protected against intranasal challenge with IDV [3 × 10
5
50% tissue culture infective dose(s) (TCID
50
)] D/OK (
n
= 6) or D/600 (
n
= 6), based on the absence of viral RNA in necropsied tissues (5 and 7 days postchallenge) using quantitative reverse transcription-PCR and
in situ
hybridization. In contrast, animals that received a sham DNA vaccine (
n
= 12) had no detectable neutralizing antibodies against IDV, and viral RNA was readily detectable in respiratory tract tissues after intranasal challenge (3 × 10
5
TCID
50
) with IDV D/OK (
n
= 6) or D/660 (
n
= 6). Using a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay, we found that IDV D/OK and D/600 infections induced apoptosis in epithelial cells lining alveoli and bronchioles, as well as nonepithelial cells in lung tissues. Our results demonstrate for the first time that the consensus IDV HEF DNA vaccine can elicit complete protection against infection from two lineages of IDV in the guinea pig model.

IMPORTANCE
Influenza D virus (IDV) infection has been associated with bovine respiratory disease complex, one of the most devastating diseases of the cattle population. Moreover, with broad host range and high environmental stability, IDV has the potential to further gain virulence or even infect humans. An efficacious vaccine is needed to prevent infection and stop potential cross-species transmission. In this study, we designed a DNA vaccine encoding the consensus hemagglutinin-esterase fusion (HEF) protein of two lineages of IDV (D/OK and D/660) and tested its efficacy in a guinea pig model. Our results showed that the consensus DNA vaccine elicited high-titer neutralizing antibodies and achieved sterilizing protection against two lineage-representative IDV intranasal infections. To our knowledge, this is the first study showing that a DNA vaccine expressing consensus HEF is efficacious in preventing different lineages of IDV infections.
Adenovirus Vector Vaccination Impacts NK Cell Rheostat Function following Lymphocytic Choriomeningitis Virus Infection
Authors: Blass Eryn , Aid Malika , Martinot Amanda J. , Larocca Rafael A. , Kang Zi Han , Badamchi-Zadeh Alexander , Penaloza-MacMaster Pablo , Reeves R. Keith , Barouch Dan H.
Published: March 2018

Natural killer (NK) cells respond rapidly as a first line of defense against infectious pathogens. In addition, NK cells may provide a “rheostat” function and have been shown to reduce the magnitude of antigen-specific T cell responses following infection to avoid immunopathology. However, it remains unknown whether NK cells similarly modulate vaccine-elicited T cell responses following virus challenge. We used the lymphocytic choriomeningitis virus (LCMV) clone 13 infection model to address whether NK cells regulate T cell responses in adenovirus vector-vaccinated mice following challenge. As expected, NK cell depletion in unvaccinated mice resulted in increased virus-specific CD4+and CD8+T cell responses and immunopathology following LCMV challenge. In contrast, NK cell depletion had minimal to no impact on antigen-specific T cell responses in mice that were vaccinated with an adenovirus serotype 5 (Ad5)-GP vector prior to LCMV challenge. Moreover, NK cell depletion in vaccinated mice prior to challenge did not result in immunopathology and did not compromise protective efficacy. These data suggest that adenovirus vaccine-elicited T cells may be less sensitive to NK cell rheostat regulation than T cells primed by LCMV infection.

IMPORTANCERecent data have shown that NK cell depletion leads to enhanced virus-elicited T cell responses that can result in severe immunopathology following LCMV infection in mice. In this study, we observed that NK cells exerted minimal to no impact on vaccine-elicited T cells following LCMV challenge, suggesting that adenovirus vaccine-elicited T cells may be less subject to NK cell regulation. These data contribute to our understanding of NK cell regulatory functions and T cell-based vaccines.
Health-related quality of life and its determinants in paediatric arterial ischaemic stroke survivors
Authors: Ghotra Satvinder K , Johnson Jeffrey A , Qiu Weiyu , Newton Amanda S , Rasmussen Carmen , Yager Jerome Y
Published: March 2018

Objective

Health-related quality of life (HRQL) instruments are patient or proxy-reported outcome measures that provide a comprehensive and subjective assessment of patient’s well-being and hence vital for health outcomes evaluation. A clear and thorough understanding of HRQL and its determinants is especially important to appropriately guide health-improving interventions. In this study, HRQL of paediatric arterial ischaemic stroke survivors was assessed using guidelines recommended for interpretation and reporting of the patient-reported outcome data. Determinants of HRQL were also explored.

Methods

Children diagnosed with arterial ischaemic stroke between 2003 and 2012 were assessed at least 1 year poststroke using the parent–proxy report versions of the Pediatric Quality of Life Inventory 4.0 and Pediatric Stroke Recurrence and Recovery Questionnaire. HRQL data were compared with population norms and used as outcome in multiple linear regression analysis.

Results

59 children were evaluated. Mean age at diagnosis of stroke was 2.2 years. Mean age at assessment and time elapsed since stroke was 7 years and 5 years, respectively. A total of 41% children had normal global outcome, whereas 51% had moderate to severe deficits. A lower overall HRQL was observed in both self and proxy reports. Parents reported the maximum impairment in emotional domain, whereas children indicated physical functioning to be the most affected. Neurological outcome, site of stroke and socioeconomic status were independently associated with overall HRQL.

Conclusions

Lower HRQL was demonstrated in children who survived arterial ischaemic stroke. Socioeconomic status of families was an important determinant of HRQL, over and above clinical parameters.
Thrombectomy for late occlusion of high flow extracranial–intracranial saphenous vein bypass graft after 27 years of patency
Authors: Silva Michael A , Alcedo Guardia Rodolfo E , Aziz-Sultan Mohammad Ali , Patel Nirav J
Published: March 2018

High flow extracranial–intracranial (EC-IC) bypass with a saphenous vein graft (SVG) has been used for more than 40 years in patients with giant aneurysms of the posterior circulation refractory to medical management, and has demonstrated high long term patency rates. We report the case of a patient treated with external carotid artery (ECA)–posterior cerebral artery SVG bypass in 1989 who presented 27 years later with paresthesias and confusion, and was found to have partial occlusion of her SVG bypass graft and a basilar occlusion. She was treated with mechanical thrombectomy of the basilar occlusion via the partially thrombosed graft, the first report of such a procedure through a high flow posterior circulation EC-IC SVG, resulting in improvement of the patient’s neurologic examination. At 27 years, this is the longest reported delay in thrombosis of a high flow SVG bypass graft, highlighting the long term patency of these grafts and the feasibility of thrombectomy through occluded bypass grafts.
Type 3 neovascularisation: long-term analysis of visual acuity and optical coherence tomography anatomical outcomes
Authors: Chae Bora , Su Daniel , Gal-Or Orly , Freund K Bailey , Sarraf David
Published: March 2018

Background

To investigate the long-term visual and optical coherence tomography (OCT) anatomical outcomes of type 3 neovascularisation (NV) and to identify any baseline predictors of poor outcomes.

Methods

In this retrospective study, patients diagnosed with treatment naïve type 3 NV were identified and categorised into two groups: good or poor vision based on final vision at 1 year. Baseline demographic features and visual acuity (VA) and baseline and 1-year spectral domain OCT (SD-OCT) anatomical findings were studied and correlated with good versus poor visual outcomes.

Results

Ten of 25 eyes were classified as having a poor visual outcome (20/50 or worse) at 1 year. Increased age (P=0.049), male gender (p=0.041) and worse baseline VA (ρs=0.61, p=0.001) were associated with poor vision at 1 year. Greater foveal atrophy was noted at 1 year in the poor visual outcome group (p=0.030). Subretinal hyper-reflective material and choroidal thinning were additional features noted more commonly in this group.

Conclusion

Increased age, male gender and lower baseline vision may be important baseline predictors of poor visual outcomes in eyes with type 3 NV. The development of central outer retinal atrophy and fibrosis, as identified with SD-OCT, may limit long-term vision in eyes with type 3 NV.
A critique of Hubbert’s model for peak oil
Authors: Jones Trevor H. , Willms N. Brad
Published: March 2018

In 1956, Shell Oil Company geologist M. King Hubbert published a model for the growth and decline over time of the production rates of oil extracted from the land mass of the continental US. Employing an estimate for the amount of ultimately recoverable oil and a logistic curve for the oil production rate, he accurately predicted a peak in US oil production for 1970. His arguments and the success of his prediction have been much celebrated, and the original paper has 1400 publication citations to date. The theory of “peak oil” (and subsequently, of natural resource scarcity in general) has consequently become associated with Hubbert and “Hubbert” curves and models. However, his prediction for the timing of a world peak oil production rate and the subsequent predictions of many others have proven inaccurate. We revisit the Hubbert model for oil extraction and provide an analysis of it and several variants in the language of (time) autonomous differential equations.
Detecting Domain-Flux Malware Using DNS Failure Traffic
Authors: Zou Futai , Li Linsen , Wu Yue , Li Jianhua , Zhang Siyu , Jiang Kaida
Published: March 2018

Domain-Flux malware is hard to detect because of the variable C&C (Command and Control) domains which were randomly generated by the technique of domain generation algorithm (DGA). In this paper, we propose a Domain-Flux malware detection approach based on DNS failure traffic. The approach fully leverages the behavior of DNS failure traffic to recognize nine features, and then mines the DGA-generated domains by a clustering algorithm and determinable rules. Theoretical analysis and experimental results verify its efficiency with both test dataset and real-world dataset. On the test dataset, our approach can achieve a true positive rate of 99.82% at false positive rate of 0.39%. On the real-world dataset, the approach can also achieve a relatively high precision of 98.3% and find out 197,026 DGA domains by analyzing DNS traffic in campus network for seven days. We found 1213 hosts of Domain-Flux malware existing on campus network, including the known Conficker, Fosniw and several new Domain-Flux malwares that have never been reported before. We classified 197,026 DGA domains and gave the representative generated patterns for a better understanding of the Domain-Flux mechanism.
Wedge-Shaped GaN Nanowalls: A Potential Candidate for Two-Dimensional Electronics and Spintronics
Authors: Deb Swarup , Dhar Subhabrata
Published: March 2018

Schrödingerand Poisson equations are solved self-consistently in order to obtain the potential and charge density distribution in [Formula: see text]-type GaN nanowalls tapered along [Formula: see text]-axis by different angles. The study shows two-dimensional (2D) quantum confinement of electrons in the central vertical plane of the wall for the entire range of tapering. Calculation of room temperature electron mobility in the 2D channel shows a steady decrease with the increase of the inclination angle of the side facets with respect to the base. However, it is interesting to note that the mobility remains to be much larger than that of bulk GaN even for the inclination angle of 65[Formula: see text]. The properties of high mobility and the vertical orientation of the 2DEG plane in this system can be exploited in fabricating highly conducting transparent interconnects and field effect transistors, which can lead to large scale integration of 2D devices in future.
Modeling Cell Size Regulation: From Single-Cell-Level Statistics to Molecular Mechanisms and Population-Level Effects
Authors: Ho Po-Yi , Lin Jie , Amir Ariel
Published: March 2018

Most microorganisms regulate their cell size. In this article, we review some of the mathematical formulations of the problem of cell size regulation. We focus on coarse-grained stochastic models and the statistics that they generate. We review the biologically relevant insights obtained from these models. We then describe cell cycle regulation and its molecular implementations, protein number regulation, and population growth, all in relation to size regulation. Finally, we discuss several future directions for developing understanding beyond phenomenological models of cell size regulation.
Modulations in extracellular calcium lead to H+-ATPase-dependent acid secretion: a clarification of PPI failure
Authors: Kitay Alice Miriam , Schneebacher Marie-Therese , Schmitt Anne , Heschl Katharina , Kopic Sascha , Alfadda Tariq , Alsaihati Abrar , Link Alexander , Geibel John Peter
Published: March 2018

The H+,K+-ATPase was identified as the primary proton secretory pathway in the gastric parietal cell and is the pharmacological target of agents suppressing acid secretion. Recently, we identified a second acid secretory protein expressed in the parietal cell, the vacuolar H+-ATPase (V-type ATPase). The aim of the present study was to further characterize H+-ATPase activation by modulations in extracellular calcium via the calcium sensing receptor (CaSR). Isolated gastric glands were loaded with the pH indicator dye BCECF-AM [2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester] to measure intracellular pH. Experiments were conducted in the absence of sodium and potassium to monitor H+-ATPase-specific transport activity. CaSR was activated with the calcimimetic R568 (400 nM) and/or by modulations in extracellular Ca2+. Elevation in calcium concentrations increased proton extrusion from the gastric parietal cell. Allosteric modification of the CaSR via R568 and calcium increased vacuolar H+-ATPase activity significantly (ΔpH/minlowCa2+(0.1mM) = 0.001 ± 0.001, ΔpH/minnormalCa2+(1.0mM) = 0.033 ± 0.004, ΔpH/minhighCa2+(5.0mM) = 0.051 ± 0.005). Carbachol significantly suppressed calcium-induced gastric acid secretion via the H+-ATPase under sodium- and potassium-free conditions. We conclude that the V-type H+-ATPase is tightly linked to CaSR activation. We observed that proton pump inhibitor (PPI) exposure does not modulate H+-ATPase activity. This elevated blood calcium activation of the H+-ATPase could provide an explanation for recurrent reflux symptoms while taking a PPI therapy.

NEW & NOTEWORTHY This study emphasizes the role of the H+-ATPase in acid secretion. We further demonstrate the modification of this proton excretion pathway by extracellular calcium and the activation of the calcium sensing receptor CaSR. The novelty of this paper is based on the modulation of the H+-ATPase via both extracellular Ca (activation) and the classical secretagogues histamine and carbachol (inactivation). Both activation and inactivation of this proton pump are independent of PPI modulation.
Effects of Dissolved Organic Matter on Sorption of Oxytetracycline to Sediments
Authors: Wang Zongzhou , Jiang Qianli , Wang Runze , Yuan Xiaoyu , Yang Shengke , Wang Wenke , Zhao Yaqian
Published: March 2018

The effects of two representative dissolved organic matters (DOMs) (derived from corrupt plants (PDOM) and chicken manure (MDOM)) on sorption characteristic of oxytetracycline to three typical sediments (first terrace (FT), river floodplain (RF), and riverbed (RB) sediments collected from the Weihe River) were investigated. Results showed that both DOMs can make the adsorption equilibrium time advance about 6 hours. The presence of DOMs changed the sorption kinetics model and the spontaneous degree of the reaction but did not change the sorption isotherm models. The adsorption of oxytetracycline (OTC) could be promoted by adding PDOM, and its maximum adsorption amount increased by 23.8% for FT, 38.0% for RB, and 28.3% for RF, respectively, whereas MDOM could inhibit the adsorption and maximum adsorption amount decreased by 23.3% for FT, 11.6% for RB, and 16.1% for RF, respectively. In addition, the DOM concentration also affected the adsorption. Overall, this study suggests that the humus-like DOM can promote the adsorption of OTC while the protein-like DOM can inhibit the adsorption of OTC to sediments, which is determined by the aromaticity, hydrophilicity, and polarity of the DOMs.