bluuebunny/crossref_metadata_2025 huggingface dataset:
Centre‐level variation in speech outcome and interventions, and factors associated with poor speech outcomes in 5‐year‐old children with non‐syndromic unilateral cleft lip and palate: The Cleft Care UK study. Part 4
Authors: Sell D. , Southby L. , Wren Y. , Wills A. K. , Hall A. , Mahmoud O. , Waylen A. , Sandy J. R. , Ness A. R.
Published: June 2017

Structured Abstract

Objectives

To investigate centre‐level variation in speech intervention and outcome and factors associated with a speech disorder in children in Cleft Care UK (CCUK).

Setting and Sample Population

Two hundred and sixty‐eight 5‐year‐old British children with non‐syndromic unilateral cleft lip and palate recruited to CCUK.

Materials and Methods

Centre‐based therapists undertook audio‐video recordings. Perceptual analysis was undertaken using the CAPS‐A tool. Speech outcomes were based on structural and articulation scores, and intelligibility/distinctiveness. Between‐centre variation in treatment and outcomes were examined using multilevel models. These models were extended to estimate the association between a range of factors (hearing loss, speech intervention, fistula, secondary speech surgery for velopharyngeal insufficiency, socio‐economic status, gender, and parental happiness with speech) and speech outcomes.

Results

There was centre‐level variation in secondary speech surgery, speech intervention, structure and intelligibility outcomes. Children with a history of speech intervention had a lower odds of poor intelligibility/distinctiveness, 0.1 (95% CI: 0.0‐0.4). Parental concern was associated with a higher odds of poor intelligibility/distinctiveness, 13.2 (95% CI: 4.9‐35.1). Poor speech outcomes were associated with a fistula, secondary speech surgery and history of hearing loss.

Conclusions

Within the centralized service there is centre‐level variation in secondary speech surgery, intervention and speech outcomes. These findings support the importance of early management of fistulae, effective management of velopharyngeal insufficiency and hearing impairment, and most importantly speech intervention in the preschool years. Parental concern about speech is a good indicator of speech status.
Patch dynamics and temporal dispersal partly shape annual plant communities in ephemeral habitat patches
Authors: Mahaut Lucie , Fried Guillaume , Gaba Sabrina
Published: June 2017

Most organisms in ephemeral habitat patches have resting stages which form a local species pool in response to temporal variations in the patch's availability and suitability. Temporal dispersal from the local species pool may, therefore, be an important process shaping the community assembly, particularly soon after patch creation, and possibly interacting with environmental filtering. As the temporal variation of the environmental conditions has a major effect on the composition of the local species pool, we investigated how well contemporary conditions (both patch availability and patch suitability) and temporal dispersal (approximated by environmental temporal variation and temporal distance) explain the changes in community composition in a given locality through successive ephemeral habitat cycles. We used arable weeds in annual crops as models. We calculated temporal weed community dissimilarity indices between weed communities surveyed in cropping seasons at intervals of two to eight years within a given field. The weeds were surveyed twice each cropping season to account for any changes in the relative contributions of temporal dispersal and contemporary conditions during the season. Patch availability explained most of the temporal weed dissimilarity, suggesting that patch dynamics have the greatest effect on weed community assembly. Temporal distance and temporal variation of the environmental conditions had more effect at the start of the cropping season than later, while patch suitability had more effect in the middle of the season. These results suggest that temporal dispersal drives the weed community assembly when ephemeral habitat patches are created. These assemblies are further shaped by environmental filtering. This is consistent with a temporal source sink dynamic mechanism where the seed bank acts as the main weed source. However, a large part of temporal weed dissimilarity remains unexplained, suggesting that other ecological processes such as spatial dispersal and founder effect may also shape the weed community.
Pooled efficacy and safety data for house dust mite sublingual immunotherapy tablets in adolescents
Authors: Matsuoka Tomokazu , Bernstein David I. , Masuyama Keisuke , Nolte Hendrik , Okamiya Kazuhiro , Seitzberg Dorthe , Nelson Harold S.
Published: June 2017

Background

House dust mite (HDM) respiratory allergy is a common and burdensome disease in children and adolescents. There are few HDM allergy immunotherapy trials in children with perennial allergic rhinitis. This post hoc analysis used pooled data to evaluate efficacy and safety of the SQ HDM sublingual immunotherapy (SLIT) tablet in adolescents (12‐17 years).

Methods

In two double‐blind, placebo‐controlled trials conducted in North America and Japan, respectively, subjects aged 12+ years with HDM allergic rhinitis were randomized to up to 1 year of treatment. The primary end‐point in both trials was the average total combined rhinitis score (TCRS) during the last 8 weeks of treatment in the active group compared with placebo. Data from subjects aged 12‐17 years were pooled (N=395).

Results

In the pooled adolescent subpopulation, average TCRS improved 22% with 12 SQ HDM vs placebo (absolute treatment difference of 1.04; P<.01). Rhinitis daily symptom score (DSS), conjunctivitis DSS and rhinitis daily medication score (DMS) were also significantly improved vs placebo in the pooled adolescent subpopulation (all P<.05). There were no new safety signals for adolescents. The frequency of adverse events was similar in adolescents and adults with the majority being mild application site‐related events.

Conclusions

Treatment with 12 SQ HDM appears to be effective and well tolerated in adolescents with HDM allergic rhinitis.
Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months
Authors: Thøstesen Lisbeth Marianne , Kjaer Henrik Fomsgaard , Pihl Gitte Thybo , Nissen Thomas Nørrelykke , Birk Nina Marie , Kjærgaard Jesper , Jensen Aksel Karl Georg , Aaby Peter , Olesen Annette Wind , Stensballe Lone Graff , Jeppesen Dorthe Lisbeth , Benn Christine Stabell , Kofoed Poul‐Erik
Published: June 2017

Background

Vaccination with Bacillus Calmette‐Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non‐specific effects, reducing non‐tuberculosis mortality, morbidity, and atopic manifestations. In this study, we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age.

Methods

The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no‐intervention control group. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency, or no Danish‐speaking parent. Follow‐up information was collected through telephone interviews at 3 and 13 months of age. Subgroups of participants were offered blood sampling at 13 months of age.

Results

By 13 months of age, the parents and/or general practitioners of 5.6% (117/2089) of the children in the BCG group and 6.1% (126/2061) of the control group suspected food allergy, resulting in a risk ratio comparing BCG‐vaccinated children with control children of 0.91 (95% CI 0.71‐1.16). Among 1370 blood samples, sensitization (Phadiatop Infant >0.35 kUA/L) was found in 55 of 743 (7.4%) children in the BCG group and 50 of 627 (8.0%) of the control group (risk ratio 0.94 [0.65‐1.36]).

Conclusion

In this randomized clinical trial, neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age.
Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonate
Authors: Shitomi Yuki , Nishida Haruto , Kusaba Takahiro , Daa Tsutomu , Yano Shinji , Arakane Motoki , Kondo Yoshiyuki , Nagai Takayuki , Abe Takashi , Gamachi Ayako , Murakami Kazunari , Etoh Tsuyoshi , Shiraishi Norio , Inomata Masafumi , Yokoyama Shigeo
Published: June 2017

Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined “gastric lanthanosis”, was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron‐microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high‐density linear appearance by CT, reflective bright‐white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron‐dense particles in the histiocytes. The particles had burr‐like skeletons resembling La crystals. Gastric lanthanosis is an under‐reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.
Relationship of temperament with oestrous behaviour, resumption of ovarian cyclicity and milk yield in post‐partum Murrah buffaloes
Authors: Choudhary KK , Bharadwaj A , Sharma RK , Jerome A , Khanna S
Published: June 2017

Contents

This study was designed to investigate the relationship of temperament with oestrus, resumption of ovarian cyclicity and milk yield in post‐partum buffaloes. For this study, 102 post‐partum Murrah buffaloes were observed for temperament in open paddock and during milking. Based on the temperament score (1–5 score), they were classified into docile, slightly restless, restless, aggressive and nervous. Oestrous behaviour was monitored twice daily in all the buffaloes along with milk yield (weekly), body weight (BW) and body condition score (BCS) at day 0, 30, 60 and 90 post‐partum. Based on the temperament score, the number of buffaloes classified as docile, slightly restless, restless and aggressive was 37 (36.27%), 28 (27.45%), 30 (29.41%) and 7 (6.86%), respectively, but none under nervous category. Number of buffaloes resuming cyclicity in various temperaments groups were as follows: docile (n = 35; 94.59%), slightly restless (n = 22; 78.57%), restless (n = 20; 66.67%) and aggressive (n = 7; 85.71%). Temperament was not correlated (p = .128; r=−.152) with oestrous behaviour. But, temperament was correlated (p < .0001; r = .384) with the resumption of cyclicity as docile and slightly restless buffaloes resumed cyclicity (p < .0016) earlier. Temperament of buffaloes was weakly correlated (p = .0017; r=−.306) with milk production with higher (p < .0358) total milk yield in docile (1022 ± 23.75 kg) and slightly restless buffaloes (948 ± 35.86 kg) as compared to other temperament groups. In summary, temperament of post‐partum buffaloes was related with resumption of ovarian cyclicity and milk yield, but not oestrous behaviour.
A brief review of intradialytic hypotension with a focus on survival
Authors: Chou Jason A. , Kalantar‐Zadeh Kamyar , Mathew Anna T.
Published: June 2017

Intradialytic hypotension (IDH), a common complication of ultrafiltration during hemodialysis therapy, is associated with high mortality and morbidity. IDH, defined as a nadir systolic blood pressure of less than 90 mm Hg on more than 30% of treatments, is a relevant definition and is correlated with mortality. Risk factors for IDH include patient demographics, anti‐hypertensive medication use, larger interdialytic weight gain, and dialysis prescription features as dialysate sodium, high ultrafiltration rate, and dialysate temperature. A high frequency of IDH events carries a substantial death risk. An ultrafiltration rate >10 mL/h/kg, and even more so >13 mL/h/kg, is highly predictive of cardiovascular and all‐cause mortality. Evidence suggests that IDH causes acute reversible segmental myocardial hypoperfusion and contractile dysfunction (myocardial stunning), which can result in long‐term loss of myocardial contractility, leading to premature death. IDH also has negative end‐organ effects on the brain and gut, contributing to mortality through stroke, and endotoxin translocation with associated inflammation and protein‐energy wasting. Given strong association of IDH and dialysis mortality, a paradigm shift to its approach is urgently needed. Randomized controlled trials are required to prospectively test drugs and monitoring devices which may reduce IDH.
The Spatial Structure of High Speed Railways and Urban Networks in China: A Flow Approach
Authors: Yang Haoran , Dijst Martin , Witte Patrick , Van Ginkel Hans , Yang Weiling
Published: June 2017

The high speed railway (HSR) has played a crucial role in the regional integration of urban networks in China. This paper analyses HSR passenger flows instead of commonly‐used time schedules for measuring different polycentricity in urban networks. Using 2013 origin/destination (O/D) passenger flow data, we analyse the spatial configurations of 99 HSR cities at the national scale in China. In addition, we compare the spatial configurations of three regional urban networks: the Pearl River Delta, the Yangzi River Delta and the Bohai Rim. The outcomes show that the three functional regions connected by HSR are the most dominant polycentric regions in China and that the Bohai Rim is less hierarchical than the other two. We conclude that the comprehensive Chinese HSR networks are largely polycentric, especially in the central and eastern regions.
Randomised feasibility study of a more liberal haemoglobin trigger for red blood cell transfusion compared to standard practice in anaemic cancer patients treated with chemotherapy
Authors: Yakymenko D. , Frandsen K. B. , Christensen I. J. , Norgaard A. , Johansson P. I. , Daugaard G. , Mau‐Sorensen M.
Published: June 2017

SUMMARY

Objectives

The primary objective of this feasibility study was to identify quality of life (QoL) scores and symptom scales as tools for measuring patient‐reported outcomes (PRO) associated with haemoglobin level in chemotherapy‐treated cancer patients. Secondary objectives included comparing QoL and symptoms between randomisation arms.

Background

Anaemia in cancer patients undergoing chemotherapy is associated with decreased QoL. One treatment option is red blood cell transfusion (RBCT). However, the optimal haemoglobin trigger for transfusion is unknown.

Methods

Patients were randomised to a haemoglobin trigger for RBCT of either < 9·7 g dL−1 (arm A) or < lower normal level, female: 11·5 g dL−1, male: 13·1 g dL−1 (arm B). Four PROs were used: Functional Assessment of Cancer Therapy‐General (FACT‐G) and the FACT‐Anaemia (FACT‐An), a Numeric Rating Scale on symptoms of anaemia and self‐reported Performance Status (PS). The association between haemoglobin and PRO variables was assessed using a linear mixed model with random effects.

Results

A total of 133 patients were enrolled, of which 86 patients received RBCT (28 in arm A, 58 in arm B). Baseline questionnaires were filled out in 79·7% of cases. Haemoglobin levels were significantly correlated with FACT‐An, FACT‐An Total Outcome Index (TOI), Functional Well‐Being, fatigue and PS. Improvement on several PRO variables was observed in both arms after RBCT, with clinically minimal important differences observed in FACT‐G, Physical Well‐Being, FACT‐An, FACT‐An TOI, fatigue and dyspnoea.

Conclusions

QoL scores of physical and functional domains as well as self‐reported anaemia‐related symptoms correlated well with haemoglobin level in chemotherapy‐treated cancer patients.
Globalisation, inequality and redistribution: Theory and evidence
Authors: Gozgor Giray , Ranjan Priya
Published: June 2017

This paper constructs a simple theoretical model to study the implications of globalisation for inequality and redistribution. It shows that when globalisation increases inequality, a policymaker interested in maximising the sum of welfares of all agents increases redistribution. Empirically, the paper examines the effects of globalisation on inequality and redistribution in a panel data set of 140 countries for the period from 1970 to 2012. It finds that both inequality and redistribution have been increasing with globalisation. The results are robust to the inclusion of many different controls and the exclusion of outliers.
The post-op brain
Authors: Leslie Mitch
Published: June 2017

Surgery can cure—but it may take a toll on cognition. Some scientists blame a body-wide inflammatory response.
Massive blow-out craters formed by hydrate-controlled methane expulsion from the Arctic seafloor
Authors: Andreassen K. , Hubbard A. , Winsborrow M. , Patton H. , Vadakkepuliyambatta S. , Plaza-Faverola A. , Gudlaugsson E. , Serov P. , Deryabin A. , Mattingsdal R. , Mienert J. , Bünz S.
Published: June 2017

Massive methane blow-outs may be responsible for clusters of kilometer-wide craters in the Barents Sea.
Regenerating optic pathways from the eye to the brain
Authors: Laha Bireswar , Stafford Ben K. , Huberman Andrew D.
Published: June 2017

Humans are highly visual. Retinal ganglion cells (RGCs), the neurons that connect the eyes to the brain, fail to regenerate after damage, eventually leading to blindness. Here, we review research on regeneration and repair of the optic system. Intrinsic developmental growth programs can be reactivated in RGCs, neural activity can enhance RGC regeneration, and functional reformation of eye-to-brain connections is possible, even in the adult brain. Transplantation and gene therapy may serve to replace or resurrect dead or injured retinal neurons. Retinal prosthetics that can restore vision in animal models may too have practical power in the clinical setting. Functional restoration of sight in certain forms of blindness is likely to occur in human patients in the near future.
Biological control of aragonite formation in stony corals
Authors: Von Euw Stanislas , Zhang Qihong , Manichev Viacheslav , Murali Nagarajan , Gross Juliane , Feldman Leonard C. , Gustafsson Torgny , Flach Carol , Mendelsohn Richard , Falkowski Paul G.
Published: June 2017

Coral skeletons form by a biologically controlled process, rather than abiotically.
Self-repairing cells: How single cells heal membrane ruptures and restore lost structures
Authors: Tang Sindy K. Y. , Marshall Wallace F.
Published: June 2017

Many organisms and tissues display the ability to heal and regenerate as needed for normal physiology and as a result of pathogenesis. However, these repair activities can also be observed at the single-cell level. The physical and molecular mechanisms by which a cell can heal membrane ruptures and rebuild damaged or missing cellular structures remain poorly understood. This Review presents current understanding in wound healing and regeneration as two distinct aspects of cellular self-repair by examining a few model organisms that have displayed robust repair capacity, including
Xenopus
oocytes,
Chlamydomonas
, and
Stentor coeruleus
. Although many open questions remain, elucidating how cells repair themselves is important for our mechanistic understanding of cell biology. It also holds the potential for new applications and therapeutic approaches for treating human disease.
Committing to socially responsible seafood
Authors: Kittinger John N. , Teh Lydia C. L. , Allison Edward H. , Bennett Nathan J. , Crowder Larry B. , Finkbeiner Elena M. , Hicks Christina , Scarton Cheryl G. , Nakamura Katrina , Ota Yoshitaka , Young Jhana , Alifano Aurora , Apel Ashley , Arbib Allison , Bishop Lori , Boyle Mariah , Cisneros-Montemayor Andrés M. , Hunter Philip , Le Cornu Elodie , Levine Max , Jones Richard S. , Koehn J. Zachary , Marschke Melissa , Mason Julia G. , Micheli Fiorenza , McClenachan Loren , Opal Charlotte , Peacey Jonathan , Peckham S. Hoyt , Schemmel Eva , Solis-Rivera Vivienne , Swartz Wilf , Wilhelm T. 'Aulani
Published: June 2017

Ocean science must evolve to meet social challenges in the seafood sector
From sequence to color
Authors: d'Ischia Marco , Messersmith Phillip B.
Published: June 2017

Tyrosine-containing tripeptides form eumelanin-like pigments with tunable properties
A microbiome variable in the HIV-prevention equation
Authors: Tuddenham Susan , Ghanem Khalil G.
Published: June 2017

Vaginal microbes thwart an antiretroviral microbicide
Reliable Detection of Group B Streptococcus in the Clinical Laboratory
Authors: Rosa-Fraile Manuel , Spellerberg Barbara
Published: June 2017

Group B streptococcus (GBS) is a leading cause of invasive neonatal infections and a significant pathogen in immunocompromised adults. Screening to detect GBS colonization in pregnant women determines the need for antibiotic prophylaxis in that pregnancy. Efficient determination of the GBS colonization status of pregnant women is crucial. Methods that maximize the probability of GBS recovery are needed. The availability of technologies such as matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), molecular techniques, and chromogenic culture media, including Granada-type media, have changed the scenario for GBS detection and identification. This review presents and evaluates novel diagnostic tools, as well as classic identification techniques, for GBS species determination.
WciG
O
-Acetyltransferase Functionality Differentiates Pneumococcal Serotypes 35C and 42
Authors: Geno K. Aaron , Bush C. Allen , Wang Mengnan , Jin Cheng , Nahm Moon H. , Yang Jinghua
Published: June 2017

Streptococcus pneumoniae
expresses capsular polysaccharides (CPSs) to protect itself from opsonophagocytic killing. The genes responsible for capsules synthesized by the Wzy-dependent mechanism, which accounts for 96 of the 98 known pneumococcal capsule types, are in a chromosomal region known as the
cps
locus. The nucleotide sequence in this region has been determined for all serotypes. In contrast, not all CPS structures have been defined. The structure of the serotype 35C polysaccharide was recently reported, but the presence of
O
-acetyltransferase genes in the serotype 35C
cps
locus suggested that it could be incomplete, as the reported structure contains no O-acetylation. In addition, the genetic distinction of serotype 35C from the closely related serotype 42 was unclear, as their reported
cps
loci are nearly identical. To clarify these discrepancies, we obtained serotype 35C and 42 clinical and reference isolates and studied their serological and genetic properties, as well as the structures of CPSs purified from reference isolates. We demonstrated that the
O
-acetyltransferase WciG was functional in serotype 35C but nonfunctional in serotype 42 due to a deletion in
wciG
. Serotype 35C was O-acetylated at the 5- and 6-positions of 3-β-galactofuranose, as well as the 2-position of 6-β-galactofuranose. However, serotype 42 has only O-acetylation at 3-β-galactofuranose, an observation consistent with its loss of WciG functionality, which is associated with O-acetylation at the 2-position and subsequent reaction with typing antiserum 35a. These findings provide a comprehensive view of the genetic, biochemical structural, and serological bases of serotypes 35C and 42.
Mumps Virus SH Protein Inhibits NF-κB Activation by Interacting with Tumor Necrosis Factor Receptor 1, Interleukin-1 Receptor 1, and Toll-Like Receptor 3 Complexes
Authors: Franz Stephanie , Rennert Paul , Woznik Maria , Grützke Josephine , Lüdde Amy , Arriero Pais Eva Maria , Finsterbusch Tim , Geyer Henriette , Mankertz Annette , Friedrich Nicole
Published: June 2017

The mumps virus (MuV) small hydrophobic protein (SH) is a type I membrane protein expressed in infected cells. SH has been reported to interfere with innate immunity by inhibiting tumor necrosis factor alpha (TNF-α)-mediated apoptosis and NF-κB activation. To elucidate the underlying mechanism, we generated recombinant MuVs (rMuVs) expressing the SH protein with an N-terminal FLAG epitope or lacking SH expression due to the insertion of three stop codons into theSHgene. Using these viruses, we were able to show that SH reduces the phosphorylation of IKKβ, IκBα, and p65 as well as the translocation of p65 into the nucleus of infected A549 cells. Reporter gene assays revealed that SH interferes not only with TNF-α-mediated NF-κB activation but also with IL-1β- and poly(I·C)-mediated NF-κB activation, and that this inhibition occurs upstream of the NF-κB pathway components TRAF2, TRAF6, and TAK1. Since SH coimmunoprecipitated with tumor necrosis factor receptor 1 (TNFR1), RIP1, and IRAK1, we hypothesize that SH exerts its inhibitory function by interacting with TNFR1, interleukin-1 receptor type 1 (IL-1R1), and TLR3 complexes in the plasma membrane of infected cells.

IMPORTANCEThe MuV SH has been shown to impede TNF-α-mediated NF-κB activation and is therefore thought to contribute to viral immune evasion. However, the mechanisms by which SH mediates NF-κB inhibition remained largely unknown. In this study, we show that SH interacts with TNFR1, IL-1R1, and TLR3 complexes in infected cells. We thereby not only shed light on the mechanisms of SH-mediated NF-κB inhibition but also reveal that SH interferes with NF-κB activation induced by interleukin-1β (IL-1β) and double-stranded RNA.
Human Herpesviruses 6A, 6B, and 7
Authors: Agut Henri , Bonnafous Pascale , Gautheret-Dejean Agnès
Published: June 2017

Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropismin vivoand, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.
Parvovirus B19
Authors: Landry Marie Louise
Published: June 2017

Primary parvovirus B19 infection is an infrequent, but serious and treatable, cause of chronic anemia in immunocompromised hosts. Many compromised hosts have preexisting antibody to B19 and are not at risk. However, upon primary infection, some patients may be able to mount a sufficient immune response to terminate active parvovirus B19 infection of erythroid precursors. The most common consequence of B19 infection in the compromised host is pure red-cell aplasia, resulting in chronic or recurrent anemia with reticulocytopenia. Anemia persists until neutralizing antibody is either produced by the host or passively administered. Parvovirus B19 should be suspected in compromised hosts with unexplained or severe anemia and reticulocytopenia, or when bone-marrow examination shows either giant pronormoblasts or absence of red-cell precursors. Diagnosis is established by detection of B19 DNA in serum in the absence of IgG antibody to B19. In some cases, IgG antibody is detected but is not neutralizing. Anti-B19 IgM may or may not be present. Therapy includes any or all of the following: red-cell transfusion, adjustment in medications to restore or improve the patient’s immune system, and administration of intravenous immunoglobulin (IVIG). Following treatment, patients should be closely monitored, especially if immunosuppression is unchanged or increased. Should hematocrit trend downward and parvovirus DNA trend upward, the therapeutic options above should be revisited. In a few instances, monthly maintenance IVIG may be indicated. Caregivers should be aware that B19 variants, though rarely encountered, can be missed or under-quantitated by some real-time polymerase-chain reaction methods.
nBio
Chip, a Lab-on-a-Chip Platform of Mono- and Polymicrobial Biofilms for High-Throughput Downstream Applications
Authors: Srinivasan Anand , Torres Nelson S. , Leung Kai P. , Lopez-Ribot Jose L. , Ramasubramanian Anand K.
Published: June 2017

With an estimated 80% of infections being associated with a biofilm mode of growth and the ensuing recalcitrance of these biofilms with respect to conventional antibiotic treatment leading to high mortality rates, there is a dire and unmet need for the development of novel approaches to prevent, treat, and control these infections. Both bacteria and fungi are capable of forming biofilms that are inherently fragile and often polymicrobial in nature, which further complicates treatment. In this work, we showcase a nanobiofilm chip as a convenient platform for culturing several hundreds of mono- or polymicrobial biofilms and for susceptibility testing. This platform enables true ultra-high-throughput screening for antimicrobial drug discovery or diagnostics or for addressing fundamental issues in microbiology.
Hendra and Nipah Virus Infection in Cultured Human Olfactory Epithelial Cells
Authors: Borisevich Viktoriya , Ozdener Mehmet Hakan , Malik Bilal , Rockx Barry
Published: June 2017

Henipaviruses are emerging zoonotic pathogens that can cause acute and severe respiratory and neurological disease in humans. The pathways by which henipaviruses enter the central nervous system (CNS) in humans are still unknown. The observation that human olfactory neurons are highly susceptible to infection with henipaviruses demonstrates that the olfactory epithelium can serve as a site of Henipavirus entry into the CNS.
Change in vision-related quality of life and influencing factors in Asians receiving treatment for neovascular age-related macular degeneration
Authors: Fenwick Eva K , Cheung Gemmy Chui Ming , Gan Alfred TL , Tan Gavin , Lee Shu Yen , Wong Doric , Yeo Ian , Mathur Ranjana , Wong Tien Y , Lamoureux Ecosse L
Published: June 2017

Aim

To assess the change in vision-related quality of life (VRQoL) after treatment for neovascular age-related macular degeneration (nAMD) and factors influencing this change in an Asian population.

Methods

In this longitudinal study, 116 patients (mean age±SD=66.5±9.9 years; 59.5% male) who underwent treatment for nAMD were recruited from a tertiary eye centre in Singapore. Best-corrected visual acuity (BCVA) and the Impact of Vision Impairment (IVI) questionnaire were evaluated at baseline and month 12. We defined three categories of BCVA change in the treated eye: BCVA gain ≥2 lines; no change in BCVA; BCVA loss ≥2 lines. The main outcome measures were the Rasch-derived IVI Reading, Mobility, and Emotional Scores. Multivariable linear regression analyses assessed the influence of sociodemographic, clinical and treatment-related factors on change in VRQoL.

Results

Following treatment, mean treated-eye BCVA improved by almost 2 lines (−0.22±0.40 logMAR, p<0.001) and 43% (n=50) patients reported a gain in BCVA of ≥2 lines. Mean±SD scores for Reading, Mobility and Emotional demonstrated positive changes of 0.43±1.73, 0.45±1.54 and 0.66±1.6, respectively (p<0.001 for all). In multivariable models, a ≥2 line improvement in BCVA was independently associated with a 47% (β=0.20; CI 0.01 to 0.39) increase in Reading Scores, but was not independently associated with Mobility or Emotional Scores.

Conclusion

Nearly half of patients undergoing treatment for nAMD reported a 2-line improvement in vision which was, in turn, associated with substantial positive increases in Reading Scores. Improvements in Mobility and Emotional Scores appear to be driven by factors other than visual acuity.
Danshen attenuates osteoarthritis-related cartilage degeneration through inhibition of NF-κB signaling pathway in vivo and in vitro
Authors: Xu Xilin , Lv Hang , Li Xiaodong , Su Hui , Zhang Xiaofeng , Yang Jun
Published: June 2017

Danshen (Salvia miltiorrhiza) is a traditional Chinese medicine herb that can alleviate the symptoms of osteoarthritis (OA) (Söder et al. 2006) in animals. However, the underlying mechanisms remain poorly understood and require further investigation. In this study, rabbits with experimentally induced OA were given an intra-articular injection of danshen (0.7 mL/day) for 5 weeks. In addition to attenuating the cartilage degeneration of OA in the rabbits, danshen decreased the expression and activity of matrix metalloproteinase 9 (MMP-9) and MMP-13, and increased the expression of their natural inhibitors: tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2. Apoptosis in osteoarthritic cartilage tissues was attenuated by danshen, accompanied with increased expression of B cell lymphoma 2 (Bcl-2) and decreased levels of Bcl-2-associated X protein (Bax). Further, danshen inhibited the nuclear accumulation of nuclear factor kappa-B (NF-κB) p65 in osteoarthritic cartilage. The therapeutic effects of danshen in vivo were comparable to that of sodium hyaluronate, which is a drug used clinically for the treatment OA. In vitro, sodium nitroprusside (SNP) was used to stimulate apoptosis in primary rabbit chondrocytes. We found that the SNP-induced apoptosis was mitigated by danshen. BAY11-7028, an inhibitor of the NF-κB pathway, augmented danshen’s anti-apoptotic effects in cells exposed to SNP. When these results are considered together, they indicate that danshen alleviates the cartilage injury in rabbit OA through inhibition of the NF-κB signaling pathway.
Eclipta prostrataImproves DSS-Induced Colitis through Regulation of Inflammatory Response in Intestinal Epithelial Cells
Authors: Kim Dae-Seung , Kim Sung-Hee , Kee Ji-Ye , Han Yo-Han , Park JinBong , Mun Jeong-Geon , Joo Moon-Jung , Jeon Yong-Deok , Kim Su-Jin , Park Sang-Hyun , Park Sung-Joo , Um Jae-Young , Hong Seung-Heon
Published: June 2017

Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text]). In addition, the release of prostaglandin E2and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1[Formula: see text] expressions in the tumor necrosis factor-[Formula: see text] stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of I[Formula: see text]B and the translocation of the nuclear factor-[Formula: see text]B (NF-[Formula: see text]B). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-[Formula: see text]B transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.
China Provides More International Public Goods
Authors: WU Xiaoping , Liang Fook LYE
Published: June 2017

With increasing clout in world affairs, China has begun to enhance its International Public Goods (IPG) provision in the footsteps of the Great Britain and the United States. Its IPG provision could be enhanced through existing IPGs, such as increasing its budget share in the United Nations, and producing IPGs out of its own initiation and design, such as the establishment of the Shanghai Corporation Organisation and Asian Infrastructure Investment Bank.
Extra- and intracranial blood flow regulation during the cold pressor test: influence of age
Authors: Flück Daniela , Ainslie Philip N. , Bain Anthony R. , Wildfong Kevin W. , Morris Laura E. , Fisher James P.
Published: June 2017

We determined how the extra- and intracranial circulations respond to generalized sympathetic activation evoked by a cold pressor test (CPT) and whether this is affected by healthy aging. Ten young [23 ± 2 yr (means ± SD)] and nine older (66 ± 3 yr) individuals performed a 3-min CPT by immersing the left foot into 0.8 ± 0.3°C water. Common carotid artery (CCA) and internal carotid artery (ICA) diameter, velocity, and flow were simultaneously measured (duplex ultrasound) along with middle cerebral artery and posterior cerebral artery mean blood velocity (MCAvmean and PCAvmean) and cardiorespiratory variables. The increases in heart rate (~6 beats/min) and mean arterial blood pressure (~14 mmHg) were similar in young and older groups during the CPT ( P < 0.01 vs. baseline). In the young group, the CPT elicited an ~5% increase in CCA diameter ( P < 0.01 vs. baseline) and a tendency for an increase in CCA flow (~12%, P = 0.08); in contrast, both diameter and flow remained unchanged in the older group. Although ICA diameter was not changed during the CPT in either group, ICA flow increased (~8%, P = 0.02) during the first minute of the CPT in both groups. Whereas the CPT elicited an increase in MCAvmean and PCAvmean in the young group (by ~20 and ~10%, respectively, P < 0.01 vs. baseline), these intracranial velocities were unchanged in the older group. Collectively, during the CPT, these findings suggest a differential mechanism(s) of regulation between the ICA compared with the CCA in young individuals and a blunting of the CCA and intracranial responses in older individuals.

NEW & NOTEWORTHY Sympathetic activation evoked by a cold pressor test elicits heterogeneous extra- and intracranial blood vessel responses in young individuals that may serve an important protective role. The extra- and intracranial responses to the cold pressor test are blunted in older individuals.
Factors contributing to lower metabolic demand of eccentric compared with concentric cycling
Authors: Peñailillo Luis , Blazevich Anthony J. , Nosaka Kazunori
Published: June 2017

This study compared muscle-tendon behavior, muscle oxygenation, and muscle activity between eccentric and concentric cycling exercise at the same work output to investigate why metabolic demand is lower during eccentric cycling than with concentric cycling. Eleven untrained men (27.1 ± 7.0 y) performed concentric cycling (CONC) and eccentric cycling (ECC) for 10 min (60 rpm) at 65% of the maximal concentric cycling power output (191 ± 45 W) 4 wk apart. During cycling, oxygen consumption (V̇o2), heart rate (HR), vastus lateralis (VL) tissue total hemoglobin (tHb), and oxygenation index (TOI) were recorded, and muscle-tendon behavior was assessed using ultrasonography. The surface electromyogram (EMG) was recorded from VL, vastus medialis (VM), rectus femoris (RF), and biceps femoris (BF) muscles, and cycling torque and knee joint angle during each revolution were also recorded. Average V̇o2 (−65 ± 7%) and HR (−35 ± 9%) were lower and average TOI was greater (16 ± 1%) during ECC than CONC, but tHb was similar between bouts. Positive and negative cycling peak crank torques were greater (32 ± 21 and 48 ± 24%, respectively) during ECC than CONC, but muscle-tendon unit and fascicle and tendinous tissue length changes during pedal revolutions were similar between CONC and ECC. VL, VM, RF, and BF peak EMG amplitudes were smaller (24 ± 15, 22 ± 18, 16 ± 17, and 18 ± 9%, respectively) during ECC than CONC. These results suggest that the lower metabolic cost of eccentric compared with concentric cycling was due mainly to a lower level of muscle activation per torque output.

NEW & NOTEWORTHY This study shows that lower oxygen consumption of eccentric compared with concentric cycling at the same workload is explained by lower muscle activity of agonist and antagonist muscles during eccentric compared with during concentric cycling.
Bone microvascular flow differs from skin microvascular flow in response to head-down tilt
Authors: Howden Michelle , Siamwala Jamila H. , Hargens Alan R.
Published: June 2017

Loss of hydrostatic pressures in microgravity may alter skin and bone microvascular flows in the lower extremities and potentially reduce wound healing and bone fracture repair. The purpose of this study was to determine the rate at which skin and bone microvascular flows respond to head-down tilt (HDT). We hypothesized that microvascular flows in tibial bone and overlying skin would increase at different rates during HDT. Tibial bone and skin microvascular flows were measured simultaneously using photoplethysmography (PPG) in a total of 17 subjects during sitting (control posture), supine, 6° HDT, 15° HDT, and 30° HDT postures in random order. With greater angles of HDT, bone microvascular flow increased significantly, but skin microvascular flow did not change. Tibial bone microvascular flow increased from the sitting control posture (0.77 ± 0.41 V) to supine (1.95 ± 1.01 V, P = 0.001) and from supine posture to 15° HDT (3.74 ± 2.43 V, P = 0.004) and 30° HDT (3.91 ± 2.68 V, P = 0.006). Skin microvascular flow increased from sitting (0.703 ± 0.75 V) to supine (2.19 ± 1.72 V, P = 0.02) but did not change from supine posture to HDT ( P = 1.0). We show for the first time that microcirculatory flows in skin and bone of the leg respond to simulated microgravity at different rates. These altered levels of blood perfusion may affect rates of wound and bone fracture healing in spaceflight.

NEW & NOTEWORTHY Our data show that bone microvascular flow increases more than cutaneous blood flow with greater degrees of head-down tilt. A higher level of perfusion in bone may give insight into the bone mineral density loss in lower extremities of astronauts and why similar tissue degradation is not observed in the skin of the same areas.
Removal of endogenous neuromodulators in a small motor network enhances responsiveness to neuromodulation
Authors: Lett Kawasi M. , Garcia Veronica J. , Temporal Simone , Bucher Dirk , Schulz David J.
Published: June 2017

We studied the changes in sensitivity to a peptide modulator, crustacean cardioactive peptide (CCAP), as a response to loss of endogenous modulation in the stomatogastric ganglion (STG) of the crab Cancer borealis. Our data demonstrate that removal of endogenous modulation for 24 h increases the response of the lateral pyloric (LP) neuron of the STG to exogenously applied CCAP. Increased responsiveness is accompanied by increases in CCAP receptor (CCAPr) mRNA levels in LP neurons, requires de novo protein synthesis, and can be prevented by coincubation for the 24-h period with exogenous CCAP. These results suggest that there is a direct feedback from loss of CCAP signaling to the production of CCAPr that increases subsequent response to the ligand. However, we also demonstrate that the modulator-evoked membrane current ( IMI) activated by CCAP is greater in magnitude after combined loss of endogenous modulation and activity compared with removal of just hormonal modulation. These results suggest that both receptor expression and an increase in the target conductance of the CCAP G protein-coupled receptor are involved in the increased response to exogenous hormone exposure following experimental loss of modulation in the STG.

NEW & NOTEWORTHY The nervous system shows a tremendous amount of plasticity. More recently there has been an appreciation for compensatory actions that stabilize output in the face of perturbations to normal activity. In this study we demonstrate that neurons of the crustacean stomatogastric ganglion generate apparent compensatory responses to loss of peptide neuromodulation, adding to the repertoire of mechanisms by which the stomatogastric nervous system can regulate and stabilize its own output.
Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase
Authors: Arai Rei , Usui-Ouchi Ayumi , Ito Yosuke , Mashimo Keitaro , Murakami Akira , Ebihara Nobuyuki
Published: June 2017

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor-α (TNF-α) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF-α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation.