bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of recombinant human growth hormone treatment on growth, body composition, and safety in infants or toddlers with Prader-Willi syndrome: a randomized, active-controlled trial
Authors: Yang Aram , Choi Jin-Ho , Sohn Young Bae , Eom Yunae , Lee Jiyoon , Yoo Han-Wook , Jin Dong-Kyu
Published: September 2019

Background

Prader-Willi syndrome (PWS) is a rare complex genetic disorder and is characterized by short stature, muscular hypotonia, abnormal body composition, psychomotor retardation, and hyperphagia. Recombinant human growth hormone (rhGH) treatment improves the symptoms in children with PWS, and early treatment results in more favorable outcomes. However, systematic studies in infants and toddlers under 2 years of age are lacking. This multicenter, randomized, active-controlled, parallel-group, open-label, Phase III study aimed to evaluate the safety of rhGH (Eutropin, LG Chem, Ltd.) and its efficacy on growth, body composition, and motor and cognitive development in infants and toddlers with PWS compared with a comparator treatment (Genotropin, Pfizer, Inc.). Eligible Korean infants or toddlers with PWS were randomly assigned to receive Eutropin or comparator (both 0.24 mg/kg/week, 6 times/week) for 1 year. Height standard deviation score (SDS), body composition, and motor and cognitive development were measured.

Results

Thirty-four subjects (less than 24 months old) were randomized into either the Eutropin (N = 17) group or the comparator (N = 17) group. After 52 weeks of rhGH treatment, height SDS and lean body mass increased significantly from baseline in both groups: the mean height SDS change (SD) was 0.75 (0.59) in the Eutropin group and 0.95 (0.66) in the comparator group, and the mean lean body mass change (SD) was 2377.79 (536.25) g in the Eutropin group and 2607.10 (641.36) g in the comparator group. In addition, percent body fat decreased significantly: the mean (SD) change from baseline was − 8.12% (9.86%) in the Eutropin group and − 7.48% (10.26%) in the comparator group. Motor and cognitive developments were also improved in both groups after the 1-year treatment. The incidence of adverse events was similar between the groups.

Conclusions

rhGH treatment for 52 weeks in infants and toddlers with PWS improved growth, body composition, and motor and cognitive development, and efficacy and safety outcomes of Eutropin were comparable to those of Genotropin. Hence, Eutropin is expected to provide safe and clinically meaningful improvements in pediatric patients with PWS.

Trial registration

The study was registered atClinicalTrials.gov(identifier: NCT02204163) on July 30, 2014.

URL:https://clinicaltrials.gov/ct2/show/NCT02204163?term=NCT02204163&rank=1
Relationship of mottling score, skin microcirculatory perfusion indices and biomarkers of endothelial dysfunction in patients with septic shock: an observational study
Authors: Kazune Sigita , Caica Anastasija , Volceka Karina , Suba Olegs , Rubins Uldis , Grabovskis Andris
Published: September 2019

Background

In patients with septic shock, the skin is often chosen for the evaluation of peripheral perfusion and oxygenation. Changes in skin microcirculatory vessel oxygen saturation and relative hemoglobin concentration can be described using a mottling score or captured with hyperspectral imaging. However, the effectiveness of the mottling score in assessing microcirculation remains to be shown. We hypothesize that the mottling score in patients with septic shock is related to skin microcirculatory perfusion indices quantified by hyperspectral imaging, biomarkers that reflect endothelium activation and damage, and clinical outcome.

Methods

Hyperspectral imaging of the knee area was performed in 95 intensive care patients with septic shock enrolled in a single-center observational study to obtain relative oxy/deoxyhemoglobin concentration values and construct anatomical maps of skin microcirculatory saturation. The blood was sampled to obtain concentrations of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-2, and syndecan-1. The spectrophotometrically obtained skin microvascular perfusion indices were compared to the mottling score and biomarker concentration. The association between mottling score, skin microcirculatory perfusion indices, and 28-day mortality was also analyzed.

Results

Microcirculatory oxygen saturation was significantly lower and total hemoglobin concentration was significantly higher in patients with a mottling score of 2 compared to those with a score of 0 (p = 0.02), with no difference between other scores. We found an association between microcirculatory oxygen saturation and PAI-1 levels (rho = − 0.3; p = 0.007). Increased mottling score and decreased microcirculatory oxygen saturation were predictive of 28-day mortality (mottling score 2 vs 0: OR 15.31, 95% CI 4.12–68.11; microcirculatory oxygen saturation: OR 0.90, 95% CI 0.85–0.95). Endothelial biomarkers did not increase the predictive value of skin microcirculatory perfusion indices.

Conclusions

Higher mottling scores are associated with lower microcirculatory oxygen saturation but with significant overlap between scores. Microcirculatory oxygen saturation is a quantitative measure of peripheral oxygenation and is more specific than the mottling score in predicting 28-day mortality.
Mitochondrial DNA variation of the ruffed grouse (Bonasa umbellus)
Authors: Honeycutt Rodney L. , Proudfoot Glenn A. , Silvy Nova J.
Published: September 2019

Objective

The ruffed grouse,Bonasa umbellus, is broadly distributed across North America and displays considerable taxonomic diversity. Except for a genetic study of some western populations of ruffed grouse, nothing is known about genetic variation in other regions of Canada and the United States. Our objective is to examine patterns of mitochondrial DNA (mtDNA) variation in the ruffed grouse across western, central, and eastern parts of its distribution. We compare patterns of mtDNA variation to those characterized by morphology and ecology. Additionally, we evaluate the demographic history of the species based on mitochondrial haplotype diversity.

Results

Patterns of mtDNA variation revealed geographic subdivision, with populations of ruffed grouse subdivided into 3 to 4 genetically distinct groups. This subdivision partially coincided with the ranges of described subspecies. Behavioral traits prohibiting long-distance movement and barriers to dispersal in response to physiography and unsuitable habitat help explain these patterns of subdivision. Historically, the ruffed grouse probably experienced a population expansion, possibly in response to changes during the Pleistocene.
Sleep experiences during different lifetime periods and in vivo Alzheimer pathologies
Authors:   for the KBASE Research Group, Choe Young Min , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Jeon So Yeon , Sohn Bo Kyung , Kim Yu Kyeong , Shin Seong A , Sohn Chul-Ho , Lee Yu Jin , Lee Dong Young
Published: September 2019

Background

Very little is known for the direction or causality of the relationship between lifetime sleep experiences and in vivo Alzheimer’s disease (AD) pathologies. This study aimed to examine the relationship between sleep experiences during the young adulthood, midlife, and late-life periods and in vivo cerebral beta-amyloid (Aβ) deposition and AD signature regional neurodegeneration in cognitively normal (CN) old adults.

Methods

This study included 202 CN old adults who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) study. All participants underwent a comprehensive clinical assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] Fluorodeoxyglucose-PET, and magnetic resonance imaging. The quality and duration of sleep were assessed for the following age periods: 20–30s, 40–50s, and the most recent month. All analyses were adjusted for age, gender, education, apolipoprotein E ε4 status, vascular risk score, Hamilton Depression Rating Scale score, and use of sleep medication.

Results

Bad sleep quality and short sleep duration during midlife were significantly associated with increased Aβ deposition and AD signature regional hypometabolism, respectively. Although current bad sleep quality appeared to be associated with increased Aβ accumulation, this association disappeared after controlling for the effects of midlife sleep quality. Neither the quality nor duration of sleep during young adulthood was related to Aβ burden or neurodegeneration.

Conclusions

Bad sleep quality during midlife increases pathological Aβ deposition in the brain, while short sleep duration during the same period accelerates regional hypometabolism.
Ovarian hyperstimulation syndrome following surgical removal of a complete hydatidiform mole: a case report
Authors: Tsubokura Hiroaki , Ikoma Yohei , Yokoe Takuya , Yoshimura Tomoo , Yasuda Katsuhiko
Published: September 2019

Background

Generally, ovarian hyperstimulation syndrome develops after superovulation caused by ovulation-inducing drugs in infertile patients. However, ovarian hyperstimulation syndrome associated with natural pregnancy is rare, and most cases of ovarian hyperstimulation syndrome have been associated with a hydatidiform mole.

Case presentation

We describe a case of a 16-year-old Japanese girl with a complete hydatidiform mole. The patient was referred for intensive examination and treatment of the hydatidiform mole and underwent surgical removal of the hydatidiform mole at 9 weeks, 5 days of gestation. Histopathological examination revealed a complete hydatidiform mole. The patient’s blood human chorionic gonadotropin level decreased from 980,823 IU/L to 44,815 IU/L on postoperative day 4, and it was below the cutoff level on postoperative day 64. Transvaginal ultrasonography on postoperative day 7 revealed a multilocular cyst measuring 82 × 43 mm in the right ovary and a multilocular cyst measuring 66 × 50 mm in the left ovary. Both ovarian cysts enlarged further. Magnetic resonance imaging on postoperative day 24 revealed that the right multilocular ovarian cyst had enlarged to 10 × 12 cm and that the left multilocular ovarian cyst had enlarged to 25 × 11 cm. Blood examination showed an elevated estradiol level as high as 3482 pg/ml. We diagnosed the patient with bilateral giant multilocular cysts accompanied by ovarian hyperstimulation syndrome because of the rapid increase in the size of the cysts. The patient complained of mild abdominal bloating; however, symptoms such as nausea, vomiting, dyspnea, and abdominal pain were not observed. Therefore, we chose spontaneous observation in the outpatient clinic. The cysts gradually decreased and disappeared on postoperative day 242.

Conclusion

Physicians should be aware that ovarian cysts can occur and can increase rapidly after abortion of a hydatidiform mole. However, the ovarian cyst can return to its original size spontaneously even if it becomes huge.
Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2–HMOX1 axis
Authors: Liu Xuewei , Song Zhongbao , Bai Juan , Nauwynck Hans , Zhao Yongxiang , Jiang Ping
Published: September 2019

Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2–HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.
A clinico-genomic analysis of soft tissue sarcoma patients reveals CDKN2A deletion as a biomarker for poor prognosis
Authors: Bui Nam Q. , Przybyl Joanna , Trabucco Sally E. , Frampton Garrett , Hastie Trevor , van de Rijn Matt , Ganjoo Kristen N.
Published: September 2019

Background

Sarcomas are a rare, heterogeneous group of tumors with variable tendencies for aggressive behavior. Molecular markers for prognosis are needed to risk stratify patients and identify those who might benefit from more intensive therapeutic strategies.

Patients and methods

We analyzed somatic tumor genomic profiles and clinical outcomes of 152 soft tissue (STS) and bone sarcoma (BS) patients sequenced at Stanford Cancer Institute as well as 206 STS patients from The Cancer Genome Atlas. Genomic profiles of 7733 STS from the Foundation Medicine database were used to assess the frequency of CDKN2A alterations in histological subtypes of sarcoma.

Results

Compared to all other tumor types, sarcomas were found to carry the highest relative percentage of gene amplifications/deletions/fusions and the lowest average mutation count. The most commonly altered genes in STS were TP53 (47%), CDKN2A (22%), RB1 (22%), NF1 (11%), and ATRX (11%). When all genomic alterations were tested for prognostic significance in the specific Stanford cohort of localized STS, only CDKN2A alterations correlated significantly with prognosis, with a hazard ratio (HR) of 2.83 for overall survival (p = 0.017). These findings were validated in the TCGA dataset where CDKN2A altered patients had significantly worse overall survival with a HR of 2.7 (p = 0.002). Analysis of 7733 STS patients from Foundation One showed high prevalence of CDKN2A alterations in malignant peripheral nerve sheath tumors, myxofibrosarcomas, and undifferentiated pleomorphic sarcomas.

Conclusion

Our clinico-genomic profiling of STS shows that CDKN2A deletion was the most prevalent DNA copy number aberration and was associated with poor prognosis.
Generalizations and applications of Young’s integral inequality by higher order derivatives
Authors: Wang Jun-Qing , Guo Bai-Ni , Qi Feng
Published: September 2019

In the paper, the authors

generalize Young’s integral inequality via Taylor’s theorems in terms of higher order derivatives and their norms, and

apply newly-established integral inequalities to estimate several concrete definite integrals, including a definite integral of a function which plays an indispensable role in differential geometry and has a connection with the Lah numbers in combinatorics, the exponential integral, and the logarithmic integral.
Oscillation of fourth-order strongly noncanonical differential equations with delay argument
Authors: Baculikova B. , Dzurina J.
Published: September 2019

The aim of this paper is to study oscillatory properties of the fourth-order strongly noncanonical equation of the form
$$ \bigl(r_{3}(t) \bigl(r_{2}(t) \bigl(r_{1}(t)y'(t) \bigr)' \bigr)' \bigr)'+p(t)y \bigl( \tau (t) \bigr)=0, $$

(

r
3

(
t
)

(

r
2

(
t
)

(

r
1

(
t
)

y
′

(
t
)
)

′

)

′

)

′

+
p
(
t
)
y

(
τ
(
t
)
)

=
0
,
where $\int ^{\infty }\frac{1}{r_{i}(s)}\,\mathrm {d}{s}<\infty $

∫
∞

1

r
i

(
s
)

d
s
<
∞
, $i=1,2,3$
i
=
1
,
2
,
3
. Reducing possible classes of the nonoscillatory solutions, new oscillatory criteria are established.
On characteristic polynomial of higher order generalized Jacobsthal numbers
Authors: Marques Diego , Trojovský Pavel
Published: September 2019

In this paper, we study a higher order generalization of the Jacobsthal sequence, namely, the $(k,c)$
(
k
,
c
)
-Jacobsthal sequence $(J^{(k,c)}_{n})$
(

J
n

(
k
,
c
)

)
for any integers n, $k\geq 2$
k
≥
2
and a real number $c>0$
c
>
0
. In particular, we find information about roots of its characteristic polynomial. For that purpose, we combine some powerful tools such as Marden’s method, the Perron–Frobenius theorem, and the Eneström–Kakeya theorem.
Cabozantinib and apixaban: an hitherto unreported interaction
Authors: Santini Daniele , Citarella Fabrizio , Vincenzi Bruno , Russano Marco , Tonini Giuseppe , Stellato Marco
Published: September 2019

The use of direct oral anticoagulant in cancer patients is an emerging issue, which seems to be an alternative to low molecular weight heparin. Every year several new drugs are approved as anticancer treatment with possible drug-drug interaction with other drugs such as oral anticoagulant. We describe, for the first time, a case of neutropenia and thrombocytopenia in a patient in treatment with cabozantinib, a novel anticancer treatment used in metastatic renal cell carcinoma, and apixaban with promptly resumption of the toxicity after the interruption of cabozantinib. This case suggest a possible interaction between these two pharmaceutical agents, which merit caution considering the spreading of the two drugs.
Role of social business in women entrepreneurship development in Bangladesh: perspectives from Nobin Udyokta projects of Grameen Telecom Trust
Authors: Ferdousi Farhana , Mahmud Parveen
Published: September 2019

Social business is a growing phenomenon in the emerging economy due to its appeal toward reducing social problems from the society. Women’s, especially rural women’s, economic activities are mainly confined to the household chores because of the existing patriarchal norms of the society. Social businesses, through providing equity funds, are creating opportunities for the women to pursue entrepreneurial career. This study attempted to analyze the role of social business for developing women entrepreneurship. Primary data were collected from 28 women Nobin Udyokta (new entrepreneurs) and four key informant interviews. The study showed that social business fund plays an important role toward women entrepreneurship development through providing financial (social business fund), human (formal or informal training), and social capital (network) to the women entrepreneurs which is necessary for sustainable entrepreneurship development. Therefore, government and non-government organizations as well as private sectors were suggested to come forward to provide more social business funds and build supportive environment for the women entrepreneurs.
Improvement of bearing capacity of soil by using natural geotextile
Authors: Panigrahi B. , Pradhan P. K.
Published: September 2019

An experimental study has been carried out to improve the bearing capacity of soils by using geotextile. In the present study geojute (gunny bags) is used as geotextile, whereas sand is used as soil media. This research presents the results of laboratory load tests on model square footings supported on reinforced sand beds. A total of 32 load tests are conducted to evaluate the effects of single layer reinforcement placed below square model footings. Parameters of testing programme of the research are the depth of reinforcement, the plan area of reinforcement and the footing size. The test results indicated that the maximum gain in ultimate bearing capacity (UBC) of footings on reinforced soil (by using geojute) is found to be increased by a factor of 3.37 as compared to soil without geojute. Also, the optimum size of reinforcement is found to be 3.5B × 3.5B irrespective of the type of reinforcing materials used. The optimum placement position of geotextile is found to be 0.5B from the base of the footing. At low settlement rates, the study on the values of BCR reveals almost the same results with regard to optimum depth and size of reinforcement mentioned above. It is found that with increase in the settlement rate, BCR increases. Also, the improvement in bearing capacity is found to increase with increase in footing size.
Characterization of bacteriocin ABC transporter ATP-binding protein produced by a newly isolated Enterococcus casseliflavus MI001 strain
Authors: Mikkili Indira , TC Venkateswarulu , Karlapudi Abraham Peele , Kodali Vidya Prabhakar , Srirama Krupanidhi
Published: September 2019

Background

ATP-binding cassette (ABC) transporters constitute one of the largest transporter protein families and play a role in diverse biological processes.

Results

In the present study, bacteriocin isolated from the Enterococcus casseliflavus MI001 strain was identified as an ABC transporter ATP-binding protein. The optimal conditions for the production of bacteriocin were found to be at 35 °C, a pH 5.5, and an incubation time of 24 h. Purification was performed using ammonium sulphate precipitation, gel filtration, and DEAE ion exchange chromatography. The bacteriocin was purified with an eightfold purification scheme resulting with a specific activity of 15,000 AU/mg. The NMR spectrum of purified bacteriocin revealed the presence of amino acids, namely lysine, methionine, cysteine, proline, threonine, tryptophan, and histidine. Further, the bacteriocin ABC transporter showed antimicrobial activity against food spoilage microorganisms.

Conclusions

The ABC transporter ATP-binding protein could be used as a potential alternative for food preservation, and it may be considered as a bio-preservative agent in food processing industries.
Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia
Authors: Sweeney Mark , Whiskey Eromona , Patel Rishi K. , Tracy Derek K. , Shergill Sukhi S. , Plymen Carla M.
Published: September 2019

Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions.

LEARNING OBJECTIVES

After reading this article you will be able to:

•

understand the relative incidence of cardiotoxic side-effects of the various SGAs

•

perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs

•

understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.
Slik phosphorylation of talin T152 is crucial for proper talin recruitment and maintenance of muscle attachment in Drosophila
Authors: Katzemich Anja , Long Jenny Yanyan , Panneton Vincent , Fisher Lucas , Hipfner David , Schöck Frieder
Published: September 2019

Talin is the major scaffold protein linking integrin receptors with the actin cytoskeleton. In Drosophila, extended talin generates a stable link between the sarcomeric cytoskeleton and the tendon matrix at muscle attachment sites. Here we identify phosphorylation sites on Drosophila talin by mass spectrometry. Talin is phosphorylated in late embryogenesis when muscles differentiate, especially on T152 in the exposed loop of the F1 domain of the talin head. Localization of talin-T150/T152A is reduced at muscle attachment sites and can only partially rescue muscle attachment compared to wild type talin. We also identify Slik as the kinase phosphorylating talin at T152. Slik localizes to muscle attachment sites, and the absence of Slik reduces the localization of talin at muscle attachment sites causing phenotypes similar to talin-T150/T152A. Thus, our results demonstrate that talin phosphorylation by Slik plays an important role in fine-tuning talin recruitment to integrin adhesion sites and maintaining muscle attachment.
Histone concentration regulates the cell cycle and transcription in early development
Authors: Chari Sudarshan , Wilky Henry , Govindan Jayalakshmi , Amodeo Amanda A.
Published: September 2019

The early embryos of many animals, including flies, fish and frogs, have unusually rapid cell cycles and delayed onset of transcription. These divisions are dependent on maternally supplied RNAs and proteins including histones. Previous work suggests that the pool size of maternally provided histones can alter the timing of zygotic genome activation (ZGA) in frogs and fish. Here, we examine the effects of under- and overexpression of maternal histones in Drosophila embryogenesis. Decreasing histone concentration advances zygotic transcription, cell cycle elongation, Chk1 activation and gastrulation. Conversely, increasing histone concentration delays transcription and results in an additional nuclear cycle before gastrulation. Numerous zygotic transcripts are sensitive to histone concentration, and the promoters of histone-sensitive genes are associated with specific chromatin features linked to increased histone turnover. These include enrichment of the pioneer transcription factor Zelda, and lack of SIN3A and associated histone deacetylases. Our findings uncover a crucial regulatory role for histone concentrations in ZGA of Drosophila.
Dynamic relationship between noseleaf and pinnae in echolocating hipposiderid bats
Authors: Zhang Shuxin , Liu Yanming , Tang Joanne , Ying Luoxiao , Müller Rolf
Published: September 2019

Old World leaf-nosed bats (family Hipposideridae) can deform the shapes of their “noseleaves” (i.e., ultrasonic emission baffles) and outer ears during echolocation behaviors. Prior work has shown that deformations on the emission as well as on the reception side can have an impact on the properties of the emitted/received sonar signals. The occurrence of the deformations on the emission and reception side raises the question if the bats coordinate these two dynamic biosonar features to achieve synergistic effects. To address this question, simultaneous three-dimensional reconstructions of the trajectories of landmarks on the dynamic noseleaf and pinna geometries have been obtained in great roundleaf bats (Hipposideros pratti). These joint kinematics data on the noseleaf and pinnae have shown both qualitative and quantitative relationships between the noseleaf and pinna motions: Large noseleaf deformations (opening or closing) tended to be associated with non-rigid pinna motions. Furthermore, closing deformations of the noseleaves tended to co-occur with closing motions of the pinna. Finally, a canonical correlation analysis of the motion trajectories has revealed a tight correlation between the motions of the landmarks on the noseleaf and both pinnae. These results demonstrate that the biosonar system of hipposiderid bats includes coordinated emission and reception dynamics.
A subset of brain neurons controls regurgitation in adult Drosophila melanogaster
Authors: Chen Yu-Chieh David , Ahmad Sameera , Amin Kush , Dahanukar Anupama
Published: September 2019

Taste is essential for animals to evaluate food quality and make important decisions about food choice and intake. How complex brains process sensory information to produce behavior is an essential question in the field of sensory neurobiology. Currently, little is known about higher order taste circuits in the brain as compared to those of other sensory systems. Here, we use the common vinegar fly, Drosophila melanogaster, to screen for candidate neurons labeled by different transgenic GAL4 lines in controlling feeding behaviors. We find that activation of one line (VT041723-GAL4) produces “proboscis holding” behavior (extrusion of the mouthpart without withdrawal). Further analysis shows that the proboscis holding phenotype indicates an aversive response, since flies pre-fed with either sucrose or water prior to neuronal activation exhibit regurgitation. Anatomical characterization of VT041723-GAL4 labeled neurons suggests that they receive sensory input from peripheral taste neurons. Overall, our study identifies a subset of brain neurons labeled by VT041723-GAL4 that may be involved in a taste circuit that controls regurgitation.
Influence of symbiotic and non-symbiotic bacteria on pheromone production in Steinernema nematodes (Nematoda, Steinernematidae)
Authors: Roder Alexandra C. , Wang Yuting , Butcher Rebecca , Stock S. Patricia
Published: September 2019

In this study, we assessed the effect of symbiotic (cognate and non-cognate) and non-symbiotic bacteria on ascaroside production of first-generation adults in two Steinernema spp.: S. carpocapsae All strain and S. feltiae SN strain. Each nematode species was reared under three bacterial scenarios: a) cognate symbiotic, b) non-cognate symbiotic strain, and c) non-cognate symbiotic species. Our results showed S. carpocapsae produced four quantifiable ascaroside molecules: asc-C5, asc-C6, asc-C7, and asc-C11. Whereas, in S. feltiae only three molecules were detected: asc-C5, asc-C7 and asc-C11. Bacterial conditions did not significantly affect the quantity of the secreted ascarosides, in first generation adults of S carpocapsae. However, in S. feltiae, Xenorhabdus nematophila All strain influenced the production of two ascaroside molecules asc-C5 and asc-C11.
Assessing the development and implementation of the Global Trigger Tool method across a large health system in Sicily
Authors: Parrinello Vincenzo , Grasso Elena , Saglimbeni Giuseppe , Patanè Gabriella , Scalia Alma , Murolo Giuseppe , Lachman Peter
Published: September 2019

Background: The Institute for Healthcare Improvement (IHI) has proposed a new method, the Global Trigger Tool (IHI GTT), to detect and monitor adverse events (AEs) and provide information to implement improvement. In 2015, the Sicilian Health System adopted IHI GTT to assess the number, types and severity levels of AEs. The GTT was implemented in 44 of 73 Sicilian public hospitals and 18,008 clinical records (CRs) were examined. Here we present the standardized application of the GTT and the preliminary results of 14,706 reviews of CRs.

Methods: IHI GTT was adapted, developed and implemented to the local context. Reviews of CRs were conducted by 199 professionals divided into 71 review teams consisting of three individuals: two of whom had clinical knowledge and expertise, and a physician to authenticate the AE. The reviewers entered data into a dedicated IT-platform. All 44 of the public hospitals were included, with approximately 300,000 yearly inpatient admissions out of a population of approximately 5 million. In total, 14,706 randomized CRs of inpatients from medicine, surgery, obstetric and ICU wards, from June 2015 to June 2018 were reviewed.

Results: In 975 (6.6%) CRs at least one AE was found. Approximately 20,000 patients of the 300,000 discharged each year in Sicily have at least one AE. In 5,574 (37.9%) CRs at least one trigger was found. A total of 1,542 AEs were found. The analysis of ROC curve shows that the presence of two triggers in a CR indicates with high probability the presence of an AE. The most frequent type of AE was in-hospital related infection.

Conclusions: The GTT is an efficient method to identify AEs and to track improvement of care. The analysis and monitoring of some triggers is important to prevent AEs. However, it is a labor-intensive method, particularly if the CRs are paper-based.
Mitochondrial dysregulation and muscle disuse atrophy
Authors: Ji Li Li , Yeo Dongwook
Published: September 2019

It is well established that mitochondria play a critical role in the metabolic and physiological adaptation of skeletal muscle to enhanced contractile activity. Several redox-sensitive signaling pathways such as PGC-1α, AMPK, IGF/Akt/mTOR, SIRT, NFκB, and FoxO are involved with extensive crosstalk to regulate vital cellular functions such as mitochondrial biogenesis, mitochondrial fusion and fission dynamics, autophagy/mitophagy, and apoptosis under altered demand and stress. However, when muscles cease contraction, such as during immobilization and denervation, mitochondria undergo a series of detrimental changes characterized by downregulation of PGC-1α and antioxidant defense, increased ROS generation, activated FoxO, NFκB, and inflammation, enhanced ubiquitination, and finally mitophagy and apoptotic cascades. The phenotypic outcome of the discord of mitochondrial homeostasis is elevated proteolysis and muscle atrophy. The demonstration that PGC-1α overexpression via transgene or in vivo DNA transfection can restore mitochondrial homeostasis and reverse myocyte atrophy supports the “mitostasis theory of muscle atrophy”.
Understanding life sciences data curation practices via user research
Authors: Venkatesan Aravind , Karamanis Nikiforos , Ide-Smith Michele , Hickford Jonathan , McEntyre Johanna
Published: September 2019

Background: Manual curation is a cornerstone of public biological data resources. However, it is a time-consuming process that urgently needs supportive technical solutions in the face of rapid data growth. Supporting scalable curation is a part of the mission of the Elixir Data Platform. Thus far, we have established infrastructure capable of ingesting and aggregating text-mined outputs from multiple providers and making these available via an API. This public API is used by Europe PMC to display specific entities and relationships on full text articles (via the SciLite application).

Methods: To ensure that the future development of this infrastructure meets the needs of curators, we carried out a user research project to understand and identify common workflow patterns and practices via an observational study. Building on these outcomes, we then devised a curator community survey to more specifically understand which entity types, sections of a paper and tools are of top priority to address.

Results: The main challenges faced by curators included the following: a) There is a need for ways to prioritise and identify relevant papers for curation as the volume of literature is large; b) Finding specific information can prove difficult; quick ways of filtering articles based on specific entities, such as experimental methods, species and other important entities, such as genes, cell lines and tissue samples, are required; and c) Transferring information from the search/annotation tools to the various curation workflows was also challenging.

Conclusions: This study lays the foundation for identifying actionable items to orient the current infrastructure towards meeting the needs of curation community, by improving text-mined annotation quality and coverage and other engineering solutions; and reusing text-mined annotations and other metadata in Europe PMC for article triage. Furthermore, this study presents an opportunity to explore customisation of triage/ranking systems to suit different curation contexts.
The development of mouthwashes without anti-gonococcal activity for controlled clinical trials: an in vitro study
Authors: Van Dijck Christophe , Cuylaerts Vicky , Sollie Piet , Spychala Anna , De Baetselier Irith , Laumen Jolein , Crucitti Tania , Kenyon Chris
Published: September 2019

Background: The oropharynx plays a major role in the development and spread of antimicrobial resistant Neisseria gonorrhoeae among men who have sex with men. Trials are currently assessing the efficacy of bactericidal mouthwashes as possible therapeutic or preventive options against these pharyngeal gonococcal infections. Controlled clinical trials require the use of a placebo mouthwash without anti-gonococcal activity. So far, no such mouthwash has been described. We describe the development of a mouthwash for this purpose.

Methods: The in vitro anti-gonococcal activity of Corsodyl®, Listerine Cool Mint®, Biotene®, phosphate buffered saline and six in-house placebo mouthwashes was evaluated. Three gonococcal isolates from patients with pharyngeal infection were exposed to the mouthwashes for a duration ranging from 30 seconds to 60 minutes. Isolates were then plated onto blood agar (5% horse blood) and incubated for 24 hours (5-7% CO2, 35 ± 2°C). Growth of N. gonorrhoeae was scored on a five-point scale (0 to 4). All experiments were conducted in duplicate.

Results: Corsodyl® and Listerine Cool Mint® were bactericidal to all isolates. For the other mouthwashes, the median growth score after 60 minutes of exposure was 4 (interquartile range 4-4) for phosphate buffered saline; 1 (interquartile range 1-3) for Biotene®; and ranged between 0 and 2 for the in-house composed mouthwashes. An in-house composed mouthwash (Placebo 6) performed best, with a growth score of 2 (interquartile range 2-3).

Conclusions: All of the evaluated potential placebo mouthwashes were bacteriostatic after gonococcal exposure of 30 to 60 minutes. In-house composed Placebo 6 showed less inhibition on gonococcal growth than Biotene® and the other in-house placebos and demonstrates, in our opinion, a good trade-off between anti-gonococcal properties and taste.
Assessment of a neuro-developmental screening tool in children in Bhutan
Authors: Wong Brian , Grundy Sara , Tshering Lhab , Tshering Kinley , Mateen Farrah J.
Published: September 2019

Background:Developmental screening tools are designed to fit the cultural context in which they are utilized, yet often find a wider international audience. This study evaluates the efficacy of one such tool, the Parental Evaluation of Developmental Status: Developmental Milestones (PEDS:DM), developed in the United States and tested in the lower income Asian country of Bhutan. We aimed to test the PEDS:DM instrument to measure neurodevelopmental delay in children in Bhutan.

Methods:In total, 96 community-dwelling Bhutanese children (3-7 years old) without diagnosed neurocognitive conditions were recruited from ambulatory clinics in urban Bhutan in 2016 as part of a larger study on retinal imaging and cognitive and growth parameters. Scoring was based on neurocognitive domains (gross and fine motor, receptive and expressive speech, self-help, social-emotional). Rates of failure (meant to indicate delay) within domains were calculated.

Results:Modifications of some standard questions were deemed necessary by the study staff to suit the cultural context, such as replacing kickball with football in a question regarding games played with rules to maintain local relevance. In a modified PEDS:DM test with these improvised modifications, the mean percentage of age-appropriate domains failed was 58.8% and the mean percent delay was 12.3% (range 0-41.4%, available in n=83). The highest prevalence of failures was 59.4% for receptive language and 76.3% for expressive language, much higher than the lowest rate of failure seen in self-help (5.4%). 

Conclusions:The PEDS:DM requires further modifications and validation studies before it can be reliably implemented to assess developmental delay in children in Bhutan. In this pilot study, the rate of delay as reported by the PEDS:DM would be scored as markedly elevated, especially when compared to available epidemiologic studies in the region.
Visualizing participant experiences in maternal and child nutrition studies using timeline mapping
Authors: Sankaran Deepa , Sharma Priyanshu , Lazarus Lisa , Swain Tapaswini , Pilli Bhanu , Kumar P. Manish , Namasivayam Vasanthakumar , Blanchard James , Moses Stephen
Published: September 2019

Iron and folic acid (IFA) supplementation is one of the most cost-effective interventions to prevent and treat anemia during pregnancy. Despite having the highest global burden of anemia among pregnant women, rates of IFA uptake in pregnancy in India are still very low, particularly in the state of Uttar Pradesh. Timeline maps were developed as a visual qualitative tool to explore the nuances of health behaviors among pregnant women with respect to antenatal care (ANC) services, including IFA consumption.  Timeline maps were used to elicit and visually document critical events pertaining to ANC services chronologically, including details on contact points with the health system and events specific to IFA distribution, consumption and counselling. The tool consists of a horizontal straight line with nine suspended boxes corresponding to each month of pregnancy, with legends on how to illustrate IFA receipt and consumption. In this instance, the woman’s last menstrual period and expected date of delivery were used as a frame of reference for the duration of pregnancy.  Six research assistants (RAs) were trained on how to use timeline maps to elicit and record participant narratives. The RAs later participated in a focus group discussion to gain insight about their experiences using the tool. The timeline maps were easy-to-use and facilitated in-depth conversations with participants. RAs were able to actively engage the participants in co-creating the maps. The visual nature of the tool prompted participants’ recall of key pregnancy events and reflexivity. Challenges reported with the tool/process included recollection of past events and potential misrepresentation of information. These highlight a need to restructure training processes. Our findings indicate that timeline maps have the potential to be used in a variety of other program contexts, and merit further exploration.
Frailty and physical performance in the context of extreme poverty: a population-based study of older adults in rural Burkina Faso
Authors: Witham Miles D. , Davies Justine I. , Bärnighausen Till , Bountogo Mamadou , Manne-Goehler Jennifer , Payne Collin F. , Ouermi Lucienne , Sie Ali , Siedner Mark J. , Harling Guy
Published: September 2019

Background: Little is known about the prevalence of frailty and about normal values for physical performance among older individuals in low-income countries, in particular those in sub-Saharan Africa. We describe the prevalence of phenotypic frailty, and values and correlates of several physical performance measures in a cohort of middle-aged and older people living in rural Burkina Faso, one of the world’s poorest communities.

Methods: We analysed data collected from participants aged over 40 in Nouna district, Burkina Faso. We measured handgrip strength, four metre walk speed, chair rise time, and derived the Fried frailty score based on grip strength, gait speed, body mass index, self-reported exhaustion, and physical activity. Frailty and physical performance indicators were then correlated with health and sociodemographic variables including comorbid disease, marital status, age, sex, wealth and activity impairment.

Results: Our sample included 2973 individuals (1503 women), mean age 54 years. 1207 (43%) were categorised as non-frail, 1324 (44%) as prefrail, 212 (7%) as frail, and 167 (6%) were unable to complete all five frailty score components. Lower grip strength, longer chair stand time, lower walk speed and prevalence of frailty rose with age. Frailty was more common in women than men (8% vs 6%, p=0.01) except in those aged 80 and over. Frailty was strongly associated with impairment of activities of daily living and with lower wealth, being widowed, diabetes mellitus, hypertension, and self-reported diagnoses of tuberculosis or heart disease. With the exception of grip strength, which was higher in women than prior international normative values, women had greater deficits than men in physical performance.

Conclusions: Phenotypic frailty and impaired physical performance were associated as expected with female sex, co-morbidities, increasing age and impaired activities of daily living. These results support the use of frailty measurements for classification of ageing related syndromes in this setting.
The Effect of the Microsoft Excel based Interactive Learning Media on the Physics Problem Solving
Authors: Astuti Irnin Agustina Dwi , Bhakti Yoga Budi
Published: September 2019

The physics problem solving is needed students to overcome the phenomenon of physics.  The development of technology in physics learning is able to explain the concept of abstract physics. This study aims to know effect of use interactive learning media based Microsoft Excel on the physics problem solving. The subject on this media is Heat and Temperature. The research method used is pretest-postest controlled group design. The analysis technique is used t-test with SPSS 16.0 with a margin of error of 5%. The results of this study showed that the mean scores of post-test treatment class students significantly better than the average score post-test control class indicated by the average score of students' post-test treatment class at 80.26 and scores the average post-test control class at 68.00 and with SPSS analyze sig value is 0.000. While the average score gain results-physics students learn physics class treatment significantly better than the average score gain results Physics students learn physics-control class indicated by the average score of physics problem solving gain of 0.77 and the treatment class the average score gain control class student physics problem solving of 0.63.
Equine Herpesvirus - the hidden threat
Authors: Burrows Imogen
Published: September 2019

Dr Imogen Burrows BVetMed CertAVP(EM) MRCVS, Lingfield Equine Vets details a recent case study and the biosecurity measures employed to prevent the spread of infection
To poultice or not to poultice?
Authors: Trayhorn Dawn
Published: September 2019

Redwings' veterinary surgeon Dawn Trayhorn answers some of the questions commonly raised by owners
The veterinary prescribing cascade: friend or foe?
Authors: Bowen Mark
Published: September 2019

Mark Bowen BVetMed MMedSci PhD DipACVIM DipECEIM DipECVSMR PFHEA FRCVS dispels some of the more common misconceptions
Colic – more than just a pain in the gut?
Authors: Watson Rebecca
Published: September 2019

Rebecca Watson MSc RVN reminds us what the horse owner should know and expect
Appleby Horse Fair: protecting and promoting
Authors: Vilela Andrea
Published: September 2019

Andrea Vilela, Education and Campaigns Manager for Redwings Horse Sanctuary, reports on this year's Appleby Horse Fair RSPCA led welfare and support initiative
Non-invasive ventilation as a prehospital intervention for acute COPD exacerbation
Authors: McCreesh Samuel
Published: September 2019

Chronic obstructive pulmonary disease (COPD) is the second most common respiratory illness in the UK, affecting over 1 million people. Acute exacerbations of COPD are a common presentation to the ambulance service and account for thousands of hospital admissions annually. Acute respiratory failure accompanies approximately 20% of exacerbations. Current prehospital treatment focuses on oxygen and pharmacological therapy to treat the underlying causes. Non-invasive ventilation (NIV) is a method of ventilatory support that does not require endotracheal intubation, avoiding significant risks associated with intubation and sedation. While some UK ambulance services have introduced NIV, UK guidelines primarily focus on hospital use. International trials have shown prehospital NIV to be more effective than standard treatment in terms of reducing the need for intubation and invasive ventilation in hospital. However, further research is necessary before NIV is introduced widely in UK prehospital paramedic practice.