bluuebunny/crossref_metadata_2025 huggingface dataset:
Esophageal diverticula are associated with propagating peristalsis: a study utilizing high‐resolution manometry
Authors: Carlson D. A. , Gluskin A. B. , Mogni B. , Koo J. , Sood R. , Lin Z. , Pandolfino J. E.
Published: December 2015

Background

Esophageal diverticula have been associated with esophageal motility disorders, most commonly achalasia. We aimed to evaluate high‐resolution manometry (HRM) motility diagnoses and pressurization patterns in patients with esophageal diverticula.

Methods

Patients were retrospectively identified for distal esophageal diverticula and previously completed HRM. High‐resolution manometries were analyzed according to the Chicago Classification, and the pressure slope of the compartmentalization phase (time between upper esophageal sphincter closure and the transition zone) of esophageal bolus transit was measured. Pressure slopes were also measured in 10 asymptomatic volunteers (controls) for comparison.

Key Results

Nineteen patients (ages 31–83) were included. Eight (42%) patients had normal motility, five (26%) had esophagogastric junction outflow obstruction, and two (11%) had jackhammer esophagus; four patients had other motility diagnoses including only one patient with achalasia. A total of six patients (32%) had at least one hypercontractile swallow. Greater compartmentalization phase pressure slopes were observed in patients at the mid‐esophageal body in both supine (median [interquartile range]: 1.9 mmHg/s [0.9, 3.6]) and upright (1.1 [0.1, 3.1]) positions than in controls (supine: −1.3 [−2.4, −0.11], p = 0.001; upright; −0.71 [−2.1, −0.02], p = 0.005).

Conclusions & Inferences

Propagating peristalsis, often with hypercontractility, was commonly seen in our cohort of patients with esophageal diverticula. Abnormal compartmentalization phase pressurization may indicate a relationship of abnormal esophageal wall mechanics and/or compliance with diverticula; however whether these findings are causal or reactionary remains unclear.
One‐carbon metabolism and epigenetics: understanding the specificity
Authors: Mentch Samantha J. , Locasale Jason W.
Published: December 2015

One‐carbon metabolism is a metabolic network that integrates nutrient status from the environment to yield multiple biological functions. The folate and methionine cycles generate S‐adenosylmethionine (SAM), which is the universal methyl donor for methylation reactions, including histone and DNA methylation. Histone methylation is a crucial part of the epigenetic code and plays diverse roles in the establishment of chromatin states that mediate the regulation of gene expression. The activities of histone methyltransferases (HMTs) are dependent on intracellular levels of SAM, which fluctuate based on cellular nutrient availability, providing a link between cell metabolism and histone methylation. Here we discuss the biochemical properties of HMTs, their role in gene regulation, and the connection to cellular metabolism. Our emphasis is on understanding the specificity of this intriguing link.
Impact of the Right Ventricular Lead Position on Clinical End Points in CRT Recipients—A Subanalysis of the Multicenter Randomized SPICE Trial
Authors: ASBACH STEFAN , LENNERZ CARSTEN , SEMMLER VERENA , GREBMER CHRISTIAN , SOLZBACH ULRICH , KLOPPE AXEL , KLEIN NORBERT , SZENDEY ISTVAN , ANDRIKOPOULOS GEORGE , TZEIS STYLIANOS , BODE CHRISTOPH , KOLB CHRISTOF
Published: December 2015

Background

The impact of right ventricular (RV) lead location on clinical end points in patients undergoing cardiac resynchronization therapy (CRT) is unclear. We evaluated the impact of different RV lead locations on clinical outcome in CRT patients enrolled in the Septal Positioning of ventricular implantable cardioverter‐defibrillator (ICD) Electrodes (SPICE) trial, which randomized recipients of implantable cardioverter defibrillators to apical versus midseptal RV lead positioning.

Methods

Ninety‐eight CRT recipients were included in the multicenter SPICE trial and followed for 12 months: Fifty‐three patients were randomized to receive an apical (A) and 45 to receive a midseptal (S) lead position. We compared echocardiographical and electrocardiographical parameters and outcome.

Results

Echocardiographic response with respect to improvement of left ventricular ejection fraction (A: +15.8 ± 14.6%, S: +9.7 ± 12.6%, P = 0.156) and reduction of left ventricular end‐diastolic diameter (A: −4.2 ± 10.7 mm, S: −7.5 ± 10.7 mm, P = 0.141) was comparable in apical and midseptal groups. Paced QRS width neither differed at prehospital discharge (A: 129 ± 21 ms, S: 135 ± 21 ms, P = 0.133) nor at 12‐month follow‐up (A: 131 ± 23 ms, S: 134 ± 28 ms, P = 0.620). No differences were found with respect to the risk of ventricular tachyarrhythmia or ICD therapy. Septal RV lead position, however, was associated with a significant longer time to a first heart failure event (P = 0.040) and a longer survival time (P = 0.019).

Conclusions

In CRT recipients, midseptal RV lead position was not superior with respect to improvement of echocardiographic parameters or paced QRS width. It did not predispose to ventricular arrhythmias or ICD therapy. The finding that midseptal lead position was associated with a longer time to first heart failure event and a longer survival time deserves further investigation.
Deep roots and soil structure
Authors: Gao W. , Hodgkinson L. , Jin K. , Watts C.W. , Ashton R.W. , Shen J. , Ren T. , Dodd I.C. , Binley A. , Phillips A.L. , Hedden P. , Hawkesford M. J. , Whalley W.R.
Published: December 2015

In this opinion article we examine the relationship between penetrometer resistance and soil depth in the field. Assuming that root growth is inhibited at penetrometer resistances > 2.5 MPa, we conclude that in most circumstances the increases in penetrometer resistance with depth are sufficiently great to confine most deep roots to elongating in existing structural pores. We suggest that deep rooting is more likely related to the interaction between root architecture and soil structure than it is to the ability of a root to deform strong soil. Although the ability of roots to deform strong soil is an important trait, we propose it is more closely related to root exploration of surface layers than deep rooting.
Hypocellular Plaque‐Like CD34‐Positive Dermal Fibroma (Medallion‐Like Dermal Dendrocyte Hamartoma) Presenting as a Skin‐Colored Dermal Nodule
Authors: Mutgi Krishna A. J. , Chitgopeker Pooja , Ciliberto Heather , Stone Mary S.
Published: December 2015

Plaque‐like CD34‐positive dermal fibromas, also known as medallion‐like dermal dendrocyte hamartomas (MDDHs), are a recently recognized group of congenital and acquired spindle cell neoplasms that may appear histologically similar to dermatofibrosarcoma protuberans. Recognizing the clinical heterogeneity of this neoplasm and the subtle pathologic differences are crucial to making the correct diagnosis and avoiding the aggressive surgical intervention required to treat a dermatofibrosarcoma protuberans. We present the case of a 9‐year‐old girl with an acquired variant of a plaque‐like CD34‐positive dermal fibroma without clinical epidermal change. Our case expands the clinical spectrum to include an acquired variant of a plaque‐like CD34‐positive dermal fibroma without clinical epidermal change. Examination of more cases is needed to determine whether all clinical variants are truly subtypes of the same neoplasm or represent distinct CD34‐positive spindle cell proliferations.
Frameshift Sequence Variants in the Human Lipase‐H Gene Causing Hypotrichosis
Authors: Mehmood Sabba , Shah Sayed Hajan , Jan Abid , Younus Muhammad , Ahmad Farooq , Ayub Muhammad , Ahmad Wasim
Published: December 2015

Hypotrichosis is a condition of abnormal hair pattern characterized by sparse to absent hair on different parts of the body, including the scalp. The condition is often characterized by tightly curled woolly hairs, discoloration of hair, and development of multiple keratin filled cysts or papules on the body. Sequence analysis of the lipase H (LIPH) gene, mapped on chromosome 3q27.3, led to the identification of a novel frameshift deletion variant (c.932delC, p.Pro311Leufs*3) in one family and previously reported 2‐bp deletion (c.659_660delTA) in five other families, inherited hypotrichosis, and woolly hair in an autosomal recessive pattern. The study further extends the body of evidence that sequence variants in the LIPH gene result in hypotrichosis and woolly hair phenotype.
Congenital Ichthyosiform Erythroderma Superimposed with Chronic Dermatophytosis: A Report of Three Siblings
Authors: Vyas Nikki S. , Kannan Swati , N. Jahnke Marla , Hu Rong‐Hua , Choate Keith A. , Shwayder Tor A.
Published: December 2015

Congenital ichthyosiform erythroderma is an autosomal recessive ichthyosis characterized by severe scaling and erythroderma. We report a family of three siblings who were all born with a collodion membrane and presented with diffuse scaling and pruritus. All three children subsequently developed chronic cutaneous dermatophyte infections requiring oral antifungals. One child developed superinfection with methicillin‐resistant Staphylococcus aureus requiring antibiotics.
Current status of treatment for pediatric rhabdomyosarcoma in the USA and Japan
Authors: Hosoi Hajime
Published: December 2015

This article reviews the current status of treatment for children with rhabdomyosarcoma, according to the four risk groups. Low‐risk subgroup A: the Children's Oncology Group in the USA recently performed a clinical trial consisting of a chemotherapy regimen with a shortened treatment period and a reduced drug dosage. Patients in this group received only four cycles of vincristine and actinomycin D (VA) after four cycles of vincristine, actinomycin D, and cyclophosphamide (VAC) with cyclophosphamide (CPM) 1.2 g/m2 and their outcome was no worse than that obtained with previous regimens. Low‐risk subgroup B: although marked improvement in survival was seen with an intensive VAC regimen with CPM 2.2 g/m2/cycle (Intergroup Rhabdomyosarcoma Study [IRS]‐V, 1997–2004), the total dose of CPM in this regimen caused serious and fatal hepatic veno‐occlusive disease during treatment and probably cannot avoid infertility or possible secondary cancer as a late effect. Thereafter, a reduced‐dose regimen consisting of four cycles of VAC with CPM 1.2 g/m2 followed by 12 cycles of VA was investigated in the next study, but the outcome appeared to be worse than in IRS‐V. Intermediate‐risk group: no significant difference was found between VAC/vincristine, topotecan and cyclophispahamide (VTC) and intensive VAC in IRS‐V. The results of a subsequent regimen of VAC with CPM 1.2 g/m2 alternating with vincristine and irinotecan are awaited. High‐risk group: overall survival is approximately 30% and has not improved over the last 25 years. Although 18 month failure‐free survival (FFS) was improved with an intensive combination therapy regimen, 36 month FFS dropped to 32% and thus better novel approaches or additive treatments are needed.
Safety of lipid emulsion in very low‐birthweight infants according to cytokine level
Authors: Ichikawa Junko , Ichikawa Go , Tsuboi Yayoi , Kuribayashi Ryota , Watabe Yoshiyuki , Sairenchi Toshimi , Suzumura Hiroshi , Arisaka Osamu
Published: December 2015

Background

The aim of this study was to verify whether lipid emulsion treatment aggravates infection and inflammation in very low‐birthweight (VLBW) infants.

Study design

Very low‐birthweight (<1500 g) infants born at <32 weeks gestational age between October 2013 and October 2014 at Dokkyo Medical University Hospital (Mibu, Tochigi, Japan) were treated with or without i.v. nutrition with a lipid emulsion. Infants were excluded who had congenital abnormalities, could not receive i.v. nutrition because of poor general condition, or on physician decision. Lipid emulsion with purified soybean oil was initiated at 0.5 g/kg/day on postnatal day 1. The dose was increased to 1 g/kg/day, and then to 1.5 g/kg/day (maximum dose). Blood tests were performed before (day 1) and after (day 8) initiation of lipid emulsion treatment. Interleukin (IL)‐6, IL‐8, monocyte chemotactic protein 1 (MCP‐1), tumor necrosis factor‐α (TNF‐α), C‐reactive protein (CRP), total bilirubin (T‐Bil), direct bilirubin (D‐Bil) and insulin were measured. Changes in respiratory condition, amount of oxygen used, and phototherapy duration were investigated.

Results

A total of 17 treated and 15 untreated VLBW infants were enrolled. IL‐6, IL‐8, MCP‐1, TNF‐α, CRP, T‐Bil, D‐Bil and insulin on days 1 and 8; respirator or surfactant use; amount of oxygen used; and phototherapy duration were not significantly different between the two groups.

Conclusions

Lipid emulsion treatment did not increase inflammatory cytokine levels or aggravate respiratory disorders. Lipid emulsions, if proven safe, could be used to treat VLBW infants soon after birth, which may prevent extrauterine growth restriction and improve intellectual development prognosis.
Optimal management for pediatric chronic myeloid leukemia
Authors: Tanizawa Akihiko
Published: December 2015

Chronic myeloid leukemia (CML) is rare among childhood leukemias. Its incidence increases with age, from 0.09/100 000 at ≤15 years old to 7.88/100 000 at ≥75 years old. There are several biological and clinical differences between pediatric and adult CML. Markedly increased leukocyte count and a higher incidence of splenomegaly are characteristic features at diagnosis in pediatric patients. The therapeutic approach to CML has changed since the introduction of the tyrosine kinase inhibitor (TKI) imatinib, followed by dasatinib and nilotinib. Given the efficacy of TKI in adult CML, TKI are regarded as the established first‐line treatment in adult patients. In 2011, a prospective phase IV study in pediatric patients showed the excellent efficacy and safety of imatinib. Imatinib is also accepted as a first‐line option for childhood chronic phase CML. Although the efficacy of dasatinib and nilotinib reported in adult studies seems very attractive for pediatric patients, neither drug has been prospectively investigated in a large pediatric cohort. TKI are designed to inhibit BCR‐ABL1 kinase, but they have unfavorable effects, so‐called “off‐target” complications, such as growth impairment. Long‐term morbidity due to TKI is unknown. Furthermore, the adverse effects on growing children have not been clearly elucidated, even though the exposure period to imatinib is relatively short. To establish the standard therapeutic management for pediatric CML, it is important to prospectively confirm the attractive outcomes obtained in adult studies via pediatric clinical trials with a careful monitoring system for TKI‐induced adverse effects, especially in growing children.
CHST14/D4ST1 deficiency: New form of Ehlers–Danlos syndrome
Authors: Kosho Tomoki
Published: December 2015

Carbohydrate sulfotransferase 14/dermatan 4‐O‐sulfotransferase‐1 (CHST14/D4ST1) deficiency represents a specific form of Ehlers–Danlos syndrome (EDS) caused by recessive loss‐of‐function mutations in CHST14. The disorder has been independently termed “adducted thumb–clubfoot syndrome”, “EDS, Kosho type”, and “EDS, musculocontractural type”. To date, 31 affected patients from 21 families have been described. Clinically, CHST14/D4ST1 deficiency is characterized by multiple congenital malformations (craniofacial features including large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low‐set and rotated ears, high palate, long philtrum, thin upper lip vermilion, small mouth, and micro‐retrognathia; multiple congenital contractures including adduction–flexion contractures and talipes equinovarus as well as other visceral or ophthalmological malformations) and progressive multisystem fragility‐related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; pneumothorax or pneumohemothorax; large subcutaneous hematomas; and diverticular perforation). Etiologically, multisystem fragility is presumably caused by impaired assembly of collagen fibrils resulting from loss of dermatan sulfate (DS) in the decorin glycosaminoglycan side chain that promotes electrostatic binding between collagen fibrils. This is the first reported human disorder that specifically affects biosynthesis of DS. Its clinical characteristics indicate that CHST14/D4ST1 and, more fundamentally, DS, play a critical role in fetal development and maintenance of connective tissues in multiple organs. Considering that patients with CHST14/D4ST1 deficiency develop progressive multisystem fragility‐related manifestations, establishment of a comprehensive and detailed natural history and health‐care guidelines as well as further elucidation of the pathophysiology in view of future etiology‐based therapy are crucial.
Animalism
Authors: Bailey Andrew M.
Published: December 2015

Among your closest associates is a certain human animal – a living, breathing, organism. You see it when you look in the mirror (go ahead; take a look). When it is sick, you don't feel too well. Where it goes, you go. And, one thinks, where you go, it must follow. Indeed, you can make it move through sheer force of will. You bear, in short, an important and intimate relation to this, your animal. So too rest of us with our animals. Animalism says that this relation is nothing short of identity. According to animalists, we do not only coincide with or constitute or inhabit or otherwise hang out with these close associates, our animals: we are them. In this article, I offer an opinionated take on what animalism might be and situate it against contemporary rivals. Then, I outline a simple case for animalism. Finally, I sketch non‐standard routes for animalists to take in light of standard challenges. My goal in all of this is to open up some new avenues of animalist thinking.
Philosophy of Climate Science Part I: Observing Climate Change
Authors: Frigg Roman , Thompson Erica , Werndl Charlotte
Published: December 2015

This is the first of three parts of an introduction to the philosophy of climate science. In this first part about observing climate change, the topics of definitions of climate and climate change, data sets and data models, detection of climate change, and attribution of climate change will be discussed.
Philosophy of Climate Science Part II: Modelling Climate Change
Authors: Frigg Roman , Thompson Erica , Werndl Charlotte
Published: December 2015

This is the second of three parts of an introduction to the philosophy of climate science. In this second part about modelling climate change, the topics of climate modelling, confirmation of climate models, the limits of climate projections, uncertainty and finally model ensembles will be discussed.
Abilities to Act
Authors: Clarke Randolph
Published: December 2015

This essay examines recent work on abilities to act. Different kinds of ability are distinguished, and a recently proposed conditional analysis of ability ascriptions is evaluated. It is considered whether abilities are causal powers. Finally, several compatibility questions concerning abilities, as well as the relation between free will and abilities of various kinds, are examined.
Improved Photodegradation of Organic Contaminants Using Nano‐TiO2 and TiO2–SiO2 Deposited on Portland Cement Concrete Blocks
Authors: Jafari Hoda , Afshar Shahrara
Published: December 2015

The photocatalytic activity of TiO2 nanoparticles (nano‐TiO2) and its hybrid with SiO2 (nano‐TiO2–SiO2) for degradation of some organic dyes on cementitious materials was studied in this work. Nanohybrid photocatalysts were prepared using an inorganic sol–gel precursor and then characterized using XRD, SEM and UV–Vis. The grain sizes were estimated by Scherrer's equation to be around 10 nm. Then, a thin layer was applied to Portland cement concrete (PCC) blocks by dipping them into nano‐TiO2 and nano‐TiO2–SiO2 solution. The efficiency of coated PCC blocks for the photocatalytic decomposition of two dyes, Malachite Green oxalate (MG) and Methylene Blue (MB), was examined under UV and visible irradiation and then monitored by the chemical oxygen demand tests. The results showed that more than 80% and 92% of MG and MB were decomposed under UV–Vis irradiation using blocks coated with nano‐TiO2–SiO2. TiO2/PCC and TiO2–SiO2/PCC blocks showed a significant ability to oxidize dyes under visible and UV lights and TiO2–SiO2/PCC blocks require less time for dye degradation. Based on these results, coated blocks have increased photocatalytic activity which can make them commercially accessible photocatalysts.
Multinodular and vacuolating neuronal tumor affecting amygdala and hippocampus: A quasi‐tumor?
Authors: Yamaguchi Maki , Komori Takashi , Nakata Yasuhiro , Yagishita Akira , Morino Michiharu , Isozaki Eiji
Published: December 2015

Multinodular and vacuolating neuronal tumors (MVNT) have been referred to as distinctive neuronal tumors whose characteristic features include multiple nodules localized in the subcortical white matter. MVNT are composed of vacuolating dysplastic neurons reactive to HuC/HuD. A significant overexpression of alpha‐internexin (INA) limited to the stroma of nodules was reported in one tumor. Since genetic analyses have failed to demonstrate any consistent alterations, the nosological position as well as the nature of MVNT, namely, neoplastic or dysplastic, remains unclear. We herein present another example of MVNT involving the amygdala and anterior hippocampus in a 41‐year‐old man. In addition to the nodular lesions described earlier, we found INA‐positive ribbon‐like lesions that replaced neuropil and extended along the hippocampal gray matter. We also identified dysplastic neurons infiltrating into the CA4 hilus of the hippocampus. Intense INA expression was present in the stroma as well as the cytoplasmic membrane of dysplastic neurons and their processes. While the invasiveness suggested a neoplasm, a relatively restrictive, either nodular or ribbon‐like growth pattern with INA‐positive abnormal neuropil suggested a hamartoma. Such quasi‐tumors should be accommodated in the World Health Organization classification of tumors of the central nervous system, as are dysembryoplastic neuroepithelial tumor and Lhermitte‐Duclos disease.
Carcinoid tumor associated with adjacent dysplastic columnar epithelium in the renal pelvis: A case report and literature review
Authors: Kim Sung Sun , Choi Chan , Kang Taek Won , Choi Yoo Duk
Published: December 2015

Carcinoid tumors are well documented in the pulmonary and gastrointestinal systems, but very rare in the urinary tract, especially in the renal pelvis. We report on a 60‐year‐old female patient who presented with left flank pain and fever. Abdominal computed tomography demonstrated a heterogeneously enhancing mass in the left renal pelvis and a stone at the left proximal ureter. Multiple parenchymal lesions were also observed, which were identified as uneven caliectasis displaying air‐fluid levels and renal parenchymal atrophy. The patient underwent simple nephro‐ureterectomy. Macroscopically, a polypoid mass was observed in the renal pelvis. Microscopically, the tumor revealed acinar, tubular, and solid pattern and was composed of small, monotonous and hyperchromatic cells. Lining epithelia in renal pelvis and ureter revealed columnar epithelia with dysplastic change. The tumor cells were positive for chromogranin A, synaptophysin, CD56, and focally positive for cytokeratin. Immunohistochemical staining of synaptophysin and chromogranin A highlighted the neuroendocrine cells in the columnar epithelium. Ki‐67 (1:50; MIB‐1) labeling index was less than 1% in the area with highest uptake. We report here a case of carcinoid tumor of the renal pelvis that was associated with adjacent dysplastic columnar epithelium.
Similar local, but different systemic, metabolomic responses of closely related pine subspecies to folivory by caterpillars of the processionary moth
Authors: Rivas‐Ubach A. , Sardans J. , Hódar J. A. , Garcia‐Porta J. , Guenther A. , Oravec M. , Urban O. , Peñuelas J.
Published: December 2015

Plants respond locally and systemically to herbivore attack. Most of the research conducted on plant–herbivore relationships at element and molecular levels have focused on the elemental composition or/and certain molecular compounds or specific families of defence metabolites showing that herbivores tend to select plant individuals or species with higher nutrient concentrations and avoid those with higher levels of defence compounds. We performed stoichiometric and metabolomics, both local and systemic, analyses in two subspecies of Pinus sylvestris under attack from caterpillars of the pine processionary moth, an important pest in the Mediterranean Basin. Both pine subspecies responded locally to folivory mainly by increasing relative concentrations of terpenes and some phenolics. Systemic responses differed between pine subspecies, and most of the metabolites presented intermediate concentrations between those of the affected parts and unattacked trees. Our results support the hypothesis that foliar nutrient concentrations are not a key factor for plant selection by adult female processionary moths for oviposition, since folivory was not associated with any of the elements analysed. Phenolic compounds generally did not increase in the attacked trees, questioning the suggestion of induction of phenolics following folivory attack and the anti‐feeding properties of phenolics. Herbivory attack produced a general systemic shift in pines, in both primary and secondary metabolism, which was less intense and chemically different from the local responses. Local pine responses were similar between pine subspecies, while systemic responses were more distant.
Capitate glandular trichomes in Aldama discolor (Heliantheae – Asteraceae): morphology, metabolite profile and sesquiterpene biosynthesis
Authors: Bombo A. B. , Appezzato‐da‐Glória B. , Aschenbrenner A.‐K. , Spring O.
Published: December 2015

The capitate glandular trichome is the most common type described in Asteraceae species. It is known for its ability to produce various plant metabolites of ecological and economic importance, among which sesquiterpene lactones are predominant. In this paper, we applied microscopy, phytochemical and molecular genetics techniques to characterise the capitate glandular trichome in Aldama discolor, a native Brazilian species of Asteraceae, with pharmacological potential. It was found that formation of trichomes on leaf primordia of germinating seeds starts between 24 h and 48 h after radicle growth indicates germination. The start of metabolic activity of trichomes was indicated by separation of the cuticle from the cell wall of secretory cells at the trichome tip after 72 h. This coincided with the accumulation of budlein A, the major sesquiterpene lactone of A. discolor capitate glandular trichomes, in extracts of leaf primordia after 96 h. In the same timeframe of 72–96 h post‐germination, gene expression studies showed up‐regulation of the putative germacrene A synthase (pGAS2) and putative germacrene A oxidase (pGAO) of A. discolor in the transcriptome of these samples, indicating the start of sesquiterpene lactone biosynthesis. Sequencing of the two genes revealed high similarity to HaGAS and HaGAO from sunflower, which shows that key steps of this pathway are highly conserved. The processes of trichome differentiation, metabolic activity and genetic regulation in A. discolor and in sunflower appear to be typical for other species of the subtribe Helianthinae.
Laboratory and Clinical Evaluation of a Feia Method for Canine Serum Progesterone Assay
Authors: Rota A , Vannozzi I , Marianelli S , Gavazza A , Lubas G
Published: December 2015

Contents

The evaluation of progesterone (P4) concentration is a valuable tool in assessing physiological reproductive events and reproductive disorders in bitches. A reliable and rapid (preferable, point of care) determination of P4 is advisable in most cases. Aims of this study were to evaluate a fluorescence enzyme immunoassay (FEIA) for canine serum P4 concentration by (i) the agreement with liquid chromatography–tandem mass spectrometry (LC/MS/MS), (ii) the association with vaginal cytology and (iii) the accuracy in the prediction of the parturition date calculated from the estimated day of ovulation. Serum samples were collected from client‐owned bitches presented between 2011 and 2014 for the evaluation of their oestrous cycle, pregnancy or reproductive disorders. The agreement between FEIA and LC/MS/MS, evaluated on 19 samples, was statistically significant (R2 = 95.7%, p < 0.001), although FEIA showed significantly higher values than LC/MS/MS (p < 0.05). In the different phases of oestrous cycle, as determined by vaginal cytology, P4 concentrations (by FEIA) were statistically different (p < 0.05): anoestrus (n = 7) 0.38 ± 0.14 ng/ml, proestrus (n = 14) 1.04 ± 0.67 ng/ml and oestrus (n = 72) 6.8 ± 7.26 ng/ml. Mean pregnancy length from the estimated day of ovulation was 62.9 ± 1.8 days. In 13 of 22 (59.1%), 19 of 22 (86.3%) and 21 of 22 (95.5%) bitches pregnancy lasted 63 ± 1, 63 ± 2 and 63 ± 3 days, respectively. Three pregnancies were outside the 61–65 days range (60, 60 and 67 days). In conclusion, the FEIA method employed can be considered reliable and, in association with vaginal cytology, effective in evaluating the canine oestrous cycle.
Comparison of continuous positive airway pressure and bosentan effect in mildly hypertensive patients with obstructive sleep apnoea: A randomized controlled pilot study
Authors: Joyeux‐Faure Marie , Jullian‐Desayes Ingrid , Pepin Jean‐Louis , Cracowski Jean‐Luc , Baguet Jean‐Philippe , Tamisier Renaud , Levy Patrick , Godin‐Ribuot Diane , Launois Sandrine H
Published: December 2015

Background and objective

Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)‐associated hypertension are therefore needed. Endothelin‐1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24‐h diastolic BP (DBP) in patients with OSA never treated by either therapy.

Methods

In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m2; apnoea–hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2‐weeks of washout, the second 4‐week period consisted of the alternative treatment (in crossover). The primary outcome was the 24‐h mean DBP change after treatment.

Results

In intention‐to‐treat analysis, the mean difference in 24‐h DBP measurements between treatments was −3.1 (−6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect.

Conclusion

In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24‐h DBP but only reduced office BP suggesting that Endothelin‐1 blockade does not play a major role in treatment of OSA‐related hypertension.
Quasi‐Uniform Spectral Schemes (QUSS), Part I: Constructing Generalized Ellipses for Graphical Grid Generation
Authors: Boyd John P.
Published: December 2015

Chebyshev and Legendre polynomial spectral methods are bedeviled by highly nonuniform grids. The separation between nearest neighbors of an N‐point grid at the center of the interval is larger than the spacing of a uniform grid with the same number of points. Quasi‐Uniform Spectral Schemes (QUSS) redistribute grid points and choose basis functions in order to recover this factor of as nearly as possible while retaining a high density of points near the endpoints to avoid the horrors of the Gibbs or Runge Phenomenon. Here, we introduce a systematic approach, dubbed “mapped cosine bases,” that embraces the widely used Kosloff/Tal‐Ezer functions as a special case. The mapped cosine approach uses grid points that are the images of a uniform grid under the coordinate mapping . Here, we show how to generalize the well‐known graphical construction of the Chebyshev grid using a circle to QUSS mappings using a generalized ellipse. This provides a way to visualize the maps and grids and the subtle differences between different mappings of the mapped cosine family. We illustrate and compare the Kosloff/Tal‐Ezer map with two new maps that use elliptic integrals and Jacobian theta functions, respectively. We show that the elliptic integral grid is an asymptotic approximation to the usual grid for prolate spheroidal functions. This suggests the conjecture that one can obtain the benefits of a prolate basis without the complications of prolate functions by using mapped polynomials instead.
Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery
Authors: Lee E. C‐H. , Muñoz C. X. , McDermott B. P. , Beasley K. N. , Yamamoto L. M. , Hom L. L. , Casa D. J. , Armstrong L. E. , Kraemer W. J. , Anderson J. M. , Maresh C. M.
Published: December 2015

Stress‐inducible Hsp72 is a potential biomarker to track risk of exertional heat illness during exercise/environmental stress. Characterization of extracellular (eHsp72) vs cellular Hsp72 (iHsp72) responses is required to define the appropriate use of Hsp72 as a reliable biomarker. In each of four repeat visits, participants (n = 6 men, 4 trials; total n = 24): (a) passively dehydrated overnight, (b) exercised (2 h) with no fluid in a hot, humid environmental chamber, (c) rested and rehydrated (1 h), (d) maximally exercised for 0.5 h, and (e) returned after 24 h of at‐home recovery and rehydration. We measured rectal temperature, hydration status (% body mass loss, urine markers, serum osmolality), and Hsp72 (ELISA, flow cytometry. eHsp72 (circulating) and iHsp72 (CD3+ PBMCs) correlated (P < 0.05) with markers of heat, exercise, and dehydration stresses. eHsp72 immediately post‐exercise (>15% above baseline, P < 0.05) decreased back to baseline levels by 1 h post‐exercise, but iHsp72 expression continued to rise and remained elevated 24 h post‐exercise (~2.5‐fold baseline, P < 0.05). These data suggest that in addition to the classic physiological biomarkers of exercise heat stress, using cellular Hsp72 as an indicator of lasting effects of stress into recovery may be most appropriate for determining long‐term effects of stress on risk for exertional heat illness.
Prevalence and severity of hip and groin pain in sub‐elite male football: a cross‐sectional cohort study of 695 players
Authors: Thorborg K. , Rathleff M. S. , Petersen P. , Branci S. , Hölmich P.
Published: December 2015

The purpose of this study was twofold: (a) to investigate the prevalence of hip and groin pain in sub‐elite male adult football in Denmark and (b) to explore the association between prevalence and duration of hip and groin pain in the previous season with the Copenhagen Hip and Groin Outcome Score (HAGOS) in the beginning of the new season. In total 695 respondents from 40 teams (Division 1–4) were included. Players completed in the beginning of the new season (July–Sept 2011) a self‐reported paper questionnaire on hip and/or groin pain during the previous season and HAGOS. In total 49% (95% CI: 45–52%) reported hip and/or groin pain during the previous season. Of these, 31% (95% CI: 26–36%) reported pain for >6 weeks. Players with the longest duration of pain during the previous season had the lowest HAGOS scores, when assessed at the beginning of the new season, P < 0.001. This study documents that half of sub‐elite male adult football players report pain in the hip and/or groin during a football season. The football players with the longest duration of pain in previous season displayed the lowest HAGOS scores in the beginning of the new season.
King‐Devick Test reference values and associations with balance measures in high school American football players
Authors: Alsalaheen B. , Haines J. , Yorke A. , Diebold J.
Published: December 2015

The King‐Devick test appears to be a promising tool in screening for concussions. However, limited evidence exists on the baseline associations between the K‐D test and age and baseline screening tools used after concussion. Additionally, there are no published reference values for the K‐D test in high school football players. The K‐D test, the Balance Error Scoring System, and the Limits of Stability (LOS) test were administered to 157 high school football players. Additionally, a subsample of 62 participants completed the test twice to examine the reliability of K‐D test. There was no relationship between the K‐D test and the BESS, or the reaction time and directional control of LOS test. Students aged between 16 and 18 years demonstrated faster K‐D test performance compared to students between 13 and 15 years of age. However, there was no association between K‐D test and history of concussion. The reliability of the K‐D test was (ICC2,1 = 0.89), and the minimal detectable change was 6.10 s. Normative reference values for high school football players are presented in this study.
A novel HLA‐C null allele, HLA‐C*08:121N
Authors: Zhang X. , Reed E. F.
Published: December 2015

HLA‐C*08:121N results from two‐nucleotide loss compared with its closest allele HLA‐C*08:01:01.
Decreased renal function and associated factors in cities, towns and rural areas of Tanzania: a community‐based population survey
Authors: Peck Robert , Baisley Kathy , Kavishe Bazil , Were Jackson , Mghamba Janneth , Smeeth Liam , Grosskurth Heiner , Kapiga Saidi
Published: December 2015

Objectives

Data on renal dysfunction in sub‐Saharan Africa, comparing urban and rural areas, have not yet been reported. Therefore, we aimed to determine the distribution of low estimated glomerular filtration rates (eGFRs) in urban and rural Tanzania, to describe factors associated with low eGFR and to quantify fractions attributable to common risk factors.

Methods

We conducted a community‐based survey of 1095 randomly selected Tanzanian adults (≥18 years). A structured questionnaire and examinations were used to document sociodemographic characteristics, diet, physical activity, anthropomorphic measurements and blood pressure. Blood tests were performed for HIV infection, diabetes mellitus and creatinine. eGFR was calculated using two equations recommended for African adults.

Results

Serum creatinine was available for 1043 participants: 170 in Mwanza city, 326 in district towns and 547 in rural areas. Mean age was 35.5 years and 54% were females. The prevalence of eGFR < 60 ml/min/1.73 m2 in these 3 strata was 2.3% (95% CI = 0.8–6.6%), 7.5% (4.7–11.8%) and 7.4% (5.1–10.6%), respectively. When age standardised to the WHO world population, prevalences were 3.8%, 10.1% and 8.1%. Factors associated with low eGFR included district town residence, older age, greater wealth, less physical activity and hypertension. Only 21% of cases with eGFR < 60 ml/min/1.73 m2 were attributable to HIV, hypertension or diabetes.

Conclusions

Decreased renal function is common in Tanzania, particularly in district towns, and unique risk factors for kidney disease may exist in this population. Population‐specific strategies for prevention, early diagnosis and treatment of kidney disease are needed for Africa.
Diabetic retinopathy in Tanzania: prevalence and risk factors at entry into a regional screening programme
Authors: Cleland Charles R. , Burton Matthew J. , Hall Claudette , Hall Anthony , Courtright Paul , Makupa William U. , Philippin Heiko
Published: December 2015

Objective

The number of adults with diabetes in sub‐Saharan Africa (SSA) is expected to almost double by 2035. This study investigated the prevalence of diabetic retinopathy (DR) and its risk factors at entry into a community‐based screening programme.

Methods

All persons with diabetes screened for retinopathy at entry into a screening programme in Kilimanjaro Region, Tanzania between November 2010 and December 2014 were included. Fundus photographs were taken with a Topcon retinal camera following pupil dilation. Data were collected on BP, random blood sugar, duration of diabetes, BMI and visual acuity on entry.

Results

A total of 3187 persons were screened for DR. The prevalence of any DR was 27.9% (95%CI 26.4–29.5%) with background diabetic retinopathy (BDR), pre‐proliferative diabetic retinopathy (PPDR) and proliferative diabetic retinopathy (PDR) having a prevalence of 19.1% (95% CI 17.7–20.4%), 6.0% (95%CI 5.2–6.8%) and 2.9% (95%CI 2.3–3.5%), respectively. Maculopathy was present in 16.1% (95%CI 14.8–17.4%) of participants. Multivariable logistic regression analysis for the presence of any DR found independent associations with duration of diabetes (P < 0.0001), systolic BP (P < 0.0001), random blood sugar (P < 0.0001) and attending a government hospital diabetic clinic (P = 0.0339).

Conclusions

This study is the first to present data from a DR screening programme in SSA. The results will provide policymakers with data to aid planning of DR screening and treatment services in the African region. The study highlights the importance of managing comorbidities within DR screening programmes.
WRKY71 accelerates flowering via the direct activation of FLOWERING LOCUS T and LEAFY in Arabidopsis thaliana
Authors: Yu Yanchong , Liu Zhenhua , Wang Long , Kim Sang‐Gyu , Seo Pil J. , Qiao Meng , Wang Nan , Li Shuo , Cao Xiaofeng , Park Chung‐Mo , Xiang Fengning
Published: December 2015

Flowering is crucial for achieving reproductive success. A large number of well‐delineated factors affecting flowering are involved in complex genetic networks in Arabidopsis thaliana. However, the underlying part played by the WRKY transcription factors in this process is not yet clear. Here, we report that WRKY71 is able to accelerate flowering in Arabidopsis. An activation‐tagged mutant WRKY71‐1D and a constitutive over‐expresser of WRKY71 both flowered earlier than the wild type (WT). In contrast, both the RNA interference‐based multiple WRKY knock‐out mutant (w71w8 + 28RNAi) and the dominant repression line (W71‐SRDX) flowered later. Gene expression analysis showed that the transcript abundance of the flowering time integrator gene FLOWERING LOCUS T (FT) and the floral meristem identity genes LEAFY (LFY), APETALA1 (AP1) and FRUITFULL (FUL) were greater in WRKY71‐1D than in the WT, but lower in w71w8 + 28RNAi and W71‐SRDX. Further, WRKY71 was shown to bind to the W‐boxes in the FT and LFY promoters in vitro and in vivo. The suggestion is that WRKY71 activity hastens flowering via the direct activation of FT and LFY.
Further observations on the clinical significance and inheritance of the low‐frequency platelet antigen HPA‐28bw
Authors: Lucas Geoffrey , Poles Anthony , Woźniak Marcin J. , Gilmore Ruth
Published: December 2015

BACKGROUND

Most recently described human platelet antigens (HPAs) have been low‐frequency polymorphisms identified in cases of fetomaternal alloimmune thrombocytopenia (FMAIT). There is limited opportunity to study the clinical significance or different antenatal management strategies in cases involving low‐frequency HPA antibodies because many are single pregnancies. We have previously described a low‐frequency platelet (PLT) antigen, HPA‐28bw, implicated in FMAIT in two of the three infants in the same family. This report describes the outcome of an additional two pregnancies in this family.

STUDY DESIGN AND METHODS

The fourth and fifth pregnancies in a HPA‐28bw–alloimmunized mother with a heterozygous partner were investigated to determine the risk of FMAIT. The presence of anti‐HPA‐28bw was assessed by paternal crossmatch studies. Prenatal HPA genotyping of amniocytes was performed to inform antenatal management.

RESULTS

GPIIb/IIIa antibodies reactive only with paternal PLTs were detected. These antibodies had been previously identified as HPA‐28bw specific using recombinant GPIIb glycoprotein mutated to contain the HPA‐28bw (V740L) mutation. The fetus in the fourth pregnancy did not inherit the HPA‐28bw mutation, no antenatal management was required, and the baby had a normal PLT count. The fetus in the fifth pregnancy did inherit the HPA‐28bw mutation. The mother received IVIG (2 g/kg/week) and prednisolone during pregnancy, and the baby was born with a normal PLT count.

CONCLUSION

Study of this family has provided a unique opportunity to assess the clinical significance of antibodies against the low‐frequency PLT antigen (HPA‐28bw) during five pregnancies and to compare the outcomes of different antenatal treatments.
A cell‐based screening assay to identify pharmaceutical compounds that enhance the regenerative quality of corneal repair
Authors: Gordon Gabriel M. , LaGier Adriana J. , Ponchel Corinne , Bauskar Aditi , Itakura Tatsuo , Jeong Shinwu , Patel Nitin , Fini M. Elizabeth
Published: December 2015

The goal of this study was to develop and validate a simple but quantitative cell‐based assay to identify compounds that might be used pharmaceutically to give tissue repair a more regenerative character. The cornea was used as the model, and some specific aspects of repair in this organ were incorporated into assay design. A quantitative cell‐based assay was developed based on transcriptional promoter activity of fibrotic marker genes ACT2A and TGFB2. Immortalized corneal stromal cells (HTK) or corneal epithelial cells (HCLE) were tested and compared to primary corneal stromal cells. Cells were transiently transfected with constructs containing the firefly luciferase reporter gene driven by transcriptional promoters for the selected fibrotic marker genes. A selected panel of seven chemical test compounds was used, containing three known fibrosis inhibitors: lovastatin (LOV), tyrphostin AG 1296 (6,7‐dimethoxy‐3‐phenylquinoxaline) and SB203580 (4‐(4‐fluorophenyl)‐2‐(4‐methylsulfinylphenyl)‐5‐(4‐pyridyl)1H‐imidazole), and four potential fibrosis inhibitors: 5‐iodotubercidin (4‐amino‐5‐iodo‐7‐(β‐D‐ribofuranosyl)‐pyrrolo(2,3‐d)pyrimidine), anisomycin, DRB (5,6‐dichloro‐1‐β‐D‐ribofuranosyl‐benzimidazole) and latrunculin B. Transfected cells were treated with TGFB2 in the presence or absence of one of the test compounds. To validate the assay, compounds were tested for their direct effects on gene expression in the immortalized cell lines and primary human corneal keratocytes using RT‐PCR and immunohistochemistry. Three “hits” were validated LOV, SB203580 and anisomycin. This assay, which can be applied in a high throughput format to screen large libraries of uncharacterized compounds, or known compounds that might be repurposed, offers a valuable tool for identifying new treatments to address a major unmet medical need. Anisomycin has not previously been characterized as antifibrotic, thus, this is a novel finding of the study.