bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly sensitive assays of autoantibodies to thyroglobulin and to thyroid peroxidase.
Authors: Beever K , Bradbury J , Phillips D , McLachlan S M , Pegg C , Goral A , Overbeck W , Feifel G , Smith B R
Published: January 2020

These highly sensitive assays are based on the interaction between thyroid autoantibodies and 125I-labeled autoantigens. Serum samples are incubated with labeled thyroid peroxidase (TPO) or thyroglobulin (Tg) to allow the formation of antibody-labeled antigen complexes. The complexes are then precipitated by addition of solid-phase Protein A. In the presence of high concentrations of TPO antibody or Tg antibody, more than 50% of the respective labeled antigen was precipitated, whereas only 1-2% was precipitated in the absence of autoantibody. Interassay CVs were 3.2% and 5.7%, respectively, for the anti-TPO and anti-Tg assays. There was no cross-reactivity between Tg antibody and TPO antibody. Results correlated highly significantly with results from other assay systems based on antigen-coated cells or plastic supports, but the assays described here were considerably more sensitive. Scatchard analysis of the assay data provided information on the affinity and serum concentration of TPO autoantibodies (ka approximately 10(9) L/mol and concentrations up to 1 g/L) and Tg autoantibodies (ka approximately 4 x 10(10) L/mol and concentrations up to 1 g/L). Overall, these assays provide a sensitive, precise, and convenient system for measuring and investigating the properties of thyroid autoantibodies.
Microassay for screening newborns for galactosemia with use of a fluorometric microplate reader.
Authors: Yamaguchi A , Fukushi M , Mizushima Y , Shimizu Y , Takasugi N , Arashima S , Ohyanagi K
Published: January 2020

We describe a microassay for measuring galactose (Gal) and galactose 1-phosphate (Gal-1-P) in dried blood spots. After a coupled enzyme reaction involving galactose dehydrogenase (GADH, EC 1.1.1.48) and alkaline phosphatase (AP, EC 3.1.3.1) in a microplate well, NADH fluorescence is measured by a highly sensitive fluorometric microplate reader, capable of rapid measurement of fluorescence (2 min per 96 samples). Within- and between-run CVs for measurements of Gal at 90 mg/L with Gal-1-P at 130 mg/L were both less than 5% (n = 8), and analytical recoveries for Gal at 90 mg/L and Gal-1-P at 130 mg/L were 98% and 92%, respectively. Five hundred dried blood-spot samples can be assayed within 2 h, with full calculation of results by an on-line microcomputer. This rapid and reliable assay system is very useful for the routine screening of newborns for galactosemia.
IgA-CK-BB complex with CK-MB electrophoretic mobility can lead to erroneous diagnosis of acute myocardial infarction.
Authors: Venta R , Geijo S A , Sánchez A C , Bao C G , Bartolome L A , Casares G , Lopez-Otin C , Alvarez F V
Published: January 2020

This patient, on admission, presented with a tentative diagnosis of myocardial infarction: the electrocardiogram showed a nonspecific ST-segment and T-wave abnormalities, and total creatine kinase (CK; EC 2.7.3.2) activity was slightly increased (238 U/L). However, a high electrophoretic value for CK-MB (50% of total CK activity) and the electrophoretic pattern of lactate dehydrogenase (EC 1.1.1.27) isoenzymes ruled out myocardial infarction. The isoenzyme migrating as CK-MB was found later to contain no immunologically normal CK-M subunits, and it was bound to IgA. A mixture of the patient's serum and a human serum control containing all CK isoenzymes showed altered electrophoretic mobility only for CK-BB, indicating that the patient's serum contained antibodies to the B unit of CK. Elution from a Sephadex G-200 column showed that the peak at which most of the anodic CK was eluted corresponded to a molecular mass of approximately 200 kDa. Evidently this atypical isoenzyme was an IgA-CK-BB complex. Because this macro CK type 1 can mimic CK-MB, it may therefore be a source of confusion.
Diabetes mellitus and survival of esophageal cancer patients after esophagectomy: a systematic review and meta-analysis
Authors: Zheng Xi , Ma Xingsheng , Deng Han-Yu , Zha Panpan , Zhou Jie , Wang Ru-Lan , Jiang Rui
Published: January 2020

Diabetes mellitus (DM) is one of the most common comorbidities in esophageal cancer patients who undergo esophagectomy. It is well established that DM has an unfavorable impact on short-term outcomes of patients with surgically treated esophageal cancer; however, whether DM has any impact on long-term survival of these patients remains unclear. We performed the first meta-analysis to investigate the impact of DM on survival of surgically treated esophageal cancer patients. We searched the following databases systematically to retrieve relevant studies on January 2, 2019: PubMed, Embase, and Web of Science. The main outcome data consisting of 3- and 5-year overall survival (OS) rates and hazard ratios (HRs) of OS were extracted to compare survival between patients with and without DM. We finally included for meta-analysis a total of eight cohort studies involving 5,044 esophageal cancer patients who underwent esophagectomy. We found no significant difference between 3-year (risk ratio [RR] = 0.94, 95% CI: 0.73–1.21; P = 0.65) and 5-year (RR = 0.92, 95% CI: 0.80–1.08; P = 0.31) OS rates between patients with and without DM after esophagectomy. Moreover, DM was not found to be an independent predictor of OS for these patients (HR = 1.10, 95% CI: 0.65–1.84; P = 0.72). Our study suggests that DM appears to have no significant impact on long-term survival of esophageal cancer patients who undergo esophagectomy. To improve the prognosis of these patients, it may be more important to control glycemic level in patients with DM who undergo esophagectomy. However, further high-quality studies with appropriate adjustment for confounding factors are needed to verify this conclusion.
Gastroesophageal reflux disease after peroral endoscopic myotomy: lest we forget what we already know
Authors: Bechara Robert , Inoue Haruhiro , Shimamura Yuto , Reed David
Published: January 2020

After the performance of the first peroral endoscopic myotomy (POEM) in 2008, POEM has now spread worldwide and has arguably become a first-line treatment option for achalasia. Recently, there is increasing debate regarding post-POEM gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD). The reported incidences of GERD vary widely, owing to the variability in the definitions used. The literature regarding GERD and achalasia patients with a focus on 24-hour pH testing, esophageal acid exposure, and fermentation and the definitions of GERD used in the POEM literature are examined. 24-hour pH testing in achalasia patients may be abnormal due to fermentation both pre- and post-treatment. It is vital that POEM operators ensure that fermentation is recognized during 24-hour pH testing and excluded in the analysis of acid exposure time (AET) used in the diagnosis of GERD. In untreated achalasia, 24-hour pH testing may suggest abnormal AET in over a third of patients. However, most abnormal AETs in untreated achalasia patients are due to fermentation rather than GER. In treated achalasia, up to half of the patients with abnormal AET may be attributable to fermentation. To have a candid discussion and appropriately address the questions surrounding post-POEM GERD, consistent definitions need to be applied. We suggest the recent definition of GERD from the Lyon Consensus to be utilized when diagnosing GERD in post-POEM patients. Further studies are required in establishing ideal parameters for 24-hour pH testing in achalasia patients.
Physical activity, cardiorespiratory fitness, and cardiovascular outcomes in individuals with atrial fibrillation: the HUNT study
Authors: Garnvik Lars E , Malmo Vegard , Janszky Imre , Ellekjær Hanne , Wisløff Ulrik , Loennechen Jan P , Nes Bjarne M
Published: January 2020

Aims

Atrial fibrillation (AF) confers higher risk of mortality and morbidity, but the long-term impact of physical activity (PA) and cardiorespiratory fitness (CRF) on outcomes in AF patients is unknown. We, therefore, examined the prospective associations of PA and estimated CRF (eCRF) with all-cause mortality, cardiovascular disease (CVD) mortality, morbidity and stroke in individuals with AF.

Methods and results

We followed 1117 AF patients from the HUNT3 study in 2006–08 until first occurrence of the outcomes or end of follow-up in November 2015. We used Cox proportional hazard regression to examine the prospective associations of self-reported PA and eCRF with the outcomes. Atrial fibrillation patients meeting PA guidelines had lower risk of all-cause [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.41–0.75] and CVD mortality (HR 0.54, 95% CI 0.34–0.86) compared with inactive patients. The respective HRs for CVD morbidity and stroke were 0.78 (95% CI 0.58–1.04) and 0.70 (95% CI 0.42–1.15). Each 1-metabolic equivalent task (MET) higher eCRF was associated with a lower risk of all-cause (HR 0.88, 95% CI 0.81–0.95), CVD mortality (HR 0.85, 95% CI 0.76–0.95), and morbidity (HR 0.88, 95% CI 0.82–0.95).

Conclusion

Higher PA and CRF are associated with lower long-term risk of CVD and all-cause mortality in individuals with AF. The findings support a role for regular PA and improved CRF in AF patients, in order to combat the elevated risk for mortality and morbidity.
Mental illness stigma after a decade of Time to Change England: inequalities as targets for further improvement
Authors: Henderson Claire , Potts Laura , Robinson Emily J
Published: January 2020

Background

England’s Time to Change programme to reduce mental health-related stigma and discrimination included a social marketing campaign using traditional and social media, and targeted middle-income groups aged 25–45 between 2009 and 2016. From 2017, the same age group on low to middle incomes were targeted, and the content focused on men’s mental health, by changing the advertising and adapting the ‘key messages’. This study investigates changes in stigma-related public knowledge, attitudes and desire for social distance in England since Time to Change began in 2008–19 and for 2017–19.

Methods

Using data from a face-to-face survey of a nationally representative quota sample of adults for England, we evaluated longitudinal trends in outcomes with regression analyses and made assumptions based on a simple random sample. The pre-existing survey used a measure of attitudes; measures of knowledge and desire for social distance were added in 2009.

Results

Reported in standard deviation units (95% CI), the improvement for knowledge for 2009–19 was 0.25 (0.19, 0.32); for attitudes, 2008–19, 0.32 (0.26, 0.39) and for desire for social distance, 2009–19 0.29 (0.23, 0.36). Significant interactions between year and both region and age suggest greater improvements in London, where stigma is higher, and narrowing of age differences. There were significant improvements between 2017 and 2019 in knowledge [0.09 (0.02, 0.16)] and attitudes [0.08 (0.02, 0.14)] but not social distance.

Conclusion

The positive changes support the effectiveness of Time to Change but cannot be definitively attributed to it. Inequalities in stigma by demographic characteristics present targets for research and intervention.
Improving Alzheimer's disease by altering gut microbiota in tree shrews with ginsenoside Rg1
Authors: Wang Limei , Lu Jiangli , Zeng Yueqin , Guo Yuqian , Wu Chao , Zhao Hongbin , Zheng Hong , Jiao Jianlin
Published: January 2020

Ginsenoside Rg1 (GRg1) has neuroprotective effects on Alzheimer's disease (AD). The occurrence and progression of AD are closely related to gut microbiota. Few studies have learned the direct relationship between GRg1 and gut microbiota. In this study, we found an original way to research this relationship by using GRg1 in the AD model of tree shrews. Morris water maze and immunohistochemistry were performed to test the cognition repairing function of GRg1 by tree shrews and 16S ribosomal RNA sequencing was used to explore the composition and abundance of gut microbiota. After GRg1 treatment, the result of Morris water maze showed an improvement in cognitive function, and immunohistochemistry revealed a decrease in tau protein. Moreover, 16SrRNA sequencing results showed the abundances of Proteobacteria and Verrucomicrobia were significantly different, and Lactobacillaceae was significantly increased in the GRg1 treatment group. It also showed that the gut microbiome with middle and high doses of GRg1 was close to the normal group. In conclusion, this study suggests that GRg1 at middle and high doses may change the abundance of gut microbiota to improve AD, and thatProteobacteria and Verrucomicrobia are key microbiota. This is the first report that has ever studied the relationship between GRg1 and gut microbiota in tree shrews.
Trends and drivers of marine fish landings in Portugal since its entrance in the European Union
Authors: Bueno-Pardo Juan , Pierce Graham J , Cabecinha Edna , Grilo Catarina , Assis Jorge , Valavanis Vasilis , Pita Cristina , Dubert Jesús , Leitão Francisco , Queiroga Henrique
Published: January 2020

Marine landings in Portugal have decreased at a higher rate than fishing effort in the last 20 years. Identifying the variables driving the quantity and composition of landings is pivotal to understand the dynamics of the fisheries sector, which entails complex social and environmental aspects. In this study, we investigate the main drivers of marine fish landings in continental Portugal between 1989 and 2014. To identify common trends in time series, and quantify the importance of environmental factors, we applied a dynamic factor analysis considering four regions and three types of gear (trawling, purse-seine, and a multi-gear fishery). Our results show the importance of fishing effort as the most relevant factor driving marine landings in Portugal, both at the long and short terms. In addition, the effect of environmental factors such as the winter river discharge and the spring East Atlantic Teleconnection index should not be neglected, probably through mechanisms affecting coastal productivity. We provide a comprehensive amount of information that permits to improve our understanding of the trends of the most important commercial species in Portugal during the period of study.
A review of two beliefs of parliamentary government in postwar Japan: Japanese/French beliefs beneath the British canopy
Authors: Kobori Masahiro
Published: January 2020

Although the 1947 Constitution of Japan was enacted under the occupation of the General Headquarters of the Allied Powers, it is thought that a British-style parliamentary government was introduced in Japan at this time. Leading constitutional scholars in postwar Japan believed in two ideas derived from the British constitutional history: (i) monistic parliamentary government and (ii) the free exercise of dissolution power by the British cabinet. Both of these ideas have been widely shared among constitutional scholars in Japan. However, in fact, these two beliefs derived from French scholars, and British constitutional scholars did not share them. The difference in substance and approach between the Japanese/French and the British interpretations was never explored in Japan. Japanese scholars sought a rational understanding of the British parliamentary government, thereby overlooking the empiricist understanding.
Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response
Authors: Lv Qinyu , Hu Qiongyue , Zhang Wenzhong , Huang Xinxin , Zhu Minghuan , Geng Ruijie , Cheng Xiaoyan , Bao Chenxi , Wang Yingyi , Zhang Chen , He Yongguang , Li Zezhi , Yi Zhenghui
Published: January 2020

Objective

Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients.

Methods

A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted.

Results

SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted  = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05).

Conclusions

Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.
A quasi-optimal variant of the hybrid high-order method for elliptic partial differential equations with H−1 loads
Authors: Ern Alexandre , Zanotti Pietro
Published: January 2020

Hybrid high-order (HHO) methods for elliptic diffusion problems have been originally formulated for loads in the Lebesgue space $L^2(\varOmega )$. In this paper we devise and analyse a variant thereof, which is defined for any load in the dual Sobolev space $H^{-1}(\varOmega )$. The main feature of the present variant is that its $H^1$-norm error can be bounded only in terms of the $H^1$-norm best error in a space of broken polynomials. We establish this estimate with the help of recent results on the quasi-optimality of nonconforming methods. We prove also an improved error bound in the $L^2$-norm by duality. Compared to previous works on quasi-optimal nonconforming methods the main novelties are that HHO methods handle pairs of unknowns and not a single function and, more crucially, that these methods employ a reconstruction that is one polynomial degree higher than the discrete unknowns. The proposed modification affects only the formulation of the discrete right-hand side. This is obtained by properly mapping discrete test functions into $H^1_0(\varOmega )$.
Trends in Morbidity, Mortality, and Cost of Hospitalizations Associated With Infectious Disease Sequelae of the Opioid Epidemic
Authors: Coyle Joseph R , Freeland Melissa , Eckel Seth T , Hart Adam L
Published: January 2020

Background

Increases in fatal drug poisonings and hepatitis C infections associated with the opioid epidemic are relatively well defined, because passive surveillance systems for these conditions exist. Less described is the association between the opioid epidemic and skin, soft-tissue, and venous infections (SSTVIs), endocarditis, sepsis, and osteomyelitis.

Methods

Michigan hospitalizations between 2016 and 2018 that included an International Classification of Diseases, Tenth Revision, Clinical Modification, code indicating substance use were examined for codes indicative of infectious conditions associated with injecting drugs. Trends in these hospitalizations were examined, as were demographic characteristics, discharge disposition, payer, and cost data.

Results

Among hospitalized patients with a substance use diagnosis code, endocarditis, osteomyelitis, sepsis, and SSTVI hospitalizations increased by 33%, 35%, 24%, and 12%, respectively between 2016 and 2018. During this time frame, 1257 patients died or were discharged to hospice. All SSTVI hospitalizations resulted in >$1.3 billion in healthcare costs. Public insurance accounted for more than two-thirds of all hospitalization costs.

Conclusions

This study describes a method for performing surveillance for infection-related sequelae of injection drug use. Endocarditis, osteomyelitis, sepsis, and SSTVI hospitalizations have increased year over year between 2016 and 2018. These hospitalizations result in significant morbidity, mortality, and healthcare costs and should be a focus of future surveillance and prevention efforts.
Sensory Nociceptive Neurons Contribute to Host Protection During Enteric Infection With Citrobacter rodentium
Authors: Ramirez Valerie T , Sladek Jessica , Godinez Dayn Romero , Rude Kavi M , Chicco Pamela , Murray Kaitlin , Brust-Mascher Ingrid , Gareau Melanie G , Reardon Colin
Published: January 2020

Background

Neurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract.

Methods

In this study, we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days postinfection and delayed pathogen clearance.

Results

Because the sensory neuropeptide CGRP (calcitonin gene-related peptide) regulates host responses during infection of the skin, lung, and small intestine, we assessed the role of CGRP receptor signaling during C rodentium infection. Although CGRP receptor blockade reduced certain proinflammatory gene expression, bacterial burden and Il-22 expression was unaffected.

Conclusions

Our data highlight that sensory nociceptive neurons exert a significant host protective role during C rodentium infection, independent of CGRP receptor signaling.
Uncovering novel susceptibility targets to enhance the efficacy of third-generation cephalosporins against ESBL-producing uropathogenic Escherichia coli
Authors: Phan Minh-Duy , Bottomley Amy L , Peters Kate M , Harry Elizabeth J , Schembri Mark A
Published: January 2020

Background

Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infection (UTI), one of the most common infectious diseases in humans. UPEC are increasingly associated with resistance to multiple antibiotics. This includes resistance to third-generation cephalosporins, a common class of antibiotics frequently used to treat UTI.

Methods

We employed a high-throughput genome-wide screen using saturated transposon mutagenesis and transposon directed insertion-site sequencing (TraDIS) together with phenotypic resistance assessment to identify key genes required for survival of the MDR UPEC ST131 strain EC958 in the presence of the third-generation cephalosporin cefotaxime.

Results

We showed that blaCMY-23 is the major ESBL gene in EC958 responsible for mediating resistance to cefotaxime. Our screen also revealed that mutation of genes involved in cell division and the twin-arginine translocation pathway sensitized EC958 to cefotaxime. The role of these cell-division and protein-secretion genes in cefotaxime resistance was confirmed through the construction of mutants and phenotypic testing. Mutation of these genes also sensitized EC958 to other cephalosporins.

Conclusions

This work provides an exemplar for the application of TraDIS to define molecular mechanisms of resistance to antibiotics. The identification of mutants that sensitize UPEC to cefotaxime, despite the presence of a cephalosporinase, provides a framework for the development of new approaches to treat infections caused by MDR pathogens.
Effects of different carbohydrate sources on taurine status in healthy Beagle dogs
Authors: Pezzali Julia Guazzelli , Acuff Heather L , Henry Will , Alexander Celeste , Swanson Kelly S , Aldrich Charles G
Published: January 2020

This study evaluated the effects of a grain-based (GB) and grain-free (GF) diet on protein utilization and taurine status in healthy Beagle dogs. Two practical dog diets sufficient in crude protein, sulfur amino acids, and taurine content were formulated with the same ingredients with exception of the carbohydrate sources. The GB contained sorghum, millet, and spelt while potatoes, peas, and tapioca starch were used in the GF. A total of 12 Beagle dogs were used in a completely randomized design with six replicates per treatment. The study consisted of an adaptation period of 2 wk followed by an experimental period of 28 d in which GB and GF were fed to the dogs. At the end of the adaptation period and every 2 wk after it (day 0, day 14, day 28), markers of taurine metabolism were analyzed in whole blood (taurine), plasma (taurine, methionine, and cystine), urine (taurine:creatinine), and fresh fecal samples (primary and secondary bile acids). Fecal samples were collected during the last 6 d of experimental period for digestibly assessment using titanium dioxide as an external marker. Taurine markers and digestibility data were analyzed in a repeated measures model and one-way ANOVA, respectively, using PROC GLIMMIX in SAS (version 9.4). Apparent crude protein digestibility was not affected by treatment, but dogs fed GF diet had lower apparent organic matter digestibility compared with those fed GB (P < 0.05). Greater plasma taurine concentrations were observed at days 14 and 28 compared with day 0; wherein dogs fed GF exhibited greater increase compared to those fed GB (P < 0.05). Whole blood taurine concentrations, plasma methionine concentrations, and urinary taurine:creatinine were also greater at days 14 and 28 compared with day 0 (P < 0.05), but no effect of diet was observed. Total bile acid excretion was similar between GF and GB groups, but dogs fed GF excreted a higher proportion of primary bile acids compared with those fed GB (25.49% vs. 12.09% at day 28, respectively). In summary, overall taurine status was not affected by dietary treatments, however, our results suggest that the higher content of oligosaccharides and soluble fibers in the GF diet may alter the composition of the fecal bile acid pool.
Decreased ADAM17 expression in the lungs of α-Klotho reduced mouse
Authors: Akasaka-Manya Keiko , Manya Hiroshi , Nadanaka Satomi , Kitagawa Hiroshi , Kondo Yoshitaka , Ishigami Akihito , Endo Tamao
Published: January 2020

The deficiency of α-Klotho in mice causes phenotypes resembling human age-associated disorders at 3–4 weeks after birth and shows short lifespans of ∼2 months. One of the crucial symptoms is pulmonary emphysema, although α-Klotho is not expressed in the lungs. α-Klotho secreted from the kidneys is probably involved in the pathology of emphysema because kidney-specific knockout mice exhibit emphysematous structural changes. We examined whether any glycan changes in α-Klotho mouse lungs were observed, because α-Klotho is reported to have glycosidase activity. Here, we found the accumulation of heparan sulphate in the microsomal fraction of α-Klotho mouse lungs. Meanwhile, a disintegrin and metalloproteinase 17 (ADAM17) expression was decreased in α-Klotho mice. From these results, it is thought that the increase in heparan sulphate is due to insufficient cleavage of the core protein by ADAM17. Additionally, a reduction in α-Klotho and a decline of ADAM17 were also observed both in normal aged mice and in senescence marker protein-30 (SMP30) knockout mice, a mouse model of premature ageing. Thus, the decrease in ADAM17 is caused by the reduction in α-Klotho. These may be involved in the deterioration of lung function during ageing and may be associated with the pathology of pulmonary emphysema.
Vital, Porcine, Gal-Knockout Skin Transplants Provide Efficacious Temporary Closure of Full-Thickness Wounds: Good Laboratory Practice-Compliant Studies in Nonhuman Primates
Authors: Holzer Paul , Adkins Jon , Moulton Krysta , Zhu Laurence , Monroy Rod , Cetrulo Curtis L
Published: January 2020

Vital, genetically engineered porcine skin transplants have long been regarded as a promising treatment option for severe burn wounds. The objective of this two-part, preclinical study was to evaluate the ability of vital, split-thickness skin xenotransplants derived from designated pathogen-free, alpha 1,3 galactosyltransferase knockout miniature swine to provide temporary wound closure of full-thickness wound defects intended to model severe and extensive, deep partial- and full-thickness burn wounds. In part 1 of the study, four full-thickness wound defects were introduced in four cynomolgus macaques recipients and, then engrafted with two xenografts and two allografts to achieve temporary wound closure. On POD-15, autografts were used to achieve definitive wound closure and were observed until POD-22. In part 2 of the study, four additional subjects each received two full-thickness wound defects, followed by two xenografts to achieve temporary wound closure, and were observed postoperatively for 30 days without further intervention. All grafts were assessed for signs of adherence to the wound bed, vascularity, and signs of immune rejection via gross clinical and histological methods. Xenograft and allograft comparators were equivalent in part 1, and later autografts were otherwise indistinguishable. In part 2, all xenotransplants demonstrated adherence, vascularity, and survival until POD-30. These were unexpected results that exceed previously published findings in similar models. Furthermore, the ensuing GLP-study report directly supported regulatory clearance, permitting a phase I clinical trial. This solution holds great promise as an alternative to human cadaver allograft, the current standard of care for the treatment of severe burns.
Circulation of Tick-Borne Spirochetes in Tick and Small Mammal Communities in Santa Barbara County, California, USA
Authors: MacDonald Andrew J , Weinstein Sara B , O’Connor Kerry E , Swei Andrea
Published: January 2020

A diversity of Borrelia burgdorferi sensu lato (Johnson, Schmid, Hyde, Steigerwalt & Brenner) (Spirochaetales: Spirochaetaceae) genomospecies, including the Lyme disease agent, Borrelia burgdorferi sensu stricto (s.s.), have been identified in the western United States. However, enzootic transmission of B. burgdorferi s.l. in small mammals and ticks is poorly characterized throughout much of the region. Here we report prevalence of B. burgdorferi s.l. in small mammal and tick communities in the understudied region of southern California. We found B. burgdorferi s.l. in 1.5% of Ixodes species ticks and 3.6% of small mammals. Infection was uncommon (~0.3%) in Ixodes pacificus Cooley and Kohls (Acari: Ixodidae), the primary vector of the Lyme disease agent to humans in western North America, but a diversity of spirochetes—including Borrelia bissettiae, Borrelia californiensis, Borrelia americana, and B. burgdorferi s.s.—were identified circulating in Ixodes species ticks and their small mammal hosts. Infection with B. burgdorferi s.l. is more common in coastal habitats, where a greater diversity of Ixodes species ticks are found feeding on small mammal hosts (four species when compared with only I. pacificus in other sampled habitats). This provides some preliminary evidence that in southern California, wetter coastal areas might be more favorable for enzootic transmission than hotter and drier climates. Infection patterns confirm that human transmission risk of B. burgdorferi s.s. is low in this region. However, given evidence for local maintenance of B. burgdorferi s.l., more studies of enzootic transmission may be warranted, particularly in understudied regions where the tick vector of B. burgdorferi s.s. occurs.
Photometric characterization of multiple populations in star clusters: the impact of the first dredge-up
Authors: Salaris Maurizio , Usher Chris , Martocchia Silvia , Dalessandro Emanuele , Bastian Nate , Saracino Sara , Cassisi Santi , Cabrera-Ziri Ivan , Lardo Carmela
Published: January 2020

The existence of star-to-star light-element abundance variations (multiple populations, MPs) in massive Galactic and extragalactic star clusters older than about 2 Gyr is by now well established. Photometry of red giant branch (RGB) stars has been and still is instrumental in enabling the detection and characterization of cluster MPs, through the appropriate choices of filters, colours, and colour combinations that are mainly sensitive to N and – to a lesser degree – C stellar surface abundances. An important issue not yet properly addressed is that the translation of the observed widths of the cluster RGBs to abundance spreads must account for the effect of the first dredge-up on the surface chemical patterns, hence on the spectral energy distributions of stars belonging to the various MPs. We have filled this gap by studying theoretically the impact of the dredge-up on the predicted widths of RGBs in clusters hosting MPs. We find that for a given initial range of N abundances, the first dredge-up reduces the predicted RGB widths in N-sensitive filters compared to the case when its effect on the stellar spectral energy distributions is not accounted for. This reduction is a strong function of age and has also a dependence on metallicity. The net effect is an underestimate of the initial N-abundance ranges from RGB photometry if the first dredge-up is not accounted for in the modelling, and also the potential determination of spurious trends of N-abundance spreads with age.
Pulsation mode switching in the pulsating star HD 81589 and a proposed classification as a field FaRPB star
Authors: van Heerden P , Engelbrecht C A , Martinez P
Published: January 2020

Extensive multicolour photometry and low-resolution spectroscopy obtained for HD 81589 place the star in the gap between δ Scuti and slowly pulsating B pulsators on the main sequence. A clear episode of pulsation mode switching has apparently occurred in HD 81589, with its primary pulsation frequency switching from 4.57 to 3.71 c d−1 in less than 6 months. The pulsation frequencies obtained for this star match remarkably well with modelled frequencies of prograde sectoral g-modes for rapidly rotating late B stars on the main sequence. This match, coupled with the rapid rotation rate determined for HD 81589, implies that HD 81589 is one of the first identified fast-rotating pulsating B-type (FaRPB) stars found in the field, complementing the sample of FaRPB stars previously discovered in the open cluster NGC 3766.
The Genomes of the Livebearing Fish Species Poeciliopsis retropinna and Poeciliopsis turrubarensis Reflect Their Different Reproductive Strategies
Authors: van Kruistum Henri , Guernsey Michael W , Baker Julie C , Kloet Susan L , Groenen Martien A M , Pollux Bart J A , Megens Hendrik-Jan
Published: January 2020

The evolution of a placenta is predicted to be accompanied by rapid evolution of genes involved in processes that regulate mother–offspring interactions during pregnancy, such as placenta formation, embryonic development, and nutrient transfer to offspring. However, these predictions have only been tested in mammalian species, where only a single instance of placenta evolution has occurred. In this light, the genus Poeciliopsis is a particularly interesting model for placenta evolution, because in this genus a placenta has evolved independently from the mammalian placenta. Here, we present and compare genome assemblies of two species of the livebearing fish genus Poeciliopsis (family Poeciliidae) that differ in their reproductive strategy: Poeciliopsis retropinna which has a well-developed complex placenta and P. turrubarensis which lacks a placenta. We applied different assembly strategies for each species: PacBio sequencing for P. retropinna (622-Mb assembly, scaffold N50 of 21.6 Mb) and 10× Genomics Chromium technology for P. turrubarensis (597-Mb assembly, scaffold N50 of 4.2 Mb). Using the high contiguity of these genome assemblies and near-completeness of gene annotations to our advantage, we searched for gene duplications and performed a genome-wide scan for genes evolving under positive selection. We find rapid evolution in major parts of several molecular pathways involved in parent–offspring interaction in P. retropinna, both in the form of gene duplications as well as positive selection. We conclude that the evolution of the placenta in the genus Poeciliopsis is accompanied by rapid evolution of genes involved in similar genomic pathways as found in mammals.
An internal deletion of ADAR rescued by MAVS deficiency leads to a minute phenotype
Authors: Bajad Prajakta , Ebner Florian , Amman Fabian , Szabó Brigitta , Kapoor Utkarsh , Manjali Greeshma , Hildebrandt Alwine , Janisiw Michael P , Jantsch Michael F
Published: January 2020

The RNA-editing protein ADAR is essential for early development in the mouse. Genetic evidence suggests that A to I editing marks endogenous RNAs as ‘self’. Today, different Adar knockout alleles have been generated that show a common phenotype of apoptosis, liver disintegration, elevated immune response and lethality at E12.5. All the Adar knockout alleles can be rescued by a concomitant deletion of the innate immunity genes Mavs or Ifih1 (MDA5), albeit to different extents. This suggests multiple functions of ADAR. We analyze AdarΔ7-9 mice that show a unique growth defect phenotype when rescued by Mavs. We show that AdarΔ7-9 can form a truncated, unstable, editing deficient protein that is mislocalized. Histological and hematologic analysis of these mice indicate multiple tissue- and hematopoietic defects. Gene expression profiling shows dysregulation of Rps3a1 and Rps3a3 in rescued AdarΔ7-9. Consistently, a distortion in 40S and 60S ribosome ratios is observed in liver cells. This dysregulation is also seen in AdarΔ2-13; Mavs−/− but not in AdarE861A/E861A; Ifih1−/− mice, suggesting editing-independent functions of ADAR in regulating expression levels of Rps3a1 and Rps3a3. In conclusion, our study demonstrates the importance of ADAR in post-natal development which cannot be compensated by ADARB1.
An antenatal alcohol service evaluation of the north-east of England and north Cumbria
Authors: Howlett Helen
Published: January 2020

Background

NHS England’s ‘Better Births’ strategy aims to improve maternal and infant health outcomes. A strategic priority identified in the north-east local maternity system is to reduce alcohol consumption in pregnancy due to the documented diverse risks of harm to mother and baby, including foetal alcohol spectrum disorder.

Aims

To evaluate current alcohol prevention, screening and treatment service provision in maternity care across the region, and inform future recommendations.

Methods

A service evaluation survey was developed to systematically consult strategic stakeholders across all nine maternity trusts in the region over a 2-month period in 2018. Content analysis was employed to identify fundamental themes and inform recommendations for practice.

Results

High variation was reported throughout regional clinical practices, service provision and staff training. For example, a number of alcohol screening tools were identified, each with diverse thresholds for referral; reported data collection and documentation practices were multifarious, incomparable and unquantifiable; audit was rare and guidelines were primarily influenced by local commissioning agreements.

Discussion

Standardized patient pathways involving alcohol screening and management practices are required, and sharing best practices will facilitate referrals and support regardless of location. The implementation of these recommendations requires appropriate leadership, commissioning and training strategies.
Clinical significance of radiological patterns of HRCT and their association with macrophage activation in dermatomyositis
Authors: Zuo Yu , Ye Lifang , Liu Min , Li Shanshan , Liu Weifang , Chen Fang , Lu Xin , Gordon Patrick , Wang Guochun , Shu Xiaoming
Published: January 2020

Objectives

To evaluate the distribution of radiological characteristics stratified by different myositis-specific autoantibodies, identify prognostic value of high-resolution CT (HRCT) patterns in DM-associated interstitial lung disease (DM-ILD), and explore the possible mechanism associated with macrophage activation.

Methods

We enrolled 165 patients with PM/DM-ILD. The distribution of HRCT radiological types with different myositis-specific autoantibodies and the relationship between radiological features and ILD course and prognosis were analysed. Additionally, the potential role of macrophage activation in rapidly progressive ILD (RP-ILD) with DM was studied.

Results

The organizing pneumonia pattern was dominant in HRCT findings of patients with DM-ILD, especially those with anti-SAE (6/6, 100%) and anti-MDA5 (46/62, 74.2%) antibodies. The ratios of organizing pneumonia and nonspecific interstitial pneumonia patterns were almost equal in patients with aminoacyl tRNA synthetase antibodies, and nonspecific interstitial pneumonia pattern was associated with a mild clinical course. Lower lung zone consolidation in HRCT was related to RP-ILD in both anti-MDA5 and anti-aminoacyl tRNA synthetase antibody-positive groups. Ferritin levels of >1000 ng/ml (odds ratio (OR), 12.3; P=0.009), elevated carcinoembryonic antigen (OR, 5.8; P=0.046) and carbohydrate antigen 19–9 (OR, 7.8; P=0.018) were independent predictors of a lower lung zone consolidation pattern in anti-MDA5 antibody-positive DM. The infiltration of CD163-positive macrophages into alveolar spaces was significantly higher in the DM-RP-ILD group than in the chronic DM-ILD group.

Conclusion

HRCT patterns are different among variable myositis-specific autoantibodies positive patients with ILD and lower zone consolidation in HRCT correlated with RP-ILD in DM. Activated macrophages may contribute to the pathogenesis of RP-ILD in DM.
COMPLIANCE TESTING FOR HUMAN BODY MODEL EXPOSURE TO ELECTROMAGNETIC FIELDS FROM A HIGH-POWER WIRELESS CHARGING SYSTEM FOR DRONES
Authors: Ahn Jangyong , Hong Seon-Eui , Kim Haerim , Chun Yangbae , Choi Hyung-Do , Kim Kibeom , Andrés Brito , Choi Junsung , Ahn Seungyoung
Published: January 2020

Recently, a wireless charging system (WCS) for drones has been extensively studied, although standards for compliance testing of a WCS for drones have yet to be established. In this study, we propose methods for human exposure assessments of a WCS for drones by comprehensively considering the various positions of the system and the postures of human body models. The electromagnetic fields from a WCS are modeled and the internal quantities of the human body models, consisting of current density, internal electric field and specific absorption rate, are calculated. The incident fields around the WCS and the internal quantities are analyzed at 140 kHz, which is the operating frequency of the WCS applied. Results of an exposure assessment based on the confirmed worst-case scenario are presented. In addition, the internal quantities depending on the human body models and the material characteristics of the simplified models are also discussed using four different anatomical and simplified human body models.
New room to maneuver? National tax policy under increasing financial transparency
Authors: Ahrens Leo , Bothner Fabio , Hakelberg Lukas , Rixen Thomas
Published: January 2020

Why have Organisation for Economic Co-operation and Development (OECD) governments raised taxes on dividends at the shareholder level since 2008? Previous research points to the importance of budget deficits and voter demand for compensatory fairness in the aftermath of the financial crisis. We complement this literature by showing that the effect of domestic drivers of tax increases on capital income crucially depends on the level of financial transparency in a country’s investment network. Low financial transparency increases the risk of capital flight in response to a tax hike, whereas high financial transparency reduces this risk. Hence, governments facing fiscal pressure become more likely to raise taxes on capital income when transparency is high. To substantiate our argument, we construct an original indicator of financial transparency in countries’ investment networks, which we utilize in a regression analysis of tax reforms by 204 cabinets in 35 OECD countries between 2001 and 2018.
Time to First Cigarette: A Potential Clinical Screening Tool for Nicotine Dependence
Authors: Branstetter Steven A. , Muscat Joshua E. , Mercincavage Melissa
Published: January 2020

Objectives:

The time to first cigarette (TTFC) of the day has been identified as the best single-item indicator of nicotine dependence. However, TTFC has not been extensively used in clinical settings and is not a criterion for tobacco use disorder, perhaps due to a lack of information about TTFC's predictive value. This review provides a synthesis of the accumulating literature on TTFC's relationships with nicotine dependence, identify gaps, and inform future clinical and epidemiologic research of potential uses of TTFC.

Methods:

A systematic review of the literature was conducted using PubMed, Google Scholar, and Web of Science ISI databases. We identified 16 articles examining the relation between TTFC and negative outcomes associated with high levels of nicotine addiction and Tobacco Use Disorders (eg, high levels of nicotine and toxicant exposure, progressive use over time, failed cessation, head-and-neck cancers).

Results:

Earlier TTFC was consistently associated with greater likelihood of cessation failure and relapse, and higher levels of biomarkers of tobacco exposure. Several of these associations were found among both adult and adolescent smokers, and remained even after accounting for smoking behaviors (eg, cigarettes/day).

Conclusions:

Earlier TTFC is a key indicator of greater nicotine dependence. Knowledge of a smoker's TTFC may allow clinicians to accurately inform smokers of health risks and assign greater resources during cessation attempts. Smokers may be able to use TTFC to self-select cessation aids and accurately assess their unique smoking-related health risks. TTFC may be a better item than cigarettes/day for accurately quantifying dependence and risk in epidemiologic studies.