bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered protein levels in bone marrow lesions of hip osteoarthritis: Analysis by proteomics and multiplex immunoassays
Authors: Shabestari Maziar , Shabestari Yashar R. , Landin Maria A. , Pepaj Milaim , Cleland Timothy P. , Reseland Janne E. , Eriksen Erik F.
Published: May 2020

Aim

To assess tissue level changes of proteome and cytokine profiles of subchondral bone in hip osteoarthritis (OA) affected by bone marrow lesions (BMLs). We compared significant protein level differences in osteoarthritic bone with BMLs to control bone without bone marrow lesions.

Methods

Subchondral bone biopsies were taken from femoral heads of end‐stage osteoarthritis patients with (BML, n = 21) and without (CON, n = 9) BMLs. Proteins were extracted through a standardized Trizol protocol and used in the subsequent analyses. Angiogenesis and bone markers were assessed using multiplex immunoassays (Luminex). Liquid chromatography tandem mass spectrometry (LC‐MS/MS) was performed to detect significant differences in proteome and peptide profiles between BML and CON.

Results

Multiplex immunoassays revealed increased tissue contents of vascular endothelial growth factors (VEGF‐A/C/D), endothelin‐1, angiopoietin‐2 and interleukin‐6 (IL‐6) in bone with BMLs compared to control bone, whereas osteoprotegerin levels were reduced. Mass spectrometry demonstrated pronounced increase in the levels of hemoglobin (73‐fold), serum albumin (30‐fold), alpha‐1‐antitrypsin (9‐fold), apolipoprotein A1 (4.7‐fold), pre‐laminin‐A/C (3.7‐fold) and collagen‐alpha1‐XII (3‐fold) in BMLs, while aggrecan core protein (ACAN) and hyaluronan and proteoglycan link protein 1 (HAPL1) decreased 37‐ and 29‐fold respectively.

Conclusion

Reduced osteoprotegerin, ACAN and HAPL1 are consistent with osteoclastic activation and high remodeling activity in BMLs. The pronounced increase in angiogenesis markers, hemoglobin and serum albumin support the presence of increased vascularity in subchondral bone affected by BMLs in OA. VEGFs and IL‐6 are known nociceptive modulators, and increased levels are in keeping with pain being a clinical feature frequently associated with BMLs.
Unraveling the complexity of human–tiger conflicts in the Leuser Ecosystem, Sumatra
Authors: Lubis M. I. , Pusparini W. , Prabowo S. A. , Marthy W. , Tarmizi  , Andayani N. , Linkie M.
Published: May 2020

Conserving large carnivores that live in close proximity to people depends on a variety of socio‐economic, political and biological factors. These include local tolerance toward potentially dangerous animals, efficacy of human–carnivore conflict mitigation schemes, and identifying and then addressing the underlying causes of conflict. The Leuser Ecosystem is the largest contiguous forest habitat for the critically endangered Sumatran tiger. Its extensive forest edge is abutted by farming communities and we predict that spatial variation in human–tiger conflict (HTC) would be a function of habitat conversion, livestock abundance, and poaching of tiger and its wild prey. To investigate which of these potential drivers of conflict, as well as other biophysical factors, best explain the observed patterns, we used resource selection function (RSF) technique to develop a predictive spatially explicit model of HTC. From 148 conflict incidences recorded from 2008 to 2018 across the Leuser Ecosystem, the areas that were closer to villages and with lower occurrence of wild prey were most susceptible to tiger attacks. From 18 districts monitored, 6 stood out for having disproportionately high levels of HTC. We recommend that these areas be prioritized with increased support from conflict mitigation teams to prevent further injuries to people, livestock or tigers; district governments address one underlying cause of HTC by supporting improved animal husbandry practices, such as tiger‐proof livestock pen construction; and, an increase in ranger patrol effort to recover wild prey populations. This type of priority setting approach has wide application for better determining the required management response to reduce conflicts between people and large carnivores in both tropical and temporal landscapes.
Effects of a selective long‐acting amylin receptor agonist on alcohol consumption, food intake and body weight in male and female rats
Authors: Kalafateli Aimilia Lydia , Vestlund Jesper , Raun Kirsten , Egecioglu Emil , Jerlhag Elisabet
Published: May 2020

Alcohol use disorder is a complex neuropsychiatric disorder affecting both males and females worldwide; however, the efficacy of current pharmacotherapies varies. Recent advances show that gut‐brain peptides, like amylin, regulate alcohol behavioural responses by acting on brain areas involved in alcohol reward processes. Thus, the activation of amylin receptors (AMYRs) by salmon calcitonin (sCT) decreases alcohol behaviours in male rodents. Given that sCT also activates the sole calcitonin receptor (CTR), studies of more selective AMYR agonists in both male and female rodents are needed to explore amylinergic modulation of alcohol behaviours. Therefore, we investigated the effects of repeated administration of a selective long‐acting AMYR agonist, NNC0174‐1213 (AM1213), on alcohol, water and food intake, as well as body weight in male and female rats chronically exposed to alcohol. We confirm our previous studies with sCT in male rats, as repeated AM1213 administration for 2 weeks initially decreased alcohol intake in both male and female rats. However, this reduction ceases in both sexes on later sessions, accompanied by an increase in males. AM1213 reduced food intake and body weight in both male and female rats, with sustained body weight loss in males after discontinuation of the treatment. Moreover, AM1213 administration for 3 or 7 days, differentially altered dopamine, serotonin and their metabolites in the reward‐related areas in males and females, providing tentative, but different, downstream mechanism through which selective activation of AMYR may alter alcohol intake. Our data provide clarified insight into the importance of AMYRs for alcohol intake regulation in both sexes.
10 kHz spinal cord stimulation for the treatment of non‐surgical refractory back pain: subanalysis of pooled data from two prospective studies
Authors: Al‐Kaisy A. , Van Buyten J. P. , Kapural L. , Amirdelfan K. , Gliner B. , Caraway D. , Subbaroyan J. , Edgar D. , Rotte A.
Published: May 2020

Spinal cord stimulation at 10 kHz is a promising therapy for non‐surgical refractory back pain; however, published data are currently limited. We present a subanalysis of prospectively collected clinical outcome data for non‐surgical refractory back pain patients treated with 10 kHz spinal cord stimulation, from the independent cohorts of two previous studies (SENZA‐RCT and SENZA‐EU). Clinical outcomes were evaluated at pre‐implantation (baseline), 3 months, 6 months and 12 months following 10 kHz spinal cord stimulator implantation. These included: pain relief; responder rate (≥ 50% pain relief from baseline); remission rate (VAS ≤ 3.0 cm); disability (Oswestry Disability Index(ODI)); and opioid use. At 3 months, average back pain decreased by 70% in the combined cohort (60% in the SENZA‐RCT and 78% in the SENZA‐EU cohorts). This was sustained at 12 months, with a 73% back pain responder rate and 68% remission rate in the combined cohort. Leg pain relief results were generally comparable to those for back pain relief. At 12 months, the combined cohort had an average decrease in ODI scores of 15.7% points from baseline and opioid use more than halved. In conclusion, 10 kHz spinal cord stimulation reduced pain, disability and opioid consumption in non‐surgical refractory back pain subjects. Application of this therapy may improve the care of non‐surgical refractory back pain patients and reduce their opioid consumption.
p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome
Authors: Lobo João , Alzamora Maria Ana , Guimarães Rita , Cantante Mariana , Lopes Paula , Braga Isaac , Maurício Joaquina , Jerónimo Carmen , Henrique Rui
Published: May 2020

Background

Testicular germ cell tumors (TGCTs) are highly sensitive to platinum‐based chemotherapy, and wild‐type p53 seems to play a pivotal role in this susceptibility. On the other hand, overexpression of MDM2 seems to entail treatment resistance and unfavorable prognosis.

Objectives

We aimed to describe p53 and MDM2 immunoexpression in a well‐characterized cohort of primary and metastatic TGCTs and evaluate associations with clinicopathological and prognostic variables, including survival.

Materials and methods

237 primary tumor samples and 12 metastases were evaluated for p53 and MDM2 immunoexpression using digital image analysis. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow‐up.

Results

A significant positive correlation between p53 and MDM2 H‐scores was found (rs = 0.590, P < .0001). Non‐seminomas showed significantly higher expression levels of both p53 and MDM2 (P = .0002, P < .0001), which peaked in embryonal carcinomas and choriocarcinomas. Percentage of immunoexpressing cells and H‐score were significantly higher in chemo‐treated metastases compared with chemo‐naïve primary tumors for MDM2 (P ≤ .0001 for both), but not for p53 (P = .919 and P = .703, respectively). Cases with higher MDM2 immunoexpression showed a statistically significant trend for association with poorer prognosis (P = .043). Relapse/progression‐free survival at 12 months post‐diagnosis was lower in the “MDM2‐high” (≥P50) vs. the “MDM2‐low” (<P50) expression groups.

Discussion and Conclusion

In TGCTs, MDM2 overexpression may indicate a more aggressive tumor phenotype, with propensity for therapy resistance and recurrence. If validated in larger multi‐institutional studies with precise quantification, it may be envisioned as a useful predictive biomarker of poor response to cisplatin.
Device‐associated multidrug‐resistant bacteria surveillance in critically ill children: 10 years of experience
Authors: Girona‐Alarcón Mònica , Fresán Elena , Garcia‐Garcia Ana , Bobillo‐Perez Sara , Balaguer Monica , Felipe Aida , Esteban Maria Esther , Jordan Iolanda
Published: May 2020

Aim

Multidrug‐resistant bacterial infections are a public health problem worldwide. However, most of the information available refers to adults. The main objectives were to determine the incidence, risk factors, and outcomes for device‐associated infections, especially those involving multidrug‐resistant bacteria.

Methods

This is a prospective, observational study. Children aged ≥1 month and <18 years admitted to the paediatric intensive care unit from 2008 to 2017, with a device‐associated infection microbiologically confirmed were included. Patients infected with resistant bacteria were compared with those who had a drug‐susceptible infection.

Results

The study included 213 patients. Out of all the device‐associated infections, 22% (48 patients) were caused by multidrug‐resistant bacteria. The most frequent were extended‐spectrum beta‐lactamase (ESBL)‐producing enterobacteria. Cardiovascular diseases, age under 1year, comorbidity, prolonged use of invasive device, and length of stay until infection were risk factors for resistant bacteria, but not specifically for ESBL‐producing bacteria. Length of stay and mortality was increased in patients with multidrug‐resistant bacteria.

Conclusion

Being under 1‐year‐old and having a cardiovascular disease were the two major risk factors for resistant bacterial infection. ESBL‐producing bacteria were the most frequent multidrug‐resistant agents. However, patients with ESBL‐producing bacteria did not have any additional risk factors, so they may have been colonised in the community.
Identifying food provenience using Sr/Ca ratio in human enamel
Authors: Sołtysiak Arkadiusz
Published: May 2020

The strontium (Sr) concentration in bioapatite of human bone and teeth reflects the Sr concentration in food that is differentiated by two major factors: an abundance of Sr in local soils and the biopurification effect along the trophic levels. Eastern Syria is an area with a relatively high concentration of Sr within the Euphrates valley and a low concentration of Sr beyond the valley. For this reason, the strontium/calcium (Sr/Ca) ratio in human enamel retrieved from skeletons buried in cemeteries within the Euphrates valley may be used as a proxy for food provenience in a local population. A sample of human teeth (N = 72) from Tell Ashara and Tell Masaikh was divided into seven temporal subsets covering periods between c.2200 bce and the early 20th century ce. A significant difference in Sr/Ca values between temporal subsets is observed. The Sr/Ca values in later subsets are negatively correlated with δ13C values, indicating the wider exploitation of steppe areas outside the valley with more wild C4 grasses and a low Sr concentration. For periods with lower Sr/Ca values (c.2200–1900 bce and 19th–20th centuries ce) there is additional textual and isotopic evidence for food transportation from outside the river valley, supporting the interpretation of Sr/Ca values as a proxy for food provenience in this specific area.
Effectiveness of a multicomponent pharmacist intervention at hospital discharge for drug‐related problems: A cluster randomised cross‐over trial
Authors: Pourrat Xavier , Leyrat Clémence , Allenet Benoît , Bouzige Brigitte , Develay Armelle , Fraysse Martial , Garnier Valérie , Halimi Jean‐Michel , Roux‐Marson Clarisse , Giraudeau Bruno
Published: May 2020

Aims

The aim of this study was to assess whether a pharmacist intervention associating medication reconciliation at discharge with a link to the community pharmacist reduces drug‐related problems (DRP) in adult patients during the 7 days after hospital discharge in 22 university or general hospitals in France.

Methods

We conducted a cluster randomised cross‐over superiority trial with hospital units as the cluster unit. The primary outcome was a composite of any kind of DRP (prescription/dispensation, patient error or gap due to no medication available) during the 7 days after discharge, assessed by phone with the patient and community pharmacist. Among secondary outcomes, we studied self‐reported unplanned hospitalisations at day 35 after discharge and severe iatrogenic problems.

Results

A total of 1092 patients were enrolled in 48 units (538 in the experimental periods and 554 in the control periods). Three patients refused to have their data analysed and were excluded from the analyses. As compared with usual care, the pharmacist intervention led to a lower proportion of patients with at least one DRP (44.0% vs 50.6%; odds ratio [OR] 0.77, 95% confidence interval [CI] 0.61–0.98) and severe iatrogenic problems (5.2% vs 8.7%; OR 0.57, 95% CI 0.35–0.93) but no significant difference in unplanned hospitalisations at day 35 (5.8% vs 4.5%; OR 1.46, 95% CI 0.91–2.35).

Conclusion

Medication reconciliation associated with communication between the hospital and community pharmacist may decrease patient exposure to DRP and severe iatrogenic problems but not unplanned hospitalisation. However, this intervention could be recommended in health policies to improve drug management.
Society of Robotic Surgery review: recommendations regarding the risk of COVID‐19 transmission during minimally invasive surgery
Authors: Porter James , Blau Elliot , Gharagozloo Farid , Martino Martin , Cerfolio Robert , Duvvuri Umamaheswar , Caceres Aileen , Badani Ketan , Bhayani Sam , Collins Justin , Coelho Rafael , Rocco Bernard , Wiklund Peter , Nathan Senthil , Parra‐Davila Eduardo , Ortiz‐Ortiz Carlos , Maes Kris , Dasgupta Prokar , Patel Vipul
Published: May 2020

Objectives

To determine the risk of COVID‐19 transmission during minimally invasive surgical (MIS) procedures

Methods

Surgical society statements regarding the risk of COVID transmission during MIS procedures were reviewed. In addition, the available literature on COVID‐19 and other viral transmission in CO2 pneumoperitoneum, as well as the presence of virus in the plume created by electrocautery during MIS was reviewed. The society recommendations were compared to the available literature on the topic to create our review and recommendations to mitigate COVID‐19 transmission.

Results

The recommendations promulgated by various surgical societies evolved over time as more information became available on COVID‐19 transmission. Review of the available literature on the presence of COVID‐19 in CO2 pneumoperitoneum was inconclusive. There is no clear evidence of the presence of COVID‐19 in plume created by electrocautery. Technologies to reduce CO2 pneumoperitoneum release into the operating room as well as filter viral particles are available and should reduce the exposure risk to operating room personnel.

Conclusion

There is no clear evidence of COVID‐19 virus in the CO2 used during MIS procedures or in the plume created by electrocautery. Until the presence or absence of COVID‐19 viral particles has been clearly established, measures to mitigate CO2 and surgical cautery plume release into the operating room should be performed. Further study on the presence of COVID‐19 in MIS pneumoperitoneum and cautery plume is needed.
Spherical Gaussian‐based Lightcuts for Glossy Interreflections
Authors: Huo Y.C. , Jin S.H. , Liu T. , Hua W. , Wang R. , Bao H.J.
Published: May 2020

It is still challenging to render directional but non‐specular reflections in complex scenes. The SG‐based (Spherical Gaussian) many‐light framework provides a scalable solution but still requires a large number of glossy virtual lights to avoid spikes as well as reduce clamping errors. Directly gathering contributions from these glossy virtual lights to each pixel in a pairwise way is very inefficient. In this paper, we propose an adaptive algorithm with tighter error bounds to efficiently compute glossy interreflections from glossy virtual lights. This approach is an extension of the Lightcuts that builds hierarchies on both lights and pixels with new error bounds and new GPU‐based traversal methods between light and pixel hierarchies. Results demonstrate that our method is able to faithfully and efficiently compute glossy interreflections in scenes with highly glossy and spatial varying reflectance. Compared with the conventional Lightcuts method, our approach generates lightcuts with only one‐fourth to one‐fifth light nodes therefore exhibits better scalability. Additionally, after being implemented on GPU, our algorithms achieve a magnitude of faster performance than the previous method.
The dimensions of evolutionary potential in biological conservation
Authors: Milot Emmanuel , Béchet Arnaud , Maris Virginie
Published: May 2020

It is now well admitted by ecologists that the conservation of biodiversity should imply preserving the evolutionary processes that will permit its adaptation to ongoing and future environmental changes. This is attested by the ever‐growing reference to the conservation of evolutionary potential in the scientific literature. The impression that one may have when reading papers is that conserving evolutionary potential can only be a good thing, whatever biological system is under scrutiny. However, different objectives, such as maintaining species richness versus ecosystem services, may express different, when not conflicting, underlying values attributed to biodiversity. For instance, biodiversity can be intrinsically valued, as worth it to be conserved per se, or it can be conserved as a means for human flourishing. Consequently, both the concept of evolutionary potential and the prescriptions derived from the commitment to conserve it remain problematic, due to a lack of explicit mention of the norms underlying different conservation visions. Here, we contend that those who advocate for the conservation of evolutionary potential should position their conception along four dimensions: what vehicles instantiate the evolutionary potential relevant to their normative commitment; what temporality is involved; how measurable evolutionary potential is, and what degree of human influence is tolerated. We need to address these dimensions if we are to determine why and when the maintenance of evolutionary potential is an appropriate target for the conservation of biodiversity.
“Mit sanfter Gewalt”: Rape and Sexual Violence in the Works of Christoph Martin Wieland
Authors: Speltz Andrea
Published: May 2020

This article contributes to the historiography of rape and sexual violence in eighteenth‐century German‐speaking Europe. Christoph Martin Wieland (1733–1813) portrays rape and sexual violence in seven literary works from the late 1750s through the mid 1770s. Wieland's texts both attack and affirm contemporaneous legal definitions and social norms governing sexual behavior. The article's main argument is that the theme of rape exposes a tension between Wieland's ideals of gender equality and his practical approach to gender relations. In theory, Wieland acknowledges every human's right to sexual self‐determination, but he nevertheless exploits sexual violence (against males and females) for comic effect, resulting in an unresolved dialectic of the Enlightenment, which underlies his texts
Ein Fallbeil für die Aufklärung. Heinrich von Kleists Michael Kohlhaas
Authors: Tolksdorf Nina
Published: May 2020

Die Kleistforschung zeigt ein reges Interesse an der Frage, wie Kleist zur Aufklärung stand. Auch der vorliegende Artikel reiht sich in diesen Themenkomplex ein und zeigt, dass Kleists Texte Postulate der Aufklärung immer wieder dadurch problematisieren, dass sie den Anspruch der Aufklärung auf Ordnung und System torpedieren. Eine der wichtigsten Tugenden der deutschen Aufklärung ist die Redlichkeit, die als Tugend der Kaufmänner verstanden wird und somit im semantischen Feld von Schulden, Schuld, Tausch und Handel zu verorten ist. Wie aber kann Michael Kohlhaas, der so viel Zerstörung anrichtet, redlich sein? Anhand eines close reading zeigt der Artikel, dass der Text selbst eine redliche Ökonomie aufweist, indem die totalitären Tendenzen von Kohlhaas immer wieder durch die Rhetorik des Textes unterbrochen werden. Es ist nicht primär Kohlhaas, der redlich ist, sondern die Darstellung des Textes.
Fatigue of a SiC/SiC ceramic composite with an ytterbium‐disilicate environmental barrier coating at elevated temperature*
Authors: Ruggles‐Wrenn Marina B. , Williams Thaddeus M.
Published: May 2020

Tension‐tension fatigue performance of a SiC/SiC composite with an ytterbium‐disilicate environmental barrier coating (EBC) was investigated at 1200°C in air and steam. The composite is reinforced with Hi‐Nicalon™ SiC fibers and has a melt‐infiltrated matrix processed by chemical vapor infiltration of SiC with subsequent infiltration with SiC particulate slurry and molten silicon. The EBC consists of a Si bond coat and an Yb2Si2O7 top coat applied via air plasma spraying. Tensile properties were evaluated at 1200°C. Tension‐tension fatigue was examined for maximum stresses of 110‐140 MPa. To assess the efficacy of EBC, experimental results obtained for the coated composite are compared to those for a control uncoated composite. Surface grit‐blasting inherent in the EBC application process degrades tensile strength of the composite. However, the EBC effectively protects the composite from oxidation embrittlement during cyclic loading in air or steam. Fatigue runout set to 200 000 cycles (55.6 hours at a frequency of 1.0 Hz) was achieved at 110 MPa in air and steam. Retained properties of pre‐fatigued specimens were characterized. Composite microstructure, along with damage and failure mechanisms were investigated. Damage and failure of the composite are attributed to the growth of cracks originating from numerous processing defects in the composite interior.
Tbet promotes CXCR6 expression in immature natural killer cells and natural killer cell egress from the bone marrow
Authors: Cuff Antonia O. , Perchet Thibaut , Dertschnig Simone , Golub Rachel , Male Victoria
Published: May 2020

Tbet‐deficient mice have reduced natural killer (NK) cells in blood and spleen, but increased NK cells in bone marrow and lymph nodes, a phenotype that is thought to be the result of defective migration. Here, we revisit the role of Tbet in NK cell bone marrow egress. We definitively show that the accumulation of NK cells in the bone marrow of Tbet‐deficient Tbx21−/− animals occurs because of a migration defect and identify a module of genes, co‐ordinated by Tbet, which affects the localization of NK cells in the bone marrow. Cxcr6 is approximately 125‐fold underexpressed in Tbx21−/−, compared with wild‐type, immature NK cells. Immature NK cells accumulate in the bone marrow of CXCR6‐deficient mice, and CXCR6‐deficient progenitors are less able to reconstitute the peripheral NK cell compartment than their wild‐type counterparts. However, the CXCR6 phenotype is largely confined to immature NK cells, whereas the Tbet phenotype is present in both immature and mature NK cells, suggesting that genes identified as being more differentially expressed in mature NK cells, such as S1pr5, Cx3cr1, Sell and Cd69, may be the major drivers of the phenotype.
Cost of managing patients with venous leg ulcers
Authors: Phillips Ceri J. , Humphreys Ioan , Thayer Dan , Elmessary Muhammad , Collins Huw , Roberts Chris , Naik Gurudutt , Harding Keith
Published: May 2020

The aim of this study was to estimate costs associated with the management of patients with venous leg ulcers (VLUs) from the perspective of the UK National Health Service (NHS). The analysis was undertaken through the Secure Anonymised Information Linkage Databank which brings together and anonymously links a wide range of person‐based data from around 75% of general practitioner (GP) practices within Wales (population coverage ~2.5 million). The data covered an 11‐year period from 2007 to 2017. All patients linked to the relevant codes were tracked through primary care settings, recording the number of GP practice visits (number of days with an event recorded), and wound treatment utilisation (eg, dressings, bandages, etc.) Resources were valued in monetary terms (£ sterling) and the costs were determined from national published sources of unit costs. This is the first attempt to estimate the costs of managing of VLUs using routine data sources. The direct costs to the Welsh NHS are considerable and represent 1.2% of the annual budget. Nurse visits are the main cost driver with annual estimates of £67.8 million. At a UK level, these costs amount to £1.98 billion. Dressings and compression bandages are also major cost drivers with annual Welsh estimates of £828 790. The direct cost of managing patients with VLUs is £7706 per patient per annum, which translates to an annual cost of over £2 billion, when extrapolated to the UK population. The primary cost driver is the number of district nurse visits. Initiatives to reduce healing times through improving accuracy of initial diagnosis, and improved evidence‐based treatment pathways would result in major financial savings.
Treatment of stage I–III periodontitis—The EFP S3 level clinical practice guideline
Authors: Sanz Mariano , Herrera David , Kebschull Moritz , Chapple Iain , Jepsen Søren , Berglundh Tord , Sculean Anton , Tonetti Maurizio S. ,   EFP Workshop Participants and Methodological Consultants
Published: May 2020

Background

The recently introduced 2017 World Workshop on the classification of periodontitis, incorporating stages and grades of disease, aims to link disease classification with approaches to prevention and treatment, as it describes not only disease severity and extent but also the degree of complexity and an individual's risk. There is, therefore, a need for evidence‐based clinical guidelines providing recommendations to treat periodontitis.

Aim

The objective of the current project was to develop a S3 Level Clinical Practice Guideline (CPG) for the treatment of Stage I–III periodontitis.

Material and Methods

This S3 CPG was developed under the auspices of the European Federation of Periodontology (EFP), following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The rigorous and transparent process included synthesis of relevant research in 15 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and consensus, on those recommendations, by leading experts and a broad base of stakeholders.

Results

The S3 CPG approaches the treatment of periodontitis (stages I, II and III) using a pre‐established stepwise approach to therapy that, depending on the disease stage, should be incremental, each including different interventions. Consensus was achieved on recommendations covering different interventions, aimed at (a) behavioural changes, supragingival biofilm, gingival inflammation and risk factor control; (b) supra‐ and sub‐gingival instrumentation, with and without adjunctive therapies; (c) different types of periodontal surgical interventions; and (d) the necessary supportive periodontal care to extend benefits over time.

Conclusion

This S3 guideline informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat periodontitis and to maintain a healthy dentition for a lifetime, according to the available evidence at the time of publication.
A tomographic study of the histological structure of teeth in the gilthead sea bream, Sparus aurata (Teleostei, Perciformes, Sparidae)
Authors: Germain Damien , Meunier François J.
Published: May 2020

X‐ray tomography shows that caniniform and molariform teeth of the gilthead sea bream, Sparus aurata, have a simplexodont plicidentine organization. Together with an insertion of the teeth in alveolae, and the presence of bony shafts sustaining the dental plate, the simplexodont plicidentine is linked to the durophagous diet of the fish.
Risk Factors for Mortality in 244 Older Adults With COVID‐19 in Wuhan, China: A Retrospective Study
Authors: Sun Haiying , Ning Ruoqi , Tao Yu , Yu Chong , Deng Xiaoyan , Zhao Caili , Meng Silu , Tang Fangxu , Xu Dong
Published: May 2020

BACKGROUND/OBJECTIVES

Previous studies have reported that older patients may experience worse outcome(s) after infection with severe acute respiratory syndrome coronavirus‐2 than younger individuals. This study aimed to identify potential risk factors for mortality in older patients with coronavirus disease 2019 (COVID‐19) on admission, which may help identify those with poor prognosis at an early stage.

DESIGN

Retrospective case‐control.

SETTING

Fever ward of Sino‐French New City Branch of Tongji Hospital, Wuhan, China.

PARTICIPANTS

Patients aged 60 years or older with COVID‐19 (n = 244) were included, of whom 123 were discharged and 121 died in hospital.

MEASUREMENTS

Data retrieved from electronic medical records regarding symptoms, signs, and laboratory findings on admission, and final outcomes of all older patients with COVID‐19, were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to explore risk factors for death.

RESULTS

Univariate analysis revealed that several clinical characteristics and laboratory variables were significantly different (ie, P < .05) between discharged and deceased patients. Multivariable logistic regression analysis revealed that lymphocyte (LYM) count (odds ratio [OR] = 0.009; 95% confidence interval [CI] = 0.001‐0.138; P = .001) and older age (OR = 1.122; 95% CI = 1.007‐1.249; P = .037) were independently associated with hospital mortality. White blood cell count was also an important risk factor (P = .052). The area under the receiver operating characteristic curve in the logistic regression model was 0.913. Risk factors for in‐hospital death were similar between older men and women.

CONCLUSION

Older age and lower LYM count on admission were associated with death in hospitalized COVID‐19 patients. Stringent monitoring and early intervention are needed to reduce mortality in these patients. J Am Geriatr Soc 68:E19–E23, 2020.
Epilepsy Lesion Localization is not Predicted by Developmental Venous Anomaly Location or its FDG‐PET Metabolic Activity
Authors: Lazor Jillian W. , Stein Joel M. , Schmitt James Eric , Davis Kathryn A. , Nabavizadeh Seyed Ali
Published: May 2020

BACKGROUND AND PURPOSE

This study's purpose is to correlate location and metabolic activity of developmental venous anomalies (DVAs) in epilepsy patients to the seizure focus as determined by ictal/interictal encephaloelectrogram (EEG).

METHODS

A retrospective search was performed for epilepsy patients with DVAs who underwent brain 18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) and magnetic resonance imaging (MRI). MRI exams were analyzed to characterize DVA location and associated structural findings. MRI and PET images were co‐registered and assessment of 18F‐FDG uptake in the DVA territory was performed. The electronic medical record was reviewed for each subject to determine seizure semiology and site of seizure focus by ictal/interictal EEG.

RESULTS

Twenty‐eight DVAs in 25 patients were included. Twelve DVAs demonstrated regional metabolic abnormality on 18F‐FDG‐PET. There was no significant correlation between DVA site and seizure focus on EEG. DVA location was concordant with EEG seizure focus in three subjects, and all three demonstrated hypometabolism on 18F‐FDG‐PET. This significance remains indeterminate, as one of these DVAs was associated with cavernoma, which could serve as the true seizure focus, and one of the patients underwent resection of the DVA without decrease in seizure frequency. Furthermore, there was no statistically significant relationship between DVA metabolic activity and DVA‐EEG lobar or laterality concordance.

CONCLUSIONS

In this sample, there is no significant correlation between location of DVA and seizure focus, and hypometabolism within the DVA territory is not predictive of EEG/DVA co‐localization. As use of 18F‐FDG‐PET for evaluation of epilepsy increases, knowledge of this poor correlation is important to avoid diagnostic confusion and potentially unnecessary surgery in epilepsy patients.
Differences by Rurality in Satisfaction with Care Among Medicare Beneficiaries
Authors: Henning‐Smith Carrie , Hernandez Ashley , Neprash Hannah , Lahr Megan
Published: May 2020

Purpose

There are stark differences between rural and urban areas in demographic characteristics, health status, and health care, yet less is known about rural‐urban differences in Medicare beneficiaries’ satisfaction with care. We seek to identify rural‐urban differences in satisfaction with care for Medicare beneficiaries and whether those differences are explained by differences in beneficiary characteristics.

Methods

We used data from the 2016 Medicare Current Beneficiary Survey (n = 10,625), in which beneficiaries indicated their level of satisfaction for 9 measures related to quality and access/affordability of care. We first assessed bivariate differences in satisfaction with care by rural‐urban location (metropolitan, rural micropolitan, and rural noncore) across each measure. We then used logistic regression to assess whether differences remained after adjusting for sociodemographic and health characteristics.

Results

For nearly all measures, satisfaction with care decreased with increasing rurality. Differences in satisfaction persisted for satisfaction with ease of getting to the doctor from home (adjusted odds ratio [AOR] micropolitan: 0.63, P = .037; AOR noncore: 0.61, P = .023) and availability of care by specialists (AOR micropolitan: 0.51, P = .001; AOR noncore: 0.61, P < .001) after adjusting for sociodemographic and health characteristics.

Conclusions

Rural Medicare beneficiaries reported lower satisfaction with care than their urban counterparts across a variety of measures, and some of these differences remained after adjustments were made for sociodemographic and health characteristics. These findings may have implications for access to and quality of care that rural Medicare beneficiaries receive and their subsequent health outcomes.
Phase 3, Multicenter Open‐Label study to investigate the efficacy of elbasvir and grazoprevir fixed‐dose combination for 8 weeks in treatment‐naïve, HCV GT1b‐infected patients, with non‐severe fibrosis
Authors: Abergel Armand , Asselah Tarik , Mallat Arianne , Chanteranne Brigitte , Faure Frederic , Larrey Dominique , Gournay Jerome , Loustaud‐Ratti Veronique , Di Martino Vincent , Fouchard‐Hubert Isabelle , Pol Stanislas , Bailly Francois , Samuel Didier , Tran Albert , Dodel Marie , Andant Nicolas , Lamblin Geraldine , Muti Leon , Reymond Maud , Teilhet Camille , Pereira Bruno , Buchard Benjamin
Published: May 2020

Background

Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed‐dose combination of grazoprevir‐elbasvir in treatment‐naïve patients, with non‐severe fibrosis.

Methods

HCV mono‐infected and treatment naïve patients with non‐severe fibrosis (Fibroscan®<9.5 kPa and Fibrotest® < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non‐1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12).

Findings

Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan®, 100 had F0‐1 fibrosis score. FIB‐4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance‐associated substitution). Then, modified intention‐to‐treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow‐up week 24.

Interpretation

Naïve patients with genotype 1b and non‐severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir‐elbasvir for 8 weeks.
Rumination syndrome: Assessment of vagal tone during and after meals and during diaphragmatic breathing
Authors: Hoshikawa Yoshimasa , Fitzke Heather , Sweis Rami , Fikree Asma , Saverymuttu Seth , Kadirkamanathan Sritharan , Iwakiri Katsuhiko , Yazaki Etsuro , Aziz Qasim , Sifrim Daniel
Published: May 2020

Background

Pathophysiology of rumination syndrome (RS) is not well understood. Treatment with diaphragmatic breathing improves rumination syndrome. The aim of the study was to characterize vagal tone in patients with rumination syndrome during and after meals and during diaphragmatic breathing.

Methods

We prospectively recruited 10 healthy volunteers (HV) and 10 patients with RS. Subjects underwent measurement of vagal tone using heart rate variability. Vagal tone was measured during baseline, test meal and intervention (diaphragmatic (DiaB), slow deep (SlowDB), and normal breathing). Vagal tone was assessed using mean values of root mean square of successive differences (RMSSD), and area under curves (AUC) were calculated for each period. We compared baseline RMSSD, the AUC and meal‐induced discomfort scores between HV and RS. Furthermore, we assessed the effect of respiratory exercises on symptom scores, and number of rumination episodes.

Key Results

There was no significant difference in baseline vagal tone between HV and RS. During the postprandial period, there was a trend to higher vagal tone in RS, but not significantly (P > .2 for all). RS had the higher total symptom scores than HV (P < .011). In RS, only DiaB decreased the number of rumination episodes during the intervention period (P = .028), while both DiaB and SlowDB increased vagal tone (P < .05 for both). The symptom scores with the 3 breathing exercises showed very similar trends.

Conclusions and inferences

Patients with RS do not have decreased vagal tone related to meals. DiaB reduced number of rumination events by a mechanism not related to changes in vagal tone.
Effects of physical training on anthropometrics, physical and physiological capacities in individuals with obesity: A systematic review
Authors: Zouhal Hassane , Ben Abderrahman Abderraouf , Khodamoradi Arash , Saeidi Ayoub , Jayavel Ayyappan , Hackney Anthony C. , Laher Ismail , Algotar Amit M. , Jabbour Georges
Published: May 2020

Increasing the amount of physical activity is an important strategy for weight loss. This systematic review summarizes recent findings on the effects of physical training on anthropometric characteristics, physical performances and physiological capacities in individuals with overweight and obesity. A systematic literature search strategy was conducted from inception until June 2019 using four electronic databases that identified 2,708 records. After screening for titles, abstracts and full texts, 116 studies were included in our final analysis. Both aerobic (e.g., endurance training) and anaerobic training (e.g., high‐intensity training, resistance training) improved body composition and physical fitness indicators in adults, adolescents and children with obesity (effect size: 0.08 < d < 2.67, trivial to very large). This systematic review suggests that both low‐ and high‐intensity training significantly reduced body weight and fat mass while increasing fat‐free mass in individuals with obesity (effect size: 0.04 <d <3.2, trivial to very large). A significant increase in VO2max also occurs in individuals with obesity in response to aerobic training or high‐intensity interval training (effect size: 0.13 < d < 6.24, trivial to very large). Further studies are needed to define the optimal combination of training intensity and duration needed to produce the most efficacious results in individuals with obesity.
Orofacial pain secondary to acoustic neuroma—A case report
Authors: Oliveira Juliana Araújo , de Freitas Pontes Karina Matthes , Regis Romulo Rocha , Nunes Tereza Nicolle Burgos , Pinto Sérgio Araújo Holanda , Pinto Fiamengui Lívia Maria Sales
Published: May 2020

Aim

The present study aimed to report a case of orofacial pain secondary to acoustic neuroma (AN).

Methods and Results

A 66‐year‐old female presented with unilateral facial pain and odontalgia. The pain was described as throbbing, dull, and constant. Tinnitus, hearing loss, dizziness, and others symptoms were also present. Due to the characteristics of the pain and clinical or radiographic findings, other possible diagnoses, such as temporomadibular disorder, tooth‐related pain, sinusitis, and primary headaches, were excluded. Somatosensory tests for allodynia and hyperalgesia showed extraoral and intraoral hypersensitivity. Magnetic resonance imaging revealed a lesion located on the right cerebellopontine angle extending into and obliterating the internal auditory canal and compressing the middle cerebral peduncle, the pons, and the cisternal segment of cranial nerve V. The patient was diagnosed with a brainstem tumor compatible with AN and trigeminal neuralgia secondary to cranial nerve V compression.

Conclusion

Although uncommon, intracranial tumors should be considered during orofacial pain evaluation to avoid iatrogenic treatment and delayed diagnosis.
Friends like this: The impact of the US–China trade war on global value chains
Authors: Mao Haiou , Görg Holger
Published: May 2020

This paper considers the indirect impact the recent tariff increases between the United States and China can have on third countries through links in global supply chains. We combine data from input–output relationships, imports and tariffs, to calculate the impact of the tariff increases by both the United States and China on cumulative tariffs paid by third countries. We show that the tariff hikes increase cumulative tariffs for other countries and thus hurt trade partners further downstream in global supply chains. We also show that this is particularly important for tariff increases on Chinese imports in the United States. These are likely to be used as intermediates in production in the United States, which are then re‐exported to third countries. The most heavily hit third countries are the closest trade partners, namely the EU, Canada and Mexico. We estimate that the tariffs impose an additional burden of around 500 million to 1 billion US dollars on these countries. China's tariffs on US imports have less of an effect.
Aid, growth and institutions in Sub‐Saharan Africa: New insights using a multiple growth regime approach
Authors: Ouedraogo Rasmane , Sourouema Windemanegda Sandrine , Sawadogo Hamidou
Published: May 2020

Numerous sub‐Saharan African countries depend heavily on foreign aid. This paper explores the impact of foreign aid on economic growth in the continent using a finite mixture model. Contrary to previous studies, we hypothesise that the effect of aid on growth differs across groups of countries with similar but unobserved characteristics. The paper incorporates the potential presence of hidden heterogeneity and tries to explain group membership of countries by using various metrics of institutional variables. Focusing on a sample of 25 countries, we find that the impact of foreign aid on growth differs across three different groups of countries. Moreover, we find that aid works best in countries with effective government, good regulatory quality and low corruption. The results are robust to a battery of robustness checks. The paper underlines the importance of incorporating the heterogeneity in growth process in studies on aid effectiveness and provides evidence that sub‐Saharan African countries should undertake deep governance reforms to benefit from foreign aid.
Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic‐pharmacodynamic analysis of tear fluid following oral administration
Authors: Tamura Norihisa , Okano Atsushi , Kuroda Taisuke , Niwa Hidekazu , Kusano Kanichi , Matsuda Yoshikazu , Fukuda Kentaro , Mita Hiroshi , Nagata Shunichi
Published: May 2020

Objective

To clarify the detailed pharmacokinetics (PK) of orally administered voriconazole in tear fluid (TF) of horses for evaluating the efficacy of voriconazole secreted into TF against equine keratomycosis.

Animals studied

Five healthy Thoroughbred horses.

Procedures

Voriconazole was administrated through a nasogastric tube to each horse at a single dose of 4.0 mg/kg. TF and blood samples were collected before and periodically throughout the 24 hours after administration. Voriconazole concentrations in plasma and TF samples were analyzed using liquid chromatography‐electrospray tandem‐mass spectrometry. The predicted voriconazole concentration in both samples following multiple dosing every 24 hours was simulated by the superposition principle.

Results

The mean maximum voriconazole concentrations in plasma and TF were 3.3 μg/mL at 1.5 h and 1.9 μg/mL at 1.6 h, respectively. Mean half‐life in both samples were 16.4 and 25.2 h, respectively. The ratio of predicted AUC0–24at steady state in TF (51.3 μg∙h/mL) to previously published minimum inhibitory concentration (MIC) ofAspergillusandFusariumspecies was >100 and 25.7, respectively.

Conclusions

This study demonstrated the detailed single‐dose PK of voriconazole in TF after oral administration and simulated the predicted concentration curves in a multiple oral dosing. Based on the analyses of PK‐PD, the simulation results indicated that repeated oral administration of voriconazole at 4.0 mg/kg/d achieves the ratio of AUC to MIC associated with treatment efficacy againstAspergillusspecies. The detailed PK‐PD analyses against pathogenic fungi in TF can be used to provide evidence‐based medicine for equine keratomycosis.