bluuebunny/crossref_metadata_2025 huggingface dataset:
TGF‐β1 activates RSC96 Schwann cells migration and invasion through MMP‐2 and MMP‐9 activities
Authors: Muscella Antonella , Vetrugno Carla , Cossa Luca Giulio , Marsigliante Santo
Published: November 2019

Following peripheral nerve injury, remnant Schwann cells adopt a migratory phenotype and remodel the extracellular matrix allowing axonal regrowth. Although much evidence has demonstrated that TGF‐β1 promotes glioma cell motility and induces the expression of extracellular matrix proteins, the effects of TGF‐β1 on Schwann cell migration has not yet been studied. We therefore investigated the cellular effects and the signal transduction pathways evoked by TGF‐β1 in rattus norvegicus neuronal Schwann RSC96 cell. TGF‐β1 significantly increased migration and invasion of Schwann cells assessed by the wound‐healing assay and by cell invasion assay. TGF‐β1‐enhanced migration/invasion was blocked by inhibition of MMP‐2 and MMP‐9. Consistently, by real‐time and western blot analyses, we demonstrated that TGF‐β1 increased MMP‐2 and MMP‐9 mRNA and protein levels. TGF‐β1 also increased MMPs activities in cell growth medium, as shown by gelatin zymography. The selective TGF‐β Type I receptor inhibitor SB431542 completely abrogated any effects by TGF‐β1. Indeed, TGF‐β1 Type I receptor activation provoked the cytosol‐to‐nucleus translocation of SMAD2 and SMAD3. SMAD2 knockdown by siRNA blocked MMP‐2 induction and cell migration/invasion due to TGF‐β1. TGF‐β1 also provoked phosphorylation of MAPKs extracellular regulated kinase 1/2 and JNK1/2. Both MAPKs were upstream to p65/NF‐kB inasmuch as both MAPKs’ inhibitors PD98059 and SP600125 or their down‐regulation by siRNA significantly blocked the TGF‐β1‐induced nuclear translocation of p65/NF‐kB. In addition, p65/NF‐κB siRNA knockdown inhibited the effects of TGF‐β1 on both MMP‐9 and cell migration/invasion. We conclude that TGF‐β1 controls RSC96 Schwann cell migration and invasion through MMP‐2 and MMP‐9 activities. MMP‐2 is controlled by SMAD2 whilst MMP‐9 is controlled via an ERK1/2‐JNK1/2‐NF‐κB dependent pathway.

image
Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs
Authors: Beresheim Amy C. , Pfeiffer Susan , Grynpas Marc
Published: November 2019

There is considerable variation in the gross morphology and tissue properties among the bones of human infants, children, adolescents, and adults. Using 18 known‐age individuals (nfemale = 8, nmale = 9, nunknown = 1; birth to 21 years old), from a well‐documented cemetery collection, Spitalfields Christ Church, London, UK, this study explores growth‐related changes in cortical and trabecular bone microstructure. Micro‐CT scans of mid‐shaft middle thoracic ribs are used for quantitative analysis. Results are then compared to previously quantified conventional histomorphometry of the same sample. Total area (Tt.Ar), cortical area (Ct.Ar), cortical thickness (Ct.Th), and the major (Maj.Dm) and minor (Min.Dm) diameters of the rib demonstrate positive correlations with age. Pore density (Po.Dn) increases, but age‐related changes to cortical porosity (Ct.Po) appear to be non‐linear. Trabecular thickness (Tb.th) and trabecular separation (Tb.Sp) increase with age, whereas trabecular bone pattern factor (Tb.Pf), structural model index (SMI), and connectivity density (Conn.D) decrease with age. Sex‐based differences were not identified for any of the variables included in this study. Some samples display clear evidence of diagenetic alteration without corresponding changes in radiopacity, which compromises the reliability of bone mineral density (BMD) data in the study of past populations. Cortical porosity data are not correlated with two‐dimensional measures of osteon population density (OPD). This suggests that unfilled resorption spaces contribute more significantly to cortical porosity than do the Haversian canals of secondary osteons. Continued research using complementary imaging techniques and a wide array of histological variables will increase our understanding of age‐ and sex‐specific ontogenetic patterns within and among human populations.
Relationship Trading in Over‐the‐Counter Markets
Authors: HENDERSHOTT TERRENCE , LI DAN , LIVDAN DMITRY , SCHÜRHOFF NORMAN
Published: November 2019

We examine the network of trading relationships between insurers and dealers in the over‐the‐counter (OTC) corporate bond market. Regulatory data show that one‐third of insurers use a single dealer, whereas other insurers have large dealer networks. Execution prices are nonmonotone in network size, initially declining with more dealers but increasing once networks exceed 20 dealers. A model of decentralized trade in which insurers trade off the benefits of repeat business and faster execution quantitatively fits the distribution of insurers' network size and explains the price–network size relationship. Counterfactual analysis shows that regulations to unbundle trade and nontrade services can decrease welfare.
Intellectual property and its foundations: Using Art. 7 and 8 to address the legitimacy of the TRIPS
Authors: Rochel Johan
Published: November 2019

This paper addresses legitimacy issues of the international IP regime by focusing on how normative resources internal to the Trade‐Related Aspects of Intellectual Property Rights (TRIPS) might be drawn upon. It combines legal analysis and political theory to account for the TRIPS’ normative foundations (Art. 7 and 8). The paper's primary contribution is to show that these special legal norms are both a locus of balancing the objectives and principles and a guiding light for the interpretation of subsequent norms contained within the treaty. Their content might best be understood using concepts coined by political theory. This combination of legal and philosophical insights identifies two levels of relevance for these special legal norms: as a specification about the type of competition in global trade foreseen by the TRIPS, and as a justification for intellectual property rights protection. To illustrate the relevance of this approach, the paper briefly considers the panel report in Plain Packaging and its use of Art. 7 and 8. Overall, the paper entails both a methodological contribution on the dialog between political theory and law on international trade, as well as a legal argument on how to unpack normative resources entailed by the TRIPS itself.
Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy
Authors: Ampuero Javier , Gil Antonio , Viloria María del Mar , Rico María Carmen , Millán Raquel , Camacho Inés , Romero‐Gómez Manuel
Published: November 2019

Background

The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE.

Methods

We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post‐load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low‐, intermediate‐ and high‐risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow‐up.

Results

The 28.3% (56/198) of the main cohort suffered from HE during the follow‐up. In the competing risk analysis, both intermediate‐ (subhazard ratio (sHR) 2.01 (95% CI 1.00‐4.14); P = .048) and high‐risk groups (sHR 4.67 (95% CI 2.19‐9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high‐risk group was two and four times greater than the intermediate‐ and low‐risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high‐risk group, while infections and electrolyte imbalance predominated in the rest of patients.

Conclusion

Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision‐making process for the adequate management of HE.
The business of managing nurses’ substance‐use problems
Authors: Ross Charlotte A. , Jakubec Sonya L. , Berry Nicole S. , Smye Victoria
Published: November 2019

Nurses’ experiences in, and the overall effectiveness of, widely used alternative‐to‐discipline programs to manage nurses’ substance‐use problems have not been adequately scrutinized. We uncovered the conflicted official and experiential ways of knowing one such alternative‐to‐discipline program in a Canadian province. We explicated this conflict through an institutional ethnography analysis. Ethnographic data from interviews with 12 nurses who were enrolled in an alternative‐to‐discipline treatment program and three program administrators, as well as institutional texts, were analyzed to explore how institutional practices and power relations co‐ordinated and managed nurses’ experiences. Analysis revealed the acritical acceptance of a standardized program not based on current norms of practice. Potential and actual conflicts of interest, power imbalances, and prevailing corporate interests were rife. Nurses were not afforded the same rights to quality ethical health care as other citizens. ‘Expert’ physicians’ knowledge was privileged while nurses’ knowledge was subordinated. Conclusions were that regulatory bodies cannot rely on the taken‐for‐granted standardized treatment model in widespread use. Individualized treatment alternatives reflecting current, scientific evidence must be offered to nurses, and nurses’ knowledge, expertise, and experiences need to be included in decision‐making processes in these programs.
Troops in “Harm's Way,” the President, and Congressional War‐Funding Decisions
Authors: Jeong Gyung‐Ho
Published: November 2019

Despite the conventional wisdom that legislators are reluctant to support funding restrictions impacting troops in harm's way, the degree of congressional deference varies across legislators. This article argues that the level of constituent support of the president affects this variation. Because the deployment of troops is a salient event that highlights the connection between the president and the war, voters' view of the president becomes an effective indicator of voters' preference regarding the war. Thus, legislators whose constituents support (oppose) the president are more (less) likely to support the president's war policy. However, in the absence of major wars, constituent support of the president has no such effect. A series of analyses of House votes demonstrates how major wars condition the significance of voters' view of the president.
Thick Red Tape and the Thin Blue Line: A Field Study on Reducing Administrative Burden in Police Recruitment
Authors: Linos Elizabeth , Riesch Nefara
Published: November 2019

Police departments struggle to recruit officers, and voluntary drop‐off of candidates exacerbates this challenge. Using four years of administrative data and a field experiment conducted in the Los Angeles Police Department, the authors analyze the impact of administrative burden on the likelihood that a candidate will remain in the recruitment process. Findings show that reducing friction costs to participation and simplifying processes improve compliance, as behavioral public administration would predict. Applicants who were offered simpler, standardized processes completed more tests and were more likely to be hired. Later reductions to perceived burden led to an 8 percent increase in compliance, with a 60 percent increase in compliance within two weeks. However, removing steps that would have allowed for better understanding of eligibility kept unqualified candidates in the process for longer, reducing organizational efficiency. These results extend the field's understanding of how administrative burden can impact the selection of talent into government.
Miconazole‐tolerant strains of Malassezia pachydermatis generated by culture in medium containing miconazole
Authors: Kano Rui , Kamata Hiroshi
Published: November 2019

Background

Tolerance of Malassezia pachydermatis to azole drugs has been reported worldwide, from strains isolated from dogs. Canine Malassezia dermatitis often is treated with shampoos containing 2% miconazole (MCZ) or other topical MCZ products.

Objectives

In the in vitro study herein, it was investigated whether MCZ‐induced amino acid substitutions in the lanosterol 14‐alpha‐demethylase (ERG11) gene 1 lead to azole tolerance in M. pachydermatis.

Methods and materials

Toleranced to MCZ was induced in an azole‐susceptible strain of M. pachydermatis (CBS1879T) by culture in medium containing MCZ. Antifungal susceptibility to MCZ, clotrimazole (CTZ) and itraconazole (ITZ) was assessed using the modified broth microdilution (BM) method. To assess the potential mechanism of tolerance in the three MCZ‐resistant strains, ERG11 was sequenced. The interaction between the calcineurin inhibitor tacrolimus and MCZ in the azole‐tolerant isolates also was examined.

Results

Three strains (NUBS19001 to NUBS19003) from CBS1879T cultured in medium containing MCZ exhibited minimum inhibitory concentrations (MICs) of 40 mg/L to MCZ, 5 mg/L to ITZ and >32 mg/L to CTZ, meaning that the isolates were tolerant. The combination of MCZ and tacrolimus exerted an indifferent effect against the MCZ‐tolerant strain. BLAST analysis using the NCBI database showed mutations in the cytochrome p450 encoded by ERG11 in the MCZ‐tolerant strains.

Conclusions

In the present in vitro study, it was shown that MCZ exposure can induce amino acid substitutions in ERG11 and subsequent tolerance of M. pachydermatis to several azoles. Whether topical therapy with azole‐containing products can exert a similar effect in vivo is a question that requires further research.
Theoretical Dynamic Modeling and Validation of Braided Pneumatic Artificial Muscles
Authors: Slightam Jonathon E. , Nagurka Mark L.
Published: November 2019

The high force-to-weight ratios of braided fluidic artificial muscles (AMs) are ideal for human scale and mobile robot applications. Prior modeling efforts focus on the theoretical static characteristics or empirical dynamic models of these actuators when pressurized. This paper develops a comprehensive high fidelity theoretical dynamic model based on first principles for braided pneumatic AMs and presents experimental validation. A novel theoretical model for the nonlinear stiffness is derived to describe the pressure–displacement behavior. The stiffness model, together with friction, damping, and inertia models, forms an equation of motion (EOM) for braided pneumatic AMs. The EOM is coupled with first-order servopneumatic pressure dynamics, resulting in a third-order system model. System model simulations are compared to experimental results of prototypes with nine different geometries. On average, the system model is able to predict the quasi-static displacement within 7% and the dynamic response within 11%. The theoretical model is also benchmarked against a high fidelity curve fit method, with the empirical method showing a 2% improvement in only quasi-static scenarios. The model promises to be useful for mechanical system and model-based control designs.
A mysterious disease is striking American beech trees
Authors: Popkin Gabriel
Published: November 2019

Researchers debate whether a tiny worm is to blame.
Generation of solar spicules and subsequent atmospheric heating
Authors: Samanta Tanmoy , Tian Hui , Yurchyshyn Vasyl , Peter Hardi , Cao Wenda , Sterling Alphonse , Erdélyi Robertus , Ahn Kwangsu , Feng Song , Utz Dominik , Banerjee Dipankar , Chen Yajie
Published: November 2019

Magnetic fields can generate spicules

Spicules are small jets of plasma from the surface of the Sun that last a few minutes. Around a million are occurring at any moment, even during periods of low solar activity. The mechanism responsible for launching spicules remains unknown, as is their contribution to heating the solar corona. Samanta
et al.
observed emerging spicules and the magnetic fields in the adjacent solar surface. They found that many spicules appear a few minutes after a patch of reverse-polarity magnetic field and that the overlying corona is heated shortly afterward. This result provides evidence that magnetic reconnection can generate spicules, which then transfer energy to the corona.

Science
, this issue p.
890
Cellular quality control by the ubiquitin-proteasome system and autophagy
Authors: Pohl Christian , Dikic Ivan
Published: November 2019

To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt to new environmental conditions and to prevent prolonged damage. We discuss the importance of two major quality control systems responsible for degradation of proteins and organelles in eukaryotic cells: the ubiquitin-proteasome system (UPS) and autophagy. The UPS and autophagy form an interconnected quality control network where decision-making is self-organized on the basis of biophysical parameters (binding affinities, local concentrations, and avidity) and compartmentalization (through membranes, liquid-liquid phase separation, or the formation of aggregates). We highlight cellular quality control factors that delineate their differential deployment toward macromolecular complexes, liquid-liquid phase-separated subcellular structures, or membrane-bound organelles. Finally, we emphasize the need for continuous promotion of quantitative and mechanistic research into the roles of the UPS and autophagy in human pathophysiology.
The role of multiple global change factors in driving soil functions and microbial biodiversity
Authors: Rillig Matthias C. , Ryo Masahiro , Lehmann Anika , Aguilar-Trigueros Carlos A. , Buchert Sabine , Wulf Anja , Iwasaki Aiko , Roy Julien , Yang Gaowen
Published: November 2019

Many factors influence global change

Global environmental change is driven by multiple natural and anthropogenic factors. With a focus on global change as it affects soils, Rilliget al.point out that nearly all published studies consider just one or two factors at a time (see the Perspective by Manning). In a laboratory experiment, they tested 10 drivers of global change both individually and in combination, at levels ranging from 2 to 10 factors. They found that soil properties, processes, and microbial communities could not be predicted from single-effect responses and that multiple factors in combination produced unsuspected responses. They concluded that single-factor studies remain important for uncovering mechanisms but that global change biology needs to embrace more fully the multitude of drivers impinging on ecosystems.

Science, this issue p.886; see also p.801
A broadly applicable cross-linker for aliphatic polymers containing C–H bonds
Authors: Lepage Mathieu L. , Simhadri Chakravarthi , Liu Chang , Takaffoli Mahdi , Bi Liting , Crawford Bryn , Milani Abbas S. , Wulff Jeremy E.
Published: November 2019

Cross-linking a range of alkyl polymers

Some alkyl polymers, such as polyethylene, can be cross-linked by using peroxides or high-energy radiation or through the addition of a radical forming agent. Others, like polypropylene, are likely to undergo chain scission, and this process tends to be uncontrolled in the distribution of the cross-links. Lepage
et al.
developed a widely applicable approach using
bis
-diazirine molecules as cross-linking agents (see the Perspective by de Zwart
et al.
). These molecules can be thermally or photochemically activated to form carbenes that readily insert into the polymer carbon-hydrogen bonds, thus leading to cross-linking. The
bis
-diazirine is nonexplosive, nonvolatile, and easily activated at relatively mild temperatures and thus could be used to fine-tune the properties of existing polymers through small chemical modifications.

Science
, this issue p.
875
; see also p.
800
Overcoming glass brittleness
Authors: Wondraczek Lothar
Published: November 2019

Thin films of flawless amorphous alumina are ductile at room temperature
The deadly diffusion of lethal technologies
Power to the People: How Open Technological Innovation Is Arming Tomorrow's Terrorists
Audrey Kurth Cronin
Oxford University Press, 2019. 440 pp.
Authors: Lucas George
Published: November 2019

From 3D-printed guns to weaponized hobby drones, open technologies pose sinister threats
Piling on the pressures to ecosystems
Authors: Manning Peter
Published: November 2019

Identifying dangerous combinations of assaults could prevent ecosystem collapse
CRISPR's unwanted anniversary
Authors: Doudna Jennifer
Published: November 2019

There are key moments in the history of every disruptive technology that can make or break its public perception and acceptance. For CRISPR-based genome editing, such a moment occurred 1 year ago—an unsettling push into an era that will test how society decides to use this revolutionary technology.
Brucella abortus
Depends on
l
-Serine Biosynthesis for Intracellular Proliferation
Authors: Révora Virginia , Marchesini María Inés , Comerci Diego J.
Published: November 2019

l
-Serine is a nonessential amino acid and a key intermediate in several relevant metabolic pathways. In bacteria, the major source of
l
-serine is the phosphorylated pathway, which comprises three enzymes:
d
-3-phosphoglycerate dehydrogenase (PGDH; SerA), phosphoserine amino transferase (PSAT; SerC), and
l
-phosphoserine phosphatase (PSP; SerB).
Pigs in a blanket: an unusual presentation of malignant ascites in prostatic adenocarcinoma
Authors: Samankan Shabnam , Taherian Mehran , Aghighi Maryam , Crossland David
Published: November 2019

Malignant ascites in prostatic acinar adenocarcinoma is very rare. We present an 84-year-old man with a rare malignant ascites due to prostatic adenocarcinoma demonstrating hepatoid differentiation by immunohistochemistry. The patient was diagnosed with the malignant ascites due to metastatic prostatic adenocarcinoma. We identified the unique cytological feature of envelopment of tumour cell clusters by benign mesothelial monolayers.
Large spontaneous perirenal haematoma following percutaneous transluminal coronary angioplasty
Authors: Attri Varinder , Parmar Kalpesh Mahesh , Prateek Tarun , Kumar Santosh
Published: November 2019

Perirenal haematoma is a rare and life-threatening condition in view of severe and ongoing blood loss. Most common causes are renal cancer, angiomyolipoma and vasculitis. Spontaneous causes of this rare entity may occur with use of anticoagulants and antiplatelets. We report a 61-year-old male patient diagnosed with large perirenal haematoma following percutaneous transluminal coronary angioplasty for myocardial infarction under heparin cover that was managed conservatively.
Experiences and challenges of adults living with type 2 diabetes mellitus presenting at the University Teaching Hospital in Lusaka, Zambia
Authors: Mwila Kunda Faith , Bwembya Phoebe Albina , Jacobs Choolwe
Published: November 2019

Objective

The study explored the experiences and challenges of adults living with type 2 diabetes mellitus (T2DM) presenting at the University Teaching Hospital (UTH) in Lusaka.

Research design

A qualitative descriptive study was conducted. The research relied on purposive sampling to select 28 participants for in-depth interviews. Participants were interviewed during clinical visits at UTH.

Results

Views from participants showed that some adults living with T2DM experienced physical and mental illnesses. Participants’ views reflected that their livelihood with T2DM was influenced by family support, poor or non-adherence to treatment guidelines and access to information, education and communication materials. The most important challenges reported were psychosocial and financial.

Conclusion

The study concluded that some adults living with T2DM experience a lot of physical sicknesses and their challenges, especially of the psychosocial nature may require professional attention. However, particular attention should be paid to the patient’s self-care and psychosocial therapy. Self-care protocols should be tailored to complement the different types of patients with diabetes and improve their quality of life.Cite Now
Trimethylamine N-oxide and incident atherosclerotic events in high-risk individuals with diabetes: an ACCORD trial post hoc analysis
Authors: Cardona Andrea , O'Brien Aaron , Bernier Matthew C , Somogyi Arpad , Wysocki Vicki H , Smart Suzanne , He Xin , Ambrosio Giuseppe , Hsueh Willa Ann , Raman Subha V
Published: November 2019

Introduction

Type 2 diabetes mellitus (T2D) confers high atherosclerotic cardiovascular disease (ASCVD) risk. The metabolite trimethylamine N-oxide (TMAO) derived via gut flora has been linked to excess ASCVD.

Research design and methods

We analyzed data, biospecimens, and major adverse cardiovascular events (MACEs) from the prospective multicenter randomized Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to assess its value in 330 high-risk individuals with T2D without evident atherosclerotic disease at enrollment.

Results

Incident cardiovascular events occurred in 165 cases; 165 controls matched by age, sex, and treatment arm experienced no incident events during follow-up. Cases and controls (mean age 64.5 years) had similar mean glycated hemoglobin (HbA1c) (8.2%) and mean 10-year ASCVD risk (23.5%); groups also had similar use of statins and antihypertensive medications at baseline and follow-up. Baseline plasma TMAO levels did not differ between groups after adjusting for ASCVD risk score, HbA1c, and estimated glomerular filtration rate, nor did TMAO distinguish patients suffering incident MACE from those who remained event-free.

Conclusions

TMAO’s prognostic value for incident ASCVD events may be blunted when applied to individuals with T2D with poor glycemic control and high baseline ASCVD risk. These results behoove further translational investigations of unique mechanisms of ASCVD risk in T2D.
Deficiency of C3a receptor attenuates the development of diabetic nephropathy
Authors: Li Xiao-Qian , Chang Dong-Yuan , Chen Min , Zhao Ming-Hui
Published: November 2019

Objective

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN.

Research design and methods

The expression of C3aR was examined in the renal specimen of patients with DN. Using a C3aR gene knockout mice (C3aR−/−), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a.

Results

Compared with normal controls, the renal expression of C3aR was significantly increased in patients with DN. C3aR−/− diabetic mice developed less severe diabetic renal damage compared with wild-type (WT) diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T-cell adaptive immunity in C3aR−/− diabetic mice compared with WT diabetic mice, and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophage infiltration. In vitro study demonstrated C3a can enhance macrophage-secreted cytokines which could induce inflammatory responses and differentiation of T-cell lineage.

Conclusions

C3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T-cell adaptive immunity, possibly by influencing macrophage-secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.
BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa
Authors: Berendsen Mike LT , van Gijzel Sjors WL , Smits Jeroen , de Mast Quirijn , Aaby Peter , Benn Christine S , Netea Mihai G , van der Ven Andre JAM
Published: November 2019

Introduction

Malaria continues to be a major cause of morbidity and mortality in sub-Saharan Africa (SSA) without effective interventions. Bacillus Calmette-Guérin (BCG) vaccine possesses protective non-specific effects, which extend beyond protection against tuberculosis. This study explores whether BCG is associated with protection against malaria in children under the age of 5 years in SSA.

Methods

We used data from the Demographic Health Survey programme, including 34 206 children from 13 SSA countries. BCG status was taken from vaccination cards when present; if not, mother’s recall was used. Presence of malaria was defined as a positive rapid diagnostic test. Maternally reported presence or absence of fever in the previous 2 weeks defined symptomatic status. Multilevel logistic regression was used to account for the two-stage cluster sampling method.

Results

Of the 34 206 children, 12 325 (36.0%) children were malaria positive and 29 766 (87.0%) were BCG vaccinated. After correction for relevant child, maternal and household factors, BCG vaccination was associated with a lower malaria prevalence (adjusted OR (aOR)=0.94, 95% CI 0.90 to 0.98), especially among children of whom BCG information was retrieved from a vaccination card (aORcard=0.88, 95% CI 0.82 to 0.94). Restricting the analysis to children from regions with suboptimal BCG coverage increased the association (aORcard=0.81, 95% CI 0.73 to 0.89). We observed an increasingly beneficial association with each month of age of the child (aORcard=0.996, 95% CI 0.993 to 0.999). BCG associations were similar for asymptomatic (aORcard=0.86, 95% CI 0.81 to 0.92) and symptomatic (aORcard=0.89, 95% CI 0.78 to 1.01) malaria.

Conclusions

BCG vaccination is associated with protection against malaria. This protection is highest in regions with suboptimal BCG coverage. These results indicate a possible role for timely BCG vaccination in the protection of malaria and its elimination by reducing the transmission reservoir. If confirmed in further research, our findings have substantial implications for global efforts to reduce malaria burden.
The patient safety practices of emergency medical teams in disaster zones: a systematic analysis
Authors: El-khani Ussamah , Ashrafian Hutan , Rasheed Shahnawaz , Veen Harald , Darwish Ammar , Nott David , Darzi Ara
Published: November 2019

Introduction

Disaster zone medical relief has been criticised for poor quality care, lack of standardisation and accountability. Traditional patient safety practices of emergency medical teams (EMTs) in disaster zones were not well understood. Improving the quality of healthcare in disaster zones has gained importance within global health policy. Ascertaining patient safety practices of EMTs in disaster zones may identify areas of practice that can be improved.

Methods

A systematic search of OvidSP, Embase and Medline databases; key journals of interest; key grey literature texts; the databases of the WHO, Médecins Sans Frontieres and the International Committee of the Red Cross; and Google Scholar was performed. Descriptive studies, case reports, case series, prospective trials and opinion pieces were included with no limitation on date or language of publication.

Results

There were 9685 records, evenly distributed between the peer-reviewed and grey literature. Of these, 30 studies and 9 grey literature texts met the inclusion criteria and underwent qualitative synthesis. From these articles, 302 patient safety statements were extracted. Thematic analysis categorised these statements into 84 themes (total frequency 632). The most frequent themes were limb injury (9%), medical records (5.4%), surgery decision-making (4.6%), medicines safety (4.4%) and protocol (4.4%).

Conclusion

Patient safety practices of EMTs in disaster zones are weighted toward acute clinical care, particularly surgery. The management of non-communicable disease is under-represented. There is widespread recognition of the need to improve medical record-keeping. High-quality data and institutional level patient safety practices are lacking. There is no consensus on disaster zone-specific performance indicators. These deficiencies represent opportunities to improve patient safety in disaster zones.
‘New Medicine Service’: supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial
Authors: Elliott Rachel Ann , Boyd Matthew J , Tanajewski Lukasz , Barber Nick , Gkountouras Georgios , Avery Anthony J , Mehta Rajnikant , Davies James E , Salema Nde-Eshimuni , Craig Christopher , Latif Asam , Waring Justin , Chuter Antony
Published: November 2019

Objective

To examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks.

Methods

Pragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective).

Results

Unadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: −£104 (95% CI −£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI −0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of −£113.9 (−1159.4, 683.7). The incremental cost-effectiveness ratio was −£2758/QALY (2.5% and 97.5%: −38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY.

Conclusions

At 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high.

Trial registration number

NCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.
Morphine for dyspnoea in chronic obstructive pulmonary disease: a before–after efficacy study
Authors: Matsuda Yoshinobu , Morita Tatsuya , Matsumoto Hirotaka , Hosoi Keita , Kusama Kayo , Kohashi Yasuo , Morishita Hiroshi , Kaku Sawako , Ariyoshi Keisuke , Oyamada Shunsuke , Inoue Yoshikazu , Iwase Satoru , Yamaguchi Takuhiro , Nishikawa Mitsunori
Published: November 2019

Objectives

Dyspnoea in patients with chronic obstructive pulmonary disease (COPD) is frequent and often persists despite conventional treatment. This study aimed to evaluate the efficacy and safety of oral morphine for dyspnoea in Japanese COPD patients.

Methods

We conducted a multi-institutional, prospective, before–after study of morphine in COPD patients with dyspnoea at rest in seven hospitals. Patients received 12 mg of oral morphine per day (or 8 mg per day if low body weight or renal impairment). Primary outcome was change in the numerical rating scale (NRS) of current dyspnoea in the evening from Day 0 to Day 2. Secondary outcomes included changes in dyspnoea intensity in the evening from Day 0 to Day 1, dyspnoea intensity between the morning from Day 0 to Day 1 and Day 2, vital signs, nausea, somnolence, anorexia and other adverse events (AEs).

Results

A total of 35 patients were enrolled in this study between October 2014 and January 2018. One patient did not receive study treatment. Data from 34 patients was analysed. The NRS of dyspnoea intensity in the evening significantly decreased from 3.9 on Day 0 (95% CI: 3.1 to 4.8) to 2.4 on Day 2 (95% CI: 1.7 to 3.1; p=0.0002). Secondary outcomes significantly improved in a similar manner. There were no apparent changes in the mean scores of the opioid-related AEs and vital signs. One patient experienced grade 3 lung infection not associated with morphine. Other AEs were mild.

Conclusion

Oral morphine is effective in alleviating dyspnoea in Japanese COPD patients.

Trial registration

UMIN000015288 (http://www.umin.ac.jp/ctr/index.htm).
The differences of clinicopathologic characteristics among subgroups of reclassified HER2 fluorescence in situ hybridization (FISH) according to the ASCO/CAP 2018 breast cancer HER2 testing guidelines
Authors: Yang Libo , Chen Min , Pu Tianjie , Wu Shuang , Wei Bing , Yang Jieliang , Bu Hong , Zhang Zhang
Published: November 2019

Aims

The aim of this study is to analyse differences in clinicopathologic features among reclassified human epidermal growth factor receptor-2 (HER2) fluorescencein situhybridization (FISH) results in breast cancers according to 2018 guidelines.

Methods

According to different ratios ofHER2copy numbers to chromosome 17 centromere numbers (HER2/CEP17) and averageHER2copy numbers, 3795 invasive breast cancers were classified into six groups. Clinicopathologic features were collected and compared among different FISH groups.

Results

There were no statistically significant differences about HER2 positive rate between 2013 and 2018 guidelines (p=0.518). After re-evaluating these cases according to 2018 guidelines, the cases that converted to a HER2 positive status had clinicopathologic features similar to samples in group 1 (ratio ≥2.0, HER2≥4.0). Compared with group 5 (ratio <2.0,HER2<4.0), the cases in groups 1 had higher histological grade, more frequent occurrence of negative oestrogen receptor and progesterone receptor status and a higher Ki67 index. The samples in group 4 (ratio <2.0, 4.0≤HER2<6.0) showed a higher histological grade and higher Ki67 index than did the samples in group 5 but had a lower histological grade and lower Ki67 index than did the samples in group 1a (ratio ≥2.0,HER2≥6.0).

Conclusion

Different categories of HER2 FISH test results have significant differences in clinicopathologic features. With no equivocal cases in 2018 HER2 guidelines, the clear division of HER2 status is helpful for making treatment recommendations about HER2 targeted therapy.
Audit of the prevalence and investigation of iron deficiency anaemia in patients with heart failure in hospital practice
Authors: Simon Steny , Ioannou Adam , Deoraj Stuart , Metaxa Sofia , Mandal Amit K J , Missouris Constantinos G
Published: November 2019

Purpose of the study

Iron deficiency anaemia (IDA) is associated with increased morbidity and mortality in heart failure patients. The aim of our audit was to evaluate the current practice in diagnosis and assessment of IDA in patients admitted with heart failure.

Study design

We conducted a retrospective audit of patients admitted to our hospital between January 2017 and June 2017 with a diagnosis of heart failure, and obtained data regarding each patient’s demographics and anaemic status. We also conducted a qualitative survey to assess healthcare professionals’ ability to diagnose IDA, and their knowledge of iron replacement in heart failure patients.

Results

Our audit identified 218 heart failure patients, nearly two-thirds (n=138, 63.3%) of which were anaemic. Of the 138 anaemic patients, only 40 had a full haematinic screen compared with 98 who had incomplete investigations (29% vs 71%, p=0.007). Iron studies were the most commonly performed haematinic investigation (n=87, 63%), and over half of these patients were iron deficient (n=49, 56.3%). Only 12 (24.5%) iron deficient patients were prescribed oral iron therapy, while 37 (75.5%) were left without iron replacement (X2=12.8, p=0.0003). Our survey demonstrated a lack of awareness among healthcare professionals with only 19.7% of participants being able to correctly define anaemia and 9.1% being aware of guidelines regarding treatment of IDA.

Conclusion

Many patients admitted to hospital with heart failure also have a concomitant diagnosis of anaemia. The aetiology of the underlying anaemia is often poorly investigated, and where IDA is identified it is poorly treated.
A quarter of patients time their early rheumatoid arthritis onset differently than physicians
Authors: Ellingwood Leah , Kudaeva Fatima , Schieir Orit , Bartlett Susan J , Bessette Louis , Boire Gilles , Hazlewood Glen S , Hitchon Carol , Keystone Edward , Tin Diane , Thorne Carter , Bykerk Vivian P , Pope Janet
Published: November 2019

Objective

Early rheumatoid arthritis (RA) treatment requires timely recognition. This large, multicentre study compared patient-reported vs physician-reported onset of early RA.

Methods

Patients from the Canadian Early ArThritis CoHort with early/suspected RA (persistent synovitis <1 year) completed questionnaires asking about the date of symptom onset; and rheumatologists date of onset for persistent synovitis. Groups with similar reported timing (patient and physician) versus differing timing of 30 days or more were compared.

Results

In 2683 patients, the median patient symptom duration (IQR) was 178 days (163) and physician-reported duration was 166 (138). 1940 (72%) patients had similar patient-reported and physician-reported onset (<30 days), whereas 497 (18%) reported onset 30 or more days preceding physicians, and 246 (9%) 30 or more days after physicians. Patients reporting onset preceding physicians had lower baseline Disease Activity Score based on 28 joint count, swollen joint counts and erythrocyte sedimentation rate (p<0.05). Patients reporting onset after physicians were more likely to be rheumatoid factor positive (p<0.001) and had higher anticitrullinated protein antibody titres (p<0.009). Regression showed low income, smoking, fibromyalgia, osteoarthritis and baseline non-methotrexate non-biological disease-modifying antirheumatic drug use were predictors for longer patient-reported symptoms. At 12 months, patients reporting longer symptom duration than physicians had lower rates of Simplified Disease Activity Index remission and higher physician global assessments.

Conclusion

Over one-fourth of patients reported differences of >1 month in symptom onset from their rheumatologist. Patients with longer symptom durations had less improvement at 1 year, which may be reflective of comorbid musculoskeletal conditions.
Hypoglycaemia associated with gastrointestinal and extragastrointestinal stromal tumour in two dogs
Authors: Lodzinska Joanna , Ballber Clara , Smith Sionagh H , Bavcar Spela
Published: November 2019

Gastrointestinal stromal tumours (GISTs) are uncommon mesenchymal tumours that originate from the interstitial cells of Cajal. As these tumours are difficult to distinguish from gastrointestinal smooth muscle tumours using standard histological techniques, their true prevalence may be underestimated. Metabolic and systemic consequences of GISTs are not well described in any species. More rarely, neoplasms with histological and immunohistochemical features similar to GISTs may occur outside the gastrointestinal tract, the so‐called extragastrointestinal stromal tumours (EGIST). EGISTs have never been described in the veterinary literature. In this article the authors present and describe clinical findings, management and treatment of two dogs with clinical hypoglycaemia induced by histologically confirmed GIST and EGIST. Hypoglycaemia resolved immediately and long term after tumour excision. To the authors’ knowledge this is the first report of hypoglycaemia associated with a canine GIST and the first case report of an EGIST in a dog.
Rehabilitation treatment for long‐term associated femoral head ostectomy muscle atrophy
Authors: Miyata Takuma , Kawamura Kazumi
Published: November 2019

Rehabilitation after femoral head ostectomy (FHO) is recommended on awakening from anaesthesia. This report summarises the effects of delayed rehabilitation in a Yorkshire terrier and two toy poodles who underwent rehabilitation beginning at 1 month, 3 months and 9 years after FHO surgery, in cases where rehabilitation was impossible immediately after surgery. Rehabilitation was conducted once per week for approximately 3 hours at our facility; we focused on underwater therapy and inclined walking. The results in the dog that underwent rehabilitation 9 years after surgery showed a poor increase in femoral muscle perimeter; in all three cases, improvement in gait was observed. If rehabilitation begins with a long delay after surgery, the end of rehabilitation will be similarly delayed. Nevertheless, the effects of rehabilitation were evident in these cases.
Endometrial osseous metaplasia and endometritis in a Thoroughbred broodmare
Authors: Savage Victoria
Published: November 2019

Endometrial osseous metaplasia is a condition characterised by the presence of mature bone fragments within the endometrium. It is rarely reported in human beings and other domestic mammals, but to the author’s knowledge has not previously been recognised in horses. This case describes a Thoroughbred broodmare presented for breeding evaluation 14 days postpartum. No previous reproductive abnormalities had been identified. Transrectal ultrasonography of the reproductive tract identified multifocal, well‐defined, irregular hyperechoic structures with acoustic shadowing within the uterine wall. Following a single, unsuccessful, reproductive cycle, the fragments were manually removed. Histopathology identified osseous metaplasia and septic endometritis. A combination of intrauterine treatments were implemented, including lavage, infusion with both N‐acetylcysteine and antibiotics. Chemical curettage was performed using an intrauterine kerosene infusion to remove the remaining microspicules and resolve the endometritis. The mare successfully conceived twin embryos. Following manual ablation of one conceptus, the remaining pregnancy was successfully carried to term.
Detection of Mycoplasma hyopneumoniae in nasal and laryngeal swab specimens in endemically infected pig herds
Authors: Moiso Nicolás , Pieters Maria , Degano Facundo , Vissio Claudina , Camacho Pablo , Estanguet Abel , Parada Julián , Tamiozzo Pablo J
Published: November 2019

Background

Apparently, laryngeal swabs (LS) are more sensitive than nasal swabs (NS) and allow earlier detection of Mycoplasma hyopneumoniae by PCR. However, antecedents about the compared detection of M hyopneumoniae with NS and LS in growing pigs, from naturally infected herds, are lacking in the literature. Thus, this study compared the PCR detection of M hyopneumoniae from NS and LS in pigs of various ages.

Methods

A longitudinal study was performed at two farms where NS and LS were collected from three consecutive groups of 20 pigs at 3, 6, 10, 16 and 22 weeks of age. All samples were analysed by nested PCR for M hyopneumoniae detection.

Results

The probability of PCR detection of M hyopneumoniae was higher in LS for pigs of all ages (odds ratio (OR)=1.87; 95 per cent confidence interval (CI) 1.31–2.67) and in 22‐week‐old pigs (OR=4.87; 95 per cent CI 2.86–8.30). The agreement between both sample types was low to moderate (kappa 0.087–0.508), highlighting that M hyopneumoniae does not appear to colonise the respiratory tract in a generalised and consistent fashion.

Conclusions

The results suggest that LS could be employed at different ages to achieve greater bacterial detection. Considering that LS is a minimally invasive, highly sensitive sample compared with the traditional NS, it could be suggested to employ this sample type for M hyopneumoniae detection in naturally infected pigs.