bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the left atrial function in the surgical management of aortic and mitral valve disease
Authors: Cameli Matteo , Sciaccaluga Carlotta , Mandoli Giulia E. , D’Ascenzi Flavio , Tsioulpas Charilaos , Mondillo Sergio
Published: July 2019

The right management of both mitral and aortic disease can be challenging, especially in asymptomatic patients. The current guidelines recommend valve repair or replacement when symptoms arise or when there is an evident left ventricular dysfunction. However, deciding the optimal surgical timing can be very difficult, since the line between the absence of symptoms and being minimally symptomatic, especially in the elderly, is blurred. Another relevant issue regards the second surgical criterion: operating on a patient with a reduced left ventricular ejection fraction or with a dilated left ventricle might jeopardize the possibility of a fully reverse remodeling of the heart after surgery. In this scenario, the left atrium might play an important role. In particular, left atrial deformation might be a very useful tool to detect early ultrastructural alterations, and help or support guiding a patient‐tailored treatment at an early stage, optimizing the outcome in the long term.
Distribution of polyamines may be altered in different scalp regions of patients with hair loss
Authors: Lee Yu Ra , Lee Jeongae , Lew Bark Lynn , Sim Woo Young , Hong Jongki , Chung Bong Chul
Published: July 2019

Hair loss, from the vertex or front of the head, generally occurs due to increased androgenic steroid levels. Androgenic steroids, particularly testosterone and dihydrotestosterone, are distributed differently across the vertex and occipital regions and are involved in inducing ornithine decarboxylase expression. Therefore, we hypothesized that the distribution of polyamines may be altered in different scalp regions. For the overall metabolic profiling of polyamines in patients with hair loss, a liquid chromatography‐mass spectrometry was used. We investigated the differential polyamine levels in different regions of the hair of patients with male pattern baldness and those with female pattern hair loss. The levels of most polyamines were higher in the vertex region than in the occipital region, and N‐acetyl polyamine levels differed significantly. We proposed to test our hypothesis by profiling polyamines in human hair fibre to evaluate the distribution of metabolites in various regions of the scalp.
Space use and inferred spawning activity of three exploited gamefish species on a large artificial reef
Authors: Logan Ryan K. , Lowe Christopher G.
Published: June 2019

Intense fishing pressure has led to changes in species composition, demography and the over‐exploitation of many coastal fishes. To restore populations, artificial reefs (ARs) are used with the assumption that new habitat will increase fish productivity. Kelp bass (Paralabrax clathratus), barred sand bass (P. nebulifer) and California sheephead (Semicossyphus pulcher) are three important recreational gamefish species in southern California. Home ranging behaviour, space use and spawning‐related activity of these three species were quantified on a large AR. Kelp bass used the largest amount of area, but space use was similar among species. While no spawning behaviour could be determined for sheephead, kelp bass exhibited two different activity patterns during spawning months and barred sand bass migrated (indicative of spawning). Results of this study indicate that this large AR is providing suitable habitat for these species, and spawning‐related activity could be a sign that this AR is meeting essential life history demands.
Co‐viability of a Mediterranean demersal fishery affected by the discard ban under alternative management scenarios
Authors: Maynou Francesc
Published: July 2019

The joint viability, or co‐viability, of a Mediterranean Sea mixed demersal fishery was examined by applying a bioeconomic fisheries model to the main seven target stocks of the fishery under biological, social and economic constraints. The stocks of interest were hake, black‐bellied angler, deep‐water rose shrimp, red mullet, blue and red shrimp, Norway lobster and blue whiting, all of which were assessed as overexploited. Their combined production corresponds to 34% by volume and 52% by value of the landings of the demersal fishery studied. Simulation scenarios based on effort reduction, changes in the selectivity pattern and implementing a fisheries restricted area were compared over the simulation horizon of 2015–2030. The latter two scenarios were also examined in terms of full or partial compliance. The effect of a discard ban on the economy of the fleet was also analysed. The results show that the fishery is not co‐viable because some stocks are not viable in the projection period, but social and economic viability was ensured in all cases. As is often the case for mixed fisheries, a unique management measure is unlikely to improve the situation of all stocks simultaneously, but all the management measures tested are better than the status quo.
Backshoring and nearshoring: An overview
Authors: Piatanesi Benedetta , Arauzo‐Carod Josep‐Maria
Published: July 2019

Increasingly, economies that have traditionally benefited from offshoring are losing some of their strategical advantages, with a consequent increase in backshoring by developed economies. This paper describes the phenomenon and tries to shed light on the current challenges, trends, and debates in the area, and on the main determinants of backshoring. A new phenomenon known as nearshoring is also analysed—this consists of relocating some previously offshored manufacturing activities so that they are now close to previous core locations, but not so close as to suffer from disagglomeration effects. This combines the advantages of offshoring and backshoring.
Identification of novel peptides with high stability against in vitro hydrolysis from bovine elastin hydrolysates and evaluation of their elastase inhibitory activity
Authors: Liu Yang , Zheng Lin , Xu Jucai , Sun‐waterhouse Dongxiao , Sun Baoguo , Su Guowan , Zhao Mouming
Published: July 2019

Surviving in the gastrointestinal tract is crucial for biopeptides to exert physiological effects in vivo. To enrich elastase inhibitory peptides with high digestive stability, elastin peptides was separated by using ultrafiltration and macroporous resin column, then changes in elastase inhibitory activity, amino acid composition and peptide profile of elastin peptides during in vitro digestion were measured. The results revealed that the fraction F3 eluted by 40% ethanol displayed high digestive stability possibly due to the high content of Pro‐containing peptides (20.25%). Particularly, thirty peptides in F3 exhibited high digestive stability and most of them contained GV and/or PG fragment. Since GV and PG could inhibit 35.70% and 51.77% elastase activity at the concentration of 20 mm, respectively, peptides in F3 survived in in vitro digestion which contained GV and PG sequence might be potential elastase inhibitors. This provides an approach for preparation of peptides with high bioactivity and digestive stability.
Monogenic autoinflammatory disorders: beyond the periodic fever
Authors: Moghaddas Fiona
Published: July 2019

The past two decades have seen an exponential increase in the number of monogenic autoinflammatory disorders described, coinciding with improved genetic sequencing techniques. This group of disorders has evolved to be heterogeneous and certainly more complex than the original four ‘periodic fever syndromes’ caused by innate immune over‐activation. This review aims to provide an update on the classic periodic fever syndromes as well as introducing the broadening spectrum of clinical features seen in more recently described conditions.
Demographic and clinical profile of cardioembolic stroke patients in Western Sydney
Authors: Ferkh Aaisha , O'Keefe Emily , Zada Matthew , Brown Paula , Duggins Andrew , Thiagalingam Aravinda , Altman Mikhail , Byth Karen , Kizana Eddy , Denniss Alan R. , Thomas Liza
Published: July 2019

Background

Cardioembolism (CE) contributes to a large proportion of ischaemic stroke.

Aims

To evaluate the demographic and clinical profile of CE stroke in Western Sydney.

Methods

A retrospective analysis of ischaemic stroke patients presenting to Westmead Hospital (January–October 2016) was performed. Strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria into different categories. Clinical and demographic data were collected on all stroke patients, and differences between CE and other stroke causes were identified.

Results

Two hundred and twenty‐eight consecutive patients (70.9 years; 53% male) were identified. By TOAST criteria, 21 (9%) had large‐artery atherosclerosis, 94 (41%) CE, 10 (5%) small‐vessel disease, 2 (1%) other aetiology and 101 (44%) undetermined aetiology. A significant proportion of CE stroke patients had cardiovascular risk factors including hypertension (66%), hypercholesterolaemia (50%), diabetes (26%) and ischaemic heart disease (28%). The majority (81%) of patients with CE had atrial flutter/flutter. CE stroke, compared with other types of stroke, was more common in females (56 vs 41%, P = 0.022) and patients with CE stroke were more likely to have previous cerebral ischaemia (34 vs 21%, P = 0.026), suggesting increased recurrence in this group. Of the patients with atrial flutter/flutter (n = 56), the majority (87%) had a high CHA2DS2‐VASC score (≥2); however, a significant proportion (55.4%) were not on anticoagulation.

Conclusions

Cardioembolic stroke remains a significant burden in Western Sydney, and it is likely that a significant proportion may be preventable, as evidenced by the substantial presence of modifiable cardiovascular risk factors, and inadequate anticoagulation of patients with atrial arrhythmias.
Oral anticoagulation after catheter ablation of atrial fibrillation and the associated risk of thromboembolic events and intracranial hemorrhage: A systematic review and meta‐analysis
Authors: Romero Jorge , Cerrud‐Rodriguez Roberto C. , Diaz Juan C. , Rodriguez Daniel , Arshad Samiullah , Alviz Isabella , Cerna Luis , Rios Saul , Monhanty Sangamitra , Natale Andrea , Garcia Mario J. , Di Biase Luigi
Published: July 2019

Aims

We sought to examine whether continuing oral anticoagulation (OAC) after catheter ablation (CA) for atrial fibrillation (AF) is associated with improved outcomes. OAC reduces morbidity and mortality in patients with AF. However, the continuation of OAC following the blanking period of CA is controversial due to conflicting published data.

Methods

A systematic review of Medline, Cochrane, and Embase was performed for studies comparing patients who were continued on OAC (ON‐OAC) vs those in which OAC was discontinued (OFF‐OAC). CHA2DS2 VASc score had to be available for the classification of patients into high‐ or low‐risk cohorts (CHA2DS2 VASc ≥ 2 and ≤ 1, respectively). The primary efficacy outcome was thromboembolic events (TE). Intracranial hemorrhage (ICH) was the primary safety outcome.

Results

Five studies comprising 3956 patients were included (mean age, 61.1 ± 2.9 years; 72.4% male, CHA2DS2 VASc ≤ 1 50.1%; CHA2DS2 VASc ≥ 2 49.9%). After a mean follow‐up of 39.6 ± 11.7 months, OAC‐continuation was associated with a significant decrease in risk of TE in the high‐risk cohort (CHA2DS2 VASc ≥ 2) (risk ratio [RR] 0.41, 95% confidence interval [CI] 0.21‐0.82, P = .01) with a RR reduction of 59%. ICH was significantly higher in the ON‐OAC group (RR, 5.78; 95% CI, 1.33‐25.08; P = .02). No significant benefit was observed in the low‐risk cohort ON‐OAC after the blanking period.

Conclusion

Continuation of OAC after CA of AF with CHA2DS2 VASc ≥ 2 is associated with a significant decreased TE risk and a favorable net clinical benefit in spite of ICH being significantly increased in the ON‐OAC group. Continued OAC offers no benefit with CHA2DS2VASC ≤ 1.
Polycystin‐1 affects cancer cell behaviour and interacts with mTOR and Jak signalling pathways in cancer cell lines
Authors: Papavassiliou Kostas A. , Zoi Ilianna , Gargalionis Antonios N. , Koutsilieris Michael
Published: June 2019

Polycystic Kidney Disease (PKD), which is attributable to mutations in the PKD1 and PKD2 genes encoding polycystin‐1 (PC1) and polycystin‐2 (PC2) respectively, shares common cellular defects with cancer, such as uncontrolled cell proliferation, abnormal differentiation and increased apoptosis. Interestingly, PC1 regulates many signalling pathways including Jak/STAT, mTOR, Wnt, AP‐1 and calcineurin‐NFAT which are also used by cancer cells for sending signals that will allow them to acquire and maintain malignant phenotypes. Nevertheless, the molecular relationship between polycystins and cancer is unknown. In this study, we investigated the role of PC1 in cancer biology using glioblastoma (GOS3), prostate (PC3), breast (MCF7), lung (A549) and colorectal (HT29) cancer cell lines. Our in vitro results propose that PC1 promotes cell migration in GOS3 cells and suppresses cell migration in A549 cells. In addition, PC1 enhances cell proliferation in GOS3 cells but inhibits it in MCF7, A549 and HT29 cells. We also found that PC1 up‐regulates mTOR signalling and down‐regulates Jak signalling in GOS3 cells, while it up‐regulates mTOR signalling in PC3 and HT29 cells. Together, our study suggests that PC1 modulates cell proliferation and migration and interacts with mTOR and Jak signalling pathways in different cancer cell lines. Understanding the molecular details of how polycystins are associated with cancer may lead to the identification of new players in this devastating disease.
Factors affecting terrestrial movement in the amphibious mangrove rivulus (Kryptolebias marmoratus)
Authors: Yin‐Liao Irene , Wright Patricia A. , Laberge Frédéric
Published: July 2019

We hypothesised that the exploration tendency of the amphibious mangrove rivulus Kryptolebias marmoratus would be inhibited in the terrestrial environment because of constraints on terrestrial locomotion or orientation. Using a novel object test, we showed that the fish explored objects in the aquatic but not the terrestrial environment, supporting the existence of constraints on terrestrial exploration. In further tests of the effects of extrinsic factors on terrestrial movement between aquatic refuges, shallow water depth simulating desiccation risk and the presence of a conspecific simulating intraspecific competition increased emersion outside of refuges, while high water salinity had no effect. These extrinsic factors had little effect on terrestrial movement between different aquatic refuges, except possibly for the lowest water depth tested. A significant association observed between emersion activity and movement between aquatic refuges suggested that terrestrial movement in K. marmoratus might depend on the tendency of individuals to emerse.
The MedSafer Study: A Controlled Trial of an Electronic Decision Support Tool for Deprescribing in Acute Care
Authors: McDonald Emily G. , Wu Peter E. , Rashidi Babak , Forster Alan J. , Huang Allen , Pilote Louise , Papillon‐Ferland Louise , Bonnici André , Tamblyn Robyn , Whitty Rachel , Porter Sandra , Battu Kiran , Downar James , Lee Todd C.
Published: June 2019

OBJECTIVES

Polypharmacy is common, costly, and harmful for hospitalized older adults. Scalable strategies to reduce the burden of potentially inappropriate medications (PIMs) are needed. We sought to leverage medication reconciliation in hospitalized older adults by pairing with MedSafer, an electronic decision support tool for deprescribing.

DESIGN

This was a nonrandomized controlled before‐and‐after study.

SETTING

The study took place on four internal medicine clinical teaching units.

PARTICIPANTS

Subjects were aged 65 years and older, had an expected prognosis of 3 or more months, and were taking five or more usual home medications.

INTERVENTION

In the baseline phase, patients received usual care that was medication reconciliation. Patients in the intervention arm also had a “deprescribing opportunity report” generated by MedSafer and provided to their in‐hospital treating team.

MEASUREMENTS

The primary outcome was ascertained at the time of hospital discharge and was the proportion of patients who had one or more PIMs deprescribed.

RESULTS

A total of 1066 patients were enrolled, and deprescribing opportunities were present for 873 (82%; 418 during the control and 455 during the intervention phases, respectively). The proportion of patients with one or more PIMs deprescribed at discharge increased from 46.9% in the control period to 54.7% in the intervention period with an adjusted absolute risk difference of 8.3% (2.9%‐13.9%). Not all classes of drugs in the intervention arm were associated with an increase in deprescribing, and new PIM starts were equally common in both arms of the study.

CONCLUSION

Using an electronic decision support tool for deprescribing, we increased the proportion of patients with one or more PIMs deprescribed at hospital discharge as compared with usual care. Although this type of intervention may help address medication overload in hospitalized patients, it also underscores the importance of powering future trials for a reduction in adverse drug events.

Trial registration: NCT02918058. J Am Geriatr Soc 67:1843–1850, 2019
Learning from Coworkers: Peer Effects on Individual Investment Decisions
Authors: OUIMET PAIGE , TATE GEOFFREY
Published: July 2019

Using unique data on employee stock purchase plans (ESPPs), we examine the influence of networks on investment decisions. Comparing employees within a firm during the same election window with metro area fixed effects, we find that the choices of coworkers in the firm's ESPP exert a significant influence on employees’ own decisions to participate and trade. Moreover, we find that the presence of high‐information employees magnifies the effects of peer networks. Given participation in an ESPP is value‐maximizing, our analysis suggests the potential of networks and targeted investor education to improve financial decision‐making.
Optimal mixed taxation, credit constraints, and the timing of income tax reporting
Authors: Boadway Robin , Garon Jean‐Denis , Perrault Louis
Published: July 2019

We study optimal income and commodity tax policy with credit‐constrained low‐income households. Workers receive an even flow of income during the tax year, but report their incomes and make tax payments (receive transfers) at the end of the year. They spend their disposable income on multiple commodities over the year. We show that differentiated subsidies on commodities can be optimal even if the Atkinson–Stiglitz Theorem conditions apply. When the optimal policy leaves low‐income households with binding credit constraints, it may be optimal to subsidize differentially the good that they consume in higher proportion. Uniform subsidies would also relax the credit constraint, but would be more costly to the government since they would equally benefit unconstrained households. Numerical examples suggest that commodity tax differentiation increases with basic needs and with the interest rate at which government borrows.
Amino acid profiles of muscle and liver tissues of Australian Merino, Damara and Dorper lambs under restricted feeding
Authors: Ribeiro David M. , Madeira Marta S. , Kilminster Tanya , Scanlon Tim , Oldham Chris , Greeff Johan , Freire João P. B. , Mourato Miguel P. , Prates José A. M. , Almeida André M.
Published: June 2019

Seasonal weight loss (SWL) is a major constraint in extensive animal production systems in the tropics and Mediterranean. The objective of this study was to characterize the amino acid profile of muscle and hepatic tissues of Australian Merino, Damara and Dorper lambs under restricted feeding to evaluate the impact of SWL at the metabolic and physiological levels. SWL induced generalized muscle protein breakdown among restricted groups of all breeds, with varying intensity. Dorper breed mobilized less muscle amino acids when under these conditions, with the Damara having frequent significant differences, namely by having lower amino acid concentrations in the muscle of restricted lambs. Damara lambs showed greater ability to catabolize branched‐chain amino acids in the muscle tissue, which indicates yet another mechanism that provides the Damara with the necessary tools to endure harsh conditions. Overall, the Damara breed mobilized more muscle amino acids than the other breeds, with a better capacity to catabolize branched‐chain amino acids in the muscle, while maintaining muscle structural integrity.
Time course of serum cobalamin, folate, and total iron binding capacity concentrations in pregnant bitches and association with hematological variables and survival
Authors: Nivy Ran , Mazaki‐Tovi Michal , Aroch Itamar , Tal Smadar
Published: July 2019

Background

Hypocobalaminemia, hypofolatemia and iron deficiency are associated with pregnancy‐related anemia (PRA) and neonatal survival (NS) in women. Similar associations have not been investigated in pregnant bitches.

Objectives

To investigate time course and associations of serum cobalamin, folate and iron status indicators with hematological variables and NS in pregnant bitches.

Animals

Forty‐eight pregnant bitches.

Methods

A prospective cohort study. Pregnancy was confirmed by abdominal ultrasonography twice during mid‐ and late pregnancy, concurrently with blood sampling. Associations among pregnancy stage, NS and laboratory variables were assessed by generalized estimating equations.

Results

Compared with midpregnancy, serum cobalamin (adjusted mean [95% confidence interval, CI]) decreased at late pregnancy (430 pg/mL [394‐466] versus 330 pg/mL [303‐357], respectively;P < .001), whereas serum folate did not. Every increment of 1 in parity number or litter size corresponded to 28.6 pg/mL (95% CI, 5.6‐51.6;P= .02) and 20.3 pg/mL (95% CI, 10.9‐29.7;P < .001) decrease in serum cobalamin concentration. Compared with midpregnancy, serum iron (P < .001) and transferrin saturation (P= .01) increased at late pregnancy. The decrease in red blood cell count (P < .001) at late pregnancy was significantly, albeit weakly, correlated with decreasing serum folate concentration (r= 0.33;P= .02). None of the measures was associated with NS.

Conclusions and Clinical Significance

Pregnancy‐related anemia was common at late pregnancy. Unlike in women, in pregnant bitches, serum iron and transferrin saturation were increased at late pregnancy. Future studies are warranted to investigate the clinical ramifications of hypocobalaminemia in pregnant bitches and the utility of prophylactic folate administration in mitigating PRA.
Activity of Prefrontal Cortex in Teachers and Students during Teaching of an Insight Problem
Authors: Takeuchi Naoyuki , Mori Takayuki , Suzukamo Yoshimi , Izumi Shin‐Ichi
Published: July 2019

Metacognitive functions are important for both teachers and students to facilitate teaching and learning. The prefrontal cortex (PFC) plays a proven role in metacognition. As a pilot study, we evaluated the PFC activity of teachers and students using near‐infrared spectroscopy devices to explore the neural mechanism of PFC underlying metacognitive function during teaching and problem‐solving processes. In 14 student‐teacher pairs, participants in the teacher role gave hints via a tablet screen to facilitate solving of a tangram puzzle task by participants in the student role. The PFC activity of teachers increased after giving hints but not while planning hints. The PFC activity of students increased upon task solving after receiving hints. The PFC of teachers might play a metacognitive role in monitoring their own teaching results. The PFC activity of students might be related to the creativity process after gaining insights, as well as metacognitive process for monitoring their own behavior.
Demographic stochasticity alters expected outcomes in experimental and simulated non‐neutral communities
Authors: Legault Geoffrey , Fox Jeremy W. , Melbourne Brett A.
Published: July 2019

Theory has shown that the effects of demographic stochasticity on communities may depend on the magnitude of fitness differences between species. In particular, it has been suggested that demographic stochasticity has the potential to significantly alter competitive outcomes when fitness differences are small (nearly neutral), but that it has negligible effects when fitness differences are large (highly non‐neutral). Here we test such theory experimentally and extend it to examine how demographic stochasticity affects exclusion frequency and mean densities of consumers in simple, but non‐neutral, consumer–resource communities. We used experimental microcosms of protists and rotifers feeding on a bacterial resource to test how varying absolute population sizes (a driver of demographic stochasticity) affected the probability of competitive exclusion of the weakest competitor. To explore whether demographic stochasticity could explain our experimental results, and to generalize beyond our experiment, we paired the experiment with a continuous‐time stochastic model of resource competition, which we simulated for 11 different fitness inequalities between competiting consumers. Consistent with theory, in both our experiments and our simulations we found that demographic stochasticity altered competitive outcomes in communities where fitness differences were small. However, we also found that demographic stochasticity alone could affect communities in other ways, even when fitness differences between competitors were large. Specifically, demographic stochasticity altered mean densities of both weak and strong competitors in experimental and simulated communities. These findings highlight how demographic stochasticity can change both competitive outcomes in non‐neutral communities and the processes underlying overall community dynamics.
Effects of electroconvulsive therapy in the systemic inflammatory balance of patients with severe mental disorder
Authors: Bioque Miquel , Mac‐Dowell Karina S. , Meseguer Ana , Macau Elisabet , Valero Ricard , Vieta Eduard , Leza Juan C. , Bernardo Miquel
Published: June 2019

Aim

There is a great interest in the role of the immune system and the inflammatory balance as key mechanisms involved in the pathophysiology of severe mental disorders. Previous studies have indicated that electroconvulsive therapy (ECT) produces changes in certain inflammatory mediators or in the immune system response. This study aimed to explore the effects of ECT on the nuclear transcription factor κB (NFκB) pathway, a main regulatory pathway of the inflammatory/immune response.

Methods

Thirty subjects with a severe mental disorder receiving treatment with ECT in our center were included. Thirteen systemic biomarkers related to the NFκB pathway were analyzed right before and 2 h after a single ECT session.

Results

An ECT session significantly decreased the expression of NFκB (P = 0.035) and of the inducible nitric oxide synthase (P = 0.012), and the plasma levels of nitrites (P = 0.027), prostaglandin E2 (P = 0.049), and 15‐deoxy‐PGJ2 (P < 0.001). Decrease in plasmatic levels of nitrites was greater in females than in males (P = 0.021). A positive correlation between the ECT stimulus load and changes in the expression of NFkB was found (P = 0.036). Thiobarbituric acid reactive substance levels were decreased in treatment responders and increased in non‐responders (P = 0.047).

Conclusion

Our study shows the effects that a single session of ECT produces on a canonical regulatory pathway of the inflammatory/innate immune system and the inflammatory balance. These biomarkers could be useful as treatment response targets and could help to clarify the biological basis of ECT action. These findings warrant greater attention in future investigations and in the translational significance of these data.
Pediatric red ear syndrome: A case report of an erythromelalgia type and review of the literature
Authors: Cinats Allison K. , Haber Richard M.
Published: July 2019

Red ear syndrome has been reported in the literature to have similarities to erythromelalgia with auricular involvement; however, the distinction between the two is controversial. Red ear syndrome has previously been classified as idiopathic (primary) or secondary, with headaches being the most common association in the idiopathic or primary form. We present a case of pediatric red ear syndrome with hand and foot involvement that we believe represents auricular erythromelalgia. In this report, we propose a classification system to unify the diagnoses of red ear syndrome and erythromelalgia and review the literature on pediatric cases of red ear syndrome.
Non‐invasive screening using ventilatory gas analysis to distinguish between chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension
Authors: Akizuki Mina , Sugimura Koichiro , Aoki Tatsuo , Kakihana Takaaki , Tatebe Shunsuke , Yamamoto Saori , Sato Haruka , Satoh Kimio , Shimokawa Hiroaki , Kohzuki Masahiro
Published: July 2019

Background and objective

Clinical presentations associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) at rest are highly similar. Differentiating between CTEPH and PAH using non‐invasive techniques remains challenging. Thus, we examined whether analysis of ventilatory gas in response to postural changes can be useful as a non‐invasive screening method for pulmonary hypertension (PH), and help differentiate CTEPH from PAH.

Methods

We prospectively enrolled 90 patients with suspected PH and performed right heart catheterization, ventilation/perfusion scan and ventilatory gas analysis. Various pulmonary function parameters were examined in the supine and sitting postures, and postural changes were calculated (Δ(supine − sitting)).

Results

In total, 25 patients with newly diagnosed PAH, 40 patients with newly diagnosed CTEPH and 25 non‐PH patients were included. ΔEnd‐tidal CO2 pressure (PETCO2) was significantly lower in patients with CTEPH and PAH than in non‐PH patients (both P < 0.001). ΔPETCO2 < 0 mm Hg could effectively differentiate PH from non‐PH (area under the curve (AUC) = 0.969, sensitivity = 89%, specificity = 100%). Postural change from sitting to supine significantly increased the ratio of ventilation to CO2 production (VE/VCO2) in the CTEPH group (P < 0.001). By contrast, VE/VCO2 significantly decreased in the PAH group (P = 0.001). Notably, CTEPH presented with higher ΔVE/VCO2 than PAH, although no differences were observed in haemodynamic and echocardiographic parameters between the two groups (P < 0.001). Furthermore, ΔVE/VCO2 > 0.8 could effectively differentiate CTEPH from PAH (AUC = 0.849, sensitivity = 78%, specificity = 88%).

Conclusion

Postural changes in ventilatory gas analysis are useful as a non‐invasive bedside evaluation to screen for the presence of PH and distinguish between CTEPH and PAH.
Combination therapy using fibrinogen γ‐chain peptide‐coated, ADP‐encapsulated liposomes and hemoglobin vesicles for trauma‐induced massive hemorrhage in thrombocytopenic rabbits
Authors: Hagisawa Kohsuke , Kinoshita Manabu , Takikawa Masato , Takeoka Shinji , Saitoh Daizoh , Seki Shuhji , Sakai Hiromi
Published: July 2019

BACKGROUND

We previously developed substitutes for red blood cells (RBCs) and platelets (PLTs) for transfusion. These substitutes included hemoglobin vesicles (HbVs) and fibrinogen γ‐chain (dodecapeptide HHLGGAKQAGDV, H12)–coated, adenosine diphosphate (ADP)‐encapsulated liposomes [H12‐(ADP)‐liposomes]. Here, we examined the efficacy of combination therapy using these substitutes instead of RBC and PLT transfusion in a rabbit model with trauma‐induced massive hemorrhage with coagulopathy.

STUDY DESIGN AND METHODS

Thrombocytopenia (PLT count approximately 40,000/μL) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion with autologous RBCs. Thereafter, lethal hemorrhage was induced in rabbits by noncompressible penetrating liver injury. Subsequently, H12‐(ADP)‐liposomes with platelet‐poor plasma (PPP), platelet‐rich plasma (PRP), or PPP alone were administered to stop bleeding. Once achieving hemostasis, HbVs, allogenic RBCs, or 5% albumin were transfused into rabbits to rescue them from fatal anemia following massive hemorrhage.

RESULTS

Administration of H12‐(ADP)‐liposomes/PPP as well as PRP (but not PPP) effectively stopped liver bleeding (100% hemostasis). The subsequent administration with HbVs as well as RBCs after hemostasis markedly rescued rabbits from fatal anemia (75% and 70% survivals for 24 hr, respectively). In contrast, 5% albumin administration rescued none of the rabbits.

CONCLUSION

Combination therapy with H12‐(ADP)‐liposomes and HbVs may be effective for damage control resuscitation of trauma‐induced massive hemorrhage.
Organophosphate intoxication in 2 dogs from ingestion of cattle ear tags
Authors: Asokan Vibha R. , Kerl Marie E. , Evans Tim , Harmon Meghan
Published: July 2019

Objective

To describe 2 cases of organophosphate intoxication through a previously unreported method of exposure.

Case series

A 2‐year‐old intact male Australian Cattle Dog (case 1) presented with progressive muscarinic and nicotinic clinical signs, and a 3‐year‐old neutered male mixed breed dog (case 2) presented after known ingestion of cattle ear tags. The dog in case 1 was discovered to have ingested cattle ear tags after abdominal radiographs. Organophosphate testing of gastric contents confirmed diazinon toxicosis. The dog in case 2 was found to be eating ear tags by the owner. The tags in case 2 contained diazinon and coumaphos. The dog in case 1 was treated with gastric lavage, gastroprotectants, prokinetics, antiemetics, pralidoxime chloride, and atropine. The dog in case 2 was treated with pralidoxime chloride. Both patients received standard supportive and nursing care and recovered completely with no further concerns.

New or unique information provided

This is a novel exposure to organophosphates that has not been reported in small animals. In dogs with relevant clinical signs and potential environmental exposure, cattle ear tag ingestion is an important differential diagnosis to consider.
Assessment of the percutaneous dilatational tracheostomy technique in experimental manikins and canine cadavers
Authors: Pardo Mariana A. , Sumner Julia P. , Friello Adele , Fletcher Daniel J. , Goggs Robert
Published: July 2019

Objective

To evaluate procedure time, ease of placement, and complication rates of percutaneous dilatational tracheostomy (PDT) compared to surgical tracheostomy (ST) in canine cadavers.

Design

Randomized crossover experimental manikin and cadaver study involving 6 novice veterinary students.

Setting

University teaching hospital.

Animals

Canine tracheostomy training manikin, 24 canine cadavers.

Interventions

None.

Measurements and Main Results

For training, each student performed 10 PDT and 10 ST procedures on a training manikin, followed by 2 PDT and 2 ST procedures on a canine cadaver. After each training procedure, feedback from bronchoscopy and observers was provided. Final PDT and ST tube placements using new equipment were performed in unused cadavers. Placements were timed, ease of placement was scored using visual analog scales (VAS, 0–10 cm), and complications were assessed by two independent observers using ordinal scales (0–3). Cadaver tracheas were explanted postprocedure to evaluate anatomical damage scores (0–3). Procedure time and VAS scores for PDT and ST procedures were analyzed using mixed‐effects linear models, accounting for student, technique, and procedure number with post hoc pairwise comparisons. Data are presented as median (range). For the final cadaver placement, there were no significant differences in placement time (300 seconds [230–1020] vs 188 seconds [116–414], P = 0.210), ease of placement (3.8 cm [2.1–5.7] vs 1.9 cm [0–4.7], P = 0.132), anatomical damage score (1 [0–2] vs 0 [0–1], P = 0.063), or equipment complications score (0 [0–1] vs 0 [0–0], P = 1.000) between PDT and ST, respectively.

Conclusions

These data suggest that PDT can be performed as quickly, as easily, and as safely as ST in a canine cadaver by novice veterinary students following manikin training. Additional studies will be required to determine if these findings can be translated into veterinary clinical practice.
Crimean–Congo Haemorrhagic Fever: Case study analysis of a sporadic outbreak from Chakwal, Pakistan
Authors: Yaqub Tahir , Oneeb Muhammad , Mukhtar Nadia , Tahir Zarfishan , Shahid Furqan , Subhan Sabir , Salman Mo
Published: July 2019

Crimean–Congo Haemorrhagic Fever (CCHF) is a deadly viral zoonotic disease, which is endemic in Pakistan. We report a case study analysis of three cases of CCHF which occurred in Chakwal, Pakistan in 2016. The disease was suspected in three patients exhibiting clinical symptoms suggestive of CCHF; two of the three patients died. The presence of CCHF was detected by seroconversion (IgG) from the surviving patient, while the antigen was detected in Hyalomma ticks originating from animals in the vicinity. This report indicates increase threat emergence of CCHF in Pakistan and highlights its zoonotic implications requiring immediate interventions under the “One‐Health” concept.
Nef anti-canonical divisors and rationally connected fibrations
Authors: Ejiri Sho , Gongyo Yoshinori
Published: June 2019

We study the Iitaka–Kodaira dimension of nef relative anti-canonical divisors. As a consequence, we prove that given a complex projective variety with klt singularities, if the anti-canonical divisor is nef, then the dimension of a general fibre of the maximal rationally connected fibration is at least the Iitaka–Kodaira dimension of the anti-canonical divisor.
Electrochemical Studies on Na0.44MnO2 as Cathode Material for Na-Ion Battery Synthesized Through Sol–Gel Auto Combustion Process
Authors: Senthilkumar M. , Jagadish K. , Satyavani T.V.S.L. , Srinivas Kumar A.
Published: June 2019

For the development of sodium ion secondary batteries, performance improvement in the positive electrode is the main area of research in recent times. Enhancement in electrochemical performance of Na0.44MnO2(NMO) material as a positive electrode material for sodium ion secondary batteries plays a vital role. In this work, the NMO orthorhombic compound was prepared through sol–gel auto combustion process and characterized. Its electrochemical properties are investigated and discussed. The material displays a discharge capacity of about 102.5 mAh/g at a low current rate (C/20), which decreases to 36.75 mAh/g at a relatively higher rate (2C). The capacity retention at C/10 after 50 cycles is 85.7%. The evaluation of Na-ion diffusion coefficients (DNa+) in NMO is accomplished by potentiostatic intermittent titration technique (PITT) test and galvanostatic intermittent titration technique (GITT) test. The obtained values for the Na-ion diffusivity are ranging between 10−14 and 10−15 cm2 s−1.
Safety, Pharmacokinetics, and Food Effect of Tebipenem Pivoxil Hydrobromide after Single and Multiple Ascending Oral Doses in Healthy Adult Subjects
Authors: Eckburg Paul B. , Jain Akash , Walpole Susannah , Moore Grayson , Utley Luke , Manyak Erika , Dane Aaron , Melnick David
Published: July 2019

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr, formerly SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing
Enterobacteriaceae
. The safety and pharmacokinetics (PK) of tebipenem were studied after administration of single and multiple ascending oral doses of TBPM-PI-HBr in fed and fasted states.
Patient-Derived Cytomegaloviruses with Different Ganciclovir Sensitivities from UL97 Mutation Retain Their Replication Efficiency and Some Kinase Activity
In Vitro
Authors: Wong Diana D. , van Zuylen Wendy J. , Hamilton Stuart T. , Steingruber Mirjam , Sonntag Eric , Marschall Manfred , Rawlinson William D.
Published: June 2019

Mutations in the cytomegalovirus UL97 kinase gene contribute to antiviral resistance. Mutations A594S and G598D from two clinical isolates were analyzed, and bacterial artificial chromosome (BAC)-engineered A594S recombinant cytomegalovirus exhibited a ganciclovir-resistant phenotype on plaque reduction. Viral replication was comparable to that of the wild type. Cell-based kinase activity and autophosphorylation of ectopically expressed proteins showed that mutants retained some kinase activity.
Antiretroviral Therapy Administration in Healthy Rhesus Macaques Is Associated with Transient Shifts in Intestinal Bacterial Diversity and Modest Immunological Perturbations
Authors: Ortiz Alexandra M. , Flynn Jacob K. , DiNapoli Sarah R. , Sortino Ornella , Vujkovic-Cvijin Ivan , Belkaid Yasmine , Sereti Irini , Brenchley Jason M.
Published: June 2019

Dysbiosis of the fecal microbiome is a common feature observed in ARV-treated people living with HIV. The degree to which HIV infection itself causes this dysbiosis remains unclear. Here, we demonstrate that medications used to treat HIV infection can influence the composition of the GI tract immune responses and its microbiome in the nonhuman primate SIV model.
High-Throughput Screening Identifies Mixed-Lineage Kinase 3 as a Key Host Regulatory Factor in Zika Virus Infection
Authors: Xu Hua , Cheng Min , Chi Xiaojing , Liu Xiuying , Zhou Jia , Lin Tianli , Yang Wei
Published: June 2019

Zika fever, an infectious disease caused by the Zika virus (ZIKV), normally results in mild symptoms. Severe infection can cause Guillain-Barré syndrome in adults and birth defects, including microcephaly, in newborns. Although ZIKV was first identified in Uganda in 1947 in rhesus monkeys, a widespread epidemic of ZIKV infection in South and Central America in 2015 and 2016 raised major concerns. To date, there is no vaccine or specific medicine for ZIKV. The significance of our research is the systematic discovery of small molecule candidates that modulate ZIKV infection, which will allow the development of antiviral therapeutics. In addition, we identified MLK3, a key mediator of host signaling pathways that can be activated during ZIKV infection and limits virus replication by inducing multiple inflammatory cytokines. These findings broaden our understanding of ZIKV pathogenesis.
Time Series Genome-Centric Analysis Unveils Bacterial Response to Operational Disturbance in Activated Sludge
Authors: Pérez María Victoria , Guerrero Leandro D. , Orellana Esteban , Figuerola Eva L. , Erijman Leonardo
Published: July 2019

Disturbance is a key determinant of community assembly and dynamics in natural and engineered ecosystems. Microbiome response to disturbance is thought to be influenced by bacterial growth traits and life history strategies. In this time series observational study, the response to disturbance of microbial communities in a full-scale activated sludge wastewater treatment plant was assessed by computing specific cellular traits of genomes retrieved from metagenomes. It was found that the genomes observed in disturbed periods have more copies of the rRNA operon than genomes observed in stable periods, whereas thein situmean relative growth rates of bacteria present during stable and disturbed periods were indistinguishable. From these intriguing observations, we infer that the length of the lag phase might be a growth trait that affects the microbial response to disturbance. Further exploration of this hypothesis could contribute to better understanding of the adaptive response of microbiomes to unsteady environmental conditions.
Proposing standardised geographical indicators of physical access to emergency obstetric and newborn care in low-income and middle-income countries
Authors: Ebener Steeve , Stenberg Karin , Brun Michel , Monet Jean-Pierre , Ray Nicolas , Sobel Howard Lawrence , Roos Nathalie , Gault Patrick , Morrissey Conlon Claudia , Bailey Patsy , Moran Allisyn C , Ouedraogo Leopold , Kitong Jacqueline F , Ko Eunyoung , Sanon Djenaba , Jega Farouk M , Azogu Olajumoke , Ouedraogo Boureima , Osakwe Chidude , Chimwemwe Chanza Harriet , Steffen Mona , Ben Hamadi Imed , Tib Hayat , Haj Asaad Ahmed , Tan Torres Tessa
Published: July 2019

Emergency obstetric and newborn care (EmONC) can be life-saving in managing well-known complications during childbirth. However, suboptimal availability, accessibility, quality and utilisation of EmONC services hampered meeting Millennium Development Goal target 5A. Evaluation and modelling tools of health system performance and future potential can help countries to optimise their strategies towards reaching Sustainable Development Goal (SDG) 3: ensure healthy lives and promote well-being for all at all ages. The standard set of indicators for monitoring EmONC has been found useful for assessing quality and utilisation but does not account for travel time required to physically access health services. The increased use of geographical information systems, availability of free geographical modelling tools such as AccessMod and the quality of geographical data provide opportunities to complement the existing EmONC indicators by adding geographically explicit measurements. This paper proposes three additional EmONC indicators to the standard set for monitoring EmONC; two consider physical accessibility and a third addresses referral time from basic to comprehensive EmONC services. We provide examples to illustrate how the AccessMod tool can be used to measure these indicators, analyse service utilisation and propose options for the scaling-up of EmONC services. The additional indicators and analysis methods can supplement traditional EmONC assessments by informing approaches to improve timely access to achieve Universal Health Coverage and reach SDG 3.
Using spatial analysis and GIS to improve planning and resource allocation in a rural district of Bangladesh
Authors: Robin T A , Khan Marufa Aziz , Kabir Nazmul , Rahaman Sk Towhidur , Karim Afsana , Mannan Imteaz Ibne , George Joby , Rashid Iftekhar
Published: July 2019

The application of a geographic information system (GIS) in public health is relatively common in Bangladesh. However, the use of GIS for planning, monitoring and decision-making by local-level managers has not been well documented. This assessment explored how effectively local government health managers used maps with spatial data for planning, resource allocation and programme monitoring. The United States Agency for International Development-funded MaMoni Health Systems Strengthening project supported the introduction of the maps into district planning processes in 2015 and 2016. GIS maps were used to support the prioritisation of underserved unions (the lowest administrative units) and clusters of disadvantaged communities for the allocation of funds. Additional resources from local government budgets were allocated to the lowest performing unions for improving health facility service readiness and supervision. Using a mixed-methods approach, the project evaluated the outputs of this planning process. District planning reports, population-based surveys, local government annual expenditure reports and service availability and utilisation data were reviewed. The goal was to determine the degree to which district planning teams were able to use the maps for their intended purpose. Key informant interviews were conducted withupazila(subdistrict) managers, elected government representatives and service providers to understand how the maps were used, as well as to identify potential institutionalisation scopes. The project observed improvements in health service availability and utilisation in the highest priority unions in 2016. Quick processing of maps during planning sessions was challenging. Nevertheless, managers and participants expressed their satisfaction with the use of spatial analysis, and there was an expressed need for more web-based GIS both for improving community-level service delivery and for reviewing performance in monthly meetings. Despite some limitations, the use of GIS maps helped local health managers identify health service gaps, prioritise underserved unions and monitor results.