bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective Sleep Duration in Older Adults: Results From The Irish Longitudinal Study on Ageing
Authors: Scarlett Siobhán , Nolan Hugh , Kenny Rose Anne , O'Connell Matthew DL
Published: October 2019

OBJECTIVE

This study assessed the distribution and correlates of objective sleep duration in the older population in Ireland.

DESIGN

Cross‐sectional study using population‐derived data from wave 3 of The Irish Longitudinal Study on Ageing.

SETTING

Community‐dwelling adults.

PARTICIPANTS

Adults, aged 50 years and older, who wore an accelerometer for at least 4 days (N = 1533).

MEASUREMENTS

Sleep was measured for at least 4 days in 1533 participants using a GENEActiv wrist‐worn accelerometer device. Sleep parameters included total sleep time (TST) and self‐reported sleep problems. TST was categorized as short and long sleep duration using US National Sleep Foundation guidelines. Linear and multinomial logistic regression models assessed sociodemographic, health, and behavioral correlates of sleep duration.

RESULTS

Mean TST for the sample was 463 minutes (SD = 72.6 minutes). Of participants, 13.9% and 16.5% measured short and long sleep duration, respectively. TST decreased as sleep problems increased, as did durations recorded in summer compared to winter recordings. Advancing age was associated with longer sleep, as was antidepressant use. Retired/unemployed participants recorded longer TST and were more likely to record long sleep compared to employed participants. Fair/poor self‐rated health and separated/divorced participants were more likely to record short sleep. Those reporting moderate or high physical activity were less likely to record short or long sleep, respectively, compared to those reporting low physical activity. Participants reporting a limiting disability were less likely to record long sleep.

CONCLUSION

Average TST was within recommended guidelines; however, a significant subset of older adults recorded sleep duration outside of the guidelines. Independent demographic and health correlates of suboptimal sleep were identified, many of which are modifiable. Patients and clinicians should be aware of factors potentially influencing sleep patterns. Longitudinal analyses to confirm directionality of relationships with potential risk factors are warranted. J Am Geriatr Soc 68:120–128, 2019
The effect of eplerenone on the renin-angiotensin-aldosterone system of rats with thyroid dysfunction
Authors: Dizaye Kawa , Mustafa Zana A
Published: October 2019

Objectives

This study was conducted to evaluate the effect of eplerenone on the RAAS and kidney function in rats with thyroid hormone disorders.

Methods

This study involved 30 male Wistar albino rats, divided into three groups. The first group (N = 6) served as a control. The second group involved 12 rats with experimentally induced hypothyroidism through receiving propylthiouracil (0.05% w/v) in drinking water for one month, which was divided into two subgroups of six rats each. The first subgroup served as a positive hypothyroid control, and the second subgroup received oral daily dose of eplerenone (100 mg/kg) for 14 days. The third group included 12 rats with induced hyperthyroidism with L-thyroxin (0.0012% w/v) in drinking water, and rats in this group were also divided into two subgroups. The first subgroup served as a positive hyperthyroid control, and the second subgroup received oral eplerenone 100 mg/kg.

Results

Eplerenone indicated a significant increase in renin and angiotensin I from 184.09 pg/ml and 178.66 pg/ml to 603.31 pg/ml and 250.88 pg/ml, respectively, meanwhile, aldosterone indicated no significant changes after inducing hypothyroidism and eplerenone administration.

The induction of hyperthyroidism led to a significant increase in angiotensin I from 248.84 pg/ml to 292.22 pg/ml. Oral administration of eplerenone for 14 days caused a significant increase aldosterone from 364.23 pg/ml to 497.02 pg/ml.

Conclusion

Eplerenone significantly increased the serum renin and angiotensin I in hypothyroid and aldosterone and angiotensin I in hyperthyroid rats. Aldosterone in hypothyroid rats was not changed by eplerenone.
The chloroplast genome of the lichen‐symbiont microalga Trebouxia sp. Tr9 (Trebouxiophyceae, Chlorophyta) shows short inverted repeats with a single gene and loss of the rps4 gene, which is encoded by the nucleus
Authors: Martínez‐Alberola Fernando , Barreno Eva , Casano Leonardo M. , Gasulla Francisco , Molins Arantzazu , Moya Patricia , González‐Hourcade María , del Campo Eva M.
Published: October 2019

The Trebouxiophyceae is the class of Chlorophyta algae from which the highest number of chloroplast genome (cpDNA) sequences has been obtained. Several species in this class participate in symbioses with fungi to form lichens. However, no cpDNA has been obtained from any Trebouxia lichen‐symbiont microalgae, which are present in approximately half of all lichens. Here, we report the sequence of the completely assembled cpDNA from Trebouxia sp. TR9 and a comparative study with other Trebouxio‐phyceae. The organization of the chloroplast genome of Trebouxia sp. TR9 has certain features that are unusual in the Trebouxiophyceae and other green algae. The most remarkable characteristics are the presence of long intergenic spacers, a quadripartite structure with short inverted repeated sequences (IRs), and the loss of the rps4 gene. The presence of long intergenic spacers accounts for a larger cpDNA size in comparison to other closely related Trebouxiophyceae. The IRs, which were thought to be lost in the Trebouxiales, are distinct from most of cpDNAs since they lack the rRNA operon and uniquely includes the rbcL gene. The functional transfer of the rps4 gene to the nuclear genome has been confirmed by sequencing and examination of the gene architecture, which includes three spliceosomal introns as well as the verification of the presence of the corresponding transcript. This is the first documented transfer of the rps4 gene from the chloroplast to the nucleus among Viridiplantae. Additionally, a fairly well‐resolved phylogenetic reconstruction, including Trebouxia sp. TR9 along with other Trebouxiophyceae, was obtained based on a set of conserved chloroplast genes.
Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi‐center randomized parallel group clinical study
Authors: Charalambous Marios , Volk Holger A. , Tipold Andrea , Erath Johannes , Huenerfauth Enrice , Gallucci Antonella , Gandini Gualtiero , Hasegawa Daisuke , Pancotto Theresa , Rossmeisl John H. , Platt Simon , De Risio Luisa , Coates Joan R. , Musteata Mihai , Tirrito Federica , Cozzi Francesca , Porcarelli Laura , Corlazzoli Daniele , Cappello Rodolfo , Vanhaesebrouck An , Broeckx Bart J.G. , Van Ham Luc , Bhatti Sofie F.M.
Published: October 2019

Background

The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail.

Objectives

To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs.

Animals

Client‐owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus.

Methods

Randomized parallel group clinical trial. Patients were randomly allocated to the IN‐MDZ (n = 21) or IV‐MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set atα < .05.

Results

IN‐MDZ and IV‐MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P= .34). The median seizure cessation time was 33 and 64 seconds for IN‐MDZ and IV‐MDZ, respectively (P= .63). When the time to place an IV catheter was taken into account, IN‐MDZ (100 seconds) was superior (P= .04) to IV‐MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN‐MDZ and IV‐MDZ, respectively.

Conclusions and Clinical Importance

Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.
Pharmacokinetic profiles of meloxicam after single IV and PO administration in Bilgorajska geese
Authors: Sartini Irene , Łebkowska‐Wieruszewska Beata , Lisowski Andrzej , Poapolathep Amnart , Owen Helen , Giorgi Mario
Published: October 2019

The purpose of this study was two‐fold: I) to determine the pharmacokinetic profile of meloxicam (MLX) in geese after intravenous (IV) and oral (PO) administration and II) to assess tissue residues in muscle, heart, liver, lung, and kidney. Ten clinically normal female Bilgorajska geese were divided into two groups (treated, n = 8; control, n = 2). Group 1 underwent a 3‐phase parallel study with a 1‐week washout period. In phase I, animals received MLX (0.5 mg/kg) by IV administration; the blood was collected up to 48 hr. In phases II and III geese were treated orally at the same dosage for the collection of blood and tissue samples, respectively. Group 2 served as control. After the extraction procedure, a validated HPLC method with UV detection was used for plasma and organ analysis. The plasma concentrations were quantifiable up to 24 hr after both the administrations. The elimination phase of MLX from plasma was similar in both the administration groups. The clearance was slow (0.00975 L/hr*Kg), the volume of distribution small (0.0487 L/kg), and the IV half‐life was 5.06 ± 2.32 hr. The average absolute PO bioavailability was 64.2 ± 24.0%. Residues of MLX were lower than the LOQ (0.1 µg/kg) in any tested tissue and at any collection time. The dosage used in this study achieved the plasma concentration, which provides analgesia in Hispaniolan Amazon parrots for 5 out of 24 hr after PO administration. MLX tissue concentrations were below the LOD of the assay in tissue (0.03 µg/ml). A more sensitive technique might be necessary to determine likely residue concentrations in tissue.
Can temptation explain housing choices over the life cycle?
Authors: Angelini Viola , Bucciol Alessandro , Wakefield Matthew , Weber Guglielmo
Published: October 2019

We use individual life history data from 12 European countries, and duration analysis that controls for unobserved heterogeneity, to investigate whether observed patterns of investment in illiquid assets and housing are consistent with predictions based on “temptation preferences”. A motivating model takes into account the standard motives for saving, but also recognises that illiquid financial assets and housing may be used by individuals who find it hard to control the temptation linked to abundant cash on hand. Even controlling for many possible motives for purchasing housing, and for unobserved heterogeneity, a large fraction of individuals become significantly more likely to buy housing after investing in illiquid assets; this finding is consistent with the predictions of the model.
Structural and biochemical characterization of iminodiacetate oxidase from Chelativorans sp. BNC1
Authors: Kang ChulHee , Jun Se‐Young , Bravo Abigail G. , Vargas Erick M. , Liu Honglei , Lewis Kevin M. , Xun Luying
Published: October 2019

Ethylenediaminetetraacetate (EDTA) is the most abundant organic pollutant in surface water because of its extensive usage and the recalcitrance of stable metal‐EDTA complexes. A few bacteria including Chelativorans sp. BNC1 can degrade EDTA with a monooxygenase to ethylenediaminediacetate (EDDA) and then use iminodiacetate oxidase (IdaA) to further degrade EDDA into ethylenediamine in a two‐step oxidation. To alleviate EDTA pollution into the environment, deciphering the mechanisms of the metabolizing enzymes is an imperative prerequisite for informed EDTA bioremediation. Although IdaA cannot oxidize glycine, the crystal structure of IdaA shows its tertiary and quaternary structures similar to those of glycine oxidases. All confirmed substrates, EDDA, ethylenediaminemonoacetate, iminodiacetate and sarcosine are secondary amines with at least one N‐acetyl group. Each substrate was bound at the re‐side face of the isoalloxazine ring in a solvent‐connected cavity. The carboxyl group of the substrate was bound by Arg265 and Arg307. The catalytic residue, Tyr250, is under the hydrogen bond network to facilitate its deprotonation acting as a general base, removing an acetate group of secondary amines as glyoxylate. Thus, IdaA is a secondary amine oxidase, and our findings improve understanding of molecular mechanism involved in the bioremediation of EDTA and the metabolism of secondary amines.
Second Rhagophthalmid Luciferase Cloned from Chinese Glow‐worm Menghuoius giganteus (Rhagophthalmidae: Elateroidea)
Authors: Liu Gui‐Chun , Dong Zhi‐Wei , Hou Qing‐Bai , He Jin‐Wu , Zhao Ruo‐Ping , Wang Wen , Li Xue‐Yan
Published: October 2019

The pH‐insensitive beetle luciferases cloned from Rhagophthalmidae, Phengodidae, and Elateridae exhibit great potential application as reporter assays for monitoring gene expression. At present, however, only one luciferase has been reported from the enigmatic and predominantly Asian distributed luminous family Rhagophthalmidae. Here, we cloned the second rhagophthalmid luciferase from the Chinese glow‐worm Menghuoius giganteus (Rhagophthalmidae: Elateroidea) by combining reverse transcription polymerase chain reaction (RT‐PCR) with rapid amplification of complementary DNA ends (RACE). The luciferase consisted of 546 amino acids and showed high identity to that of Rhagophthalmus ohbai (90.4%). The recombinant M. giganteus luciferase was produced in vitro and exhibited significant bioluminescent activity under neutral conditions (pH 7.8), with low KM for D‐luciferin (2.2 μm) and ATP (53 μm). Activity was highest at 10°C and inactivation occurred at 45°C. This luciferase showed pH‐insensitivity and maximum emission spectrum at 560 nm. Phylogenetic analyses based on the deduced amino acids indicated a close relationship between the M. giganteus luciferase and that of R. ohbai. These results increase our understanding of rhagophthalmid luciferases and provide a new resource for the application of luciferases.
Does foreign direct investment expand the capability set in the host economy? A sectoral analysis
Authors: Kannen Peter
Published: October 2019

Most empirical studies examining the impact of foreign direct investment (FDI) on economic development use aggregate monetary‐based measures such as GDP or TFP growth as indicators for development. We deviate from this approach and use instead the recently developed economic complexity index; this measure summarises the complexity of the productive structure of an economy, and its values can be interpreted as the number of capabilities present in a country. These capabilities are units of productive knowledge necessary for the production of goods, and goods differ in the number of necessary capabilities. Furthermore, we use sectoral FDI data to take differences between sectors of an economy into account, since the number of necessary capabilities also varies between the sectors. In our empirical analysis, covering 63 developing and developed countries over the period 2005–14, we find that FDI in the tertiary sector has a statistically significant and robust positive effect on the number of capabilities, whereas FDI in the primary and secondary sectors generally does not increase the capability set of an economy.
Seguros y agroindustria: Riesgos en la agricultura y mecanismos de trasferencia disponibles en el mercado
Authors: Ríos Urzúa Vicente
Published: October 2019

Actualmente el mercado agrícola representa un importante foco de desarrollo industrial centrado en nuevas tecnologías que buscan mejorar calidades y condiciones de producción, preservar productos y aumentar la vida de anaquel de las cosechas. Aumentar el tiempo de postcosecha de la producción agrícola implica necesariamente aumentar la cadena de custodia y mantenimiento de los productos, lo que deviene en riesgos de mayor continuidad para el productor o, derechamente, nuevos riesgos. En ese contexto, cobra especial relevancia conocer cómo ha reaccionado el mercado asegurador frente a este nuevo escenario, y cómo han influido las nuevas tecnologías en la creación de nuevos seguros o mecanismos de transferencia de riesgos.
La razón poética en Zambrano: algunas claves interpretativas para desentrañar su sentido
Authors: García Restrepo Gladys Del Socorro
Published: October 2019

El presente artículo aporta a la comprensión del sentido de la razón poética en la obra de María Zambrano desde una aproximación hermenéutica. Este objetivo es relevante teniendo en cuenta que la razón poética se constituye en el eje del pensamiento filosófico de Zambrano y, a su vez, se vislumbra como una vía que propone la autora para construir una mirada más humana de la racionalidad, menos arrogante y que enriquece las dimensiones ontológicas y antropológicas del hombre. La reflexión se presenta en tres momentos: en el primero se intentará mostrar una reforma al entendimiento, que involucra la vida humana de forma integral, de tal manera que la razón trascienda y permita comprender la complejidad histórica del hombre y la urgente necesidad de volver sobre sí mismo. En el segundo se centrará la atención sobre el nuevo humanismo zambraniano, sustentado en la razón poética y misericordiosa, como antídoto ante el fantasma de la guerra, y el tercero se detiene en la obra Claros del bosque para indicar al lector los tres momentos hermenéuticos a los que posiblemente se enfrentará, al intentar comprender el reino de la razón poética.
Natural Convection From a Vertical Plate Embedded in a Non-Darcy Bidisperse Porous Medium
Authors: Pătrulescu F. O. , Groşan T. , Pop I.
Published: October 2019

This paper studies the steady, free convection boundary layer flow about a vertical, isothermal plate embedded in a non-Darcy bidisperse porous medium (BDPM). An appropriate mathematical model is proposed. The boundary layer analysis leads to a system of partial differential equations containing inertial, interphase momentum, thermal diffusivity ratio, thermal conductivity ratio, permeability ratio, modified thermal capacity, and convection parameters. These equations that govern the flow and heat transfer in the f-phase and the p-phase are solved numerically using an algorithm based on the bvp4c routine from matlab. The dependences of the dimensionless velocities and temperatures profiles, as well as of the Nusselt numbers on the governing parameters are investigated. The features of the flow and heat transfer characteristics for different values of the governing parameters are analyzed and discussed in details.
Nonhomogeneous Model for the Mixed Convection and Entropy Generation of a Nanofluid in a Lid-Driven Inclined Enclosure With Discrete Heat Source
Authors: Dutta S. , Bhattacharyya S. , Pop I.
Published: October 2019

A numerical study on the mixed convection of Al2O3–water nanofluid in a lid-driven inclined square enclosure partially heated from below is performed based on Buongiorno's two phase model. The velocity of the nanoparticles relative to the base fluid is considered due to thermophoresis and Brownian diffusion. The thermophysical properties of the nanofluid are assumed to be dependent on temperature as well as the nanoparticle volume fraction. A control volume method over a staggered grid arrangement is used to discretize the governing equations. The discretized equations of two-dimensional continuity, momentum, energy, and volume fraction are solved through a pressure-correction-based semi-implicit method for pressure linked equations (SIMPLE) algorithm. The effects of relevant parameters such as nanoparticle diameter (25 nm ≤ dp ≤ 90 nm), Richardson number (0.1≤Ri≤5), nanoparticle bulk volume fraction (0 ≤φb≤ 0.05) on the mixed convection of the nanofluid is studied by considering the inclination angle of the enclosure to vary between 0 deg and 60 deg. The entropy generation as well as the Bejan number is evaluated to illustrate the thermodynamic optimization of the mixed convection. Both the heat transfer and entropy generation are higher in the nanofluid compared to the clear fluid and the rate of increment in entropy generation remains lower than the rate by which the heat transfer is augmented in the nanofluid. We find that due to the presence of the Brownian diffusion and thermophoresis in the nonhomogeneous model, a higher heat transfer is yielded as compared to the homogeneous model. The discrepancy between the homogeneous and nonhomogeneous models is significant when the mixed convection is dominated by the shear force. When the mixed convection is dominated by the thermal buoyancy, an increase in positive inclination angle of the enclosure creates a significant increment in the heat transfer.
A versatile computational approach for the numerical modelling of parametric acoustic array
Authors: Červenka Milan , Bednařík Michal
Published: October 2019

This work presents a versatile computational approach for the numerical modelling of a parametrically generated low-frequency sound. The proposed method is based on the quasi-linear approximation, and it does not employ the paraxial approximation. The primary acoustic field is calculated by the Rayleigh integral or the boundary element method; the secondary difference-frequency field is calculated by the finite element method. As governing wave equations, a general second-order wave equation for acoustic pressure, the Westervelt equation, and Kuznetsov equation are tested, and the corresponding numerical results are compared. The proposed approach allows studying the near-field, far-field, as well as the off-axis field of the difference-frequency wave parametrically radiated from complex emitters. As numerical examples, parametric radiation from a baffled piston and a piston combined with a horn are examined.
A near-field error sensing strategy for compact multi-channel active sound radiation control in free field
Authors: Tao Jiancheng , Guo Qin , Qiu Xiaojun
Published: October 2019

Noise reduction performance of a compact active sound radiation control system is significantly affected by locations of the error microphones which are required to be installed near the primary source. In this paper, near-field error sensing for multi-channel active radiation control systems in free field is investigated, and it is found that the optimal locations of error sensors for minimizing the sum of squared sound pressure are between the primary source and the secondary sources distributed uniformly on a sphere surface surrounding the primary source. Both simulation and experiment results show that the optimal locations of error microphones are independent of the type of primary source when there are sufficient secondary sources. These optimal locations remain unchanged at low frequencies and move toward secondary sources when the secondary source number increases. Therefore, for active radiation control applications in low frequency range, a compact multi-channel system can be developed by locating error microphones between the primary source and secondary sources.
Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children in a Randomized Controlled Trial
Authors: Berthaud Romain , Benaboud Sihem , Hirt Déborah , Genuini Mathieu , Oualha Mehdi , Castelle Martin , Briand Coralie , Artru Solène , Norsa Lorenzo , Boyer Olivia , Foissac Frantz , Bouazza Naïm , Tréluyer Jean-Marc
Published: October 2019

Methicillin-resistant staphylococcal infections are a global burden. Area under the concentration-time curve to MIC (AUC/MIC) ratio is the pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range is narrow, difficult to achieve because of a wide intersubject variability, especially in children, and is not routinely targeted since the AUC is rarely available.
Genome Sequences of Three
Lactobacillus
Species Strains of the Stomach of the White-Footed Deermouse (Peromyscus leucopus)
Authors: Bassam Khalil , Milovic Ana , Barbour Alan G.
Published: October 2019

Three colony types of
Lactobacillus
were isolated from the stomach of LL colony stock
Peromyscus leucopus
deermice, a reservoir for several human zoonoses. Genome sequences revealed two isolates to be new strains of
Lactobacillus animalis
and
Lactobacillus reuteri
. The third was distinct from known species and was provisionally designated
Lactobacillus
sp. strain LL6.
Complete Genome Sequence of Potential Deoxynivalenol-Degrading Bacterium Youhaiella tibetensis Type Strain F4
Authors: Wang Yang , Wang Songxue
Published: October 2019

Here, we report the first complete genome sequence of the potential deoxynivalenol-degrading strain
Youhaiella tibetensis
F4
T
(China General Microbiological Culture Collection Center [CGMCC] 1.12719
T
). To the best of our knowledge, this is also the first announcement of the complete genome sequence of a
Youhaiella
species.
Rapid visual recovery following intravenous tocilizumab in glucocorticoid resistant refractory giant cell arteritis
Authors: Svasti-Salee Carl Richard , Mollan Susan P , Morgan Ann W , Quick Vanessa
Published: October 2019

A 72-year-old man presented with a short history of headache, jaw claudication, double vision, amaurosis fugax and distended temporal arteries. A diagnosis of giant cell arteritis (GCA) was confirmed on temporal artery ultrasound and temporal artery biopsy. Despite treatment with high-dose oral glucocorticoid (GC) and multiple pulses of intravenous methylprednisolone, his vision deteriorated to hand movements in one eye. 8 mg/kg intravenous tocilizumab, a humanised, recombinant anti-IL-6 receptor antibody, was administered within 48 hours of vision loss and continued monthly, resulting in marked visual improvement within days, as well as sustained remission of GCA. This case suggests a possible role for tocilizumab as a rescue therapy to prevent or recover visual loss in patients with GCA resistant to GC treatment, termed refractory GCA. Further research is required to elucidate the role of intravenous administration of tocilizumab in this setting.
Change in paradigm: impact of an IBD medical home on the outpatient management of acute severe ulcerative colitis
Authors: Tam Vernissia , Schwartz Marc , Holder-Murray Jennifer , Salgado Pogacnik Javier
Published: October 2019

A 72-year-old man presents with acute severe ulcerative colitis (ASUC), initially partially responsive to intravenous steroids and infliximab over a 3-day hospital stay. Following discharge and over the course of 15 days, his care was coordinated by the inflammatory bowel disease medical home team, who conducted clinical laboratory assessments and two outpatient flexible sigmoidoscopies to evaluate endoluminal disease activity and treatment response prior to proceeding with a laparoscopic total abdominal colectomy and creation of end ileostomy following medical failure. He was admitted to the hospital for a total of only 7 days, which included attempted medical management of ASUC, surgery and postoperative recovery.
B cell acute lymphoblastic leukaemia presenting with isolated soft tissue tumours: the non-myeloid sarcoma
Authors: Tousifullah Mohammad , Gupta Aditya Kumar , Meena Jagdish Prasad , Seth Rachna
Published: October 2019

Soft tissue leukaemic masses are a well-described clinical feature of myeloid haematological neoplasms. In paediatric acute lymphoblastic leukaemia (ALL), such soft tissue leukaemic sarcomas have not been reported as a presenting feature. Here we report a 3-year-old boy with ALL who presented to us with isolated soft tissue swellings for a duration of 9 months. The significance of these ‘non-myeloid’ sarcomas in paediatric ALL is uncertain.
Acute psychosis and concurrent rhabdomyolysis unveiling diagnosis of hypothyroidism
Authors: Mohamed Mouhand FH , Mahgoub Ali B , Sardar Sundus , Elzouki Abdel-Naser
Published: October 2019

Neuropsychiatric and muscular symptoms can develop as part of hypothyroidism. However, frank psychosis or rhabdomyolysis due to hypothyroidism are uncommon and have been reported rarely as the first presenting features of hypothyroidism. We report a case of a 44-year-old man who presented with a 2-week history of delusions, hallucinations and mild bilateral leg pain, without apparent signs of myxedema. Investigations revealed raised thyroid stimulation hormone >100 mIU/L and high creatine kinase >21 000 U/L. Diagnosis of hypothyroidism-induced psychosis and rhabdomyolysis was made. He received thyroxine, olanzapine and a short course of steroids. His symptoms improved after 2 weeks of treatment and he remained free of symptoms at 6 months of follow-up. To the best of our knowledge, this is the first case of concomitant psychosis and rhabdomyolysis leading to hypothyroidism diagnosis. This case highlights the importance of hypothyroidism screening when faced with unexplained psychosis or rhabdomyolysis, especially if combined.
Xanthogranulomatous pyelonephritis with associated renal cell carcinoma
Authors: Moss Basil Francis , Potter Laura , Cliff Andrew , Kumar Manal
Published: October 2019

Xanthogranulomatous pyelonephritis is associated with obstruction, stones and infection. CT is the mainstay of diagnosis, but appearances can mimic other conditions, including renal cell carcinoma. Nephrectomy is commonly recommended, but conservative treatment with antibiotics has been described after tissue diagnosis. We present a case of xanthogranulomatous pyelonephritis with concomitant renal cell carcinoma, which was an association that was suggested in 1988 and supported by subsequently reported cases. Conservative management of biopsy or cytology proven xanthogranulomatous pyelonephritis is unsafe, as an area of synchronous malignant tumour may be missed: we recommend it only in patients unfit for nephrectomy.
Towards universal health coverage: what are the system requirements for effective large-scale community health worker programmes?
Authors: Lehmann Uta , Twum-Danso Nana A Y , Nyoni Jennifer
Published: October 2019

Against the background of efforts to strengthen health systems for universal health coverage and health equity, many African countries have been relying on lay members of the community, often referred to as community health workers (CHWs), to deliver primary healthcare services. Growing demand and great variability in definitions, roles, governance and funding of CHWs have prompted the need to revisit CHW programmes and provide guidance on the implementation of successful programmes at scale. Drawing on the synthesised evidence from two extensive literature reviews, this article determines foundational elements of functioning CHW programmes, focusing in particular on the systems requirements of large-scale programmes. It makes recommendations for the effective development of large-scale CHW programmes. The key foundational elements of successful CHW programmes identified are (1)embeddedness, connectivity and integrationinto the larger system of healthcare service delivery; (2)cadre differentiation and role clarityin order to maintain clear scopes of work and accountability; (3)sound programme design based on local contextual factors and effective people management; and (4)ongoing monitoring, learning and adaptingbased on accurate and timely local data in order to ensure optimal fit to local context since one size does not fit all. We conclude that CHWs are an investment in health systems strengthening and community resilience with enormous potential for contributing to universal health coverage and the sustainable development goals if well designed and managed. While the evidence base is uneven and mixed, it provides extensive insight and knowledge to strengthen, scale up and sustain CHW programmes throughout Africa.
Towards universal health coverage: reforming the neglected district health system in Africa
Authors: Tumusiime Prosper , Kwamie Aku , Akogun Oladele B , Elongo Tarcisse , Nabyonga-Orem Juliet
Published: October 2019

In most African countries, the district sphere of governance is a colonial creation for harnessing resources from the communities that are located far away from the centre with the assistance of minimally skilled personnel who are subordinate to the central authority with respect to decision-making and initiative. Unfortunately, postcolonial reforms of district governance have retained the hierarchical structure of the local government. Anchored to such a district arrangement, the (district) health system (DHS) is too weak and impoverished to function in spite of enormous knowledge and natural resources for a seamless implementation of universal health coverage (UHC). Sadly, the quick-fix projects of the 1990s with the laudable intention to reduce the burden of disease within a specified time-point dealt the fatal blow on the DHS administration by diminishing it to a stop-post and a warehouse for commodities (such as bednets and vaccines) destined for the communities. We reviewed the situation of the district in sub-Saharan African countries and identified five attributes that are critical for developing a UHC-friendly DHS. In this analytical paper, we discuss decision-making authority, coordination, resource control, development initiative and management skills as critical factors. We highlight the required strategic shifts and recommend a dialogue for charting an African regional course for a reformed DHS for UHC. Further examination of these factors and perhaps other ancillary criteria will be useful for developing a checklist for assessing the suitability of a DHS for the UHC that Africa deserves.
Offering patients a choice for colorectal cancer screening: a quality improvement pilot study in a quality circle of primary care physicians
Authors: Martin Yonas , Braun Leo Alexander , Janggen Marc-Andrea , Tal Kali , Biller-Andorno Nikola , Ducros Cyril , Selby Kevin , Auer Reto , Rohrbasser Adrian
Published: October 2019

Background

Guidelines recommend primary care physicians (PCPs) offer patients a choice between colonoscopy and faecal immunochemical test (FIT) for colorectal cancer (CRC) screening. Patients choose almost evenly between both tests but in Switzerland, most are tested with colonoscopy while screening rates are low. A quality circle (QC) of PCPs is an ideal site to train physicians in shared decision-making (SDM) that will help more patients decide if they want to be tested and choose the test they prefer.

Objective

Systematically assess CRC screening status of eligible 50–75 y.o. patients and through SDM increase the proportion of patients who have the opportunity to choose CRC screening and the test (FIT or colonoscopy).

Methods

Working through four Plan-Do-Study-Act (PDSA) cycles in their QC, PCPs adapted tools for SDM and surmounted organisational barriers by involving practice assistants. Each PCP included 20, then 40 consecutive 50–75 y.o. patients, repeatedly reported CRC status as well as the proportion of eligible patients with whom CRC screening could be discussed and patients’ decisions.

Results

9 PCPs initially included 176, then 320 patients. CRC screening status was routinely noted in the electronic medical record and CRC screening was implemented in daily routine, increasing eligible patients’ chance to be offered screening. Over a year, screening rates trended upwards, from 37% to 40% (p=0.46) and FIT use increased (2%–7%, p=0.008). Initially, 7/9 PCPs had no patient ever tested with FIT; after the intervention, only 2/8 recorded no FIT tests.

Conclusions

Through data-driven PDSA cycles and significant organisational changes, PCPs of a QC systematically collected data on CRC screening status and implemented SDM tools in their daily routine. This increased patients’ chance to discuss CRC screening. The more balanced use of FIT and colonoscopy suggests that patients’ values and preferences were better respected.
Snapshot of current carotid artery stenting practice and accreditation in the USA
Authors: Sacks David , Farrell Mary Beth , Katzen Barry T , Lally Mary , Matsumura Jon S , Merrill Nancy
Published: October 2019

Objective

The aim of this exploratory study was to compare the performance of carotid artery stenting (CAS) best practices between Intersocietal Accreditation Commission (IAC) accredited facilities and non-accredited facilities certified by the Centers for Medicare and Medicaid Services (CMS).

Methods

A random, anonymous survey was sent to CMS and IAC accredited facilities querying facility routine performance of 16 CAS procedure components found in published guidelines and utilised during clinical trials.

Results

There were 28 responses (response rate=17%). Significant differences were found between the CMS and the IAC facilities for four of 16 procedure measures: determination of modified Rankin Scale score prior to stenting (p=0.012, 95% CI 20% to 80%), accurate measurement of per cent stenosis using electronic callipers (p=0.005, 95% CI 24% to 84%), confirmation of anticoagulation with activated clotting time greater than 250 s prior to crossing the lesion (p=0.03, 95% CI 7% to 69%), and comparison of facility outcomes to accepted benchmarks for stroke and death (p=0.03, 95% CI 7% to 69%). Overall, IAC facilities performed all 16 procedures more frequently (97%) than CMS facilities (66%) (p<0.001, 95% CI 24% to 36%).

Conclusions

Although the sample size was small, the results demonstrated IAC accredited facilities are more likely to follow best practices, to use quantitative tools to select appropriate patients, and quantitively measure patient-centred clinical outcomes compared with CMS certified facilities. The findings raise the question as to the value of CMS certification versus IAC accreditation as a requirement for reimbursement.
Comparing targeted thrust manipulation with general thrust manipulation in patients with low back pain. A general approach is as effective as a specific one. A randomised controlled trial
Authors: McCarthy Christopher J , Potter Louise , Oldham Jackie A
Published: October 2019

Background

Spinal manipulation is commonly used to treat back pain. The application of spinal manipulation has traditionally involved an element of targeting the technique to a level of the spine where the proposed movement dysfunction is sited. We evaluated the effects of a targeted manipulative thrust versus a thrust applied generally to the lumbar region.

Methods

A randomised controlled clinical trial in patients with low back pain following CONSORT (Consolidated Standards of Reporting Trials) guidelines. Sixty subjects were randomly allocated to two groups: one group received a targeted manipulative thrust (n=29) and the other a general manipulation thrust (GT) (n=31) to the lumbar spine. Thrust was either localised to a clinician-defined symptomatic spinal level or an equal force was applied through the whole lumbosacral region. We measured pressure-pain thresholds (PPTs) using algometry and muscle activity (magnitude of stretch reflex) via surface electromyography. Numerical ratings of pain and Oswestry Disability Index scores were collected.

Results

Repeated measures of analysis of covariance revealed no between-group differences in self-reported pain or PPT for any of the muscles studied.

A GT procedure—applied without any specific targeting—was as effective in reducing participants’ pain scores as targeted approaches.

Trial registration number

ISRCTN11994230.
METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance
Authors: Wang Qiang , Chen Chen , Ding Qingqing , Zhao Yan , Wang Zhangding , Chen Junjie , Jiang Zerun , Zhang Yan , Xu Guifang , Zhang Jingjing , Zhou Jianwei , Sun Beicheng , Zou Xiaoping , Wang Shouyu
Published: October 2019

Objective

N6-methyladenosine (m6A) RNA methylation and its associated methyltransferase METTL3 are involved in tumour initiation and progression via the regulation of RNA function. This study explored the biological function and clinical significance of METTL3 in gastric cancer (GC).

Design

The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human GC cohort. The biological role and mechanism of METTL3 in GC tumour growth and liver metastasis were determined in vitro and in vivo.

Results

The level of m6A RNA was significantly increased in GC, and METTL3 was the main regulator involved in the abundant m6A RNA modification. METTL3 expression was significantly elevated in GC tissues and associated with poor prognosis. Multivariate Cox regression analysis revealed that METTL3 expression was an independent prognostic factor and effective predictor in human patients with GC. Moreover, METTL3 overexpression promoted GC proliferation and liver metastasis in vitro and in vivo. Mechanistically, P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of HDGF mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability. Secreted HDGF promoted tumour angiogenesis, while nuclear HDGF activated GLUT4 and ENO2 expression, followed by an increase in glycolysis in GC cells, which was correlated with subsequent tumour growth and liver metastasis.

Conclusions

Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in GC, indicating that METTL3 expression is a potential prognostic biomarker and therapeutic target for human GC.
Potential of ‘stacking’ early childhood interventions to reduce inequities in learning outcomes
Authors: Molloy Carly , O'Connor Meredith , Guo Shuaijun , Lin Colleen , Harrop Christopher , Perini Nicholas , Goldfeld Sharon
Published: October 2019

Background

Early childhood interventions are critical for reducing child health and development inequities. While most research focuses on the efficacy of single interventions, combining multiple evidence-based strategies over the early years of a child’s life may yield greater impact. This study examined the association between exposure to a combination of five evidence-based services from 0 to 5 years on children’s reading at 8–9 years.

Methods

Data from the nationally representative birth cohort (n=5107) of the Longitudinal Study of Australian Children were utilised. Risk and exposure measures across five services from 0 to 5 years were assessed: antenatal care, nurse home-visiting, early childhood education and care, parenting programme and the early years of school. Children’s reading at 8–9 years was measured using a standardised direct assessment. Linear regression analyses examined the cumulative effect of five services on reading. Interaction terms were examined to determine if the relationship differed as a function of level of disadvantage.

Results

A cumulative benefit effect of participation in more services and a cumulative risk effect when exposed to more risks was found. Each additional service that the child attended was associated with an increase in reading scores (b=9.16, 95% CI=5.58 to 12.75). Conversely, each additional risk that the child was exposed to was associated with a decrease in reading skills (b=−14.03, 95% CI=−16.61 to −11.44). Effects were similar for disadvantaged and non-disadvantaged children.

Conclusion

This study supports the potential value of ‘stacking’ early interventions across the early years of a child’s life to maximise impacts on child outcomes.
Optimised molecular genetic diagnostics of Fanconi anaemia by whole exome sequencing and functional studies
Authors: Bogliolo Massimo , Pujol Roser , Aza-Carmona Miriam , Muñoz-Subirana Núria , Rodriguez-Santiago Benjamin , Casado José Antonio , Rio Paula , Bauser Christopher , Reina-Castillón Judith , Lopez-Sanchez Marcos , Gonzalez-Quereda Lidia , Gallano Pia , Catalá Albert , Ruiz-Llobet Ana , Badell Isabel , Diaz-Heredia Cristina , Hladun Raquel , Senent Leonort , Argiles Bienvenida , Bergua Burgues Juan Miguel , Bañez Fatima , Arrizabalaga Beatriz , López Almaraz Ricardo , Lopez Monica , Figuera Ángela , Molinés Antonio , Pérez de Soto Inmaculada , Hernando Inés , Muñoz Juan Antonio , del Rosario Marin Maria , Balmaña Judith , Stjepanovic Neda , Carrasco Estela , Cuesta Isabel , Cosuelo José Miguel , Regueiro Alexandra , Moraleda Jimenez José , Galera-Miñarro Ana Maria , Rosiñol Laura , Carrió Anna , Beléndez-Bieler Cristina , Escudero Soto Antonio , Cela Elena , de la Mata Gregorio , Fernández-Delgado Rafael , Garcia-Pardos Maria Carmen , Sáez-Villaverde Raquel , Barragaño Marta , Portugal Raquel , Lendinez Francisco , Hernadez Ines , Vagace José Manue , Tapia Maria , Nieto José , Garcia Marta , Gonzalez Macarena , Vicho Cristina , Galvez Eva , Valiente Alberto , Antelo Maria Luisa , Ancliff Phil , Garcia Francisco , Dopazo Joaquin , Sevilla Julian , Paprotka Tobias , Pérez-Jurado Luis Alberto , Bueren Juan , Surralles Jordi
Published: October 2019

Purpose

Patients with Fanconi anaemia (FA), a rare DNA repair genetic disease, exhibit chromosome fragility, bone marrow failure, malformations and cancer susceptibility. FA molecular diagnosis is challenging since FA is caused by point mutations and large deletions in 22 genes following three heritability patterns. To optimise FA patients’ characterisation, we developed a simplified but effective methodology based on whole exome sequencing (WES) and functional studies.

Methods

68 patients with FA were analysed by commercial WES services. Copy number variations were evaluated by sequencing data analysis with RStudio. To test FANCA missense variants, wt FANCA cDNA was cloned and variants were introduced by site-directed mutagenesis. Vectors were then tested for their ability to complement DNA repair defects of a FANCA-KO human cell line generated by TALEN technologies.

Results

We identified 93.3% of mutated alleles including large deletions. We determined the pathogenicity of three FANCA missense variants and demonstrated that two FANCA variants reported in mutations databases as ‘affecting functions’ are SNPs. Deep analysis of sequencing data revealed patients’ true mutations, highlighting the importance of functional analysis. In one patient, no pathogenic variant could be identified in any of the 22 known FA genes, and in seven patients, only one deleterious variant could be identified (three patients each with FANCA and FANCD2 and one patient with FANCE mutations)

Conclusion

WES and proper bioinformatics analysis are sufficient to effectively characterise patients with FA regardless of the rarity of their complementation group, type of mutations, mosaic condition and DNA source.