Will the Real Cryptic Pocket Please Stand Out?

http://bit.ly/2G0LjJJ

Comparison of Dendritic Cell Activation by Virus-Based Vaccine Delivery Vectors Emphasizes the Transcriptional Downregulation of the Oxidative Phosphorylation Pathway

Human Gene Therapy, Ahead of Print.


http://bit.ly/2G1JIDs

Peritoneal carcinomatosis in non-small-cell lung cancer: retrospective multicentric analysis and literature review

Future Oncology, Ahead of Print.


http://bit.ly/2RhgJxh

The Optimal Duration of Adjuvant Therapy for Stage III Colon Cancer: the European Perspective

Opinion statement

The International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration was created to pool data from different studies worldwide in order to assess whether a shorter duration of adjuvant treatment in colon cancer could maintain the expected benefit while reducing toxicity. The results of the IDEA trials were clinically relevant. They confirmed a two- to sixfold reduction in neurotoxicity for the shorter duration across trials. Overall, the 3-year disease-free survival was very similar: only 0.9% lower for the 3 months group. However, the results were partially unexpected, because they revealed a difference among chemotherapy regimens (CAPOX better than FOLFOX) and risk groups within stage III. The similar outcome between 3 and 6 months of CAPOX coupled with the substantial reduction in toxicity makes us use the CAPOX regimen for 3 months for most stage III patients. An exception to this general rule is the patient with very high risk, i.e., either T4N1b-T4anyN2 or anyTN2b where we use 6 months of CAPOX. Our take from the trial results is also that FOLFOX should never be given for 3 months and preferably not used at all in the adjuvant setting. The conduction of the IDEA enterprise was truly global. The European contribution was major with three fourths of patients enrolled in the four European trials. Herein, we review the results of the "3 versus 6" trials and the literature regarding the interpretation of the collected data in Europe and in the rest of the world.

http://bit.ly/2CIuekt

Imaging features of adrenal masses

Abstract

The widespread use of imaging examinations has increased the detection of incidental adrenal lesions, which are mostly benign and non-functioning adenomas. The differentiation of a benign from a malignant adrenal mass can be crucial especially in oncology patients since it would greatly affect treatment and prognosis. In this setting, imaging plays a key role in the detection and characterization of adrenal lesions, with several imaging tools which can be employed by radiologists. A thorough knowledge of the imaging features of adrenal masses is essential to better characterize these lesions, avoiding a misinterpretation of imaging findings, which frequently overlap between benign and malignant conditions, thus helping clinicians and surgeons in the management of patients. The purpose of this paper is to provide an overview of the main imaging features of adrenal masses and tumor-like conditions recalling the strengths and weaknesses of imaging modalities commonly used in adrenal imaging.

http://bit.ly/2WlHuo0

Lean Body Mass in Childhood Linked to Lung Function at 15

FRIDAY, Jan. 25, 2019 -- Higher lean body mass during childhood and adolescence is associated with higher lung function at age 15 years for both sexes, according to a study published online Jan. 11 in the American Journal of Respiratory and Critical...

http://bit.ly/2UeDBzu

Direct-Acting Antivirals Not Tied to Liver Cancer Recurrence

FRIDAY, Jan. 25, 2019 -- Direct-acting antiviral (DAA) therapy is not associated with increased overall or early hepatocellular carcinoma (HCC) recurrence among patients with a previous complete response to HCC treatment, according to a study...

http://bit.ly/2sITWAS

Assay Aids Anticoagulant Dosing of Obese Patients for Bariatric Sx

FRIDAY, Jan. 25, 2019 -- Endogenous thrombin potential (ETP) may provide better information than anti-factor Xa (anti-XA) in determining the best dosage for blood thinners among obese patients undergoing bariatric surgery, according to a study...

http://bit.ly/2Uo5F3J

Oncologists Have Low Awareness of LGBTQ Issues

FRIDAY, Jan. 25, 2019 -- Most oncologists report a lack of knowledge about treating lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) patients, according to survey results published online Jan. 16 in the Journal of Clinical...

http://bit.ly/2FPE6gj

Virtual Video Visits Liked by Patients, Providers

FRIDAY, Jan. 25, 2019 -- Virtual video visits can effectively replace office visits for selected patients across medical specialties without sacrificing quality of care or patient-physician communication, according to a study published in the...

http://bit.ly/2Uipbym

Correction to: Neuronal apoptosis in the brainstem medulla of sudden unexpected death in infancy (SUDI), and the importance of standardized SUDI classification

In the original version of this manuscript Table 3, SIDS I column currently reads 1/8 (13) for the following: Bed share/co-sleeping (%), Found prone and co-sleep/bed-share (%), Co-sleep/bedshare and smoke exposure (%). However, the correct value should be '0/8 (0)'. Consequently, the correct p value.

http://bit.ly/2G1VttJ

PAK4 phosphorylates fumarase and blocks TGF-{beta}-induced cell growth arrest in lung cancer cells

The metabolic activity of fumarase (FH) participates in gene transcription linking to tumor cell growth. However, whether this effect is implicated in lung cancer remains unclear. Here, we show TGF-β induces p38-mediated FH phosphorylation at Thr 90, which leads to a FH/CSL (also known as RBP-Jκ) /p53 complex formation and FH accumulation at p21 promoter under concomitant activation of Notch signaling; in turn, FH inhibits histone H3 Lys 36 demethylation and thereby promotes p21 transcription and cell growth arrest. In addition, FH is massively phosphorylated at the Ser 46 by PAK4 in NSCLC cells; and PAK4-phosphorylated FH binds to 14-3-3, resulting in cytosolic detention of FH and prohibition of FH/CSL/p53 complex formation. Physiologically，FH Ser 46 phosphorylation promotes tumorigenesis through its suppressive effect on FH Thr 90 phosphorylation-mediated cell growth arrest in non-small cell lung cancer (NSCLC) cells and correlates with poor prognosis in lung cancer patients. Our findings uncover an uncharacterized mechanism underlying the local effect of FH on TGF-β induced-gene transcription, on which the inhibitory effect from PAK4 promotes tumorigenesis in lung cancer.

http://bit.ly/2sO17HR

Interplay between TRAP1 and sirtuin-3 modulates mitochondrial respiration and oxidative stress to maintain stemness of glioma stem cells

Glioblastoma (GBM) cancer stem cells (CSC) are primarily responsible for metastatic dissemination, resistance to therapy, and relapse of GBM, the most common and aggressive brain tumor. Development and maintenance of CSC require orchestrated metabolic rewiring and metabolic adaptation to a changing microenvironment. Here we show that cooperative interplay between the mitochondrial chaperone TRAP1 and the major mitochondria deacetylase sirtuin-3 (SIRT3) in glioma stem cells (GSC) increases mitochondrial respiratory capacity and reduces production of reactive oxygen species. This metabolic regulation endowed GSC with metabolic plasticity, facilitated adaptation to stress (particularly reduced nutrient supply), and maintained "stemness." Inactivation of TRAP1 or SIRT3 compromised their interdependent regulatory mechanisms, leading to metabolic alterations, loss of stemness, and suppression of tumor formation by GSC in vivo. Thus, targeting the metabolic mechanisms regulating interplay between TRAP1 and SIRT3 may provide a novel therapeutic option for intractable GBM patients.

http://bit.ly/2Mx1BuX

MYC-Mediated Translation of PD-L1 Promotes Liver Cancer Immune Escape [Research Watch]

MYC and KRAS^G12D exhibit distinct roles in the post-transcriptional regulation of immune checkpoints.

http://bit.ly/2sOEfbk

B Cell-Derived Antibodies Promote Lymph Node Metastasis in Breast Cancer [Research Watch]

Pathogenic IgG produced by tumor-educated B cells drives formation of a lymph node premetastatic niche.

http://bit.ly/2MyZN4F

New Endpoints, Programs Used for Drug Approvals [News in Brief]

FDA greenlighted 17 novel cancer agents in 2018, including two OK'd with nontraditional data.

http://bit.ly/2sO14vF

NPM1 Mutations Create a Targetable Shared Neoantigen in AML [Research Watch]

Targeting a mutant NPM1-derived neoantigen has antitumor activity against AML cells.

http://bit.ly/2Mx1xeH

Subject‐specific loads on the lumbar spine in detailed finite element models scaled geometrically and kinematics‐driven by radiography images

Abstract

Traditional load‐control musculoskeletal and finite element (FE) models of the spine fail to accurately predict in vivo intervertebral joint loads due mainly to the simplifications and assumptions when estimating redundant trunk muscle forces. An alternative powerful protocol that bypasses the calculation of muscle forces is to drive the detailed FE models by image‐based in vivo displacements. Development of subject‐specific models, however, both involves the risk of extensive radiation exposures while imaging in supine and upright postures and is time consuming in terms of the reconstruction of the vertebrae, discs, ligaments and facets geometries. This study therefore aimed to introduce a remedy for the development of subject‐specific FE models by scaling the geometry of an existing detailed FE model of the T12‐S1 lumbar spine. Five subject‐specific scaled models were driven by their own radiography image‐based displacements in order to predict joint loads, ligament forces, facet joint forces, and disc fiber strains during relaxed upright as well as moderate flexion and extension tasks. The predicted intradiscal pressures were found in adequate agreement with in vivo data for upright, flexion, and extension tasks. There were however large inter‐subject variations in the estimated joint loads and facet forces.

http://bit.ly/2B6gxvB

Albumin-Bilirubin (ALBI) as an accurate and simple prognostic score for chronic hepatitis B-related liver cirrhosis

The Albumin–Bilirubin (ALBI) score was developed to predict the long-term prognosis of hepatocellular carcinoma patients. We aimed to investigate the performance of ALBI for predicting severity and long-term prognosis of chronic hepatitis B-related liver cirrhosis (CHB-LC).

http://bit.ly/2Tbg95X

Prevalence of Pulmonary Embolism Among Emergency Department Patients With Syncope: A Multicenter Prospective Cohort Study

The prevalence of pulmonary embolism among patients with syncope is understudied. In accordance with a recent study with an exceptionally high pulmonary embolism prevalence, some advocate evaluating all syncope patients for pulmonary embolism, including those with another clear cause for their syncope. We seek to evaluate the pulmonary embolism prevalence among emergency department (ED) patients with syncope.

http://bit.ly/2Ui4uCG

Spectrum of neurodevelopmental disease associated with the GNAO1 guanosine triphosphate–binding region

Summary

Objective

To characterize the phenotypic spectrum associated with GNAO1 variants and establish genotype‐protein structure‐phenotype relationships.

Methods

We evaluated the phenotypes of 14 patients with GNAO1 variants, analyzed their variants for potential pathogenicity, and mapped them, along with those in the literature, on a three‐dimensional structural protein model.

Results

The 14 patients in our cohort, including one sibling pair, had 13 distinct, heterozygous GNAO1 variants classified as pathogenic or likely pathogenic. We attributed the same variant in two siblings to parental mosaicism. Patients initially presented with seizures beginning in the first 3 months of life (8/14), developmental delay (4/14), hypotonia (1/14), or movement disorder (1/14). All patients had hypotonia and developmental delay ranging from mild to severe. Nine had epilepsy, and nine had movement disorders, including dystonia, ataxia, chorea, and dyskinesia. The 13 GNAO1 variants in our patients are predicted to result in amino acid substitutions or deletions in the GNAO1 guanosine triphosphate (GTP)‐binding region, analogous to those in previous publications. Patients with variants affecting amino acids 207‐221 had only movement disorder and hypotonia. Patients with variants affecting the C‐terminal region had the mildest phenotypes.

Significance

GNAO1 encephalopathy most frequently presents with seizures beginning in the first 3 months of life. Concurrent movement disorders are also a prominent feature in the spectrum of GNAO1 encephalopathy. All variants affected the GTP‐binding domain of GNAO1, highlighting the importance of this region for G‐protein signaling and neurodevelopment.

http://bit.ly/2RhRoTY

Taurine potentiates the anticonvulsive effect of the GABAA agonist muscimol and pentobarbital in the immature mouse hippocampus

Summary

Objective

The high incidence of epileptic seizures in neonates and their frequent refractoriness to pharmacologic therapies require identification of new therapeutical options. Therefore, we investigated whether the modulatory effect of taurine on γ‐aminobutyric acid (GABA)_A receptors can enhance the anticonvulsive potential of the GABA_A receptor agonist muscimol and of the barbiturate pentobarbital.

Methods

We performed field potential recordings in in toto hippocampus preparations of immature (postnatal days 4‐7) C57Bl/6 mouse pups. Spontaneous epileptiform activity was induced by the continuous presence of the potassium channel blocker 4‐aminopyridine and the glycinergic antagonist strychnine in Mg²⁺‐free solutions.

Results

Bath application of 0.1 μmol/L muscimol increases the occurrence of recurrent epileptiform discharges, whereas they are significantly attenuated in a dose‐dependent manner by muscimol in concentrations between 0.5 and 5 μmol/L. Taurine at concentrations between 0.1 and 0.5 mmol/L induces a proconvulsive effect, but upon coapplication, it significantly augments the anticonvulsive effect of moderate muscimol doses (0.5‐1 μmol/L). In addition, the anticonvulsive effect of 100 and 200 μmol/L pentobarbital is increased significantly in the presence of 0.5 μmol/L taurine.

Significance

These observations demonstrate that taurine can indeed enhance the anticonvulsive effects of muscimol and pentobarbital, suggesting that taurine may act as a positive modulator on GABA_A receptors. Thus, interfering with the modulatory taurine binding site of GABA_A receptors or the interstitial taurine concentration may provide new therapeutical options for anticonvulsive therapies in neonates.

http://bit.ly/2Wk17wY

Medication treatment for attention‐deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy

Summary

Objective

Attention‐deficit/hyperactivity disorder (ADHD) affects 10%‐30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy.

Methods

A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within‐individual to adjust for unmeasured, time?constant confounding.

Results

Among 995 individuals who initiated ADHD medication during follow‐up, within‐individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person‐years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57‐0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders.

Significance

We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.

http://bit.ly/2RhRivA

An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy

Here, we present a protocol to study the pathophysiology of proliferative diabetic retinopathy by using patient-derived, surgically-excised, fibrovascular tissues for three-dimensional native tissue characterization and ex vivo culture. This ex vivo culture model is also amenable for testing or developing new treatments.

http://bit.ly/2HyzqgB

Designing Porous Silicon Films as Carriers of Nerve Growth Factor

Here, we present a protocol to design and fabricate nanostructured porous silicon (PSi) films as degradable carriers for the nerve growth factor (NGF). Neuronal differentiation and outgrowth of PC12 cells and mice dorsal root ganglion (DRG) neurons are characterized upon treatment with the NGF-loaded PSi carriers.

http://bit.ly/2TfQYzc

Genetic Engineering of Dictyostelium discoideum Cells Based on Selection and Growth on Bacteria

Dictyostelium discoideum is a popular model organism to study complex cellular processes such as cell migration, endocytosis, and development. The utility of the organism is dependent on the feasibility of genetic manipulation. Here, we present methods to transfect Dictyostelium discoideum cells that overcome existing limitations of culturing cells in liquid media.

http://bit.ly/2B6LPmb

Assessing Stem Cell DNA Integrity for Cardiac Cell Therapy

Here, we provide a detailed description of an experimental setup for an analysis of the assessment of DNA integrity in stem cells prior to cell transplantation.

http://bit.ly/2TgOEbe

Current Status and Growth of Nuclear Theranostics in Singapore

Abstract

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of 'personalised' medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore. We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy. We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

http://bit.ly/2FXNspA

Additive Manufacturing of Functionally Graded Ceramic Materials by Stereolithography

This manuscript describes the processing of single multifunctional ceramic components (e.g., combinations of dense-porous structures) additively manufactured by stereolithography.

http://bit.ly/2MCA7V2

Novel Sequence Discovery by Subtractive Genomics

The purpose of this protocol is to use a combination of computational and bench research to find novel sequences that cannot be easily separated from a co-purifying sequence, which may be only partially known.

http://bit.ly/2sOKoEy

Probing Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices via Laser Flash Photolysis of Photoactivatable Nicotine

This article presents a method for studying nicotinic acetylcholine receptors (nAChRs) in mouse brain slices by nicotine uncaging. When coupled with simultaneous patch clamp recording and 2-photon laser scanning microscopy, nicotine uncaging connects nicotinic receptor function with cellular morphology, providing a deeper understanding of cholinergic neurobiology.

http://bit.ly/2MzNJA6

Americans Used Less Eye Care in 2014 Versus 2008

FRIDAY, Jan. 25, 2019 -- Americans were less likely to use eye care in 2014 versus 2008 but had decreased difficulty affording eyeglasses from 2014 onward, according to a study published online Jan. 24 in JAMA Ophthalmology. Varshini Varadaraj,...

http://bit.ly/2Hyb46r

Cognitive Scores After Kidney Transplant Tied to Frailty

FRIDAY, Jan. 25, 2019 -- Frail kidney transplant recipients have lower cognitive scores than nonfrail recipients four years after transplant, according to a study published online Jan. 24 in the Journal of the American Society of Nephrology. Nadia...

http://bit.ly/2Hymasl

Improved Genetic Risk Score Aids Type 1 Diabetes Classification

FRIDAY, Jan. 25, 2019 -- An improved type 1 diabetes (T1D) genetic risk score (GRS), the T1D GRS2, is highly useful for classifying adult incident diabetes type and improving newborn screening, according to a study published in the February issue of...

http://bit.ly/2S9b7K7

Home-Based Program Achieves Hypertension Control

FRIDAY, Jan. 25, 2019 -- A new home-based care delivery program can provide efficient and effective blood pressure (BP) control in individuals with hypertension, according to a study recently published in Clinical Cardiology. Naomi D. Fisher, M.D.,...

http://bit.ly/2S2Y5Op

2003 to 2015 Saw Increase in Outpatient Benzodiazepine Use

FRIDAY, Jan. 25, 2019 -- Outpatient benzodiazepine use increased from 2003 to 2015, according to a study published online Jan. 25 in JAMA Network Open. Sumit D. Agarwal, M.D., and Bruce E. Landon, M.D., from Harvard Medical School in Boston,...

http://bit.ly/2HxY5BI

Assessment Tools Aid Risk Planning at Nursing Homes

FRIDAY, Jan. 25, 2019 -- Better use of risk assessment tools, like the Changes in Health and End-stage disease Signs and Symptoms (CHESS) score, can help nursing homes identify which new residents are at risk for hospitalization or death within the...

http://bit.ly/2S2Y2Cd

Report IDs Areas Lacking Good Practice in Health Tech Assessment

FRIDAY, Jan. 25, 2019 -- In a report published in the January issue of Value in Health, an ISPOR--The Professional Society for Health Economics and Outcomes Research working group indicates the lack of good practices in three areas of health...

http://bit.ly/2Hu5HW1

Suicide Incidence Up in Autism Spectrum Disorder 2013 to 2017

FRIDAY, Jan. 25, 2019 -- Between 2013 and 2017, the cumulative incidence of suicide was higher in the autism spectrum disorder (ASD) population compared with the non-ASD population, according to a study published online Jan. 21 in Autism...

http://bit.ly/2S2XYSZ

Many Teens Not Up to Date on HPV Vaccination

FRIDAY, Jan. 25, 2019 -- Many adolescents do not complete human papillomavirus (HPV) vaccination before turning 13 or 15 years old, according to a report published online Jan. 17 in the Journal of Infectious Diseases. Robert A. Bednarczyk, Ph.D.,...

http://bit.ly/2HyaK7J

Texting Intervention Engages Patients After Joint Arthroplasty

FRIDAY, Jan. 25, 2019 -- A text-messaging (Short Message Service [SMS]) bot is effective for increasing patient engagement after primary total knee or hip arthroplasty, according to a study published in the Jan. 16 issue of The Journal of Bone &...

http://bit.ly/2S2XV9L

Folate pathway genetic polymorphisms modulate methotrexate-induced toxicity in childhood acute lymphoblastic leukemia

Abstract

Background

Acute lymphoblastic leukemia (ALL) is one of the major malignancies affecting children in Jordan. Methotrexate (MTX) is the cornerstone of chemotherapy for ALL, and works by targeting enzymes involved in the folate pathway. We hypothesize that genetic polymorphisms of the folate pathway are associated with MTX toxicity in children with ALL.

Methods

A total of 64 children with ALL were included in this study; 31 (48.4%) boys and 33 (51.6%) girls aged 2–16 years. The folate pathway genes were genotyped using polymerase chain reaction followed by sequencing and studying the association between genetic polymorphisms and MTX toxicity.

Results

The immunophenotype was B-lineage in 55 patients (85.9%) and T-lineage in nine patients (14.1%). All genetic polymorphisms, except for dihydropyrimidine dehydrogenase polymorphisms, were associated with hematological toxicities and did not appear to precipitate any non-hematological adverse events. Patients with ALL carrying dominant alleles of methylene tetrahydrofolate (MTHFR) C677T and dihydrofolate reductase 19 bp deletion were at a higher risk of developing severe leucopenia [OR (95% CI) = 4.5 (1.2–17), p = 0.03; 5.4 (1.6–17.8); p = 0.006] while minor allele carriers of MTHFR A1298C were more likely to develop neutropenia [OR (95% CI) = 6.1 (1.3–29.5); 0.04]. Furthermore, dominant allele carriers of thymidylate synthase 1494 del6 were at a higher risk of developing neutropenia [OR (95% CI) = 6 (1.2–31.1); p = 0.04].

Conclusion

Genetic polymorphisms of the folate pathway may modulate MTX-induced toxicity in childhood ALL.

http://bit.ly/2WicXYq

High frequency of coagulase-positive staphylococci carriage in healthy wild boar with detection of MRSA of lineage ST398-t011

Abstract

The objective was to determine the frequency and the diversity of coagulase-positive staphylococci (CoPS) in nasal samples of healthy wild boar, to study their resistance phenotypes/genotypes and to check the occurrence of the MRSA-ST398. Nasal samples of 371 wild boars were collected in Spain for staphylococci and MRSA recovery. Staphylococci identification was performed by MALDI-TOF. The susceptibility to eleven antimicrobials was tested by disc-diffusion and the presence of resistance genes by PCR. Molecular typing and virulence factors determination were carried out by PCR and sequencing. The rate of CoPS carriage (S. aureus, S. hyicus, and S. pseudintermedius) in wild boar was of 17.8% (13.7%, 2.7% and 1.6%, respectively). Susceptibility to all tested antimicrobials was shown in 74.5% of S. aureus, and one strain was MRSA [lineage ST398-t011-agrI, carrying blaZ, mecA, tet(M) and tet(K) genes]. Twenty-two spa-types and 17 STs were detected among S. aureus, including: ST398/CC398 (n = 1), ST2328-ST133/CC133 (n = 20), ST425/CC425 (n = 7), ST5/CC5 (n = 5), ST1/CC1 (n = 3), ST130/CC130 (n = 2), and ST88/CC88 (n = 1). Two spa-types (t02, t15) and four STs (ST455, ST796, ST797, ST798) were detected among the six S. pseudintermedius isolates recovered, and all of them carried the lukF/S-I and siet virulence genes. All S. hyicus isolates were susceptible to antimicrobials tested.

http://bit.ly/2HuEK4E

Floodplain soil and its bacterial composition are strongly affected by depth

Abstract

We studied bacterial abundance and community structure of five soil cores using high-throughput sequencing of the 16S rRNA gene. Shifts in the soil bacterial composition were more pronounced within a vertical profile than across the landscape. Soil organic carbon (SOC) and nitrogen (N) concentrations decreased exponentially with soil depth and revealed a buried carbon-rich horizon between 0.8 and 1.3 m across all soil cores. This buried horizon was phylogenetically similar to its surrounding subsoils supporting the idea that the type of carbon, not necessarily the amount of carbon was driving the apparent similarities. In contrast to other studies, Nitrospirae was one of our major phyla with relatively high abundances throughout the soil profile except for the surface soil. Although depth is the major driver shaping soil bacterial community structure, positive correlations with SOC and N concentrations, however, were revealed with the bacterial abundance of Acidobacteria, one of the major, and Gemmatimonadetes, one of the minor phyla in our study. Our study showed that bacterial diversity in soils below 2.0 m can be still as high if not higher than in the above laying subsurface soil suggesting that various bacteria throughout the soil profile influence major biogeochemical processes in floodplain soils.

http://bit.ly/2S9Vi62

Prognostic impact of polypharmacy and drug interactions in patients with advanced cancer

Abstract

The risk of potential drug–drug interactions (PDI) is poorly studied in oncology. We included 105 patients with advanced non-small-cell lung cancer (NSCLC), 100 patients with advanced breast cancer (BC) and 100 patients of the palliative care unit (PCU) receiving systemic palliative treatment between 2010 and 2015. All patients suffered from advanced incurable cancer and received basic palliative care. PDI were assessed using the hospINDEX of all drugs approved in Switzerland in combination with a specific drug interaction software. Primary study objective was to assess the prognostic impact of PDI per patient cohort using Kaplan–Meier statistics. The median number of comedications was 5 (range 0–15). Major-risk PDI were detected in 74 patients (24.3%). The number of comedications was significantly associated with PDI (p < 0.0001). Major-risk PDI increased from 14% in patients with < 4 comedications to 24% in patients with 4–7 comedications, 40% with 8–11 comedications and 67% in patients with > 11 comedications. Median overall survival (OS) was 8.6 months in NSCLC, 33 months in BC and 1.2 months in PCU patients. PDI were significantly associated with inferior OS in BC (HR = 1.32, 95% CI 1.01–1.74, p = 0.049), but not in NSCLC (HR = 1.11, 95% CI 0.84–1.47, p = 0.45) or PCU (HR = 1.12, 95% CI 0.86–1.45, p = 0.41). PDI remained significantly associated with OS in BC (HR = 1.32, p = 0.049) in the adjusted model. In conclusion, PDI are frequent in patients with advanced cancer and increased caution with polypharmacy is warranted when treating such patients.

http://bit.ly/2RODwWv

A phase Ib dose allocation study of oral administration of lucitanib given in combination with fulvestrant in patients with estrogen receptor-positive and FGFR1 -amplified or non-amplified metastatic breast cancer

Abstract

Purpose

The primary objective of this multicentric dose allocation and dose expansion study was to determine the MTD and the DLTs of the lucitanib (a tyrosine kinase inhibitor of the FGFR/VEGFR/PDFGR pathways)/fulvestrant combination.

Methods

Postmenopausal women with ER+/HER2− mBC, who have relapsed during or after treatment with fulvestrant, were eligible. The study had a dose allocation part to assess the tolerability of the combination followed by a dose expansion part.

Results

Eighteen patients with ER+, mBC were enrolled; median age was 66 years, 50% had a PS: 0 and all had received previous endocrine treatment. The study was prematurely terminated after 18 patients (15 in part 1 and 3 in part 2) based on preclinical experiments that failed to confirm the hypothesis that addition of lucitanib would reverse sensitivity to endocrine treatments. Based on data of global lucitanib development, it was decided to stop the dose allocation at 12.5 mg and to start the dose expansion part at 10 mg/day. The most common grade ≥ 3 toxicities (> 10% of patients) were hypertension (78%) and asthenia (22%). All patients required at ≥ 1 interruption, 13 patients (72%) required ≥ 1 dose reduction. Three patients (72%) withdrew from the study for AEs (at 10 mg). Three patients achieved a confirmed PR (10 mg n = 1; 12.5 mg n = 2).

Conclusion

Although the combination is feasible it requires close monitoring of the patients for the management of adverse events. Further investigation is required to better understand the potential role of FGFR inhibition in reversing resistance to endocrine treatment.

http://bit.ly/2CGHBBI

Disparity of the Chinese elderlys health-related quality of life between urban and rural areas: a mediation analysis

Objectives

This study aimed to examine the urban–rural disparity in health-related quality of life (HRQoL) of the Chinese elderly and to explore the mediating roles of socioeconomic status (SES) and frequency of contact with children in the relationship between urban/rural areas and HRQoL.

Methods

This cross-sectional study used data from China Health and Retirement Longitudinal Study for 2015–2016, involving 12 369 Chinese aged 45 years and over. HRQoL of respondents was measured by three-level EuroQol five dimensions (EQ-5D-3L). SES, based on principal components analysis, was combined by the individual possessions of durable consumer goods and houses. Frequency of contact with children was derived from the responses to whether they live with children and how often they contact with them. Mediation analyses were performed to examine the mediating effects of SES and frequency of contact in the relationship between urban/rural areas and HRQoL.

Results

Urban respondents had higher scores of HRQoL than rural respondents (p<0.05). As SES and frequency of contact with children increased, the scores of HRQoL of the elderly went up as well. Mediation analyses proved the possible mediating effects of SES and frequency of contact in the relationship between urban/rural areas and HRQoL (0.0713 and 0.0064). The indirect effects induced by SES and frequency of contact were 65.45% and 5.90%, respectively.

Conclusions

There was a significant difference in HRQoL between urban and rural middle-aged and elderly participants, which was partially mediated by urban–rural disparities in SES and frequency of contact with children. Higher SES and frequency of contact with children contributed to higher health status in the Chinese elderly.

http://bit.ly/2Wm3IX1

Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity--a retrospective study

Objective

The role of platelet-to-lymphocyte ratio (PLR) as an indicator of inflammation has been the focus of research recently. We aimed to investigate the prognostic value of PLR for sepsis.

Design

A retrospective cohort study.

Setting and participants

Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. Data on 5537 sepsis patients were analysed.

Methods

Logistic regression was used to explore the association between PLR and hospital mortality. Subgroup analyses were performed based on vasopressor use, acute kidney injury (AKI) and a Sequential Organ Failure Assessment (SOFA) score >10.

Results

In the logistic model with linear spline function, a PLR >200 was significantly (OR 1.0002; 95% CI 1.0001 to 1.0004) associated with mortality; the association was non-significant for PLRs ≤200 (OR 0.997; 95% CI 1.19 to 1.67). In the logistic model using the PLR as a design variable, only high PLRs were significantly associated with mortality (OR 1.29; 95% CI 1.09 to 1.53); the association with low PLRs was non-significant (OR 1.15; 95% CI 0.96 to 1.38). In the subgroups with vasopressor use, AKI and a SOFA score >10, the association between high PLR and mortality was non-significant; this remained significant in the subgroups without vasopressor use (OR 1.39; 95% CI 1.08 to 1.77) and AKI (OR 1.54; 95% CI 1.20 to 1.99) and with a SOFA score ≤10 (OR 1.51; 95% CI 1.17 to 1.94).

Conclusions

High PLRs at admission were associated with an increased risk of mortality. In patients with vasopressor use, AKI or a SOFA score >10, this association was non-significant.

http://bit.ly/2RioALn

Association between benzodiazepine use and risks of chronic-onset poststroke pneumonia: a population-based cohort study

Objectives

To investigate the association between benzodiazepine (BZD) use and the risk of chronic-onset poststroke pneumonia.

Design

Population-based propensity-matched retrospective cohort study.

Setting

Taiwan's National Health Insurance Research Database.

Participants

Patients newly diagnosed with stroke between 2000 and 2012 were identified and, after propensity score matching, 7516 patients were enrolled. Among these, 3758 patients received BZDs after stroke while 3758 did not.

Outcome measures

HRs for developing pneumonia over 1 month after stroke according to BZD use were assessed using Cox proportional hazards regression models. Analyses according to cumulative defined daily doses (cDDDs) of BZDs and stratification for age and sex were also performed.

Results

During a mean follow-up time of 4.4 years, 1027 patients in the BZD cohort and 478 patients in the non-BZD cohort developed pneumonia over 1 month after stroke. Patients using BZDs after stroke had a higher pneumonia risk than did those not using BZDs (52.2vs32.6 per 1000 person-years, adjusted HR (aHR)=2.21, 95% CI (CI)=1.97 to 2.48, p<0.001). Analyses based on cumulative BZD dose revealed that all BZD user subgroups were associated with a higher risk of pneumonia. The aHRs for patients taking 1–90, 91–365 and >365 cDDDs of BZDs were 2.28 (95% CI=2.01 to 2.58; p<0.001), 2.09 (95% CI=1.77 to 2.47; p<0.001) and 2.08 (95% CI=1.72 to 2.52; p<0.001), respectively. The significant association between BZD use and increased pneumonia risk persisted even after stratifying subgroups by age and sex.

Conclusions

BZD use is associated with an increased risk of chronic-onset poststroke pneumonia.

http://bit.ly/2Wm4aob

Protocol for a mixed-methods exploratory investigation of care following intensive care discharge: the REFLECT study

Introduction

A substantial number of patients discharged from intensive care units (ICUs) subsequently die without leaving hospital. It is unclear how many of these deaths are preventable. Ward-based management following discharge from ICU is an area that patients and healthcare staff are concerned about. The primary aim of REFLECT (Recovery Following Intensive Care Treatment) is to develop an intervention plan to reduce in-hospital mortality rates in patients who have been discharged from ICU.

Methods and analysis

REFLECT is a multicentre mixed-methods exploratory study examining ward care delivery to adult patients discharged from ICU. The study will be made up of four substudies. Medical notes of patients who were discharged from ICU and subsequently died will be examined using a retrospective case records review (RCRR) technique. Patients and their relatives will be interviewed about their post-ICU care, including relatives of patients who died in hospital following ICU discharge. Staff involved in the care of patients post-ICU discharge will be interviewed about the care of this patient group. The medical records of patients who survived their post-ICU stay will also be reviewed using the RCRR technique. The analyses of the substudies will be both descriptive and use a modified grounded theory approach to identify emerging themes. The evidence generated in these four substudies will form the basis of the intervention development, which will take place through stakeholder and clinical expert meetings.

Ethics and dissemination

Ethical approval has been obtained through the Wales Research and Ethics Committee 4 (17/WA/0107). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media.

Trial registration number

ISRCTN14658054.

http://bit.ly/2RdUusb

Home self-administration of intravenous antibiotics as part of an outpatient parenteral antibiotic therapy service: a qualitative study of the perspectives of patients who do not self-administer

Objectives

This study aimed to use a theoretical approach to understand the determinants of behaviour in patients not home self-administering intravenous antibiotics.

Setting

Outpatient care: included patients were attending an outpatient clinic for intravenous antibiotic administration in the northeast of Scotland.

Participants

Patients were included if they had received more than 7 days of intravenous antibiotics and were aged 16 years and over. Twenty potential participants were approached, and all agreed to be interviewed. 13 were male with a mean age of 54 years (SD +17.6).

Outcomes

Key behavioural determinants that influenced patients' behaviours relating to self-administration of intravenous antibiotics.

Design

Qualitative, semistructured in-depth interviews were undertaken with a purposive sample of patients. An interview schedule, underpinned by the Theoretical Domains Framework (TDF), was developed, reviewed for credibility and piloted. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically using the TDF as the coding framework.

Results

The key behavioural determinants emerging as encouraging patients to self-administer intravenous antibiotics were the perceptions of being sufficiently knowledgeable, skilful and competent and that self-administration afforded the potential to work while administering treatment. The key determinants that impacted their decision not to self-administer were lack of knowledge of available options, a perception that hospital staff are better trained and anxieties of potential complications.

Conclusion

Though patients are appreciative of the skills and knowledge of hospital staff, there is also a willingness among patients to home self-administer antibiotics. However, the main barrier emerges to be a perceived lack of knowledge of ways of doing this at home. To overcome this, a number of interventions are suggested based on evidence-based behavioural change techniques.

http://bit.ly/2Wm42oH

Utilisation of the principles of the Armed Forces Covenant in NHS Trusts and Clinical Commissioning Groups across England: a freedom of information investigation

Objectives

To determine the extent to which National Health Service (NHS) service providers appoint a named Armed Forces veteran lead or champion, and to explore the commissioning of veteran-specific services by Clinical Commissioning Groups.

Design

A convergent mixed method design was used to improve understanding obtained from the information provided by respondents on their practice. The study comprised two parts: phase 1 involved NHS Trusts, and phase 2 involved Clinical Commissioning Groups.

Setting

All NHS Trusts and Clinical Commissioning Groups in England were contacted using a freedom of information request.

Participants

All NHS trusts and Clinical Commissioning Groups across England.

Interventions

Initially, existing national websites were searched to gather information within the public domain. An audit was carried out, using the Freedom of Information Act (FOIA) 2000 to gather further information.

Primary and secondary outcome measures

The FOIA 2000 applies to UK Government departments and public authorities, including NHS Trusts in England, Wales and Northern Ireland.

Results

Responses from the freedom of information requests illustrate inconsistencies in relation to adopting the principles of the Armed Forces Covenant. The inconsistencies extend to the practice of appointing an Armed Forces Veteran Lead or an Armed Forces Veteran Champion. There is also evidence to suggest a lack of commitment to and understanding of policy guidance in relation to Clinical Commissioning Group responsibility for commissioning veteran-specific services.

Conclusions

Findings from this study support the case for making improvements to, and improving the consistency of, commissioning practices for veterans.

http://bit.ly/2RfYacN

HIV-related excess mortality and age-related comorbidities in patients with HIV aged >=60: a relative survival analysis in the French DatAIDS cohort

Objective

The objective was to evaluate the association between age-related comorbidities (ARCs) and 5-year HIV-related excess mortality in people living with HIV aged ≥60 years.

Design

Cohort study using relative survival analysis (Estève's model).

Setting

The French multicentre prospective Dat'AIDS cohort that involves 12 French hospitals.

Participants

Inclusion of 1415 HIV-1 infected patients actively followed aged ≥60 years on January 2008, with a 5-year follow-up period in the late combination antiretroviral therapy era.

Results

Among 1415 patients included, 154 died. By multivariable analysis, factors predictive of 5-year HIV-related excess mortality were non-AIDS-related cancer (adjusted excess HR (aEHR)=2.94; 95% CI 1.32 to 6.57), cardiovascular disease (aEHR=6.00; 95% CI 2.45 to 14.65), chronic renal disease (aEHR=4.86; 95% CI 2.24 to 10.53), cirrhosis (aEHR=3.58; 95% CI 1.25 to 10.28), hepatitis C co-infection (aEHR=3.63; 95% CI 1.44 to 9.12), body mass index<18.5 kg/m² (aEHR=4.10; 95% CI 1.61 to 10.48) and having a CD4 cell count ≤200/mm³ (aEHR=5.79; 95% CI 2.28 to 14.69).

Conclusions

ARCs, particularly cardiovascular disease and chronic renal disease, are predictive of HIV-related excess mortality, with an increase in hazard similar to that of CD4 cell count.

Trial registration number

NCT02898987.

http://bit.ly/2WgvoN2

Multicentre, open-label, randomised controlled clinical trial to assess the efficacy and safety of appropriate target values for lipid management in patients who have mild-to-moderate stenotic lesions with high-risk plaques in coronary arteries: study protocol

Introduction

To detect patients at high risk of developing myocardial infarction, plaque characteristics as well as the degree of stenosis in coronary arteries should be evaluated. However, unstable plaque or severe calcification detected via coronary artery CT (CACT) is not reflected in risk stratification according to current guidelines. It is hypothesised that patients with high-risk findings on CACT (even those without proven history of coronary artery diseases; CAD) should be strictly managed to lower their low-density lipoprotein cholesterol (LDL-C) levels to targets of secondary prevention. Currently, however, there is no evidence based on prospective randomised intervention studies to prove this hypothesis.

Methods and analysis

Patients with mild-to-moderate stenotic lesions with positive remodelling or severe calcification, but without any history of CAD, will be randomly allocated to group A (reduce LDL-C to <120~160 mg/dL according to the primary prevention criteria based on the Japan Atherosclerosis Society (JAS) Guideline for Prevention of Atherosclerotic Cardiovascular Diseases 2017) and group B (reduce LDL-C to <70 mg/dL according to the secondary prevention criteria for high risk based on the JAS Guideline). They will be strictly managed to achieve the LDL-C targets. We will follow-up and evaluate the composite endpoints consisting of major cardiovascular events (death from CAD, non-fatal myocardial infarction, operation for coronary revascularisation and stroke) and stenosis progression or new stenosis development for 3 years.

Ethics and dissemination

The study was approved by the National Hospital Organization Central Research Ethics Committee. The results of this study are scheduled to be published within 2 years after study completion via conference presentation or journal publication.

Trial registration number

UMIN000031136.

http://bit.ly/2Ri9W6G

Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis

Objective

To systematically review the literature relating to the impact of multiple co-occurring modifiable risk factors for cognitive decline and dementia.

Design

A systematic review and meta-analysis of the literature relating to the impact of co-occurring key risk factors for incident cognitive decline and dementia. All abstracts and full text were screened independently by two reviewers and each article assessed for bias using a standard checklist. A fixed effects meta-analysis was undertaken.

Data sources

Databases Medline, Embase and PsycINFO were searched from 1999 to 2017.

Eligibility criteria

For inclusion articles were required to report longitudinal data from participants free of cognitive decline at baseline, with formal assessment of cognitive function or dementia during follow-up, and an aim to examine the impact of additive or clustered comorbid risk factor burden in with two or more core modifiable risk factors.

Results

Seventy-nine full-text articles were examined. Twenty-two articles (18 studies) were included reporting data on >40 000 participants. Included studies consistently reported an increased risk associated with greater numbers of intraindividual risk factors or unhealthy behaviours and the opposite for healthy or protective behaviours. A meta-analysis of studies with dementia outcomes resulted in a pooled relative risk for dementia of 1.20 (95% CI 1.04 to 1.39) for one risk factor, 1.65 (95% CI 1.40 to 1.94) for two and 2.21 (95% CI 1.78 to 2.73) for three or more, relative to no risk factors. Limitations include dependence on published results and variations in study outcome, cognitive assessment, length of follow-up and definition of risk factor exposure.

Conclusions

The strength of the reported associations, the consistency across studies and the suggestion of a dose response supports a need to keep modifiable risk factor exposure to a minimum and to avoid exposure to additional modifiable risks. Further research is needed to establish whether particular combinations of risk factors confer greater risk than others.

PROSPERO registration number

42016052914.

http://bit.ly/2Rf2j0P

Efficacy of biological drugs in short-duration versus long-duration inflammatory bowel disease: a protocol for a systematic review and an individual-patient level meta-analysis of randomised controlled trials

Introduction

Crohn's disease (CD) and ulcerative colitis (UC) are remitting–relapsing inflammatory diseases often culminating in disease complications and/or need for surgery. Biologic monoclonal antibody drugs ('Biologics') are efficacious for both diseases, but there are no systematic assessments of their efficacy if administered early after disease onset ('top-down' strategy) vis-à-vis later in the course of disease ('step-up' approach).

Methods and analysis

Electronic databases (MEDLINE, EMBASE/EMBASE classic Cochrane CENTRAL register of controlled trials, the Cochrane IBD Group Specialised Trials Register and Clinicaltrials.gov registry) will be searched to identify all randomised placebo-controlled clinical trials of food and drug administration (FDA)-approved biologics for CD and UC (by March 2016). Two independent reviewers will screen identified papers, extract data and assess the risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. Individual-patient-level data (IPD) will be extracted from the identified trials through data-sharing platforms for pharmaceutical companies' sponsored trials and by contacting principal investigators of independent investigator-initiated trials. We will analyse induction of remission in patients with early-disease (<18 months since disease onset) versus patients with longer disease duration, using a generalised linear mixed effect model and by a two-stage approach using coefficient for the treatment-by-subgroup interaction within each trial. We will perform receiver operator curve analysis of optimal disease duration for response. Analyses will be separate for CD and UC. This first-of-its-kind meta-analysis at IPD level of interaction of disease duration with the response to biologics in UC and CD may elucidate the impact of early initiation of biologics, which is of paramount importance for clinical practice and management strategies of inflammatory bowel disease.

Ethics and dissemination

This meta-analysis was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. Findings will be published in peer-reviewed journal and disseminated via scientific meetings and links with organisations.

PROSPERO registration number

CRD42018041961.

http://bit.ly/2WhciX3

Prevalence of frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka: a population-based cross-sectional study

Objective

Our main objective was to describe the prevalence and associated sociodemographic factors of frailty and pre-frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka.

Design

Community-based cross-sectional study.

Setting

The study was conducted in rural areas of Kegalle district in Sri Lanka.

Participants

A total of 746 community-dwelling older adults aged ≥60 years were included in the study.

Results

The prevalence of frailty and pre-frailty in rural Kegalle district was 15.2% (95% CI 12.3% to 18.6%) and 48.5% (95% CI 43.8% to 53.2%), respectively. We found a strong association between age and both frailty and pre-frailty. There were strong associations between longest-held occupation and frailty and education level and pre-frailty.

Conclusions

The prevalence of frailty in this rural Sri Lankan older population was high compared with high-income and upper middle-income countries. The profile of health and social care services in Sri Lanka needs to address frailty and its consequences.

http://bit.ly/2Wm3vTJ

Five-year standardised mortality ratios in a cohort of homeless people in Dublin

Objective

To calculate standardised mortality ratios (SMRs) for a cohort of homeless people in the Dublin region over a 5-year period and to examine leading causes of death.

Setting

Homeless services reporting deaths from homeless persons in their care across the Dublin Homeless Region.

Methods

Death data among people who experience homelessness was acquired from the Dublin Region Homeless Executive (2011–2015) and validated from both death certificates and records from the Dublin Coroner's Office.

Participants

Two hundred and nine deaths were recorded; of these 201 were verified (n=156 males, 77.6%). Deaths that could not be verified by certificate or coroners record were excluded from the study.

Results

SMRs were 3–10 times higher in homeless men and 6–10 times higher in homeless women compared with the general population. Drug and alcohol-related deaths were the leading cause of death, accounting for 38.4% of deaths in homeless individuals. These were followed by circulatory (20%) and respiratory causes (13%).

Conclusion

Mortality rates among homeless persons are exceptionally high. Services and programmes, particularly housing and those targeting overdose and alcoholism, are urgently needed to prevent premature mortality in this vulnerable population.

http://bit.ly/2RfYcRX

Sex-specific intergenerational trends in morbidity burden and multimorbidity status in Hong Kong community: an age-period-cohort analysis of repeated population surveys

Objectives

Prevalence of multimorbidity has been increasing worldwide. While population ageing undoubtedly contributes, secular trends have seldom been decomposed into age, period and cohort effects to investigate intergenerational differences. This study examines the birth cohort effect on morbidity burden and multimorbidity in Hong Kong community.

Design

Sex-specific age-period-cohort analysis with repeated cross-sectional surveys.

Setting

A territory-wide population survey database.

Participants

69 636 adults aged 35 or above who participated in the surveys in 1999, 2001, 2005 or 2008.

Main outcome measures

Morbidity burden was operationalised as number of chronic conditions from a list of 14, while multimorbidity was defined as a dichotomous status of whether participants had two or more conditions.

Results

For both sexes, there was an upward inflection (positive change) of risk of increased morbidity burden starting from cohort 1955–1959. For men born after 1945–1954, there was a trend of lower risk (relative risk=0.63, 95% CI 0.50 to 0.80 for 1950–1954 vs 1935–1939) which continued through subsequent cohorts but with no further declines. In women, there had been a gradual increase of risk, although only significant for cohort 1970–1974 (relative risk=1.90, 95% CI 1.08 to 1.34 vs 1935–1939). Similar results were found for dichotomous multimorbidity status.

Conclusions

The trend of lower risk starting from men born in 1945–1954 may be due to a persistent decline in smoking rates since the 1980s. On the other hand, the childhood obesity epidemic starting from the late 1950s coincided with the observed upward inflection of risk for both sexes, that is, notably more drastic increase of risk in women and the levelling-off of the decline of risk in men. These findings highlight that the cohort effects on morbidity burden and multimorbidity may be sex-specific and contextual. By examining such effects in different world populations, localised sex-specific and generation-specific risk factors can be identified to inform policy-making.

http://bit.ly/2WfW8xn

Long-term follow-up for Psychological stRess in Intensive CarE (PRICE) survivors: study protocol for a multicentre, prospective observational cohort study in Australian intensive care units

Introduction

There are little published data on the long-term psychological outcomes in intensive care unit (ICU) survivors and their family members in Australian ICUs. In addition, there is scant literature evaluating the effects of psychological morbidity in intensive care survivors on their family members. The aims of this study are to describe and compare the long-term psychological outcomes of intubated and non-intubated ICU survivors and their family members in an Australian ICU setting.

Methods and analysis

This will be a prospective observational cohort study across four ICUs in Australia. The study aims to recruit 150 (75 intubated and 75 non-intubated) adult ICU survivors and 150 family members of the survivors from 2015 to 2018. Long-term psychological outcomes and effects on health-related quality of life (HRQoL) will be evaluated at 3 and 12 months follow-up using validated and published screening tools. The primary objective is to compare the prevalence of affective symptoms in intubated and non-intubated survivors of intensive care and their families and its effects on HRQoL. The secondary objective is to explore dyadic relations of psychological outcomes in patients and their family members.

Ethics and dissemination

The study has been approved by the relevant human research ethics committees (HREC) of Australian Capital Territory (ACT) Health (ETH.11.14.315), New South Wales (HREC/16/HNE/64), South Australia (HREC/15/RAH/346). The results of this study will be published in a peer-reviewed medical journal and presented to the local intensive care community and other stakeholders.

Trial registration number

ACTRN12615000880549; Pre-results.

http://bit.ly/2RfSSy6

Spatial barriers and the bypassing of nearby dental clinics for dental services: a secondary data analysis in Korea

Objective

This study aimed to calculate the distance patients travel to dental clinics, the rate of bypassing nearby dental clinics and the distance covered when bypassing nearby dental clinics, and explored factors associated with patients' spatial access to dental clinics.

Design

A secondary data analysis.

Setting

Korea Health Panel.

Participants

We included users of dental care services from 2008 to 2011. A total of 2375 patients and 15 978 dental visits were analysed.

Primary outcome measures

Korea Health Panel data (2008–2011) were used to geocode patients' and healthcare facilities' addresses. The distance travelled was calculated using road network information. To analyse the panel data, we adopted a generalised estimating equation: geographical measures on the choice of dental care facility were examined based on sex, age, educational level, equivalent income, treatment details and regional classification.

Results

The median distance travelled to a dental clinic was 1.8 km, which is farther for rural (8.4 km) than for urban (1.5 km) patients. The bypass rate was 58.9%. Patients bypassing nearby dental clinics travelled 9.6 times farther for dental care (p<0.001). Unlike bypass distance, travel distance was not associated with equivalent income. People with higher education and those with implants/orthodontic treatment were more likely to bypass nearby dental clinics and travelled 1.27 times and 1.17 times farther (p<0.01), respectively.

Conclusions

Given the spatial barrier to available dental resources, factors associated with spatial access were mostly the same between travel and bypass distance except for equivalent income. The findings of this study suggest that spatial distance acts as a utilisation barrier and demands additional opportunity cost. At the same time, patients' preferences for services also increase their willingness to bypass nearby dental clinics and travel greater distances.

http://bit.ly/2WjTerh

Features and trends of thyroid cancer in patients with thyroidectomies in Beijing, China between 1994 and 2015: a retrospective study

Objectives

This study aims to summarise the features and trends of thyroid carcinoma in the past two decades in China.

Design, setting and participants

Clinical data obtained from 10 798 patients treated by thyroidectomy from 1994 to 2015 at the Department of General Surgery of the People's Liberation Army General Hospital, Beijing, China were retrospectively analysed.

Outcome measures

Incidence and histopathological features of thyroid cancer were compared and the risk factors for local lymph node metastasis analysed.

Results

Our data indicated a significant increase in the detection of thyroid cancer (from 16.8% to 69.8%, p<0.01). Among the 5235 thyroid cancer cases, papillary thyroid carcinoma (PTC) was the most common histotype, accounting for 95.1% of all malignancies over the 22-year period. Among the 4979 PTCs, micro-PTCs (mPTC) with the largest diameter ≤10 mm has gradually become the dominant form, and its percentage in PTCs has increased from 13.3% in the biennial period of 1994–1995 to 51.2% in 2010–2011. Furthermore, the size of the tumour has decreased significantly from 2.3±1.1 cm in 1994 to 1.2±0.9 cm in the largest diameter (p<0.01), while the average age at diagnosis and female dominance remained unchanged during the period. Logistic regression showed that tumour nodules>1 cm and male gender were the main risk factors for local lymph node metastasis (LNM), whereas patients over 45 years had lower risk.

Conclusions

During the 22-year period, an increased detection of thyroid cancer, particularly mPTC, was found while the occurrence of LNM decreased. Our results suggest that the current preoperative diagnosis and risk stratification are adequate, supporting the published guidelines for the diagnosis of thyroid cancer.

http://bit.ly/2RhnrDw

Burnout among obstetricians and paediatricians: a cross-sectional study from China

Objectives

Hospitals devoted to maternal and child health represent unique healthcare institutions in China. Healthcare professionals in these hospitals attend to health services for women and children, and also provide technical services and support for district maternal and children's healthcare as well as family planning. However, few studies have examined occupational burnout among doctors employed in these hospitals. This research addresses the gap in the literature.

Methods

A cross-sectional survey of obstetricians and paediatricians from 11 maternal and child health hospitals across China was conducted May through June 2017. A total of 678 people completed a self-administered questionnaire. The survey included questions about demographics, doctor–patient relationships and networks of support as well as characteristics designed to capture the occurrence of burnout, such as emotional exhaustion, cynicism and professional efficacy. T-test, variance and multiple regression analyses were used to examine the data.

Results

The research revealed that 56.6% of obstetricians and paediatricians exhibited signs of occupational burnout. Poor doctor–patient relationships and high average number of weekly hours worked contributed to burnout. Additionally, low family support corresponded to physicians' low sense of professional efficacy.

Conclusions

Several factors have contributed to occupational burnout among paediatricians and obstetricians at maternal and child health hospitals in China, including lack of family support, poor doctor–patient relationships and heavy workloads.

http://bit.ly/2WrlSXE

Learning from the transfer of a fellowship programme to support primary care workforce needs in the UK: a qualitative study

Objectives

Service redesign, including workforce development, is being championed by UK health service policy. It is allowing new opportunities to enhance the roles of staff and encourage multiprofessional portfolio working. New models of working are emerging, but there has been little research into how innovative programmes are transferred to and taken up by different areas. This study investigates the transferability of a 1-year post-Certification of Completion of Training fellowship in urgent and acute care from a pilot in the West Midlands region of England to London and the South East.

Design

A qualitative study using semistructured interviews supplemented by observational data of fellows' clinical and academic activities. Data were analysed using a thematic framework approach.

Setting and participants

Two cohorts of fellows (15 in total) along with key stakeholders, mentors, tutors and host organisations in London and the South East (LaSE). Fellows had placements in primary and secondary care settings (general practice, emergency department, ambulatory care, urgent care and rapid response teams), together with academic training.

Results

Seventy-six interviews were completed with 50 participants, with observations in eight clinical placements and two academic sessions. The overall structure of the West Midlands programme was retained and the core learning outcomes adopted in LaSE. Three fundamental adaptations were evident: broadening the programme to include multiprofessional fellows, changes to the funding model and the impact that had on clinical placements. These were felt to be key to its adoption and longer-term sustainability.

Conclusion

The evaluation demonstrates a model of training that is adaptable and transferable between National Health Service regions, taking account of changing national and regional circumstances, and has the potential to be rolled out widely.

http://bit.ly/2RfSlw6

Electronic patient reported outcomes to support care of patients with traumatic brain injury: PRiORiTy study qualitative protocol

Introduction

Traumatic brain injury (TBI) represents a major health and socioeconomic problem internationally. The expansive nature of injuries results in a heterogeneous population. The degree and type of long-term impacts following TBI and improvement following injury are highly variable. The use of electronic Patient Reported Outcomes Measures (ePROMs) could help identify residual impacts of TBI and support patient management and care. The Patient Reported Outcomes Research in Trauma study is a qualitative study exploring the long-term symptoms and impacts that are experienced by those with TBI and the potential utility of an ePROM platform to collect real-time information on patient symptoms and quality of life to inform treatment and identify support needs.

Methods and analysis

Semi-structured telephone and face-to-face interviews will be conducted with approximately 30–40 individuals recruited from five groups: (1) people with TBI; (2) carers and relatives of individuals with TBI; (3) TBI healthcare professionals; (4) researchers and (5) third sector staff members and volunteers working with those with TBI. Data will be analysed using directed thematic analysis employing an iterative coding frame that will be modified as analysis progresses. Intercoder triangulation will be employed to enhance credibility.

Ethics and dissemination

This study was approved by the West Midlands—Black Country Research Ethics Committee (Ref: 18/WM/0033). Findings will be disseminated via conference presentations, peer-reviewed journals, social media (@CPROR_UoB; http://www.birmingham.ac.uk/cpror) and the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre.

http://bit.ly/2WfW4O9

Dairy product consumption and development of cancer: an overview of reviews

Objectives

To provide a comprehensive systematic overview of current evidence from pooled analyses/meta-analyses and systematic reviews (PMASRs) pertaining to dairy consumption and incident cancer and/or all-cause or cancer-specific mortality.

Design

Overview of reviews.

Setting

Community setting.

Participants

The unit of analysis is PMASRs. A total of 42 PMASRs was included in this overview of reviews.

Interventions/exposures

Any dairy product consumption (eg, milk, yogurt, etc).

Primary and secondary outcomes measures

Primary outcome measure is development of any type of cancer. Secondary outcome measures are all-cause mortality and cancer-specific mortality.

Results

From 9693 citations identified, we included 42 PMASRs (52 study reports) published between 1991 and 2017. Thirty-one (74%) of these was pooled analyses/meta analyses, and only 11 (26%) were systematic reviews and meta-analyses. There was a wide variability in the type of study designs included within the other PMASRs, thus contributing to variable and, in instances, divergent estimates of cancer risk for several cancer subtypes. For example, only one systematic review and meta-analysis exclusively included prospective study designs. Most PMASRs were of low to moderate quality based on the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scores. The median AMSTAR score was 5 (IQR 2–7). Our overview identified conflicting evidence from PMASRs on association between dairy consumption and incident cancers or mortality. Heterogeneity in summary estimates reflected the inclusion of variable study designs and overall low methodological quality of individual PMASRs.

Conclusions

The association between dairy consumption and cancer risk has been explored in PMASRs with a variety of study designs and of low to moderate quality. To fully characterise valid associations between dairy consumption and risk of cancer and/or mortality rigorously conducted, PMASRs including only high-quality prospective study designs are required.

Trial registration number

CRD42017078463.

http://bit.ly/2Rhw8xC

The Uznadze illusion reveals similar effects of relative size on perception and action

Abstract

Milner and Goodale (the visual brain in action, Oxford University Press Inc., Oxford, 1995) proposed a functional dissociation between vision-for-action and vision-for-perception (i.e., the "two-visual system hypothesis", TVSH). Supporting the TVSH, it has been claimed that visual illusions affect perception but not actions. However, at least for the Ebbinghaus illusion, numerous studies have revealed consistent illusion effects on grasping. Thus, whether illusions affect actions remains controversial. To further investigate the dissociation predicted by the TVSH, we used a visual version of the Uznadze illusion (the same stimulus will feel smaller after feeling a larger stimulus and larger after feeling a smaller stimulus). Based on kinematic recordings of finger aperture in a motor (precision grip) and a perceptual task (manual estimation), we report two main findings. First, both action and perception are strongly affected by the Uznadze illusion. Second, the illusion decreases similarly in both tasks when inducing-induced pairs had different shape and color, in comparison to the equivalent condition where these features are the same. These results are inconsistent with a perception–action dissociation as predicted by the TVSH and suggest that, at least in the present conditions, vision-for-perception and vision-for-action are similarly affected by contextual cues.

http://bit.ly/2TcZD5G

Spatial and feature-based attention to expressive faces

Abstract

Facial emotion is an important cue for deciding whether an individual is potentially helpful or harmful. However, facial expressions are inherently ambiguous and observers typically employ other cues to categorize emotion expressed on the face, such as race, sex, and context. Here, we explored the effect of increasing or reducing different types of uncertainty associated with a facial expression that is to be categorized. On each trial, observers responded according to the emotion and location of a peripherally presented face stimulus and were provided with either: (1) no information about the upcoming face; (2) its location; (3) its expressed emotion; or (4) both its location and emotion. While cueing emotion or location resulted in faster response times than cueing unpredictive information, cueing face emotion alone resulted in faster responses than cueing face location alone. Moreover, cueing both stimulus location and emotion resulted in a superadditive reduction of response times compared with cueing location or emotion alone, suggesting that feature-based attention to emotion and spatially selective attention interact to facilitate perception of face stimuli. While categorization of facial expressions was significantly affected by stable identity cues (sex and race) in the face, we found that these interactions were eliminated when uncertainty about facial expression, but not spatial uncertainty about stimulus location, was reduced by predictive cueing. This demonstrates that feature-based attention to facial expression greatly attenuates the need to rely on stable identity cues to interpret facial emotion.

http://bit.ly/2B2UbLG

SETD3 is a positive regulator of DNA-damage-induced apoptosis

SETD3 is a positive regulator of DNA-damage-induced apoptosis

SETD3 is a positive regulator of DNA-damage-induced apoptosis, Published online: 25 January 2019; doi:10.1038/s41419-019-1328-4

SETD3 is a positive regulator of DNA-damage-induced apoptosis

https://go.nature.com/2G06fk8

LINC01939 inhibits the metastasis of gastric cancer by acting as a molecular sponge of miR-17-5p to regulate EGR2 expression

LINC01939 inhibits the metastasis of gastric cancer by acting as a molecular sponge of miR-17-5p to regulate EGR2 expression

LINC01939 inhibits the metastasis of gastric cancer by acting as a molecular sponge of miR-17-5p to regulate EGR2 expression, Published online: 25 January 2019; doi:10.1038/s41419-019-1344-4

LINC01939 inhibits the metastasis of gastric cancer by acting as a molecular sponge of miR-17-5p to regulate EGR2 expression

https://go.nature.com/2FP21N4

Retraction Note: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

Retraction Note: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

Retraction Note: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma, Published online: 25 January 2019; doi:10.1038/s41419-019-1300-3

Retraction Note: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

https://go.nature.com/2G0VzBS

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1, Published online: 25 January 2019; doi:10.1038/s41419-019-1341-7

The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

https://go.nature.com/2FN7oMx

KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis

KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis

KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis, Published online: 25 January 2019; doi:10.1038/s41419-019-1305-y

KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis

https://go.nature.com/2G0VyOk

The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function

The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function

The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function, Published online: 25 January 2019; doi:10.1038/s41419-019-1349-z

The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function

https://go.nature.com/2FPxIWd

Histone methyltransferase NSD2 regulates apoptosis and chemosensitivity in osteosarcoma

Histone methyltransferase NSD2 regulates apoptosis and chemosensitivity in osteosarcoma

Histone methyltransferase NSD2 regulates apoptosis and chemosensitivity in osteosarcoma, Published online: 25 January 2019; doi:10.1038/s41419-019-1347-1

Histone methyltransferase NSD2 regulates apoptosis and chemosensitivity in osteosarcoma

https://go.nature.com/2FN7gN3

Delayed Treatment (≥5 Days) by Flow Diversion of Ruptured Blister-Like Cerebral Aneurysms

Abstract

Background and Purpose

Ruptured blister-like aneurysms (BLAs) are challenging lesions to treat, without any consensus on their management. Few studies have evaluated the safety and effectiveness of flow diverter stents (FDS) for this indication, with promising results. The goal was to evaluate the safety and effectiveness of a delayed (≥5 days) flow diversion strategy for the treatment of ruptured intracranial BLAs.

Material and Methods

A monocentric retrospective analysis of a prospectively collected database of intracranial aneurysms was performed. Eight consecutive patients with 9 ruptured intracranial BLAs from November 2010 to June 2018 were included in the study. The BLA treatment with FDS was delayed from the rupture (minimum rupture to treatment delay = 5 days, mean = 16.9 ± 9.2 days). Procedure-related complications were systematically recorded. Rebleeding occurrences were systematically assessed. Long-term clinical and angiographic follow-ups were recorded.

Results

No procedure-related death was recorded. Neither early nor late rebleeding was observed and one (12.5%) major procedure-related complication occurred (ischemic stroke). Most of the patients (5/8; 62.5%) had an mRS <2 at discharge. The immediate periprocedural control angiogram showed a complete exclusion of the aneurysm in one patient (12.5%) but at follow-up (mean delay = 19.8 months) all patients had a complete aneurysm occlusion. All patients had a long-term mRS <2.

Conclusion

This case series suggests that a delayed treatment (≥5 days after the hemorrhagic event) of ruptured BLAs with FDS is feasible, and may be safe and effective in terms of rebleeding prevention and long-term angiographic outcome.

http://bit.ly/2DwWuYP

Methods for monitoring the progression of cell death, cell disassembly and cell clearance

Abstract

Cell death through apoptosis, necrosis, necroptosis and pyroptosis, as well as the clearance of dead cells are crucial biological processes in the human body. Likewise, disassembly of dying cells during apoptosis to generate cell fragments known as apoptotic bodies may also play important roles in regulating cell clearance and intercellular communication. Recent advances in the field have led to the development of new experimental systems to identify cells at different stages of cell death, measure the levels of apoptotic cell disassembly, and monitor the cell clearance process using a range of in vitro, ex vivo and in vivo models. In this article, we will provide a comprehensive review of the methods for monitoring the progression of cell death, cell disassembly and cell clearance.

http://bit.ly/2FOQSvC

Characteristics of single pivotal trials supporting regulatory approvals of novel non‐orphan, non‐oncology drugs in EU and US from 2012 to 2016

Abstract

For regulatory approval of a new medicine, the gold standard for demonstration of efficacy has traditionally been a minimum of two positive, adequate, and well‐controlled clinical trials. Nevertheless, drugs to treat cancer and rare diseases are usually approved based on a single and often uncontrolled pivotal trial. In contrast, little is known about single pivotal trial approvals for non‐orphan, non‐oncology drugs. Between 2012 and 2016, 23 novel therapeutic drugs were approved by the FDA and/or the EMA for 27 non‐orphan, non‐oncology indications each based on a single pivotal trial. While there was considerable variation in the nature and strength of the efficacy evidence supporting these drug approvals, the majority (85%) of the pivotal trials were randomized and controlled. For all superiority trials, the primary outcome was met with a statistical significance of p ≤ 0.005. Most approvals were supported by additional efficacy data from non‐pivotal studies.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RRJO7V

Does in vitro CYP down‐regulation translate to in vivo drug‐drug interactions? Preclinical and clinical studies with 13‐cis‐retinoic acid

Abstract

All‐trans‐retinoic acid (atRA) down‐regulates CYP2D6 in several model systems. The aim of this study was to determine whether all active retinoids downregulate CYP2D6 and whether in vitro downregulation translates to in vivo drug‐drug interactions (DDI). atRA, 13cisRA, and 4‐oxo‐13cisRA all decreased CYP2D6 mRNA in human hepatocytes in a concentration‐dependent manner. The in vitro data predicted ~50% decrease in CYP2D6 activity in humans after dosing with 13cisRA. However, the geometric mean AUC ratio for dextromethorphan between treatment and control was 0.822 indicating a weak induction of dextromethorphan clearance following 13cisRA treatment. Similarly, in mice treatment with 4‐oxo‐13cisRA induced mRNA expression of multiple mouse Cyp2d genes. In comparison, a weak induction of CYP3A4 in human hepatocytes translated to a weak in vivo induction of CYP3A4. This data suggests that in vitro CYP down‐regulation may not translate to in vivo DDIs, and better understanding of the mechanisms of CYP down‐regulation is needed.

This article is protected by copyright. All rights reserved.

http://bit.ly/2CHl3kh

Predicting efavirenz concentrations in the brain tissue of HIV‐infected individuals and exploring their relationship to neurocognitive impairment

Abstract

Sparse data exist on the penetration of antiretrovirals into brain tissue. In this work we present a framework to use efavirenz pharmacokinetic (PK) data in plasma, cerebrospinal fluid (CSF) and brain tissue of eight rhesus macaques to predict brain tissue concentrations in HIV‐infected individuals. We then perform exposure‐response analysis with the model‐predicted efavirenz area under the concentration‐time curve (AUC) and neurocognitive scores collected from a group of 24 HIV‐infected participants. Adult rhesus macaques were dosed daily with 200 mg efavirenz (as part of a four‐drug regimen) for ten days. Plasma was collected at eight time points over ten days and at necropsy, while CSF and brain tissue were collected at necropsy. In the clinical study, data were obtained from one paired plasma and CSF sample of participants prescribed efavirenz, and neuropsychological test evaluations were administered across 15 domains. PK modeling was performed using ADAPT v5.0 with the iterative two stage estimation method. An 8‐compartment model best described efavirenz distribution across the plasma, CSF and brain tissue of rhesus macaques and humans. Model predicted median brain tissue concentrations in humans were 31 ng/ml and 8,000 ng/ml respectively. Model‐predicted brain tissue AUC was highly correlated with plasma AUC (rho=0.99, p<0.001) but not CSF AUC (rho=0.34, p=0.1) and did not show any relationship with neurocognitive scores (rho<0.05, p>0.05). This analysis provides an approach to estimate PK the brain tissue in order to perform pharmacokinetic‐pharmacodynamic analyses at the target site.

This article is protected by copyright. All rights reserved.

http://bit.ly/2COpDgS

Health professionals’ perceptions of a midwifery model of woman-centred care implemented on a hospital labour ward

Publication date: Available online 25 January 2019

Source: Women and Birth

Author(s): Ingela Lundgren, Marie Berg, Christina Nilsson, Olof Asta Olafsdottir

Abstract

Background

Theoretical models as a basis for midwives' care have been developed over recent decades. Although there are similarities between these models, their usefulness in practice needs to be researched in specific cultural contexts.

Aim

To explore whether, when adopted by midwives on labour wards, a midwifery model of woman-centred care (MiMo) was useful in practice from the viewpoint of a variety of health professionals.

Methods

Data were collected from a variety of health professionals before and after an intervention of implementating MiMo at a hospital-based labour ward in Sweden, using nine focus group interviews with a total of 43 participants: midwives (n = 16), obstetricians (n = 8), assistant nurses (n = 11) and managers (n = 8). The text from interviews was analysed using content analysis.

Findings

From expressing no explicit need of a midwifery model of woman-centred care before the intervention, there was a shift in midwives, obstetricians and managers perceptions towards identifying advantages of using the MiMo as it gives words to woman-centred midwifery care. Such shift in perception was not found among the assistant nurses.

Discussion

Clarification of the various roles of health professionals is needed to develop the model. Heavy workloads and stress were barriers to implementing the model. Thus, more support is needed from organisational management.

Conclusions

The model was useful for all professional groups, except for assistant nurses. Further studies are needed in order to clarify the various professional roles and interdisciplinary collaborations in making the MiMo more useful in daily maternity care.

http://bit.ly/2sM3zib

Two-stage CNNs for computerized BI-RADS categorization in breast ultrasound images

Quantizing the Breast Imaging Reporting and Data System (BI-RADS) criteria into different categories with the single ultrasound modality has always been a challenge. To achieve this, we proposed a two-stage gr...

http://bit.ly/2UmSzUn

A 3D Macroporous Alginate Graphene Scaffold with an Extremely Slow Release of a Loaded Cargo for In Situ Long‐Term Activation of Dendritic Cells

A reduced‐graphene‐oxide containing 3D macroporous alginate scaffold with high loading, a slow release, and good mechanical properties is synthesized for long‐term in situ modulation of dendritic cells. After mice are vaccinated with the scaffold loaded with ovalbumin, granulocyte‐macrophage colony‐stimulating factor, and CpG, this scaffold suppresses tumor growth by significant activation of dendritic cells and cytotoxic T cells for a long time.

Abstract

Ex vivo manipulation of autologous antigen‐presenting cells and their subsequent infusion back into the patient to dictate immune response is one of the promising strategies in cancer immunotherapy. Here, a 3D alginate scaffold embedded with reduced graphene oxide (rGO) is proposed as a vaccine delivery platform for in situ long‐term activation of antigen‐presenting dendritic cells (DCs). High surface area and hydrophobic surface of the rGO component of the scaffold provide high loading and a very slow release of a loaded antigen, danger signal, and/or chemoattractant from the scaffold. This approach offers long‐term bioavailability of the loaded cargo inside the scaffold for manipulation of recruited DCs. After mice are subcutaneously vaccinated with the macroporous alginate graphene scaffold (MAGS) loaded with ovalbumin (OVA) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), this scaffold recruits a significantly high number of DCs, which present antigenic information via major histocompatibility complex class I for a long period. Furthermore, an MAGS loaded with OVA, GM‐CSF, and CpG promotes production of activated T cells and memory T cells, leading to the suppression of OVA‐expressing B16 melanoma tumor growth in a prophylactic vaccination experiment. This study indicates that an MAGS can be a strong candidate for long‐term programming and modulating immune cells in vivo.

http://bit.ly/2TeyuiT

Nanomedicine, Biofabrication, Tissue Engineering and Much More – Advanced Healthcare Materials Welcomes 2019

http://bit.ly/2Tbm7E0

Deciphering myeloid-derived suppressor cells: isolation and markers in humans, mice and non-human primates

Abstract

In cancer, infection and inflammation, the immune system's function can be dysregulated. Instead of fighting disease, immune cells may increase pathology and suppress host-protective immune responses. Myeloid cells show high plasticity and adapt to changing conditions and pathological challenges. Despite their relevance in disease pathophysiology, the identity, heterogeneity and biology of myeloid cells is still poorly understood. We will focus on phenotypical and functional markers of one of the key myeloid regulatory subtypes, the myeloid derived suppressor cells (MDSC), in humans, mice and non-human primates. Technical issues regarding the isolation of the cells from tissues and blood, timing and sample handling of MDSC will be detailed. Localization of MDSC in a tissue context is of crucial importance and immunohistochemistry approaches for this purpose are discussed. A minimal antibody panel for MDSC research is provided as part of the Mye-EUNITER COST action. Strategies for the identification of additional markers applying state of the art technologies such as mass cytometry will be highlighted. Such marker sets can be used to study MDSC phenotypes across tissues, diseases as well as species and will be crucial to accelerate MDSC research in health and disease.

http://bit.ly/2UfOhOw

A within‐subject clinical trial on the conversion of mandibular 2‐implant to 3‐implant overdenture: Patient‐centered outcomes and willingness to pay

Abstract

Objectives

To examine the impact of adding a third midline implant with stud attachment to a mandibular 2‐implant overdenture on patient‐oriented outcomes.

Methods

In this pre–post design clinical trial, following the standard procedures, mandibular 2‐implant overdentures of 17 edentulous individuals (61.9 ± 6.6 years) were converted to 3‐implant overdentures by adding a stud attachment to an unloaded midline implant. Patient‐oriented outcomes included patient expectations and satisfaction with implant overdenture as well as willingness to pay the cost of conversion. Data were collected at baseline and at the 6‐week follow‐up using visual analog and binary scales as well as open‐ended questions. Statistical analysis included descriptive statistics, Spearman's correlation, Fisher exact test, Mann‐Whitney U, and the exact sign test.

Results

After connecting the third midline implant to the mandibular 2‐implant overdenture, there was a statistically significant decrease in the anteroposterior movement (p = 0.005) as evaluated by clinicians. Moreover, study participants reported an increase in perceived stability of the overdenture (95% CI 0.68‐1.00, p = 0.002), and in their ability to speak (95% CI 0.63‐1.00, p = 0.008). The addition of a third implant met the expectations of 94% of patients in regard to lower denture stability, 100% for retention, and 82.4% for comfort. The mandibular 3‐implant overdenture increased patient general satisfaction over a short period of time, but this improvement was not statistically significant. About 80% of patients would recommend this type of prosthesis to their peers but only 47% of them would agree to pay a large increase in the cost of treatment compared to a 2‐implant overdenture.

Conclusions

The addition of a midline third implant to an existing mandibular 2‐ implant overdenture resulted in several improved patient reported outcomes.

This article is protected by copyright. All rights reserved.

http://bit.ly/2WhTR4M

Optimization on production of konjac oligo‐glucomannan and their effect on the gut microbiota

The results showed that low‐molecular weight KOG (LKOG) from purification step with concentration of 9.54 mg/ml and a prebiotic index (PI) of 0.76 was successfully produced. LKOG can enhance the production of butyric acid in the colon with the highest concentration (8.24 mM) found at 72 hr fermentation.

Abstract

Konjac glucomannan (KGM) is a polysaccharide extracted from Amorphophallus konjac, and its degradation product is konjac oligo‐glucomannan (KOG). The aim of this study was to produce KOG from KGM and to evaluate its effect on the gut microbiota in fecal batch culture. KOG was produced by enzymatic hydrolysis using β‐mannanase. The optimum conditions were as follows: reaction temperature of 48°C, reaction time of 4 hr, pH of 5.5 and E/S of 0.05% followed by purification step using 3,000 NMWC ultrafiltration (UF) membrane pore size. The effect of KOG on changes in human fecal bacterial populations and short‐chain fatty acids (SCFAs) production was evaluated. The results showed that low‐molecular weight KOG (LKOG) from purification step with concentration of 9.54 mg/ml, and a prebiotic index (PI) of 0.76 was successfully produced. LKOG can enhance the production of butyric acid in the colon with the highest concentration (8.24 mM) found at 72 hr fermentation.

http://bit.ly/2CJ3DE4

Effect of storage time on antioxidant activity and inhibition on α‐Amylase and α‐Glucosidase of white tea

Aging time could enhance the flavor of white tea by inducing alteration in the chemicals but not the bioactivities.

Abstract

White tea is considered as a special kind of tea not only for its simplest process, but also for its endurable storage. However, little studies have been done about the changes of white tea with increasing aging time, including its composition and health‐imparting effects. In the present work, white tea aged 1 year (WT‐1), 3 years (WT‐3), and 5 years (WT‐5) were collected. Their major chemical compounds, antioxidant activities, and inhibitory effects on α‐Amylase and α‐Glucosidase were evaluated. Results showed that white tea of different storage time showed good antioxidant activity in DPPH, ABTS, and FRAP assay, which decreases with the prolongation of storage time. The inhibitory effects on α‐Amylase and α‐Glucosidase which are key enzymes related to type II diabetes in vitro, are also observed in the similar trend. Meanwhile, prolongation of storage time decreased the content of polyphenols, the main bioactive compounds in tea, which may lead to decrease in the activities investigated.

http://bit.ly/2RQvts6

Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations

We performed a systematic review of 31 studies regarding the effects of bergamot derivatives (extract, juice, essential oil, polyphenolic fraction) on lipid profile, glycemic status, skin, bone, and mental health. The results of this our support the efficacy of Bergamot as a modulator of lipid profile. Compared to placebo, bergamot aromatherapy does not appear to be useful in order to improve mental health. As regards the other aspects, the data are not sufficient to express a definitive indication.

Abstract

We summarize the effects of bergamot (extract, juice, essential oil, and polyphenolic fraction) on cardiovascular, bone, inflammatory, skin diseases, mood alteration, anxiety, pain, and stress. This review included a total of 31 studies (20 studies on humans with 1709 subjects and 11 in animals (rats and mice)). In humans, bergamot‐derived extract (BE) exerts positive effects on hyperlipidemia with an oral dose from 150 mg to 1000 mg/day of flavonoids administered from 30 to 180 days, demonstrating an effect on body weight and in modulating total cholesterol, triglycerides, LDL, and HDL. Studies in animals confirm promising data on glucose control (500/1000 mg/day of BE with a treatment lasting 30 days) are available in rats. In animals models, bergamot essential oil (BEO, 10 mg/kg or 20 mg/kg daily for 20 weeks) increases bone volume, decreases psoriatic plaques, increases skin collagen content, and promotes hair growth. Bergamot juice (20 mg/kg) is promising in terms of pro‐inflammatory cytokine reduction. In humans, aromatherapy (from 15 to 30 min) does not appear to be useful in order to reduce stress, anxiety, and nausea, compared to placebo. Compared to baseline, BE topical application and BEO aromatherapy reduce blood diastolic and systolic pressure and could have a significant effect on improving mental conditions.

http://bit.ly/2CJWD9M

Response surface optimization for recovery of polyphenols and carotenoids from leaves of Centella asiatica using an ethanol‐based solvent system

Centella asiatica is herb, a leafy vegetables in tropical country and posses many health benefits. Rich in phenolics and carotenoids. Extraction is important for possible application in functional foods and nutraceutical industries.

Abstract

Response surface methodology has been used to optimize the extraction conditions for total phenolics and carotenoids from leaves of Centella asiatica. Solvent concentration (30%–100%), extraction temperature (30–60°C), and extraction time (30–90 min) were used as the independent variables. A second‐order polynomial model produced a satisfactory fitting of the experimental data with regard to total phenolics (R ² = 84.75%, p < 0.004) and carotenoid (R ² = 78.74, p < 0.019) contents. The optimum extraction conditions of ethanol concentration, extraction temperature, and extraction time for phenolics were 6.1%, 70.2°C, and 110.5 min and for carotenoids, the optimum parameters were 100%, 70.2°C, and 110.5 min, respectively. The optimal predicted contents for total phenolics (9.03 mg Gallic Acid Equivalent (GAE)/g DW) and carotenoid (8.74 mg/g DW) values in the extracts were agreed with the experimental values obtained with optimum extraction conditions for each response, and also they possess significantly higher total antioxidant capacity.

http://bit.ly/2RRkcb6

Effect of clove powder on quality characteristics and shelf life of kimchi paste

Effects of clove powder on kimchi paste quality were investigated. Clove powder delayed changes in pH, titratable acidity, and reducing sugar content and inhibited total aerobic and lactic acid bacterial growth. Treatment with clove powder can potentially extend kimchi paste shelf life.

Abstract

Clove has been shown to extend the shelf life of various foods. This study investigated whether it can prolong the shelf life of kimchi paste. Clove powder at concentrations of 0%, 0.5%, 1%, 1.5%, and 2% was added to kimchi paste, which was then sealed and stored at 10°C for 20 days. Changes in microbial counts, gas composition, sugar and organic acid contents, pH, titratable acidity, and reducing sugar content were evaluated. Adding clove powder inhibited the growth of total aerobic and lactic acid bacteria and delayed changes in O₂ and CO₂ concentration and sugar and organic acid contents. It also slowed the decrease in pH, increase in titratable acidity, and changes in reducing sugar content. These results indicate that clove powder effectively prolongs the quality attributes and thus extends the shelf life of kimchi paste.

http://bit.ly/2CInG5x

Recovery of high value‐added protein from enzyme‐assisted aqueous extraction (EAE) of soybeans by dead‐end ultrafiltration

Ultrafiltration can be applicable to recover high value‐added protein from enzyme‐assisted aqueous extraction of soybeans and remove undesired components from the resulting protein products. The recovered protein had comparable amino acid profile to soybean protein concentrate, while consisted of significantly decreased levels of trypsin inhibitors and phytate (p < 0.05), indicating high quality of the recovered protein.

Abstract

The skim fraction (SF) obtained from enzyme‐assisted aqueous extraction (EAE) of soybeans is a by‐product with high protein content of up to 60.67%. As such, it is of great interest to develop an efficient method to recover protein from this fraction. In this study, the potential of dead‐end ultrafiltration (UF) in recovering skim protein extracted with different proteases was evaluated. Two polyethersulfone (PES) membranes with molecular weight cutoffs (MWCO) of 3 kDa and 5 kDa were utilized. Results revealed that the membrane with the MWCO of 5 kDa exhibited better filtration efficiency, since higher permeate flux values and lower impurity rejections were observed. Compared with Flavourzyme and Protex 7L, Alcalase 2.4L and Protex 6L exhibited stronger hydrolyzing ability, resulting in higher filtration fluxes but lower protein rejection coefficients. The recovered protein showed comparable amino acid profile to SPC, while with significantly reduced levels of trypsin inhibitors and phytate (p < 0.05), indicating high quality of the recovered protein. Overall, UF can be applicable to recover high value‐added protein from EAE of soybeans and remove undesired components from the resulting protein products.

http://bit.ly/2RNiqYx