A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

Abstract: Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.

Mao|Jianxin|J|
Huang|Shichao|S|
Liu|Shangfeng|S|
Feng|Xiao-Lin|XL|
Yu|Miao|M|
Liu|Junjun|J|
Sun|Yi Eve|YE|
Chen|Guoliang|G|
Yu|Yang|Y|
Zhao|Jian|J|
Pei|Gang|G|

D048049:Extracellular Signal-Regulated MAP Kinases

neurodegeneration
asarone
ERK cascade
neural progenitor cell proliferation
traditional herb medicines


Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats.

Abstract:
OBJECTIVE
To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways.

METHODS
Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK].

RESULTS
EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist.

CONCLUSIONS
EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

Chen|Xin-Yu|XY| Yang|Lu-Ping|LP| Zheng|Ya-Ling|YL| Li|Yu-Xi|YX| Zhong|Dong-Ling|DL| Jin|Rong-Jiang|RJ| Li|Juan|J|

electroacupuncture
vascular smooth muscle cells
MAPK signaling pathway
hypertension
PI3K/Akt signaling pathway


Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19.

Abstract:
OBJECTIVES
To assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events.

METHOD
Retrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes.

RESULTS
The active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47-70) in the active group and 65 (47-77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation.

CONCLUSIONS
Patients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

Lamback|Elisa Baranski|EB|
Oliveira|Monica Amorim de|MA|
Haddad|Andrea Ferreira|AF|
Vieira|André Filipe Marcondes|AFM|
Neto|Armando Leão Ferreira|ALF|
Maia|Taciana da Silva|TDS|
Chrisman|Juliana de Rezende|JR|
Spineti|Pedro Pimenta de Mello|PPM|
Mattos|Marco Antonio de|MA|
Costa|Eduardo|E|

Severe acute respiratory syndrome coronavirus 2


A systematic review of cohort studies of the quality of life in HIV/AIDS patients after antiretroviral therapy.

Abstract: The aim of this paper was to review cohort studies that analyze changes in the quality of life of people living with HIV/AIDS. We searched the PubMed and EmBase databases from inception to December 2012 for primary cohort studies of the quality of life of people living with HIV/AIDS after combination antiretroviral therapy (cART). Two independent reviewers screened and selected published studies of quality of life that had been followed up for more than 12 weeks after the beginning of cART. Data from the papers were analyzed to identify common characteristics of the effects of cART on the quality of life of HIV/AIDS patients. Eight cohort studies were found: only four were assessed as high quality and four were assessed as moderate quality. None of the studies described patient selection. Six studies followed the patients for one year or more, and the other studies for less than 6 months. Seven studies reported quality of life had been improved after initiation of cART, and one study reported no change. Previous research suggested that cART improved the quality of life of AIDS patients for a limited time, so further research for longer periods is needed to confirm this outcome.

Jin|Yantao|Y| Liu|Zhibin|Z| Wang|Xin|X| Liu|Huixin|H| Ding|Guowei|G| Su|Yingying|Y| Zhu|Lin|L| Wang|Ning|N|

combination combined antiretroviral therapy


An investigation into the nature and potential of in-situ surfactants for low energy miniemulsification.

Abstract:
HYPOTHESIS
It has been reported that surfactants generated in-situ are more efficient than their preformed analogues in preparation of miniemulsions for application in miniemulsion polymerization but conflicting experimental evidence exists over their use. Herein, the potential of preparing miniemulsions using in-situ generated surfactants is evaluated using KOH/oleic acid as a model system.

EXPERIMENTS
The kinetics of miniemulsification using either preformed or in-situ generated potassium oleate were evaluated by monitoring the evolution of droplet size, pH and conductivity during miniemulsification using sonication. Subsequently, the kinetics of surfactant adsorption to the monomer/water interface were studied using dynamic interfacial tension measurements. Finally, the ability of in-situ generated potassium oleate to produce miniemulsions under low shear was evaluated under a range of conditions.

FINDINGS
No difference in the evolution of droplet size, pH or conductivity was observed between the two surfactant systems when sonication was applied. Dynamic interfacial tension measurements showed that using in-situ generated potassium oleate, interfacial tension is significantly lower initially, but at long times the two surfactant systems reach similar values. Low shear emulsification by in-situ generated potassium oleate resulted in a bimodal droplet distribution. Only at very low oil contents with high surfactant concentration is the number of nanometer sized droplets large enough to account for a miniemulsion polymerization mechanism.

Ballard|Nicholas|N|
Salsamendi|Maitane|M|
Carretero|Paula|P|
Asua|José M|JM|

Surfactant
Miniemulsion
Interfacial reaction
Spontaneous emulsification


Exceptional adsorption of arsenic by zirconium metal-organic frameworks: Engineering exploration and mechanism insight.

Abstract: Highly stable zirconium metal-organic frameworks (UiO-66 and UiO-66(NH2)) had been synthesized and investigated to remove arsenic (As) from contaminated water. The As(III, V) removal performance was studied by batch experiments and adsorption kinetics. At the pH of 9.2 ± 0.1, UiO-66 had exceptional removal capacities of 205.0 and 68.21 mg/g for As(III) and As(V), respectively. The As removal processes were exothermic and verified as chemisorption reactions according to the calculation of Gibbs free energy and Dubinin-Radushkevich (D-R) isotherm model. Fixed-bed reactor removal experiments indicated that the number of effective treatment volumes reached 2270 and 1775 BVs for As(III) and As(V), respectively, until the most stringent As regulation level of 10 μg/L (initial As concentration at 100 μg/L) was reached. FTIR and XPS study indicated that ZrO bonds of zirconium metal-organic frameworks played a vital role in As adsorption. XANES revealed the As adsorption on UiO-66 without the change of oxidation state. More intriguingly, EXAFS spectra demonstrated the main formation of bidentate mononuclear complexes for As(V), and bidentate binuclear complexes for As(III) on the hexanuclear Zr cluster of UiO-66. The advantages of nontoxicity, high stability, high As adsorption capacity, low-cost and easy availability confirm the highly promising application of zirconium metal-organic frameworks in As-contaminated wastewater remediation.

He|Xingyu|X| Deng|Fang|F| Shen|Tingting|T| Yang|Liming|L| Chen|Dezhi|D| Luo|Jianfeng|J| Luo|Xubiao|X| Min|Xiaoye|X| Wang|Fang|F|

Adsorption
Arsenic
Metal-organic frameworks
Water remediation


Acute Kidney Function Declines in the Context of Decongestion in Acute Decompensated Heart Failure.

Abstract:
OBJECTIVES
This study aimed to examine whether incorporation of a comprehensive set of measures of decongestion modifies the association of acute declines in kidney function with outcomes.

BACKGROUND
In-hospital acute declines in kidney function occur in approximately 20% to 30% of patients admitted with acute decompensated heart failure (ADHF) and may be associated with adverse outcomes.

METHODS
Using data from EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan), we used multivariable Cox regression models to evaluate the association between in-hospital changes in estimated glomerular filtration rate (eGFR) with death and a composite outcome of cardiovascular death and hospitalization for heart failure. We evaluated eGFR declines within the context of changes in markers of volume overload including b-type natriuretic peptide (BNP), N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and weight, as well as changes in measures of hemoconcentration including hematocrit, albumin, and total protein.

RESULTS
Among 3,715 patients over a median follow-up of 9.9 months, every 30% decline in eGFR was associated with higher risk of both death (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.07 to 1.31) and the composite outcome (HR: 1.09; 95% CI: 1.01 to 1.18) in adjusted models. The acute decline in eGFR was no longer associated with higher risk of either outcome as long as there was evidence of decongestion, either by declines in BNP, NT-proBNP, or weight or by increases in hematocrit, albumin or total protein. Interaction testing between decline in eGFR and changes in hematocrit, albumin, and total protein was statistically significant (p interaction of <0.01 for death and p interaction of ≤0.01 for composite for all 3 biomarkers). Interaction between change in eGFR and changes in BNP (p interaction = 0.07 for death; p interaction = 0.08 for composite), NT-proBNP (p interaction = 0.15 for death; p interaction = 0.18 for composite) and weight (p interaction = 0.13 for death; p interaction = 0.19 for composite) did not meet statistical significance.

CONCLUSIONS
Overall, acute declines in eGFR are associated with adverse outcomes, with evidence of modification by changes in markers of decongestion, suggesting that they are no longer associated with adverse outcomes if these markers are concomitantly improving.

McCallum|Wendy|W|
Tighiouart|Hocine|H|
Testani|Jeffrey M|JM|
Griffin|Matthew|M|
Konstam|Marvin A|MA|
Udelson|James E|JE|
Sarnak|Mark J|MJ|

D065092:Antidiuretic Hormone Receptor Antagonists

decongestion
hemoconcentration
cardiorenal
worsening renal function


Interstitial lung abnormalities and pulmonary fibrosis in COVID-19 patients: a short-term follow-up case series.

Abstract: Fibrotic lung changes are well-known complications of SARS, MERS, and ARDS from other causes and are anticipated in recovered COVID patients. However, there is limited data so far showing a temporal relationship between lung changes on imaging in the acute phase and follow-up imaging after recovery from the infection. We present 12 patients who demonstrate the development of interstitial lung changes and pulmonary fibrosis in the same distribution and pattern as the acute phase findings, up to 6 months after the acute infection, demonstrating a direct relationship between these changes and COVID-19 pneumonia.

Fibrosis
COVID-19
Recovered
HRCT
Temporal imaging


Processing of Prosody and Semantics in Sepedi and L2 English.

Abstract: A phoneme-detection task shows that listeners of Sepedi use semantic information in processing but not prosody (Experiment 1). Sepedi is a language with no grammaticalised prosodic expression of focus. Sepedi listeners detected phoneme targets faster when the phoneme-bearing words were focussed (as opposed to unfocussed) but not when occurring in a context conducive to prosodic emphasis (as opposed to non-conducive). Experiment 2 tested the role of semantic focus and prosody in processing by Sepedi L1/English L2 listeners (English being a language with systematic focus-to-accent mapping). Non-native listeners detected phoneme-bearing words faster in focussed condition (as opposed to unfocussed) and in accented condition (as opposed to deaccented). The results suggest that the L2 prosodic structure is exploited by Black South African English listeners even if this feature is not present in their L1. Our experiments replicate the pattern of results found in Akker and Cutler's (Biling Lang Cogn 6:81-96, 2003) experiment for Dutch L1/ English L2 listeners, even with listeners whose L1 does not use prosody the way English does.

Prosodic emphasis
Focus-to-accent mapping
Non-native listening
Bantu (Sepedi)
L1/L2 processing
Prosodic processing
Semantic processing


Current Status on the Functional Characterization of Chemosensory Receptors of Cydia pomonella (Lepidoptera: Tortricidae).

Abstract: Cydia pomonella (Lepidoptera: Tortricidae) is a major pest of apple, pear and walnuts. For its control, alternative strategies targeting the olfactory system, like mating disruption, have been combined with insecticide applications. The efficacy of these strategies headed the direction of efforts for the functional characterization of codling moth chemosensory receptors to implement further control methods based on chemical sensing. With the advent of transcriptomic analysis, partial and full-length coding sequences of chemosensory receptors have been identified in antennal transcriptomes of C. pomonella. Extension of partial coding sequences to full-length by polymerase chain reaction (PCR)-based techniques and heterologous expression in empty neurons of Drosophila melanogaster and in Human Embryonic Kidney cells allowed functional studies to investigate receptor activation and ligand binding modalities (deorphanization). Among different classes of antennal receptors, several odorant receptors of C. pomonella (CpomORs) have been characterized as binding kairomones (CpomOR3), pheromones (CpomOR6a) and compounds emitted by non-host plants (CpomOR19). Physiological and pharmacological studies of these receptors demonstrated their ionotropic properties, by forming functional channels with the co-receptor subunit of CpomOrco. Further investigations reported a novel insect transient receptor potential (TRPA5) expressed in antennae and other body parts of C. pomonella as a complex pattern of ribonucleic acid (RNA) splice-forms, with a possible involvement in sensing chemical stimuli and temperature. Investigation on chemosensory mechanisms in the codling moth has practical outcomes for the development of control strategies and it inspired novel trends to control this pest by integrating alternative methods to interfere with insect chemosensory communication.

functional characterization
chemosensory receptors
Cydia pomonella
Drosophila empty neuron system
human embryonic kidney (HEK293T) cells


The influence of weather on avian spring migration phenology: What, where and when?

Abstract: Over the past decades, spring arrival and passage of most short- and medium-distance migrating birds in the Northern Hemisphere have advanced. Changes in spring temperature at the passage or arrival area have been most frequently shown to be related to these changes in spring migration phenology. In most studies, preliminary assumptions are made on both the spatial location and the specific time frame of the weather influencing spring migration phenology. We performed a spatially explicit time-window analysis of the effect of weather on mean spring passage dates of nine short- and medium-distance passerines. We analysed data from standardized daily captures at the Helgoland (Germany) constant-effort site, in combination with gridded daily temperature, precipitation and wind data from the NCEP data set over a 55-year period (1960-2014), across the whole of West Europe and North Africa. Although we allowed for a time window of any length at any location, nevertheless incorporating various measures to avoid spurious correlations, time windows at the likely wintering or spring stopover grounds were almost exclusively selected as the best predicting variables (96%-100% of identified variables). The weather variables at the wintering and stopover grounds explain up to 77% of the interannual variability in spring passage. Yet, the response of spring migration phenology to weather at the winter or stopover areas does not fully explain the observed trends. Spring migration phenology is, hence, strongly driven by weather at the wintering and stopover grounds, but additional mechanisms are needed to fully explain the advancement of spring migration. Our results also clearly show that previously illustrated correlations, or the lack thereof, between spring migration phenology and weather at the passage or arrival location are due to spatio-temporal correlations in the weather data. This spatial mismatch might have led to false conclusions, especially the further away the wintering or stopover sites are.

temperature
time-window analysis
precipitation
wind
bird migration
climate change
environmental plasticity
spatio-temporal analysis


Quantitative Structure Activity Relationship study of the Anti-Hepatitis Peptides employing Random Forests and Extra-trees regressors.

Abstract: Antimicrobial peptides are host defense peptides being viewed as replacement to broad-spectrum antibiotics due to varied advantages. Hepatitis is the commonest infectious disease of liver, affecting 500 million globally with reported adverse side effects in treatment therapy. Antimicrobial peptides active against hepatitis are called as anti-hepatitis peptides (AHP). In current work, we present Extratrees and Random Forests based Quantitative Structure Activity Relationship (QSAR) regression modeling using extracted sequence based descriptors for prediction of the anti-hepatitis activity. The Extra-trees regression model yielded a very high performance in terms coefficient of determination (R2) as 0.95 for test set and 0.7 for the independent dataset. We hypothesize that the developed model can further be used to identify potentially active anti-hepatitis peptides with a high level of reliability.

Mishra|Gunjan|G|
Sehgal|Deepak|D|
Valadi|Jayaraman K|JK|

Quantitative structure activity relationship (QSAR)


"Dial-In" Emission from a Unique Flexible Material with Polarization Tuneable Spectral Intensity.

Abstract: The development of organic photoluminescent materials, which show promising roles as catalysts, sensors, organic light-emitting diodes, logic gates, etc., is a major demand and challenge for the global scientific community. In this context, a photoclick polymerization method is adopted for the growth of a unique photoluminescent three-dimensional (3D) polymer film, E, as a model system that shows emission tunability over the range 350-650 nm against the excitation range 295-425 nm. The DFT analysis of energy calculations and π-stacking supports the spectroscopic observations for the material exhibiting a broad range of emission owing to newly formed chromophoric units within the film. Full polarization spectroscopic Mueller matrix studies were employed to extract and quantify the molecular orientational order of both the ground (excitation) and excited (emission) state anisotropies through a set of newly defined parameters, namely the fluorescence diattenuation and fluorescence polarizance. The information contained in the recorded fluorescence Mueller matrix of the organic polymer material provided a useful way to control the spectral intensity of emission by using pre- and post-selection of polarization states. The observation was based on the assumption that the longer lifetime of the excited dipolar orientation is attributed to the compactness of the film.

polarization
photoluminescence
anisotropy
density functional calculations
pi-pi interactions


Application of a parametric model in the mortality risk analysis of ICU patients with severe COPD.

Abstract:
OBJECTIVE
To evaluate the mortality risk factors of patients with severe chronic obstructive pulmonary disease (COPD) in the intensive care unit (ICU) by utilizing parametric model of survival analysis, and to estimate patients' prognoses based on the risk and survival functions in the model.

METHODS
The clinical data and outcomes of COPD patients admitted to a respiratory intensive care unit (RICU) at Beijing Chao-Yang Hospital from January 2009 to June 2014 were prospectively collected. Based on the clinical outcomes, these patients were divided into a survival group and a death group. A univariate analysis was conducted to identify statistically significant variables. According to the distribution characteristics of these data, residual plots were prepared for an exponential model, a Weibull model and a Gamma model. The Gamma model was determined to be the best fitted for these data and was used as the analytical tool. Therefore, the variables with differences obtained from the univariate analysis were put into the Gamma model to determine the patients' mortality risk factors. The risk and survival functions were also generated according to the model formula.

RESULTS
A total of 160 patients (111 survival, 49 death) were enrolled. The univariate analysis showed that, compared with the survival group, patients in the death group had higher Charlson Comorbidity Index score (CCI), higher body temperature, higher white blood cell counts, higher proportions of neutrophils, higher serum creatinine levels and higher pH levels; lower resting carbon dioxide pressure (PCO2 ); and more cases complicated with invasive pulmonary aspergillosis (IPA). A further analysis with the Gamma model revealed that concurrent or non-concurrent IPA, white blood cell count, pH level and PCO2 were associated with the patients' mortality risk and that the predicted value (PV) of the patients' mortality risk = 2.8655 + 0.4070 × IPA + 0.0048 × WBC + 0.0049 × pH - 0.0097 × PCO2 . Moreover, the survival function formula was obtained according to the Gamma model: S(x) = 1 - I (0.7507 x, -3.3773), where I is an incomplete gamma function.

CONCLUSION
Formula generated from parametric model may help to predict the prognosis of patients with severe COPD in ICU, and this method need to be evaluated in further studies. According to our formula, IPA is an important risk factor of mortality for patients with severe COPD in the ICU.

He|Hangyong|H| Sun|Ying|Y| Sun|Bing|B| Zhan|Qingyuan|Q|

D029424:Pulmonary Disease, Chronic Obstructive

parametric model
mortality risk
chronic obstructive pulmonary disease
survival analysis


The exopolysaccharide matrix: a virulence determinant of cariogenic biofilm.

Abstract: Many infectious diseases in humans are caused or exacerbated by biofilms. Dental caries is a prime example of a biofilm-dependent disease, resulting from interactions of microorganisms, host factors, and diet (sugars), which modulate the dynamic formation of biofilms on tooth surfaces. All biofilms have a microbial-derived extracellular matrix as an essential constituent. The exopolysaccharides formed through interactions between sucrose- (and starch-) and Streptococcus mutans-derived exoenzymes present in the pellicle and on microbial surfaces (including non-mutans) provide binding sites for cariogenic and other organisms. The polymers formed in situ enmesh the microorganisms while forming a matrix facilitating the assembly of three-dimensional (3D) multicellular structures that encompass a series of microenvironments and are firmly attached to teeth. The metabolic activity of microbes embedded in this exopolysaccharide-rich and diffusion-limiting matrix leads to acidification of the milieu and, eventually, acid-dissolution of enamel. Here, we discuss recent advances concerning spatio-temporal development of the exopolysaccharide matrix and its essential role in the pathogenesis of dental caries. We focus on how the matrix serves as a 3D scaffold for biofilm assembly while creating spatial heterogeneities and low-pH microenvironments/niches. Further understanding on how the matrix modulates microbial activity and virulence expression could lead to new approaches to control cariogenic biofilms.

D018441:Biofilms
D060833:Cellular Microenvironment
D003731:Dental Caries
D003773:Dental Plaque
D006801:Humans
D006863:Hydrogen-Ion Concentration
D011135:Polysaccharides, Bacterial
D013295:Streptococcus mutans
D014774:Virulence

dental caries
extracellular matrix
heterogeneity
Streptococcus mutans
glucosyltransferases
pH microenvironment


Application of PCR for Specific Diagnosis of Leptospirosis in Humans in Ukraine.

Abstract: Leptospirosis remains one of the most widespread zoonotic diseases in the world and Ukraine, in particular. Ukrainian clinicians have been faced with early detection of the disease due to the availability of only a serological method for routine diagnostics in Ukraine, namely the microscopic agglutination test (MAT). This paper demonstrates the first results of the complex application of MAT and polymerase chain reaction (PCR) for routine verification of leptospirosis, which were first applied simultaneously in Lviv Oblast of Ukraine in 2016. We examined the sera of 150 patients clinically suspected of leptospirosis, 31 of whom were treated at the Lviv Oblast Clinical Hospital for Infectious Diseases (LOCHID). The application of PCR during the first seven days of the disease allowed increasing the share of confirmed leptospirosis cases by 16,1% in patients that were treated in LOCHID during 2016-2017.

Zubach|Olena|O| Semenyshyn|Oksana|O| Vasiuynets|Lilya|L| Velychko|Oksana|O| Zinchuk|Alexander|A|

Leptospirosis
diagnostics
polymerase chain reaction
microagglutination test


Trans-oral endoscopic partial adenoidectomy does not worsen the speech after cleft palate repair.

Abstract:
INTRODUCTION
Adenoid hypertrophy may play a role in velopharyngeal closure especially in patients with palatal abnormality; adenoidectomy may lead to velopharyngeal insufficiency and hyper nasal speech. Patients with cleft palate even after repair should not undergo adenoidectomy unless absolutely needed, and in such situations, conservative or partial adenoidectomy is performed to avoid the occurrence of velopharyngeal insufficiency. Trans-oral endoscopic adenoidectomy enables the surgeon to inspect the velopharyngeal valve during the procedure.

OBJECTIVE
The aim of this study was to assess the effect of transoral endoscopic partial adenoidectomy on the speech of children with repaired cleft palate.

METHODS
Twenty children with repaired cleft palate underwent transoral endoscopic partial adenoidectomy to relieve their airway obstruction. The procedure was completely visualized with the use of a 70° 4mm nasal endoscope; the upper part of the adenoid was removed using adenoid curette and St. Claire Thompson forceps, while the lower part was retained to maintain the velopharyngeal competence. Preoperative and postoperative evaluation of speech was performed, subjectively by auditory perceptual assessment, and objectively by nasometric assessment.

RESULTS
Speech was not adversely affected after surgery. The difference between preoperative and postoperative auditory perceptual assessment and nasalance scores for nasal and oral sentences was insignificant (p=0.231, 0.442, 0.118 respectively).

CONCLUSIONS
Transoral endoscopic partial adenoidectomy is a safe method; it does not worsen the speech of repaired cleft palate patients. It enables the surgeon to strictly inspect the velopharyngeal valve during the procedure with better determination of the adenoidal part that may contribute in velopharyngeal closure.

Abdel-Aziz|Mosaad|M| Khalifa|Badawy|B| Shawky|Ahmed|A| Rashed|Mohammed|M| Naguib|Nader|N| Abdel-Hameed|Asmaa|A|

Cleft palate
Adenoid hypertrophy
Velopharyngeal insufficiency
Endoscopic adenoidectomy
Adenoidectomia endoscópica
Fenda palatina
Hipertrofia da adenoide
Insuficiência velofaríngea


A Colloidal-Quantum-Dot Infrared Photodiode with High Photoconductive Gain.

Abstract: The photodiode is a prevailing architecture for photodetection with the merits of fast response and low dark current. However, an ideal photodiode is also desired for both high responsivity and high external quantum efficiency (EQE), which may facilitate more applications. Here the photoconducting effect in a photodiode is discussed and an Au-PbS colloidal quantum dot (CQD)-indium tin oxide Schottky junction photodiode is fabricated. The long carrier lifetime and improved carrier mobility in tetrabutylammonium iodide-modified PbS CQDs cooperating with the proper band structure and an ultrashort channel in the diode enable the photodiode with high photoconductive gain, realizing an EQE of ≈400% and a responsivity (R) of 5.15 A W-1 while simultaneously achieving a response time of 110 µs and a specific detectivity of 1.96 × 1010 Jones under 1550 nm illumination. In addition, this CQD-based photodiode is stable, low cost, and compatible with complementary metal oxide semiconductor technology. All of these promise this device great potential in applications.

infrared photodiodes
photoconductive gain
colloidal quantum dots


Policy, Research and Residents' Perspectives on Built Environments Implicated in Heart Disease: A Concept Mapping Approach.

Abstract: An underrepresentation of stakeholder perspectives within urban health research arguably limits our understanding of what is a multi-dimensional and complex relationship between the built environment and health. By engaging a wide range of stakeholders using a participatory concept mapping approach, this study aimed to achieve a more holistic and nuanced understanding of the built environments shaping disease risk, specifically cardiometabolic risk (CMR). Moreover, this study aimed to ascertain the importance and changeability of identified environments through government action. Through the concept mapping process, community members, researchers, government and non-government stakeholders collectively identified eleven clusters encompassing 102 built environmental domains related to CMR, a number of which are underrepresented within the literature. Among the identified built environments, open space, public transportation and pedestrian environments were highlighted as key targets for policy intervention. Whilst there was substantive convergence in stakeholder groups' perspectives concerning the built environment and CMR, there were disparities in the level of importance government stakeholders and community members respectively assigned to pedestrian environments and street connectivity. These findings support the role of participatory methods in strengthening how urban health issues are understood and in affording novel insights into points of action for public health and policy intervention.

Stankov|Ivana|I|
Howard|Natasha J|NJ|
Daniel|Mark|M|
Cargo|Margaret|M|

policy
built environment
concept mapping
cardiometabolic risk
community participation
researcher perspectives


Maternal chronic disease and breastfeeding outcomes: a Canadian population-based study.

Abstract: Background: The prevalence of chronic disease in pregnant women has consistently risen over the past two decades. Substantial evidence demonstrates that maternal chronic disease is associated with adverse medical outcomes like preterm birth, but less research has characterized postpartum outcomes such as infant feeding practices. It is recommended that infants be exclusively breastfed from birth to 6 months given the numerous health benefits it provides.Objective: To determine the association between maternal chronic disease and breastfeeding outcomes.Methods: We analyzed cross-sectional self-report data from the 2015/2016 Canadian Community Health Survey, restricted to women who gave birth within 2 years of data collection (n = 2100, rounded). The exposure was professionally diagnosed chronic physical disease (e.g. diabetes, arthritis, heart disease). The outcomes were breastfeeding non-initiation and early cessation of breastfeeding before 6 months. Multivariable logistic regression modeling was used to estimate adjusted odds ratios (AOR) with 95% confidence intervals (CIs). Estimates were bootstrapped and weighted to represent the national population.Results: Overall, 11.9% (95% CI 9.8-14.1) of women reported chronic disease, and were more likely to be single, be Canadian born, have low education, and be overweight/obese than women without chronic disease. The mean maternal age was approximately 30 years in both groups. Women with chronic disease had similar odds of breastfeeding non-initiation (AOR 0.96, 95% CI 0.54-1.71) and early cessation of any breastfeeding (AOR 1.40, 95% CI 0.82-2.40), but over twice the odds of early cessation of exclusive breastfeeding (AOR 2.48, 95% CI 1.49-4.12) compared to unaffected women.Conclusion: Mothers with chronic disease initiate and continue some form of breastfeeding to six months as often as their unaffected peers. However, they have substantially higher odds of ceasing exclusive breastfeeding before the recommended 6 months. Findings suggest a need to investigate the reasons for this disparity to ensure that appropriate breastfeeding support is available for women with chronic disease and their children.

chronic disease
Breastfeeding
postpartum
Canadian Community Health Survey


Golgi-localized cation/proton exchangers regulate ionic homeostasis and skotomorphogenesis in Arabidopsis.

Abstract: Multiple transporters and channels mediate cation transport across the plasma membrane and tonoplast to regulate ionic homeostasis in plant cells. However, much less is known about the molecular function of transporters that facilitate cation transport in other organelles such as Golgi. We report here that Arabidopsis KEA4, KEA5, and KEA6, members of cation/proton antiporters-2 (CPA2) superfamily were colocalized with the known Golgi marker, SYP32-mCherry. Although single kea4,5,6 mutants showed similar phenotype as the wild type under various conditions, kea4/5/6 triple mutants showed hypersensitivity to low pH, high K+ , and high Na+ and displayed growth defects in darkness, suggesting that these three KEA-type transporters function redundantly in controlling etiolated seedling growth and ion homeostasis. Detailed analysis indicated that the kea4/5/6 triple mutant exhibited cell wall biosynthesis defect during the rapid etiolated seedling growth and under high K+ /Na+ condition. The cell wall-derived pectin homogalacturonan (GalA)3 partially suppressed the growth defects and ionic toxicity in the kea4/5/6 triple mutants when grown in the dark but not in the light conditions. Together, these data support the hypothesis that the Golgi-localized KEAs play key roles in the maintenance of ionic and pH homeostasis, thereby facilitating Golgi function in cell wall biosynthesis during rapid etiolated seedling growth and in coping with high K+ /Na+ stress.

D060888:Real-Time Polymerase Chain Reaction

cell wall biosynthesis
organelle transport
pH regulation
salinity tolerance


Incidence of Fever Following Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

Abstract:
BACKGROUND
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic method for mediastinal and hilar lymphadenopathy. This study aimed to investigate the incidence of fever following EBUS-TBNA.

METHODS
A total of 684 patients who underwent EBUS-TBNA from May 2010 to July 2012 at Seoul National University Hospital were retrospectively reviewed. The patients were evaluated for fever by a physician every 6-8 hours during the first 24 hours following EBUS-TBNA. Fever was defined as an increase in axillary body temperature over 37.8℃.

RESULTS
Fever after EBUS-TBNA developed in 110 of 552 patients (20%). The median onset time and duration of fever was 7 hours (range, 0.5-32 hours) after EBUS-TBNA and 7 hours (range, 1-52 hours), respectively, and the median peak body temperature was 38.3℃ (range, 37.8-39.9℃). In most patients, fever subsided within 24 hours; however, six cases (1.1%) developed fever lasting longer than 24 hours. Infectious complications developed in three cases (0.54%) (pneumonia, 2; mediastinal abscess, 1), and all three patients had diabetes mellitus. The number or location of sampled lymph nodes and necrosis of lymph node were not associated with fever after EBUS-TBNA. Multiple logistic regression analysis did not reveal any risk factors for developing fever after EBUS-TBNA.

CONCLUSION
Fever is relatively common after EBUS-TBNA, but is transient in most patients. However, clinicians should be aware of the possibility of infectious complications among patients with diabetes mellitus.

Kim|Seo Yun|SY|
Lee|Jin Woo|JW|
Park|Young Sik|YS|
Lee|Chang-Hoon|CH|
Lee|Sang-Min|SM|
Yim|Jae-Joon|JJ|
Kim|Young Whan|YW|
Han|Sung Koo|SK|
Yoo|Chul-Gyu|CG|

Endoscopic Ultrasound-Guided Fine Needle Aspiration


Transcranial DC stimulation modifies functional connectivity of large-scale brain networks in abstinent methamphetamine users.

Abstract:
Background
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool suited to alter cortical excitability and activity via the application of weak direct electrical currents. An increasing number of studies in the addiction literature suggests that tDCS modulates subjective self-reported craving through stimulation of dorsolateral prefrontal cortex (DLPFC). The major goal of this study was to explore effects of bilateral DLPFC stimulation on resting state networks (RSNs) in association with drug craving modulation. We targeted three large-scale RSNs; the default mode network (DMN), the executive control network (ECN), and the salience network (SN).

Methods
Fifteen males were recruited after signing written informed consent. We conducted a double-blinded sham-controlled crossover study. Twenty-minute "real" and "sham" tDCS (2 mA) were applied over the DLPFC on two separate days in random order. Each subject received both stimulation conditions with a 1-week washout period. The anode and cathode electrodes were located over the right and left DLPFC, respectively. Resting state fMRI was acquired before and after real and sham stimulation. Subjective craving was assessed before and after each fMRI scan. The RSNs were identified using seed-based analysis and were compared using a generalized linear model.

Results
Subjective craving decreased significantly after real tDCS compared to sham stimulation (p = .03). Moreover, the analysis shows significant modulation of DMN, ECN, and SN after real tDCS compared to sham stimulation. Additionally, alteration of subjective craving score was correlated with modified activation of the three networks.

Discussion
Given the observed alteration of the targeted functional brain networks in methamphetamine users, new potentials are highlighted for tDCS as a network intervention strategy and rsfMRI as a suitable monitoring method for these interventions.

Shahbabaie|Alireza|A|
Ebrahimpoor|Mitra|M|
Hariri|Ali|A|
Nitsche|Michael A|MA|
Hatami|Javad|J|
Fatemizadeh|Emad|E|
Oghabian|Mohammad Ali|MA|
Ekhtiari|Hamed|H|0000-0001-6902-8798

D000697:Central Nervous System Stimulants

D065908:Transcranial Direct Current Stimulation

functional connectivity
transcranial direct current stimulation
noninvasive brain stimulation
resting state fMRI
large‐scale brain networks
methamphetamine craving


Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders.

Abstract: Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalization of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with bilateral basal ganglia abnormalities on brain MRI was undertaken in this international multicentre cohort study. Three hundred and five MRI scans belonging to 201 children with 34 different disorders were rated using a standard radiological scoring proforma. In addition, literature review on MRI patterns was undertaken in these 34 disorders and 59 additional disorders reported with bilateral basal ganglia MRI abnormalities. Cluster analysis on first MRI findings from the study cohort grouped them into four clusters: Cluster 1-T2-weighted hyperintensities in the putamen; Cluster 2-T2-weighted hyperintensities or increased MRI susceptibility in the globus pallidus; Cluster 3-T2-weighted hyperintensities in the globus pallidus, brainstem and cerebellum with diffusion restriction; Cluster 4-T1-weighted hyperintensities in the basal ganglia. The 34 diagnostic categories included in this study showed dominant clustering in one of the above four clusters. Inflammatory disorders grouped together in Cluster 1. Mitochondrial and other neurometabolic disorders were distributed across clusters 1, 2 and 3, according to lesions dominantly affecting the striatum (Cluster 1: glutaric aciduria type 1, propionic acidaemia, 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome and thiamine responsive basal ganglia disease associated with SLC19A3), pallidum (Cluster 2: methylmalonic acidaemia, Kearns Sayre syndrome, pyruvate dehydrogenase complex deficiency and succinic semialdehyde dehydrogenase deficiency) or pallidum, brainstem and cerebellum (Cluster 3: vigabatrin toxicity, Krabbe disease). The Cluster 4 pattern was exemplified by distinct T1-weighted hyperintensities in the basal ganglia and other brain regions in genetically determined hypermanganesemia due to SLC39A14 and SLC30A10. Within the clusters, distinctive basal ganglia MRI patterns were noted in acquired disorders such as cerebral palsy due to hypoxic ischaemic encephalopathy in full-term babies, kernicterus and vigabatrin toxicity and in rare genetic disorders such as 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome, thiamine responsive basal ganglia disease, pantothenate kinase-associated neurodegeneration, TUBB4A and hypermanganesemia. Integrated findings from the study cohort and literature review were used to propose a diagnostic algorithm to approach bilateral basal ganglia abnormalities on MRI. After integrating clinical summaries and MRI findings from the literature review, we developed a prototypic decision-making electronic tool to be tested using further cohorts and clinical practice.

pattern recognition
basal ganglia
MRI
striatum
striatal necrosis


Understanding Latino Grandparents Raising Grandchildren Through a Bioecological Lens.

Abstract: The purpose of this article is to provide a summary of the published research addressing the challenges and strengths of Latino grandparents raising grandchildren in the United States. Using the bioecological framework as a guide to organize and understand the published literature addressing Latino grandparent caregivers, we examined refereed articles published over the past 19 years. This framework provides a lens for understanding and situating research on Latino grandparents raising grandchildren to discover Latino grandparents' strengths and challenges. The areas of foci include financial challenges, intergenerational relationships, reasons for caregiving, health status, language barriers, and culture. This article concludes with future research opportunities and a call to action for more research on Latino grandparents raising grandchildren.

Mendoza|Angela Nancy|AN|
Fruhauf|Christine A|CA|
Bundy-Fazioli|Kimberly|K|
Weil|Joyce|J|

Latino
grandparent caregivers
Hispanic
custodial care
custodial grandparent
kinship care


Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury.

Abstract: Retinal ganglion cell (RGC) injury is one of the important pathological features of diabetes-induced retinal neurodegeneration. Increasing attention has been paid to find strategies for protecting against RGC injury. Long noncoding RNAs (lncRNAs) have emerged as the key regulators of many cell functions. Here, we show that Sox2OT expression is significantly down-regulated in the retinas of STZ-induced diabetic mice and in the RGCs upon high glucose or oxidative stress. SOX2OT knockdown protects RGCs against high glucose-induced injury in vitro. Moreover, Sox2OT knockdown plays a neuroprotective role in diabetes-related retinal neurodegeneration in vivo. Sox2OT knockdown could regulate oxidative stress response in RGCs and diabetic mouse retinas. Sox2OT knockdown plays an anti-oxidative role via regulating NRF2/HO-1 signaling activity. Taken together, Sox2OT knockdown may be a therapeutic strategy for the prevention and treatment of diabetes-induced retinal neurodegeneration.

Li|Chao-Peng|CP| Wang|Shu-Hong|SH| Wang|Wen-Qi|WQ| Song|Shu-Guang|SG| Liu|Xiu-Ming|XM|

Retinal ganglion cell (RGC)
Long noncoding RNA
NRF2/HO-1 signaling
Diabetic retinopathy


Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1.

Abstract:
AIMS
Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy than ductal carcinoma. In molecular terms, MBCs usually cluster with triple-negative breast cancers (TNBCs), but have a worse prognosis than TNBCs. Studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. The aim of the present study was to characterise MBCs on a molecular level and test programmed death-ligand 1 (PD-L1) biomarker expression in MBCs for future therapeutic interventions.

METHODS
We profiled 297 samples (MBC (n=75), TNBC (n=106), human epidermal growth factor receptor 2 (HER2)-positive breast cancers (n=32) and hormone-positive breast cancers (n=84)) by next-generation sequencing. Immunohistochemistry for PD-L1 and programmed cell death 1 (PD-1) expression was performed using automated procedures.

RESULTS
The most commonly mutated genes in MBCs included TP53 (56%) and PIK3CA (23%). Pathogenic mutations in other genes, including HRAS, FBXW7, PTEN, AKT1 and SMAD4, were rare. PD-L1 expression was detected in a significantly higher proportion of MBCs (46%) than in other subtypes (6% each in hormone-positive and HER2-positive breast cancers, and 9% in TNBC, not otherwise specified, p<0.001). PD-1-positive tumour infiltrating lymphocytes (TILs) varied greatly in MBCs.

CONCLUSIONS
Comprehensive profiling of a large cohort of this rare subtype of breast carcinoma highlighted the predominance of TP53 mutation and increased PD-L1 expression in carcinoma cells. These results can be exploited in clinical trials using immune checkpoint inhibitors.

Joneja|Upasana|U| Vranic|Semir|S| Swensen|Jeffrey|J| Feldman|Rebecca|R| Chen|Wangjuh|W| Kimbrough|Jeffrey|J| Xiao|Nianqing|N| Reddy|Sandeep|S| Palazzo|Juan|J| Gatalica|Zoran|Z|

D064726:Triple Negative Breast Neoplasms

BREAST CANCER
BREAST PATHOLOGY
GENETICS
TUMOUR BIOLOGY


Social Capital and Mental Health among Older Adults Living in Urban China in the Context of COVID-19 Pandemic.

Abstract: Although social capital has been found to be an important social determinant of mental health in later life, research on social capital in the context of COVID-19 and the interplay among subdimensions of social capital is lacking. The present study examined the mediating role of cognitive social capital on the relationship between structural social capital and mental health among older adults in urban China in the context of the COVID-19 pandemic. Data were collected from the Yangpu district in Shanghai, China, in July-August 2020. A quota sampling approach was used to recruit 472 respondents aged 60 years and older from 23 communities in the Yangpu district. Mental health was measured by depressive symptoms and life satisfaction. Cognitive social capital was assessed through trust and reciprocity, and structural social capital was assessed through organization memberships, and COVID-19 related volunteering and citizenship activity. Structural equation modeling was used to test the mediation model. The results show that cognitive social capital had a full mediation effect on the association between structural social capital and mental health indicators (life satisfaction: b = 0.122, SD = 0.029, p < 0.001; depressive symptoms: b = -0.343, SD = 0.119, p < 0.01). The findings indicate that social capital can play an important role in sustaining and improving mental health in the context of the COVID-19 pandemic. Policy and intervention implications are discussed.

older adults
urban China
cognitive social capital
structural social capital
depressive symptoms
life satisfaction


Adaptive vs. non-adaptive cognitive training by means of a personalized App: a randomized trial in people with multiple sclerosis.

Abstract:
BACKGROUND
Cognitive impairment is common in multiple sclerosis (MS), but the definition of the best cognitive rehabilitation tools and features is still an open issue among researchers. The aims of the present study were to evaluate the effectiveness of COGNI-TRAcK (a customized application software delivering personalized working memory-based exercises) on cognitively impaired people with MS and to investigate the effects of an adaptive vs. a non-adaptive cognitive training administered by means of COGNI-TRAcK.

METHODS
Twenty eight patients (20 women, age 47.5 ± 9.3 years, Expanded Disability Status Scale score 3.8 ± 1.9) were randomized in two homogeneous groups, both performing a 8-week home-based cognitive rehabilitation treatment by means of COGNI-TRAcK. The study group (ADAPT-gr) underwent an adaptive training given by the automatic adjustment of tasks difficulty to the subjects' performance, whilst the control group (CONST-gr) was trained at constant difficulty levels. Before and after the treatment, patients' cognitive status was assessed using a gold standard neuropsychological evaluation. Moreover, the mostly affected cognitive domains in MS (i.e., attention, concentration and information processing speed) were also assessed 6 months after the end of the treatment.

RESULTS
The analysis of variance showed a significant Group*Time interaction in six out of ten tests of the cognitive evaluation. Post-hoc analysis revealed a significant improvement between the performances before and after the intervention only in the ADAPT-gr in tests evaluating verbal memory acquisition (p <0.05) and delayed recall (p = 0.001), verbal fluency (p = 0.01), sustained attention, concentration and information processing speed (p < 0.01). This last effect was maintained also after 6 months (p < 0.05).

CONCLUSIONS
We concluded that COGNI-TRAcK represents a suitable tool to administer a personalized training to cognitively impaired subjects and that an adaptive working load is a crucial feature determining the effectiveness of cognitive treatment, allowing transfer effects to several cognitive domains and long-term maintenance of results.

Pedullà|Ludovico|L|
Brichetto|Giampaolo|G|
Tacchino|Andrea|A|
Vassallo|Claudio|C|
Zaratin|Paola|P|
Battaglia|Mario Alberto|MA|
Bonzano|Laura|L|
Bove|Marco|M|

Multiple sclerosis
Cognitive rehabilitation
Application software
Adaptive working load
Personalized treatment


Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747).

Abstract:
OBJECTIVE
To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC).

PATIENTS AND METHODS
Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 × 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves.

RESULTS
The per-patient cost for ZA was £12 667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was £8 005. Sr89 was associated with a cost of £13 230, £1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively.

CONCLUSIONS
The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness-to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources.

Andronis|Lazaros|L|0000-0001-7998-7431
Goranitis|Ilias|I|
Pirrie|Sarah|S|
Pope|Ann|A|
Barton|Darren|D|
Collins|Stuart|S|
Daunton|Adam|A|
McLaren|Duncan|D|
O'Sullivan|Joe M|JM|
Parker|Chris|C|
Porfiri|Emilio|E|
Staffurth|John|J|
Stanley|Andrew|A|
Wylie|James|J|
Beesley|Sharon|S|
Birtle|Alison|A|
Brown|Janet E|JE|
Chakraborti|Prabir|P|
Hussain|Syed A|SA|
Russell|J Martin|JM|
Billingham|Lucinda J|LJ|
James|Nicholas D|ND|

D000971:Antineoplastic Combined Chemotherapy Protocols

D050071:Bone Density Conservation Agents

zoledronic acid
bone protecting treatments
castrate-refractory prostate cancer
quality of life
Sr89
cost-effectiveness analysis


Effect of 3:7 ratio of Astragalus total saponins and Curcumin on the diabetic nephropathy rats model.

Abstract:
Objective
Study the effect of the 3:7 ratio of Astragalus total saponins and Curcumin on the model of diabetic nephropathy rats, and explore its mechanisms.

Methods
Diabetic nephropathy rats model was established by high-fat and high-sugar feed feeding combined with streptozotocin (STZ) injection in sublingual vein. Measured fasting blood glucose of rats on the 10, 20 and 30th day, and measured urine protein content in urine of rats on 30th days. Two hours after the last administration, measured glycated serum protein (GSP), insulin antibody (IA), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), malondialdehyde (MDA), insulin, superoxide dismutase (SOD), glutathione (GSH), urea nitrogen (BUN), creatinine (Cr) in the serum and calculated the renal index of rat. Take the viscera of pancreas and kidney, and HE staining, so as to observe pathological changes.

Result
Astragalus total saponins and Curcumin 3:7 compatibility each dose group can significantly reduce the diabetic nephropathy rats blood glucose of 30th days, significantly reduce the level of GSP, IA, TG, TC, LDL (P < 0.01), and reduce MDA levels with different degrees (P < 0.01 or P < 0.05), and significantly increase the level of insulin (P < 0.01), increase the level of HDL, SOD and GSH with different degrees (P < 0.01 or P < 0.05 or P > 0.05); Astragalus total saponins and Curcumin 3:7 compatibility each dose group also can decrease renal index, UN, and Cr levels with different degrees and improve the pathological changes of pancreatic tissue and kidney tissue in diabetic nephropathy rats with different degrees (P < 0.01 or P < 0.05 or P > 0.05).

Conclusion
The 3:7 ratio of Astragalus total saponins and Curcumin can achieve the treatment and protection effects on diabetic nephropathy rats by improve the glycometableolism, insulin resistance, lipid metableolism, oxidative stress levels, and pathological changes.

Liu|Baosong|B| Miao|Jinxin|J| Peng|Mengfan|M| Liu|Tianyuan|T| Miao|Mingsan|M|

Astragalus total saponins
Curcumin
Diabetic nephropathy
Glycometableolism
Lipid metableolism
Oxidative stress


Examining the criterion-related validity of the Pervasive Developmental Disorder Behavior Inventory.

Abstract: The Pervasive Developmental Disorder Behavior Inventory is a questionnaire designed to aid in the diagnosis of pervasive developmental disorders or autism spectrum disorders. The Pervasive Developmental Disorder Behavior Inventory assesses adaptive and maladaptive behaviors associated with pervasive developmental disorders and provides an age-standardized Autism Composite score. In previous research, the Pervasive Developmental Disorder Behavior Inventory has demonstrated moderate to strong reliability and validity. This study aimed to replicate and extend previous research by investigating the criterion-related validity of the Pervasive Developmental Disorder Behavior Inventory. Data from 40 children were analyzed in relation to other measures. The Pervasive Developmental Disorder Behavior Inventory adaptive scores were moderately correlated with cognitive and adaptive behavior scores as expected. However, no significant correlations were found between the maladaptive and Autism Composite scores of the Pervasive Developmental Disorder Behavior Inventory and the Childhood Autism Rating Scale. Results lead to concerns regarding the validity of some scores of the Pervasive Developmental Disorder Behavior Inventory.

D002659:Child Development Disorders, Pervasive


Arterial stiffness is associated with cardiovascular and cancer mortality in cancer patients: Insight from NHANESIII.

Abstract:
Background
Cancer survivors are at greater risk for cardiovascular disease (CVD) than second malignancy, resulting in a decreased quality of life and increased cost of care. Additional knowledge of CVD prevention by identifying possible risk factors has clinical relevance. Our main objective was to determine the relevance of a clinical index of arterial stiffness, pulse pressure, in predicting CVD mortality in cancer patients, with a second objective to examine its relationship with cancer mortality.

Methods
We retrospectively analyzed 781 cancer patients from Third National Health and Nutrition Examination Survey and Linked Mortality File, including demographic, anthropometric, blood pressure, and cause of death. Kaplan-Meier survival curve and Cox hazard regression analyses were performed to assess the relationship between pulse pressure and cardiovascular, cancer, and all-cause mortality.

Results
During a mean follow-up time of 8.1 years, 603 deaths, 257 cancer and 151 CVD, occurred. In unadjusted models, the risk of CVD, cancer, and all-cause mortality were 3.8-fold, 5.3-fold, and 1.6-fold higher, respectively, for pulse pressure ≥70 mmHg compared to <50 mmHg. Adjusted analyses revealed a higher CVD mortality in cancer patients <65 years with a pulse pressure 60-70 mmHg (adjusted hazard ratio, 5.26; 95%CI, 1.12-24.78) when compared to pulse pressure of <50 mmHg. Pulse pressure was not associated with risk of all-cause, CVD, or cancer in those ≥65 years.

Conclusion
Pulse pressure, an index of arterial stiffness, is predictive of CVD mortality in cancer patients. Our findings support non-invasive office-setting measurements of arterial stiffness to identify high risk patients.

Parr|Shannon K|SK|
Steele|Catherine C|CC|
Hammond|Stephen T|ST|
Turpin|Vanessa Rose G|VRG|
Ade|Carl J|CJ|

NHANES III, Third National Health and Nutrition Examination Survey


Recent Advances in Fiber Supercapacitors: Materials, Device Configurations, and Applications.

Abstract: Fiber supercapacitors (SCs), with their small size and weight, excellent flexibility and deformability, and high capacitance and power density, are recognized as one of the most robust power supplies available for wearable electronics. They can be woven into breathable textiles or integrated into different functional materials to fit curved surfaces for use in day-to-day life. A comprehensive review on recent important development and progress in fiber SCs is provided, with respect to the active electrode materials, device configurations, functions, integrations. Active electrode materials based on different electrochemical mechanisms and intended to improve performance including carbon-based materials, metal oxides, and hybrid composites, are first summarized. The three main types of fiber SCs, namely parallel, twist, and coaxial structures, are then discussed, followed by the exploration of some functions including stretchability and self-healing. Miniaturized integration of fiber SCs to obtain flexible energy fibers and integrated sensing systems is also discussed. Finally, a short conclusion is made, combining with comments on the current challenges and potential solutions in this field.

fiber supercapacitors
flexible electronics
nanomaterials


Uterine artery embolization in association with methotrexate infusion for the treatment of tubal ectopic pregnancy.

Abstract: Objective To investigate the safety, feasibility, and effectiveness of uterine artery embolization in association with methotrexate (MTX) infusion for the treatment of tubal ectopic pregnancy. Methods Fifty-one patients with tubal ectopic pregnancy were referred for interventional management. All patients received super-selective arteriography of the uterine artery, were infused with 50-100 mg methotrexate (MTX) through a catheter, and underwent embolization of the uterine artery with a gel-foam pledge. Clinical presentation, findings of physical examination, β-HCG values, and the size of the ectopic mass were documented for comparison. The concentration of MTX in blood was evaluated at 0.5, 6, 12, 24, 36, and 48 hours after the procedure. Results Forty-seven out of the 51 patients had clinical resolution of their tubal pregnancy (92.2%). The average time for the β-HCG value to decrease and come back to normal was 9.16 ± 2.54 days (mean +/- SD). MTX levels in peripheral blood could not be detected for patients who received 50 or 75 mg MTX at 36 hours after the procedure, while the MTX level was 0.01 μmol/L at 48 hours after the procedure for patients who received 100 mg. Out of the 4 cases whose ectopic mass size was ≥5 cm, 3 failed to respond to the treatment; however, those whose ectopic mass size was ≤5 cm responded positively to the treatment, regardless of the β-HCG concentration and abdominal bleeding, except for 1 patient who had to undergo laparoscopy for severe abdominal pain and who showed a reduction in her β-HCG level. Conclusion Uterine artery embolization in association with methotrexate infusion is safe and effective in the treatment of tubal ectopic pregnancy, especially for those women with mild to moderate bleeding, or for those at risk of a major hemorrhage. The selection criterion of mass size >5 cm should, therefore, be carefully considered.

Li|Zhi|Z| Xu|Wenjian|W| Hu|Bo|B| Li|Mingming|M| Zhou|Jianwei|J| Ni|Caifang|C|

embolization, therapeutic
radiology, interventional
tubal, pregnancy


SIRT1-dependent modulation of methylation and acetylation of histone H3 on lysine 9 (H3K9) in the zygotic pronuclei improves porcine embryo development.

Abstract:
Background
The histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD+-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development.

Results
Our results show that SIRT1 activators resveratrol and BML-278 increased H3K9 methylation and suppressed H3K9 acetylation in both the paternal and maternal pronucleus. Inversely, SIRT1 inhibitors nicotinamide and sirtinol suppressed methylation and increased acetylation of pronuclear H3K9. Evaluation of early embryonic development confirmed positive effect of selective SIRT1 activation on blastocyst formation rate (5.2 ± 2.9% versus 32.9 ± 8.1% in vehicle control and BML-278 group, respectively; P ≤ 0.05). Stimulation of SIRT1 activity coincided with fluorometric signal intensity of ooplasmic ubiquitin ligase MDM2, a known substrate of SIRT1 and known limiting factor of epigenome remodeling.

Conclusions
We conclude that SIRT1 modulates zygotic histone code, obviously through direct deacetylation and via non-histone targets resulting in increased H3K9me3. These changes in zygotes lead to more successful pre-implantation embryonic development and, indeed, the specific SIRT1 activation due to BML-278 is beneficial for in vitro embryo production and blastocyst achievement.

Adamkova|Katerina|K| Yi|Young-Joo|YJ| Petr|Jaroslav|J| Zalmanova|Tereza|T| Hoskova|Kristyna|K| Jelinkova|Pavla|P| Moravec|Jiri|J| Kralickova|Milena|M| Sutovsky|Miriam|M| Sutovsky|Peter|P| Nevoral|Jan|J|0000-0002-2048-7325

Epigenetics
Embryonic development
SIRT1
H3K9 methylation
Sirtuin


Naringin improves lipid metabolism in a tissue-engineered liver model of NAFLD and the underlying mechanisms.

Abstract:
AIMS
Nonalcoholic fatty liver disease (NAFLD) is a lipid metabolism disorder. Naringin (a main active ingredient in Ganshuang granules) is a flavanone that has been demonstrated to exert hepatoprotective and antifibrotic effects. The present study aimed to use a novel tissue-engineered fatty liver model to assess the effects and mechanisms of naringin on NAFLD.

MAIN METHODS
Intracellular triglyceride (TG) was examined by oil red O staining and commercial kits. The proteins associated with lipid metabolism were measured by western blotting and/or qPCR. Very low-density lipoprotein (VLDL) was measured by ELISA. A CCK8 assay was used to assess the cytotoxicity of naringin. Molecular docking was used to predict the interactions and binding patterns between naringin and target proteins.

KEY FINDINGS
Naringin significantly reduced intracellular TG accumulation by 52.7% in tissue-engineered fatty (TEF) livers, and also the level of pyruvate dehydrogenase kinase 4. Naringin downregulated CD36 and proliferator activated-receptor γ expression, reducing the uptake of FFAs; naringin also downregulated de novo liposynthetases by reducing acetyl CoA carboxylase, fatty acid synthetase etc. in TEF livers. Moreover, naringin increased the expression of proliferator activated-receptor α (PPAR-α) and carnitine palmitoyltransferase 1 to improve the oxidation of fatty acids. The levels of VLDL secreted from TEF livers were reduced by 24.7% after naringin treatment. Molecular docking analyses determined the bioactivity of naringin through its specific binding to CD36 and PPAR-α.

SIGNIFICANCE
Naringin improved lipid metabolism disorders in TEF livers by reducing fatty acid uptake and de novo lipogenesis and increasing fatty acid oxidation. CD36 and PPAR-α might be specific targets of naringin.

Zhang|Xiaohui|X| Zhang|Yizhi|Y| Gao|Wen|W| Guo|Zhihao|Z| Wang|Kun|K| Liu|Shuang|S| Duan|Zhongping|Z| Chen|Yu|Y|

D065626:Non-alcoholic Fatty Liver Disease

Naringin
Lipid metabolism
Tissue-engineered liver
Nonalcoholic fatty liver disease


Outcomes mapping study for childhood vaccination communication: too few concepts were measured in too many ways.

Abstract:
OBJECTIVES
The objectives of this article are to (1) comprehensively catalog outcomes measured in trials of childhood vaccination communication interventions and (2) analyze patterns and trends in outcome selection. To achieve these objectives, we developed a Trial Outcomes Map for vaccination communication.

STUDY DESIGN
We searched the Cochrane Central Register of Controlled Trials for trials of childhood vaccination communication interventions, extracting verbatim all outcome information from included trials. Through thematic grouping, we categorized outcomes based on conceptual similarities, forming a Trial Outcomes Map.

RESULTS
We identified 112 relevant trials containing 209 outcomes. Thematic analysis revealed three overarching Outcome Categories: consumer-, vaccination-, and health system-related outcomes. These categories contain 21 Outcome Types (eg, "knowledge," "cost"), measured using 66 different Outcome Variables. Vaccination outcomes were measured most frequently and health system-related outcomes least frequently. Consumer outcomes are increasingly measured in more recent trials.

CONCLUSION
The number of measures used for the same outcomes complicates data synthesis and interpretation. Despite recent trends toward including consumer outcomes, intermediate outcome measurement is lacking, hampering understanding of how and why vaccination communication interventions do or do not work. This Map may improve outcome consistency in future trials and will contribute to a forthcoming core outcome set.

Kaufman|Jessica|J|
Ryan|Rebecca|R|
Bosch-Capblanch|Xavier|X|
Cartier|Yuri|Y|
Cliff|Julie|J|
Glenton|Claire|C|
Lewin|Simon|S|
Rada|Gabriel|G|
Ames|Heather|H|
Muloliwa|Artur Manuel|AM|
Oku|Afiong|A|
Oyo-Ita|Angela|A|
Hill|Sophie|S|

D018849:Controlled Clinical Trials as Topic

Outcome
Outcomes map
Vaccination
Communication
Core outcome set
Methodology
Outcome categorisation


Development and validation of multivariable mortality risk-prediction models in older people undergoing an interRAI home-care assessment (RiskOP).

Abstract:
Background
Currently, one-year survival of older people with complex co-morbidities is unpredictable. Identifying older adults with a reduced life expectancy will lead to more targeted care and better healthcare resource allocation.

Methods
Development and validation of one-year and three-month mortality risks in people aged ≥65 years who had completed an International Resident Assessment Instrument-Home Care (interRAI-HC) assessment between July 2012 and March 2018. Data was split into development (90%) and validation data sets (10%). A multivariable logistic regression model using data from 108 interRAI questions across multiple domains was developed and validated using discrimination metrics and calibration curves. Variables each explaining at least 1% of the model were then used to develop and validate a parsimonious model. Subgroups by sex, age, ethnicity, and comorbidities were evaluated.

Findings
There were 104,436 persons (60.2% female; mean age 82.1 years) in the study cohort of whom 20,972 (20.1%) died within one year. The full multivariable model had area under the curves (AUCs) of 0.778 to 0.795 in the 5 validation datasets and was well calibrated. After variable reduction a parsimonious model consisted of 16 variables and was well calibrated and the AUC remained high: 0.773 (0.769 to 0.777). The three-month parsimonious model comprised 22 variables and was well calibrated with an AUC of 0.843 (95%CI: 0.839 to 0.848).

Interpretation
These community-based risk prediction models accurately predict mortality in older people with complex co-morbidities. They may contribute to both forecasting for policy making and clinical decision making regarding an individual's needs.

Funding
The New Zealand Health Research Council.

Pickering|John W|JW|
Abey-Nesbit|Rebecca|R|
Allore|Heather|H|
Jamieson|Hamish|H|


Maternal and Perinatal Outcomes among Maternity Waiting Home Users and Non-Users in Rural Rwanda.

Abstract: Most maternal and perinatal deaths could be prevented through timely access to skilled birth attendants. Women should access appropriate obstetric care during pregnancy, labor, and puerperium. Maternity waiting homes (MWHs) permit access to emergency obstetric care when labor starts. This study compared maternal and perinatal outcomes among MWH users and non-users through a retrospective cohort study. Data were collected through obstetric chart reviews and analyzed using STATA version 15. Of the 8144 deliveries reported between 2015 and 2019, 1305 women had high-risk pregnancies and were included in the study. MWH users had more spontaneous vaginal deliveries compared to non-users (38.6% versus 16.8%) and less cesarean sections (57.7% versus 76.7%). Maternal morbidities such as postpartum hemorrhage occurred less frequently among users than non-users (2.13% versus 5.64%). Four women died among non-users while there was no death among users. Non-users had more stillbirths than users (7.68% versus 0.91%). The MWH may have contributed to the observed differences in outcomes. However, many women with high risk pregnancies did not use the MWH, indicating a probable gap in awareness, usefulness, or their inability to stay due to other responsibilities at home. Use of MWHs at scale could improve maternal and perinatal outcomes in Rwanda.

maternity waiting home
maternal morbidity
stillbirth
maternal mortality
prior caesarean section


Truncating de novo mutations in the Krüppel-type zinc-finger gene ZNF148 in patients with corpus callosum defects, developmental delay, short stature, and dysmorphisms.

Abstract:
BACKGROUND
Krüppel-type zinc finger genes (ZNF) constitute a large yet relatively poorly characterized gene family. ZNF genes encode proteins that recognize specific DNA motifs in gene promotors. They act as transcriptional co-activators or -repressors via interaction with chromatin remodeling proteins and other transcription factors. Only few ZNF genes are currently linked to human disorders and identification of ZNF gene-associated human diseases may help understand their function. Here we provide genetic, statistical, and clinical evidence to support association of ZNF148 with a new intellectual disability (ID) syndrome disorder.

METHODS
Routine diagnostic exome sequencing data were obtained from 2172 patients with ID and/or multiple congenital anomalies.

RESULTS
In a cohort of 2172 patient-parent trios referred for routine diagnostic whole exome sequencing for ID and/or multiple congenital anomalies (MCA) in the period 2012-2016, four patients were identified who carried de novo heterozygous nonsense or frameshift mutations in the ZNF148 gene. This was the only ZNF gene with recurrent truncating de novo mutations in this cohort. All mutations resulted in premature termination codons in the last exon of ZNF148. The number of the de novo truncating mutations in the ZNF148 gene was significantly enriched (p = 5.42 × 10-3). The newly described ZNF148-associated syndrome is characterized by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations.

CONCLUSIONS
We propose ZNF148 as a gene involved in a newly described ID syndrome with a recurrent phenotype and postulate that the ZNF148 is a hitherto unrecognized but crucial transcription factor in the development of the corpus callosum. Our study illustrates the advantage of whole exome sequencing in a large cohort using a parent-offspring trio approach for identifying novel genes involved in rare human diseases.

Stevens|Servi J C|SJ|
van Essen|Anthonie J|AJ|
van Ravenswaaij|Conny M A|CM|
Elias|Abdallah F|AF|
Haven|Jaclyn A|JA|
Lelieveld|Stefan H|SH|
Pfundt|Rolph|R|
Nillesen|Willy M|WM|
Yntema|Helger G|HG|
van Roozendaal|Kees|K|
Stegmann|Alexander P|AP|
Gilissen|Christian|C|
Brunner|Han G|HG|

D061085:Agenesis of Corpus Callosum
D001483:Base Sequence
D057215:Body Dysmorphic Disorders
D002648:Child
D004268:DNA-Binding Proteins
D002658:Developmental Disabilities
D005260:Female
D006801:Humans
D007231:Infant, Newborn
D008297:Male
D017384:Sequence Deletion
D014157:Transcription Factors

De novo mutations
ZNF148
Intellectual disability
Whole exome sequencing
Premature termination codon
Corpus callosum development
ZBP-89


Comparing Costs and Outcomes of Treatments for Irritable Bowel Syndrome With Diarrhea: Cost-Benefit Analysis.

Abstract:
BACKGROUND
Irritable bowel syndrome (IBS) is one of the most expensive gastroenterological conditions and is an ideal target for developing a value-based care model. We assessed the comparative cost-benefit of treatments for IBS with diarrhea (IBS-D), the most common IBS subtype from insurer and patient perspectives.

METHODS
We constructed a decision analytic model assessing trade-offs among guideline-recommended and recently FDA-approved drugs, supplements, low FODMAP diet, cognitive behavioral therapy (CBT). Outcomes and costs were derived from systematic reviews of clinical trials and national databases. Health-gains were represented using quality-adjusted life years (QALY).

RESULTS
From an insurer perspective, on-label prescription drugs (rifaximin, eluxadoline, alosetron) were significantly more expensive than off-label treatments, low FODMAP, or CBT. Insurer treatment preferences were driven by average wholesale prescription drug prices and were not affected by health gains in sensitivity analysis within standard willingness-to-pay ranges up to $150,000/QALY-gained. From a patient perspective, prescription drug therapies and neuromodulators appeared preferable due to a reduction in lost wages due to IBS with effective therapy, and also considering out-of-pocket costs of low FODMAP food and out-of-pocket costs to attend CBT appointments. Comparative health outcomes exerted influence on treatment preferences from a patient perspective in cost-benefit analysis depending on a patients' willingness-to-pay threshold for additional health-gains, but health outcomes were less important than out-of-pocket costs at lower willingness-to-pay thresholds.

CONCLUSIONS
Costs are critical determinants of IBS treatment value to patients and insurers, but different costs drive patient and insurer treatment preferences. Divergent cost drivers appear to explain misalignment between patient and insurer IBS treatment preferences in practice.

Shah|Eric D|ED|
Salwen-Deremer|Jessica K|JK|
Gibson|Peter R|PR|
Muir|Jane G|JG|
Eswaran|Shanti|S|
Chey|William D|WD|

Value-Based Care
QALY
Pricing
Value
Comparative Effectiveness
Coverage
Economic Analysis
ICER
Markov


Computed tomography diagnosis of primary hyperparathyroidism.

Abstract: The article presents data on modern approaches to the diagnosis of various manifestations of hyperparathyroidism according to multispiral computed tomography, which do not require morphological verification and ensure the correctness of the diagnostic process. The radiological picture and differential diagnostics of changes from parathyroid glands and bone structures at hyperparathyroidism are described in detail.

Buryakina|S A|SA|
Tarbaeva|N V|NV|
Volevodz|N N|NN|
Dedov|I I|II|
Kovalevich|L D|LD|
Karmazanovskiy|G G|GG|

D006801:Humans
D049950:Hyperparathyroidism, Primary
D010280:Parathyroid Glands
D014057:Tomography, X-Ray Computed

computed tomography
adenoma of parathyroid gland
cancer of the parathyroid gland.
hyperplasia of the parathyroid gland


Mental health services use among adults with or without mental disorders: Do development stages matter?

Abstract:
BACKGROUND
Mental health services (MHS) use is a complex behaviour that does not only concern individuals with current mental disorder. To date, few studies have examined age-related contextualisation of MHS use. Reasons for seeking help may vary according to development stages in adulthood.

AIMS
This study aimed to determine which predisposing, enabling and need factors, using Andersen's model, were associated with MHS use according to adult development stages among individuals with or without current psychiatric diagnosis.

METHODS
Three age groups were examined: 18- to 29-year-olds (n = 775), 30- to 49-year-olds (n = 1,560) and 50- to 64-year-olds (n = 960). Data were obtained from the Montreal Longitudinal Catchment Area Study. Bivariate and multivariate logistic regression analyses were conducted for each age group separately to determine which predisposing, enabling and need factors were associated with MHS use in the past 12 months.

RESULTS
For 18- to 29-year-olds, one enabling factor (Internet search) and two need factors (presence of major depressive disorder and number of stressful events) were positively associated with MHS use. For 30- to 49-year-olds, one predisposing factor (family history of mental disorder), four enabling factors (not currently working or in school, perceiving neighbourhood disorder, social cohesion and Internet searching) and one need factor (major depressive disorder) correlated with help seeking. For 50- to 64-year-olds, two predisposing factors (family history of mental disorder and higher self-perceived stigma), two enabling factors (low satisfaction in personal relationship and Internet searching) and one need factor (alcohol dependence) were associated with MHS use.

CONCLUSIONS
Factors associated with MHS use differ according to adult development stages. Programmes and policies should be based on age-related contextualisation to increase MHS use.

mental health
development
Andersen’s model
Service utilisation
emerging adulthood
middle adulthood


The Influence of Composition and Manufacturing Approach on the Physical and Rehydration Properties of Milk Protein Concentrate Powders.

Abstract: This study investigated the physical and rehydration properties of milk protein concentrate (MPC) powders with five different protein contents (i.e., 38.9, 53.7, 63.6, 74.1, and 84.7%, w/w) prepared by recombining the ultrafiltration (UF) retentate and UF permeate of skim milk. Powder density and flowability increased, while the powder particle size decreased with decreasing powder protein content. The amount of non-wetting MPC powder decreased with decreasing protein content, demonstrating greater wettability for lower protein powders. At protein contents >65% (w/w), the dispersibility and solubility of the powders decreased significantly, likely due to the greater hydrophobic interactions between casein proteins and a lower concentration of lactose. Therefore, as the protein content of the MPC powders was decreased, their rehydration properties improved. The results obtained in this study provide novel insights into the relationship between the composition of recombined UF retentate and UF permeate streams on the subsequent powder particle size, density, and rehydration properties, and demonstrate that such powders possess similar properties to those prepared using conventional direct membrane filtration.

rehydration
milk protein concentrate powder
solubility
spray drying


Bacterial identification by lipid profiling using liquid atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry.

Abstract: Background In recent years, mass spectrometry (MS) has been applied to clinical microbial biotyping, exploiting the speed of matrix-assisted laser desorption/ionization (MALDI) in recording microbe-specific MS profiles. More recently, liquid atmospheric pressure (AP) MALDI has been shown to produce extremely stable ion flux from homogenous samples and 'electrospray ionization (ESI)-like' multiply charged ions for larger biomolecules, whilst maintaining the benefits of traditional MALDI including high tolerance to contaminants, low analyte consumption and rapid analysis. These and other advantages of liquid AP-MALDI MS have been explored in this study to investigate its potential in microbial biotyping. Methods Genetically diverse bacterial strains were analyzed using liquid AP-MALDI MS, including clinically relevant species such as Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Bacterial cultures were subjected to a simple and fast extraction protocol using ethanol and formic acid. Extracts were spotted with a liquid support matrix (LSM) and analyzed using a Synapt G2-Si mass spectrometer with an in-house built AP-MALDI source. Results Each species produces a unique lipid profile in the m/z range of 400-1100, allowing species discrimination. Traditional (solid) MALDI MS produced spectra containing a high abundance of matrix-related clusters and an absence of lipid peaks. The MS profiles of the bacterial species tested form distinct clusters using principle component analysis (PCA) with a classification accuracy of 98.63% using a PCA-based prediction model. Conclusions Liquid AP-MALDI MS profiles can be sufficient to distinguish clinically relevant bacterial pathogens and other bacteria, based on their unique lipid profiles. The analysis of the lipid MS profiles is typically excluded from commercial instruments approved for clinical diagnostics.

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


The effects of whole milk compared to skim milk and apple juice consumption in breakfast on appetite and energy intake in obese children: a three-way randomized crossover clinical trial.

Abstract:
Background
A limited number of studies have examined the effect of dairy on satiety and short-term energy intake among children; furthermore we are not aware of any study comparing high and low-fat dairy products regarding their effect on appetite and short-term energy intake. Our objective was to assess the effect skim milk (SM) compared to whole milk (WM) and apple juice (AJ) on satiety and energy intake at lunch among 10-12 y children with obesity.

Methods
Fifty children with obesity who aged 10-12 y were randomized to consume a fixed content breakfast with 240 ml of SM, AJ, or WM for two consecutive days. The study was a three-way randomized crossover study; therefore each participant served as his/her own control. The total appetite, hunger, fullness, desire to eat and prospective consumption were measured using a visual analogue scale (VAS) before breakfast and every one hour after breakfast until a freely consumed lunch. VAS scores and energy intakes were compared using repeated measures procedure.

Results
Forty-eight participants (24 girls and 24 boys) completed the study. The energy intake was not different between SM, AJ and WM periods (adjusted mean ± standard error (SE) of energy intake: SM = 831.27 ± 30.64 Kcal, AJ = 794.92 ± 28.72 Kcal, WM = 798.87 ± 24.09 Kcal; P = 0.56). The effect was the same for either gender. Children reported higher satiety score 4 h after drinking WM with breakfast compared with SM (P < 0.05). The same association was found only in girls. Furthermore, SM significantly reduced appetite compared to AJ, 2 h after preloads in girls (P < 0.05).

Conclusions
Full-fat milk may have favorable effects on satiety but not energy intake in subsequent meal compared to skim milk among the children with obesity. Future studies with longer follow-up periods are needed to confirm these results.

Trial registration
The study protocol was registered with the Iranian registry of clinical trials on 9th October 2016 (registration ID: IRCT2016072012571N5).

Skim milk
appetite
Energy intake
Full-fat milk
Child
dairy fat


Molecular epidemiology of rotavirus in four provinces of Angola before vaccine introduction.

Abstract: Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. J. Med. Virol. 88:1511-1520, 2016. © 2016 Wiley Periodicals, Inc.

Esteves|Aida|A| Nordgren|Johan|J| Pereira|Joana|J| Fortes|Filomeno|F| Dimbu|Rafael|R| Saraiva|Nilton|N| Mendes|Cristina|C| Istrate|Claudia|C|

D015023:Democratic Republic of the Congo


Social Media in Dermatology and an Overview of Popular Social Media Platforms.

Abstract:
Purpose of Review
Social media provides an accessible and increasingly popular avenue for sharing healthcare information, networking, and outreach in dermatology. We provide an overview of prominent social media platforms, also known as applications or apps, as well as a discussion of their influence and implications for the field.

Recent Findings
The various collaborative features of Facebook, Twitter, Instagram, TikTok, YouTube, Snapchat, and other emerging platforms have proven appealing to organizations and users seeking dermatology-related content and medical advice. However, the potential for propagation of inaccurate or even dangerous information is high.

Summary
Despite the risks associated with social media usage, dermatology can benefit from opportunities to connect and engage with audiences through these platforms. Dermatologists should be encouraged to increase their presence on multiple social media apps to dispel and counteract misleading posts with evidence-based knowledge.

Szeto|Mindy D|MD|
Mamo|Andrina|A|
Afrin|Antara|A|
Militello|Michelle|M|
Barber|Cara|C|0000-0003-4207-8634

Facebook
Twitter
Instagram
TikTok
YouTube
Social media applications


Pediatric laryngotracheal reconstruction with tissue-engineered cartilage in a rabbit model.

Abstract:
OBJECTIVES/HYPOTHESIS
To develop an effective rabbit model of in vitro- and in vivo-derived tissue-engineered cartilage for laryngotracheal reconstruction (LTR).

STUDY DESIGN
1) Determination of the optimal scaffold 1% hyaluronic acid (HA), 2% HA, and polyglycolic acid (PGA) and in vitro culture time course using a pilot study of 4 by 4-mm in vitro-derived constructs analyzed on a static culture versus zero-gravity bioreactor for 4, 8, and 12 weeks, with determination of compressive modulus and histology as outcome measures. 2) Three-stage survival rabbit experiment utilizing autologous auricular chondrocytes seeded in scaffolds, either 1% HA or PGA. The constructs were cultured for the determined in vitro time period and then cultured in vivo for 12 weeks. Fifteen LTRs were performed using HA cartilage constructs, and one was performed with a PGA construct. All remaining specimens and the final reconstructed larynx underwent mechanical testing, histology, and glycosaminoglycan (GAG) content determination, and then were compared to cricoid control specimens (n = 13) and control LTR using autologous thyroid cartilage (n = 18).

METHODS
1) One rabbit underwent an auricular punch biopsy, and its chondrocytes were isolated and expanded and then encapsulated in eight 4 by 4-mm discs of 1% HA, 2% HA, PGA either in rotary bioreactor or static culture for 4, 8, and 12 weeks, respectively, with determination of compressive modulus, GAG content, and histology. 2) Sixteen rabbits underwent ear punch biopsy; chondrocytes were isolated and expanded. The cells were seeded in 13 by 5 by 2.25-mm UV photopolymerized 1% HA (w/w) or calcium alginate encapsulated synthetic PGA (13 × 5 × 2 mm); the constructs were then incubated in vitro for 12 weeks (the optimal time period determined above in paragraph 1) on a shaker. One HA and one PGA construct from each animal was tested mechanically and histologically, and the remaining eight (4 HA and 4 PGA) were implanted in the neck. After 12 weeks in vivo, the most optimal-appearing HA construct was used as a graft for LTR in 15 rabbits and PGA in one rabbit. The seven remaining specimens underwent hematoxylin and eosin, Safranin O, GAG content determination, and flexural modulus testing. At 12 weeks postoperative, the animals were euthanized and underwent endoscopy. The larynges underwent mechanical and histological testing. All animals that died underwent postmortem examination, including gross and microhistological analysis of the reconstructed airway.

RESULTS
Thirteen of the 15 rabbits that underwent LTR with HA in vitro- and in vivo-derived tissue-engineered cartilage constructs survived. The 1% HA specimens had the highest modulus and GAG after 12 weeks in vitro. The HA constructs became well integrated in the airway, supported respiration for the 12 weeks, and were histologically and mechanically similar to autologous cartilage.

CONCLUSIONS
The engineering of in vitro- and in vivo-derived cartilage with HA is a novel approach for laryngotracheal reconstruction. The data suggests that the in vitro- and in vivo-derived tissue-engineered approaches may offer a promising alternative to current strategies used in pediatric airway reconstruction, as well as other head and neck applications.

LEVEL OF EVIDENCE
NA. Laryngoscope, 126:S5-S21, 2016.

Jacobs|Ian N|IN|
Redden|Robert A|RA|
Goldberg|Rachel|R|
Hast|Michael|M|
Salowe|Rebecca|R|
Mauck|Robert L|RL|
Doolin|Edward J|EJ|

D000818:Animals
D002358:Cartilage, Articular
D002478:Cells, Cultured
D019902:Chondrocytes
D004195:Disease Models, Animal
D007818:Laryngeal Diseases
D058753:Laryngoplasty
D010865:Pilot Projects
D011817:Rabbits
D023822:Tissue Engineering
D054457:Tissue Scaffolds
D014133:Tracheal Diseases

hyaluronic acid (HA)
Polyglycolic acid (PGA)
compressive modulus
glycosaminoglycan (GAG)
flexural modulus