Cytotoxicity, Intracellular Replication, and Contact-Dependent Pore Formation of Genotyped Environmental Legionella pneumophila Isolates from Hospital Water Systems in the West Bank, Palestine.

Abstract: Legionella pneumophila is the causative agent of Legionnaires' disease. Due to the hot climate and intermittent water supply, the West Bank, Palestine, can be considered a high-risk area for this often fatal atypical pneumonia. L. pneumophila occurs in biofilms of natural and man-made freshwater environments, where it infects and replicates intracellularly within protozoa. To correlate the genetic diversity of the bacteria in the environment with their virulence properties for protozoan and mammalian host cells, 60 genotyped isolates from hospital water systems in the West Bank were analyzed. The L. pneumophila isolates were previously genotyped by high resolution Multi Locus Variable Number of Tandem Repeat Analysis (MLVA-8(12)) and sorted according to their relationship in clonal complexes (VACC). Strains of relevant genotypes and VACCs were compared according to their capacity to infect Acanthamoeba castellanii and THP-1 macrophages, and to mediate pore-forming cytotoxicity in sheep red blood cells (sRBCs). Based on a previous detailed analysis of the biogeographic distribution and abundance of the MLVA-8(12)-genotypes, the focus of the study was on the most abundant L. pneumophila- genotypes Gt4(17), Gt6 (18) and Gt10(93) and the four relevant clonal complexes [VACC1, VACC2, VACC5 and VACC11]. The highly abundant genotypes Gt4(17) and Gt6(18) are affiliated with VACC1 and sequence type (ST)1 (comprising L. pneumophila str. Paris), and displayed seroroup (Sg)1. Isolates of these two genotypes exhibited significantly higher virulence potentials compared to other genotypes and clonal complexes in the West Bank. Endemic for the West Bank was the clonal complex VACC11 (affiliated with ST461) represented by three relevant genotypes that all displayed Sg6. These genotypes unique for the West Bank showed a lower infectivity and cytotoxicity compared to all other clonal complexes and their affiliated genotypes. Interestingly, the L. pneumophila serotypes ST1 and ST461 were previously identified by in situ-sequence based typing (SBT) as main causative agents of Legionnaires' disease (LD) in the West Bank at a comparable level. Overall, this study demonstrates the site-specific regional diversity of L. pneumophila genotypes in the West Bank and suggests that a combination of MLVA, cellular infection assays and hierarchical agglomerative cluster analysis allows an improved genotype-based risk assessment.

Zayed|Ashraf R|AR|0000-0002-4327-6168
Pecellin|Marina|M|
Jaber|Lina|L|
Butmeh|Suha|S|
Bahader|Shereen A|SA|
Steinert|Michael|M|
Höfle|Manfred G|MG|
Brettar|Ingrid|I|
Bitar|Dina M|DM|

genotype
Legionella pneumophila
virulence
clonal complex
Gt10(93)
VACC11
MLVA


Prevalence and Potential Predictors of Frailty among Community-Dwelling Older Persons in Northern Thailand: A Cross-Sectional Study.

Abstract: This study aimed to determine the prevalence and associated factors of frailty among Thai older persons. A cross-sectional study was conducted with a representative sample of 1806 older persons aged 60 years or older. Frailty was assessed by Fried's frailty phenotypes, which consists of five criteria, namely, unintended weight loss, exhaustion, slow walking, weak handgrip and decreased physical activity. Older people who met 3 in 5, 1-2 in 5, and none of the criteria were considered frail, pre-frail and non-frail respectively. The prevalence was calculated and multinomial logistic regression was performed. Prevalence rates of frailty, pre-frailty and non-frailty were 13.9% (95% CI 9.9 to 18.8), 50.9% (95% CI 47.5 to 54.1) and 35.1% (95% CI 31.5 to 39.9), respectively. Increasing age, lower education, having no spouse, poorer health perception, increasing number of comorbidities, osteoarthritis and smaller mid-arm circumference increased the risk of frailty (p < 0.001). The prevalence of geriatric frailty syndrome in this study was much higher than that of developed countries but was lower than that of less developed countries. Factors associated with frailty reflect common characteristics of disadvantaged older persons in Thailand.

prevalence
predictors
frailty
community-dwelling
older persons


Effects of 17β-estradiol on cardiac Na(+)/K(+)-ATPase in high fat diet fed rats.

Abstract: The aim of this study was to investigate in vivo effects of estradiol on Na(+)/K(+)-ATPase activity/expression in high fat (HF) diet fed rats. Adult male Wistar rats were fed normally (Control, n = 7) or with a HF diet (Obese, n = 14) for 10 weeks. After 10 weeks, half of the obese rats were treated with estradiol (Obese + Estradiol, n = 7, 40 μg/kg, i.p.) as a bolus injection and 24 h after treatment all the rats were sacrificed. Estradiol in vivo in obese rats in comparison with obese non-treated rats led to a statistically significant increase in concentration of serum Na(+) (p < 0.05), Na(+)/K(+)-ATPase activity (p < 0.01), expression of α1 (p < 0.01) and α2 (p < 0.05) subunit of Na(+)/K(+)-ATPase, both PI3K subunits p85 (p < 0.01), p110 (p < 0.05), and association of IRS-1 with p85 (p < 0.05), while significantly decrease expression of AT1 (p < 0.05) and Rho A (p < 0.01) proteins. Our results suggest that estradiol in vivo in pathophysiological conditions, such as obesity accompanied with insulin resistance stimulates activity and expression of Na(+)/K(+)-ATPase by a mechanism that involves the participation of IRS-1/PI3K/Akt signaling. In addition, the decreasing level of AT1 and Rho A proteins estradiol probably attenuates the detrimental effect of obesity to decreased IRS-1/PI3K association and consequently reduce Na(+)/K(+)-ATPase activity/expression.

Obradovic|Milan|M|
Zafirovic|Sonja|S|
Jovanovic|Aleksandra|A|
Milovanovic|Emina Sudar|ES|
Mousa|Shaker A|SA|
Labudovic-Borovic|Milica|M|
Isenovic|Esma R|ER|

D055504:Insulin Receptor Substrate Proteins


A history of FMD research and control programmes in Southeast Asia: lessons from the past informing the future.

Abstract: Foot and mouth disease (FMD) is a major animal health problem within Southeast Asia (SEA). Although Indonesia and more recently the Philippines have achieved freedom from FMD, the disease remains endemic on continental SEA. Control of FMD within SEA would increase access to markets in more developed economies and reduce lost productivity in smallholder and emerging commercial farmer settings. However, despite many years of vaccination by individual countries, numerous factors have prevented the successful control of FMD within the region, including unregulated 'informal' transboundary movement of livestock and their products, difficulties implementing vaccination programmes, emergence of new virus topotypes and lineages, low-level technical capacity and biosecurity at national levels, limited farmer knowledge on FMD disease recognition, failure of timely outbreak reporting and response, and limitations in national and international FMD control programmes. This paper examines the published research of FMD in the SEA region, reviewing the history, virology, epidemiology and control programmes and identifies future opportunities for FMD research aimed at the eventual eradication of FMD from the region.

D000822:Animal Husbandry
D000818:Animals
D001210:Asia, Southeastern
D035843:Biomedical Research
D003140:Communicable Disease Control
D019353:Endemic Diseases
D005536:Foot-and-Mouth Disease
D049673:History, 20th Century
D049674:History, 21st Century
D014730:Veterinary Medicine

Southeast Asia
Buffalo
cattle
foot and mouth disease virus
pig


Practitioner perspectives from seven health professional groups on core competencies in the context of chronic care.

Abstract: The prevalence of chronic illness is growing worldwide and management is increasingly undertaken by interprofessional teams, yet education is still generally provided in separate professions. The aim of this study was to explore the perspectives of New Zealand healthcare practitioners from seven professional groups involved in chronic care (general practice medicine, nursing, occupational therapy, pharmacy, physiotherapy, social work, and speech language therapy) on the core competencies required of those working in this area. The study was set in the context of the chronic care and shared decision-making (SDM) models. The core competencies for chronic care practitioners proposed by the World Health Organisation were used to shape the research questions. Focus groups with expert clinicians (n = 20) and semi-structured interviews with practitioners (n = 32) were undertaken. Findings indicated a high level of agreement that the core competencies were appropriate and relevant for chronic care practitioners but that many educational and practice gaps existed and interprofessional education in New Zealand was not currently addressing these gaps. Among the key issues highlighted for attention by educators and policy-makers were the following: teams and teamwork, professional roles and responsibilities, interprofessional communication, cultural competence, better engagement with patients, families, and carers, and common systems, information sharing and confidentiality.

Fouche|Christa|C| Kenealy|Timothy|T| Mace|Jennifer|J| Shaw|John|J|

D000328:Adult
D001291:Attitude of Health Personnel
D002908:Chronic Disease
D003219:Confidentiality
D003299:Cooperative Behavior
D054521:Cultural Competency
D003657:Decision Making
D005260:Female
D017144:Focus Groups
D006801:Humans
D033183:Interdisciplinary Communication
D007400:Interprofessional Relations
D007407:Interviews as Topic
D008297:Male
D009520:New Zealand
D010348:Patient Care Team
D011361:Professional Competence
D024382:Professional Role
D011368:Professional-Family Relations
D011369:Professional-Patient Relations

Focus groups
interviews
interprofessional education
professional competence
shared decision making


Variance analysis as a tool to predict the mechanism underlying synaptic plasticity.

Abstract:
BACKGROUND
The strength of synaptic transmission onto a neuron depends on the number of functional vesicle release sites (N), the probability of vesicle release (Pr), and the quantal size (Q). Statistical tools based on the quantal model of synaptic transmission can be used to acquire information on which of these parameters is the source of plasticity. However, quantal analysis depends on assumptions that may not be met at central synapses.

NEW METHOD
We examined the merit of quantal analysis to extract the mechanisms underlying synaptic plasticity by applying binomial statistics on the variance in amplitude of postsynaptic currents evoked at Schaffer collateral-CA1 (Sc-CA1) synapses in mouse hippocampal slices. We extend this analysis by combining the conventional inverse square of the coefficient of variation (1/CV2) with the variance-to-mean ratio (VMR).

RESULTS
This method can be used to assess the relative, but not absolute, contribution of N, Pr and Q to synaptic plasticity. The changes in 1/CV2 and VMR values correctly reflect experimental modifications of N, Pr and Q at Sc-CA1 synapses.

COMPARISON WITH EXISTING METHODS
While the 1/CV2 depends on N and Pr, but is independent of Q, the VMR is dependent on Pr and Q, but not on N. Combining both allows for a rapid assessment of the mechanism underlying synaptic plasticity without the need for additional electrophysiological experiments.

CONCLUSION
Combining the 1/CV2 with the VMR allows for a reliable prediction of the relative contribution of changes in N, Pr and Q to synaptic plasticity.

van Huijstee|Aile N|AN|
Kessels|Helmut W|HW|

Variance analysis
Plasticity
Synapses
Electrophysiology
AMPA-receptor


Small Caliber Bulletproof Test of Warships' Hulls.

Abstract: The article presents the characteristics of 1.3964 steel and the results of firing a 7.62 mm projectile with a steel core. A simplified Johnson-Cook material model for steel and projectile was used. Then, a FEM (finite element method) simulation was prepared to calibrate the material constants and boundary conditions necessary to be used in simulations of the entire hull model. It was checked how projectile modeling affects the FEM calculation results. After obtaining the simulation results consistent with the experimental results, using the model of a modern minehunter, the resistance of the ship's hull to penetration by a small-caliber projectile was tested.

FEM (finite element method)
minehunter
bullet resistance
fast-changing processes
impact resistance


Effectiveness of Inhaled Aromatherapy on Chemotherapy-Induced Nausea and Vomiting: A Systematic Review.

Abstract: Chemotherapy-induced nausea and vomiting (CINV) are among the most common and feared side effects of cancer treatments. Their presence has a negative impact on the quality of life and morbidity associated with the disease. Despite increasingly effective antiemetic treatments, 40% of cancer patients experience CINV during the acute or delayed phase of their treatment. This distressing experience lived through by a large number of people makes it a priority in the improvement of cancer patients and a daily concern for nurses in cancer care units. In an attempt to alleviate this problem, the idea of using aromatherapy as supportive care has led the authors to research the knowledge available on this subject.  The purpose of this systematic review was to examine the existing scientific evidence regarding the effectiveness of respiratory aromatherapy on CINV in addition to standard treatment compared with their recommended management in people with cancer.  Systematic review.  This review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines and queried six databases (PubMed, Scopus, Cochrane Database, Embase, CINAHL, and Google Scholar). An analysis of the risk of bias using the Cochrane "Risks of Bias" tools and a qualitative synthesis of the results of the studies were carried out.  Eleven studies were included, nine in adults and two in children. Seven out of nine studies showed statistically significant results in adults with either direct or dry inhalation. Four out of seven alleviated both nausea and vomiting thanks to peppermint, ginger essential oil; three decreased nausea only with chamomilla, ginger or cardamom essential oil. Atmospheric diffusion and the use of inhaled aromatherapy in children did not show any benefit.  Results appear promising for the use of direct inhaled aromatherapy in the management of CINV. However, most of the studies found the women concerned suffered from gynecologic cancers and had certain methodological limitations. Indeed, small samples and a wide variety of interventions were studied (different essential oils, number of drops of essential oils used, method of administration, etc.), making it impossible so far to generalize these results. Studies with a more robust methodology and larger samples will make it possible to confirm the potential usefulness of this complementary treatment.

chemotherapy-induced nausea and vomiting


Effect of quorum sensing and quorum sensing inhibitors on the expression of serine protease gene in Hafnia alvei H4.

Abstract: The serp gene codes for a protease that is considered to be an important factor associated with quorum sensing (QS)-based food spoilage caused by microorganisms. In this study, we evaluated the effect of temperature (4-37 °C) and QS inhibitors on the production of N-acyl-L-homoserine lactones (AHLs) and relative expression of the luxR/I, as well as serp in Hafnia alvei H4. Production of AHLs and expression of luxR/I were found to reach maximum levels at 10 °C, suggesting that the QS system of H. alvei H4 might have higher activity at low temperatures; similar result was also obtained for serp expression. Mutants of H. alvei H4 deficient in QS were used to identify the regulation of QS on serp expression. Significant reduction (P < 0.05) in serp expression was found in the mutants ∆luxR, ∆luxI, and ∆luxR/I, with ∆luxI and ∆luxR/I showing greater reduction than ∆luxR. Minimum inhibition concentrations (MIC) of Benzyl isothiocyanate and 3-Methylthiopropyl isothiocyanate for H. alvei H4 were determined to be 7.813 and 15.625 mM, respectively. Furthermore, the expression of serp, as well as that of luxR and luxI, was significantly repressed (P < 0.05) by the two QS inhibitors at 1/8 MIC and 1/16 MIC, indicating that these inhibitors might repress serp expression through affecting luxR and luxI expression in H. alvei H4. The findings of this study, therefore, suggested that food spoilage caused by H. alvei could be controlled through the application of QS inhibitors.

Zhu|Yaolei|Y| Sang|Xue|X| Li|Xue|X| Zhang|Yanan|Y| Hao|Hongshun|H| Bi|Jingran|J| Zhang|Gongliang|G| Hou|Hongman|H|

D015964:Gene Expression Regulation, Bacterial

Quorum sensing
Inhibitor
Serine protease
Hafnia alvei


Clinical Assessment of Fluid Balance is Incomplete for Colorectal Surgical Patients.

Abstract:
BACKGROUND AND AIMS
Fluid balance for the surgical patient has been proven very important for the postoperative outcome and development of complications. The aim of this study was to evaluate, for the first time in modern times, the accordance between nurse-based fluid charting (cumulated fluid balance) and body weight change for general surgical patients.

MATERIAL AND METHODS
This was a descriptive study with prospectively collected data from two clinical randomized multicenter trials. A total of 113 patients from American Society of Anesthesiology group I-III undergoing elective colorectal surgery were included. Cumulated fluid balance and body weight change were charted preoperatively and daily at the same time during a postoperative period of 6 days. Differences were calculated by subtracting cumulated fluid balance from body weight change (1 g = 1 mL), and agreement was assessed by making Bland-Altman plots as well as Pearson correlations.

RESULTS
From day 1 to 4, the mean difference between cumulated fluid balance and body weight change was below 0.4 kg/L. On day 5 and 6, the discrepancies increased with mean differences of, respectively, 1.2 kg/L (p < 0.002*) and 2 kg/L (p < 0.0001*). Bland-Altman plots showed increasingly poor agreement for all postoperative days with wide limits of agreement, ranging from more than 6 kg/L to almost 10 kg/L. Pearson correlations were moderate to strong at all times ranging from 0.437 (day 1) to 0.758 (day 4).

CONCLUSIONS
The accordance between cumulated fluid balance and body weight change for colorectal surgical patients is relatively good for the first four postoperative days, however, with large uncertainty, whereas on the fifth and sixth postoperative day, the discrepancy is statistically and clinically significant. The fluid chart cannot stand alone in interpretation of the patient's fluid balance; body weight and clinical judgment is indispensable.

patients
Body weight
colorectal surgery
postoperative period
fluid therapy
humans
water–electrolyte balance


Duodenal perforation in a 12-month old child with severe malaria.

Abstract: Peptic ulcer disease (PUD) in children remains rare and difficult to diagnose before the onset of complications. We report on a case of a 12-month child with perforated duodenal ulcer, association with malaria. The severity of the febrile presentation and the positive laboratory confirmation of malaria delayed the diagnosis of PUD. Surgical intervention was successful and without significant sequelae. An awareness of the possibility, and a lower threshold for considering PUD in children may help prevent complications.

Goldman|Nina|N| Punguyire|Damien|D| Osei-Kwakye|Kingsley|K| Baiden|Frank|F|

malaria
Peptic ulcer disease
children
intestinal perforation


17β-Hydroxysteroid dehydrogenase type 10 predicts survival of patients with colorectal cancer and affects mitochondrial DNA content.

Abstract: Mitochondrial energy production is reduced in tumor cells, and altered mitochondrial respiration contributes to tumor progression. Synthesis of proteins coded by mitochondrial DNA (mtDNA) requires the correct processing of long polycistronic precursor RNA molecules. Mitochondrial RNase P, composed of three different proteins (MRPP1, HSD10, and MRPP3), is necessary for correct RNA processing. Here we analyzed the role of RNase P proteins in colorectal cancer. High HSD10 expression was found in 28%; high MRPP1 expression in 40% of colorectal cancers, respectively. Expression of both proteins was not significantly associated with clinicopathological parameters. Survival analysis revealed that loss of HSD10 expression is associated with poor prognosis. Cox regression demonstrated that patients with high HSD10 tumors are at lower risk. High HSD10 expression was significantly associated with high mtDNA content in tumor tissue. A causal effect of HSD10 overexpression or knock down with increased or reduced mtDNA levels, respectively, was confirmed in tumor cell lines. Our data suggest that HSD10 plays a role in alterations of energy metabolism by regulating mtDNA content in colorectal carcinomas, and HSD10 protein analysis may be of prognostic value.

Amberger|Albert|A|
Deutschmann|Andrea J|AJ|
Traunfellner|Pia|P|
Moser|Patrizia|P|
Feichtinger|René G|RG|
Kofler|Barbara|B|
Zschocke|Johannes|J|


Long-Term Potato Virus X (PVX)-Based Transient Expression of Recombinant GFP Protein in Nicotiana benthamiana Culture In Vitro.

Abstract: Plant molecular farming has a great potential to produce valuable proteins. Transient expression technology provides high yields of recombinant proteins in greenhouse-grown plants, but every plant must be artificially agroinfiltrated, and open greenhouse systems are less controlled. Here, we propose to propagate agrobacteria-free plants with high-efficient long-term self-replicated transient gene expression in a well-controlled closed in vitro system. Nicotiana benthamiana plant tissue culture in vitro, with transient expression of recombinant GFP, was obtained through shoot induction from leaf explants infected by a PVX-based vector. The transient expression occurs in new tissues and regenerants due to the natural systemic distribution of viral RNA carrying the target gene. Gene silencing was delayed in plants grown in vitro, and GFP was detected in plants for five to six months. Agrobacteria-free, GFP-expressing plants can be micropropagated in vitro (avoiding an agroinfiltration step), "rejuvenated" through regeneration (maintaining culture for years), or transferred in soil. The mean GFP in the regenerants was 18% of the total soluble proteins (TSP) (0.52 mg/g of fresh leaf weight (FW). The highest value reached 47% TSP (2 mg/g FW). This study proposes a new method for recombinant protein production combining the advantages of transient expression technology and closed cultural systems.

transient expression
Nicotiana benthamiana
recombinant proteins
plant tissue culture
green fluorescent protein (GFP)
potato virus X (PVX)
viral vector


Cytomegalovirus and varicella zoster virus seropositivity of Iranian patients with multiple sclerosis: A population-based study.

Abstract: Multiple Sclerosis is a demyelinating disease of the central nervous system (CNS) affecting young individuals with age range of 20-40years of age. The precise mechanism underlying the disease is still unclear. Some viruses have been proposed to play roles in disease causation. In this study, we recruited 800 MS patients along with 1000 healthy individuals to determine the seropositivity of anti-CMV and anti-VZV IgG titers using enzyme-linked immunosorbent assay (ELISA). Our results showed significant higher titers of anti-CMV and anti-VZV IgG titers in serum of MS patients with respect to healthy individuals (for both p<0.001). It seems that CMV and VZV play a key role in MS pathogenesis.

Karampoor|Sajad|S| Zahednasab|Hamid|H| Ramagopalan|Sreeram|S| Mehrpour|Masoud|M| Etemadifar|Masoud|M| Alsahebfosoul|Fereshteh|F| Keyvani|Hossein|H|

Cytomegalovirus
Varicella zoster virus
Multiple sclerosis
Elisa


Development of an assay to simultaneously measure orotic acid, amino acids, and acylcarnitines in dried blood spots.

Abstract:
BACKGROUND
Orotic aciduria in the presence of hyperammonemia is a key indicator for a defect in the urea cycle, specifically ornithine transcarbamylase (OTC) deficiency. Current newborn screening (NBS) protocols can detect several defects of the urea cycle, but screening for OTC deficiency remains a challenge due to the lack of a suitable assay. The purpose of this study was to develop a high-throughput assay to measure orotic acid in dried blood spot (DBS) specimens as an indicator for urea cycle dysfunction, which can be readily incorporated into routine NBS.

METHODS
Orotic acid was extracted from DBS punches and analyzed using flow-injection analysis tandem mass spectrometry (FIA-MS/MS) with negative-mode ionization, requiring <2 min/sample run time. This method was then multiplexed into a conventional newborn screening assay for analysis of amino acids, acylcarnitines, and orotic acid.

RESULTS
We describe 2 assays which can quantify orotic acid in DBS: a stand-alone method and a combined method for analysis of orotic acid, amino acids, and acylcarnitines. Both methods demonstrated orotic acid recovery of 75-85% at multiple levels of enrichment. Precision was also comparable to traditional FIA-MS/MS methods. Analysis of residual presumptively normal NBS specimens demonstrated a 5:1 signal to noise ratio and the average concentration of orotic acid was approximately 1.2 μmol/l. The concentration of amino acids and acylcarnitines as measured by the combined method showed no significant differences when compared to the conventional newborn screening assay. In addition, retrospective analysis of confirmed patients and presumptively normal newborn screening specimens suggests potential for the methods to identify patients with OTC deficiency, as well as other urea cycle defects.

CONCLUSION
The assays described here quantify orotic acid in DBS using a simple extraction and FIA-MS/MS analysis procedures that can be implemented into current NBS protocols.

Held|Patrice K|PK|
Haynes|Christopher A|CA|
De Jesús|Víctor R|VR|
Baker|Mei W|MW|

Orotic acid
Newborn screening
Urea cycle defects
Ornithine transcarbamylase deficiency


Development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing CHO cell lines with optimized choline content.

Abstract: A chemically defined platform basal medium and feed media were developed using a single Chinese hamster ovary (CHO) cell line that produces a monoclonal antibody (mAb). Cell line A, which showed a peak viable cell density of 5.9 × 106 cells/mL and a final mAb titer of 0.5 g/L in batch culture, was selected for the platform media development. Stoichiometrically balanced feed media were developed using glucose as an indicator of cell metabolism to determine the feed rates of all other nutrients. A fed-batch culture of cell line A using the platform fed-batch medium yielded a 6.4 g/L mAb titer, which was 12-fold higher than that of the batch culture. To examine the applicability of the platform basal medium and feed media, three other cell lines (A16, B, and C) that produce mAbs were cultured using the platform fed-batch medium, and they yielded mAb titers of 8.4, 3.3, and 6.2 g/L, respectively. The peak viable cell densities of the three cell lines ranged from 1.3 × 107 to 1.8 × 107 cells/mL. These results show that the nutritionally balanced fed-batch medium and feeds worked well for other cell lines. During the medium development, we found that choline limitation caused a lower cell viability, a lower mAb titer, a higher mAb aggregate content, and a higher mannose-5 content. The optimal choline chloride to glucose ratio for the CHO cell fed-batch culture was determined. Our platform basal medium and feed media will shorten the medium-development time for mAb-producing cell lines.

Fed-batch culture
Choline
Chinese hamster ovary (CHO) cells
Chemically defined medium


Assessment of upper limb use in children with typical development and neurodevelopmental disorders by inertial sensors: a systematic review.

Abstract: Understanding development of bimanual upper limb (UL) activities in both typical and atypical conditions in children is important for: i) tailoring rehabilitation programs, ii) monitoring progress, iii) determining outcomes and iv) evaluating effectiveness of treatment/rehabilitation. Recent technological advances, such as wearable sensors, offer possibilities to perform standard medical monitoring. Body-worn motion sensors, mainly accelerometers, have shown very promising results but, so far, these studies have mainly focused on adults. The main aim of this review was to report the evidence of UL activity of both typically developing (TD) children and children with neurodevelopmental disorders (NDDs) that are reliably reported and comparable, using a combination of multiple wearable inertial sensors, both in laboratory and natural settings. Articles were selected from three research databases (PubMed, Web of Science and EBSCO). Included studies reported data on children aged 0-20 years old simultaneously wearing at least two inertial sensors on upper extremities. The collected and reported data were relevant in order to describe the amount of physical activity performed by the two ULs separately. A total of 21 articles were selected: 11 including TD, and 10 regarding NDDs. For each article, a review of both clinical and technical data was performed. We considered inertial sensors used for following aims: (i) to establish activity intensity cut-points; (ii) to investigate validity and reliability of specified markers, placement and/or number of inertial sensors; (iii) to evaluate duration and intensity of natural UL movements, defined motor tasks and tremor; and (iv) to assess efficacy of certain rehabilitation protocols. Our conclusions were that inertial sensors are able to detect differences in use between both hands and that all reviewed studies support use of accelerometers as an objective outcome measure, appropriate in assessing UL activity in young children with NDDs and determining intervention effectiveness. Further research on responsiveness to interventions and consistency with use in real-world settings is needed. This information could be useful in planning UL rehabilitation strategies.

Upper limb
Children
Typical development
Neurodevelopmental disorders
Inertial sensor
Actigraphs
Asymmetry
Bimanual activity
Hand dominance


Fear of coronavirus (COVID-19) and mental health outcomes in Palestine: The mediating role of social support.

Abstract: The current investigation was conducted to test the correlation between fear due to coronavirus (COVID-19) and mental health outcomes (stress, depression, and anxiety) and the mediating role of social support during the Covid-19 Pandemic in Palestine. Structural equation modeling (SEM) was performed to test the conceptual model, where fear of Covid-19 was considered as a predictor, social support as a mediating variable, and mental health (stress, depression, and anxiety) as outcomes. The participants involved were 370 Palestinians, 266 females, and the remaining were males. Participants were recruited through online methods; Facebook advertising, Network email, and Twitter during the COVID-19 in Palestine. Results of the study showed that fear related to COVID-19 was positively and significantly correlated with mental health outcomes (anxiety; r = .29, p < .01, depression; r = .25, p < .01, and stress; r = .36, p < .01), while negatively correlated to perceived emotional support (r = -.30, p < .01), support seeking (r = -.29, p < .01), and received support (r = -.31, p < .01). Results of SEM indicated a standardized total effect of social support on mental health outcomes (βX, M = -.57; p < .001), and an indirect but statistically significant effect (via social support, βX, M, Y = -. 286; p < .01). These results indicate that social support fully mediated the relationship between fear associated with COVID-19 and mental health distress (stress, depression, and anxiety). The current study supported previous findings demonstrating that fear related to COVID-19 positively correlated with mental health distress (depression, anxiety, and stress). In addition, social support mediated the relationship between fear of COVID19 and mental health outcomes. However, further investigations are needed to test the correlation between current study variables and other associated factors and develop intervention programs targeting affected populations during crises to enhance mental health outcomes.

COVID-19
Mental health outcomes
Palestine
Social support
Fear of disease


Clinical relevance of bone remodelling around conventional and conservative (short-stem) total hip arthroplasty implants.

Abstract: Based on data from the existing literature, we can safely suggest that bone mineral changes around cementless and cemented conventional femoral stems, and conservative femoral stems, are not predictive of either satisfactory or unsatisfactory total hip arthroplasty long term clinical outcomes. Additionally, studies with a follow up shorter than 5-10 years are perhaps clinically irrelevant. These observations may be helpful in interpreting the existing literature.

Bone remodeling
total hip arthroplasty
conventional femoral stem
conservative femoral stem
stress shielding


Systematic benchmark of ancient DNA read mapping.

Abstract: The current standard practice for assembling individual genomes involves mapping millions of short DNA sequences (also known as DNA 'reads') against a pre-constructed reference genome. Mapping vast amounts of short reads in a timely manner is a computationally challenging task that inevitably produces artefacts, including biases against alleles not found in the reference genome. This reference bias and other mapping artefacts are expected to be exacerbated in ancient DNA (aDNA) studies, which rely on the analysis of low quantities of damaged and very short DNA fragments (~30-80 bp). Nevertheless, the current gold-standard mapping strategies for aDNA studies have effectively remained unchanged for nearly a decade, during which time new software has emerged. In this study, we used simulated aDNA reads from three different human populations to benchmark the performance of 30 distinct mapping strategies implemented across four different read mapping software-BWA-aln, BWA-mem, NovoAlign and Bowtie2-and quantified the impact of reference bias in downstream population genetic analyses. We show that specific NovoAlign, BWA-aln and BWA-mem parameterizations achieve high mapping precision with low levels of reference bias, particularly after filtering out reads with low mapping qualities. However, unbiased NovoAlign results required the use of an IUPAC reference genome. While relevant only to aDNA projects where reference population data are available, the benefit of using an IUPAC reference demonstrates the value of incorporating population genetic information into the aDNA mapping process, echoing recent results based on graph genome representations.

Oliva|Adrien|A|0000-0001-9950-7220 Tobler|Raymond|R| Cooper|Alan|A| Llamas|Bastien|B| Souilmi|Yassine|Y|

benchmarking
ancient DNA
reference bias
alignment


Patent ductus arteriosus stenting: ductal dissection and spasm in pulmonary atresia with intact ventricular septum.

Abstract: Ductal dissection is rarely mentioned but intractable complication of ductal stenting. We demonstrate the dissection image under fluoroscopy and the use of a relatively large stent as an applicable treatment.

Patent ductus arteriosus stent
ductal dissection
ductal spasm


Four new synonyms and a new combination in Parnassia (Celastraceae).

Abstract: Parnassia yunnanensis had been previously described based on mixed specimens containing materials partially belonging to Parnassia cacuminum, which makes the application of Parnassia yunnanensis ambiguous. Therefore, we lectotypified Parnassia yunnanensis and meanwhile synonymized Parnassia lanceolata var. oblongipetala under it. Parnassia yunnanensis var. longistipitata was found more similar to Parnassia cacuminum rather than Parnassia yunnanensis, thus a new combination, Parnassia cacuminum var. longistipitata comb. nov. was proposed. Furthermore, other three names (Parnassia vevusta, Parnassia degeensis and Parnassia kangdingensis) were reduced to synonyms of Parnassia cacuminum too.

Parnassia Taxonomy lectotypification morphology


Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum.

Abstract: Aberrant sialylation in glycoproteins and glycolipids is a characteristic feature of malignancy. Human sialidases, which catalyze the removal of sialic acid residues from glycoconjugates, have been implicated in cancer progression. They have been detected in a wide variety of human cells and tissues, but few studies have focused on their existence in human serum. Among the four types identified to date, we previously demonstrated that plasma membrane-associated ganglioside sialidase (NEU3) is markedly upregulated in various human cancers, including examples in the colon and prostate. Here, using a sensitive assay method, we found a significant increase of sialidase activity in the serum of patients with prostate cancer compared with that in healthy subjects having low activity, if any. Activity was apparent with gangliosides as substrates, but only to a very limited extent with 4-methylumbelliferyl sialic acid, a good synthetic substrate for sialidases other than human NEU3. The serum sialidase was also almost entirely immunoprecipitated with anti-NEU3 antibody, but not with antibodies for other sialidases. Interestingly, sera additionally contained inhibitory activity against the sialidase and also against recombinant human NEU3. The sialidase and inhibitor activities could be separated by exosome isolation and by hydrophobic column chromatography. The serum sialidase was assessed by a sandwich ELISA method using two anti-NEU3 antibodies. The results provide strong evidence that the serum sialidase is, in fact, NEU3, and this subtype may, therefore, be a potential utility for novel diagnosis of human cancers.

Hata|Keiko|K| Tochigi|Tatsuo|T| Sato|Ikuro|I| Kawamura|Sadafumi|S| Shiozaki|Kazuhiro|K| Wada|Tadashi|T| Takahashi|Kohta|K| Moriya|Setsuko|S| Yamaguchi|Kazunori|K| Hosono|Masahiro|M| Miyagi|Taeko|T|

sialidase
ganglioside
prostate cancer
Cancer serum
diagnostic marker


Stabilizing lactate production through repeated batch fermentation of food waste and waste activated sludge.

Abstract: Bio-valorization of organic waste streams, such as food waste and waste activated sludge, to lactic acid (LA) has recently drawn much attention. It offers an opportunity for resource recovery, alleviates environmental issues and potentially turns a profit. In this study, both stable and high LA yield (0.72 ± 0.15 g/g total chemical oxygen demand) and productivity rate (0.53 g/L•h) were obtained through repeated batch fermentation. Moreover, stable solubilization and increase in the critical hydrolase activities were achieved. Depletions of ammonia and phosphorus were correlated with the LA production. The relative abundance of the key LA bacteria genera (i.e., Alkaliphilus, Dysgonomonas, Enterococcus and Bifidobacterium) stabilized in the repeated batch reactor at a higher level (44.5 ± 2.53%) in comparison with the batch reactor (26.2 ± 4.74%). This work show a practical way for the sustainable valorization of organic wastes to LA by applying the repeated batch mode during biological treatment.

Xu|Xianbao|X| Zhang|Wenjuan|W| Gu|Xia|X| Guo|Zhichao|Z| Song|Jian|J| Zhu|Daan|D| Liu|Yanbiao|Y| Liu|Yanan|Y| Xue|Gang|G| Li|Xiang|X| Makinia|Jacek|J|

Food waste
Waste activated sludge
Lactic acid
Co-fermentation


Kissing interactions for the design of a multicolour fluorescence anisotropy chiral aptasensor.

Abstract: The development of enantioselective assays and sensors has received much attention for the determination of enantiomeric impurities. Herein, we demonstrated that the previously reported aptamer kissing complex (AKC) assay strategy can be implemented for designing a chiral tool that allows both the simultaneous enantiomer quantification and the enantiopurity analysis. D- and L-arginine vasopressin (AVP) were employed as model enantiomeric targets. The D- and L-AVP engineered aptamers (aptaswitch) were used as recognition units whereas the Fluorescein or Texas Red labelled D- and L-hairpin probes (aptakiss) served as probes of the enantiomer-dependent AKC formation. The orthogonal fluorescence anisotropy signaling scheme at two different emission wavelengths permitted the concomitant sensing of the AVP enantiomers in a single sample, under a high-throughput microplate format. It was also shown that the AKC-based enantioselective sensor allowed the enantiomeric impurity detection at a level as low as 0.01%.

Chovelon|Benoit|B| Fiore|Emmanuelle|E| Faure|Patrice|P| Peyrin|Eric|E| Ravelet|Corinne|C|

Fluorescence anisotropy
Aptamer kissing complex
Enantiomeric purity
Orthogonal detection


Development of a silica monolith modified with Fe3O4 nano-particles in centrifugal spin column format for the extraction of phosphorylated compounds.

Abstract: In this study, citrate-stabilised iron oxide nano-particles (∼16 nm) have been immobilised on commercial silica monolithic centrifugal spin columns (MonoSpin) for the extraction of phosphorylated compounds. Two alternative strategies were adopted involving either direct electrostatic attachment to an aminated MonoSpin (single-layer method) in the first instance, or the use of a layer-by-layer method with poly(diallyldimethylammonium) chloride. Field-emission scanning electron spectroscopy and energy-dispersive X-ray spectroscopy was used for confirming notably higher coverage of nano-particles using the layer-by-layer method (2.49 ± 0.53 wt%) compared with the single-layer method (0.43 ± 0.30 wt%). The modified monolith was used for the selective separation/extraction of adenosine monophosphate, adenosine diphosphate and adenosine triphosphate with elution using a phosphate buffer. A reversed-phase liquid chromatographic assay was used for confirming that adenosine, as a non-phosphorylated control was not retained on the modified MonoSpin devices, whereas recovery of 80% for adenosine monophosphate, 86% for adenosine diphosphate and 82% for adenosine triphosphate was achieved.

Alwy|Ali|A|
Clarke|Sarah P|SP|
Brougham|Dermot F|DF|
Twamley|Brendan|B|
Paull|Brett|B|
White|Blánaid|B|
Connolly|Damian|D|

Silica monoliths
Centrifugal spin columns
Iron oxide
Nano particles
Nucleotide extraction


Integration of Microstrip Slot Array Antenna with Dye-Sensitized Solar Cells.

Abstract: This paper describes the integration of microstrip slot array antennas with dye-sensitized solar cells that can power array antennas at 5.8 GHz, ensuring normal communications. To appraise the antennas, a 2 × 2 circularly polarized microstrip slot array antenna integrated with dye-sensitized solar cells using a stacked design method was analyzed, fabricated and measured. The size of the entire array is 140 mm × 140 mm, where the size of each solar cell is 35 mm × 35 mm. The results show that the effect of the antenna has a slight influence on the output performance of the solar cells, and the interference of the output current of the solar cells to the antenna feeding system is negligible. The gain of the array antenna increases by 0.12 dB and the axial ratio is reduced to 1.50 dB after the integration of dye-sensitized solar cells. The integration saves a lot of space, and has the ability of self-sustaining power generation, thus providing reliable and long-term communication for various communication systems.

Bai|Bowen|B|0000-0002-0971-4427 Zhang|Zheng|Z| Li|Xiaoping|X| Sun|Chao|C| Liu|Yanming|Y|

integration
dye-sensitized solar cells
antenna array
solar antenna


Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

Abstract:
BACKGROUND
A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers.

METHODS
A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed.

FINDINGS
155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition.

CONCLUSIONS
Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

genetics
genetic variation
medical
neurodegenerative diseases


Phosphorus sorption capacity of biochars from different waste woods and bamboo.

Abstract: Four biochars were made via pyrolysis at 500 °C using different waste plant materials, including tree branches from Cinnamonum campora (L.) Pres (CCP), Eriobotrya japonica (Thunb.) Lindl (EJL), Rohdea roth (RR) and bamboo shoots (Phyllostachys sulphurea) (PS). Phosphorus sorption capacities of the biochars were studied by isothermal experiments on their sorption kinetics. Results show that P sorption to the three wood biochars (CCP, EJL, and RR) fitted well with Lagergren pseudo second order model. However, P release was found in the PS biochar and sand amended with the PS biochar treatments during the isothermal sorption experiment. Phosphorus sorption capacity of the CCP biochar, EJL biochar and RR biochar was 4,762.0, 2, 439.0 and 1, 639.3 mg/kg, respectively. The CCP biochar showed the highest P sorption capacity due to its higher pH, lower dissolved P content, larger surface area (23.067 m2/g) and pore volume (0.058 cm3/g). The PS biochar showed the lowest P sorption due to its higher dissolved P content, more carboxyl groups, and smaller surface area (2.982 m2/g) and pore volume (0.017 cm3/g). Results suggest that the CCP biochar could be a potential alternative adsorbent for P sorption, such as removing P in wastewater treatment by constructed wetlands.

Li|Yingxue|Y| Xu|Defu|D| Guan|Yidong|Y| Yu|Kewei|K| Wang|Wenhua|W|

phosphorus
sorption
Biochar
constructed wetland


Prevalence and factors associated with H. pylori infection in Saudi patients with dyspepsia.

Abstract:
Background
Helicobacter pylori (H. pylori) is a major cause of peptic ulcer disease (PUD) and chronic active gastritis that may progress to gastric cancer. Globally, it has been estimated that 50% or more of the world's population is infected by H. pylori, making it the most widespread infection across the globe.

Objectives
To determine the prevalence of H. pylori infection and to identify factors associated with H. pylori infection in Saudi patients presenting with dyspepsia.

Methods
In this prospective cross-sectional study, a total of 404 gastric biopsies were endoscopically obtained from 404 patients with dyspepsia from September 2014 to April 2016 (Jazan Province, Saudi Arabia). The specimens were analyzed using the real-time polymerase chain reaction (PCR). The data was examined using descriptive statistics as well as determining the prevalence, and employing Chi square and Fisher exact test. A p-value of ≤0.05 was considered statistically significant in examining the research hypotheses.

Results
The overall prevalence of H. pylori in Jazan Province was 46.5% (95% CI: 41.7-51.4) and the prevalence was lower among those > 55 years old. Prevalence was higher among urban (50.0%; 95% CI: 43.1-56.8) versus rural (42.1%; 95% CI: 35.1-49.3), but with no significant difference. Prevalence did not show significant difference among different Body Mass Index (BMI) categories, ranging from 40.2% to 47.7%. The prevalence of H. pylori in females was 47.1% (95% CI: 40.4-53.9) versus 45.6% (95% CI: 38.7-52.6) in males. Histopathology findings were associated with H. pylori infection with prevalence of 58.1% among patients with chronic active gastritis, compared to 24.1% and 34.8% among mild and chronic gastritis, respectively.

Conclusion
Our results indicate that there is a high prevalence of H. pylori among Saudi patients with dyspepsia. Prevalence of H. pylori was high in ages below 55 years. Chronic active gastritis was significantly associated with H. pylori infection. In depth studies are needed to determine associated factors with of H pylori infection in the region.

Akeel|Mohammed|M|
Elmakki|Erwa|E|
Shehata|Atef|A|
Elhafey|Ahmed|A|
Aboshouk|Thanaa|T|
Ageely|Hussein|H|
Mahfouz|Mohammed Salih|MS|


Drug-carrier binding and enzymatic carrier digestion in amorphous solid dispersions containing proteins as carrier.

Abstract: In order to further explain the ability of gelatin 50PS and bovine serum albumin (BSA) to generate supersaturation of a series of poorly soluble drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole, naproxen, phenylbutazone and phenytoin), drug-polymer binding was investigated using solution NMR and equilibrium dialysis experiments. Binding characteristics of the biopolymers were compared to those of PVP, PVPVA and HPMC. Since both biopolymers are prone to enzymatic digestion, we evaluated the influence of proteolytic enzymes like pepsin and pancreatin on the dissolution properties of poorly soluble compounds when formulated as amorphous solid dispersions with gelatin 50PS and BSA. Evidence is being presented that supports the importance of drug-polymer binding in inducing and stabilizing supersaturation of poorly soluble drugs and enhancing dissolution from ASDs. In fact, BSA displayed drug binding with nearly all tested model drugs while in case of gelatin 50PS binding was observed for 5 out of 12 drugs. Addition of pepsin or pancreatin during dissolution of the biopolymer-containing ASDs leads to a drop in the concentration of the drug pointing to enzymatic digestion of the gelatin and BSA. However, after digestion, these formulations still outperformed their crystalline counterparts.

Pas|Timothy|T|
Bergonzi|Alessandra|A|
Lescrinier|Eveline|E|
Vergauwen|Bjorn|B|
Van den Mooter|Guy|G|

D004337:Drug Carriers
D065546:Drug Liberation
D005780:Gelatin
D010194:Pancreatin
D010434:Pepsin A
D004364:Pharmaceutical Preparations
D012710:Serum Albumin, Bovine

Darunavir Ethanolate (PubChem CID: 23725083)


Low-Temperature Growth of ZnO Nanowires from Gravure-Printed ZnO Nanoparticle Seed Layers for Flexible Piezoelectric Devices.

Abstract: Zinc oxide (ZnO) nanowires (NWs) are excellent candidates for the fabrication of energy harvesters, mechanical sensors, and piezotronic and piezophototronic devices. In order to integrate ZnO NWs into flexible devices, low-temperature fabrication methods are required that do not damage the plastic substrate. To date, the deposition of patterned ceramic thin films on flexible substrates is a difficult task to perform under vacuum-free conditions. Printing methods to deposit functional thin films offer many advantages, such as a low cost, low temperature, high throughput, and patterning at the same stage of deposition. Among printing techniques, gravure-based techniques are among the most attractive due to their ability to produce high quality results at high speeds and perform deposition over a large area. In this paper, we explore gravure printing as a cost-effective high-quality method to deposit thin ZnO seed layers on flexible polymer substrates. For the first time, we show that by following a chemical bath deposition (CBD) process, ZnO nanowires may be grown over gravure-printed ZnO nanoparticle seed layers. Piezo-response force microscopy (PFM) reveals the presence of a homogeneous distribution of Zn-polar domains in the NWs, and, by use of the data, the piezoelectric coefficient is estimated to be close to 4 pm/V. The overall results demonstrate that gravure printing is an appropriate method to deposit seed layers at a low temperature and to undertake the direct fabrication of flexible piezoelectric transducers that are based on ZnO nanowires. This work opens the possibility of manufacturing completely vacuum-free solution-based flexible piezoelectric devices.

Garcia|Andrés Jenaro Lopez|AJL|
Sico|Giuliano|G|
Montanino|Maria|M|
Defoor|Viktor|V|
Pusty|Manojit|M|0000-0003-1015-4057
Mescot|Xavier|X|
Loffredo|Fausta|F|
Villani|Fulvia|F|
Nenna|Giuseppe|G|
Ardila|Gustavo|G|0000-0003-1610-7788

gravure printing
flexible electronics
mechanical energy harvesting
nanogenerator chemical synthesis
piezoelectric sensor


Relation of Frailty to Outcomes in Percutaneous Coronary Intervention.

Abstract: There is growing awareness that frailty may be an important marker of adverse outcomes in PCI but there is no literature from national cohorts. This study examines a national cohort of patients who underwent percutaneous coronary intervention (PCI) regarding the prevalence of frailty, changes over time, and associated outcomes. The National Inpatients Sample was used to identify adults who underwent PCI procedures between 2004 and 2014. Frailty risk was measured using a validated Hospital Frailty Risk Score (HFRS) using the cutoffs <5, 5-15 and >15 for low, intermediate and high HFRS. From 7,306,007 admissions, a total of 94.58% of admissions were for patients who had a low HFRS(<5), 5.39% had an intermediate HFRS(5-15) and 0.03% had a high HFRS(>15). The prevalence of intermediate or high frailty risk patients has increased over time from 1.9% in 2004 to 11.7% in 2014. The incidence of in-hospital death increased from 1.0% with low HFRS to 13.9% with high HFRS. Mean length of stay also increased from 2.9 days to 17.1 days from low to high HFRS. High frailty risk was independently associated with an OR 9.91 95%CI 7.17-13.71 for in-hospital death, OR 4.99 95%CI 3.82-6.51 for bleeding and OR 3.96 95%CI 3.00-5.23 for vascular injury as compared to patients with low risk of HFRS. While rare in frequency overall, frailty is increasing in prevalence in recent years and intermediate and high HFRS associated with increased odds of mortality compared to low risk of frailty.

Kwok|Chun Shing|CS|
Achenbach|Stephan|S|
Curzen|Nick|N|
Fischman|David L|DL|
Savage|Michael|M|
Bagur|Rodrigo|R|
Kontopantelis|Evangelos|E|
Martin|Glen P|GP|
Steg|P Gabriel|PG|
Mamas|Mamas A|MA|

Frailty
Percutaneous coronary intervention
Mortality
Complications


Temporal air quality (NO2, O3, and PM10) changes in urban and rural stations in Catalonia during COVID-19 lockdown: an association with human mobility and satellite data.

Abstract: In this study, changes in air quality by NO2, O3, and PM10 in Barcelona metropolitan area and other parts of Catalonia during the COVID-19 lockdown with respect to pre-lockdown and to previous years (2018 and 2019) were evaluated. Selected air monitoring stations included 3 urban (Gràcia, Vall d'Hebron, and Granollers), 1 control site (Fabra Observatory), 1 semi-urban (Manlleu), and 3 rural (Begur, Bellver de Cerdanya, and Juneda). NO2 lockdown levels showed a diminution, which in relative terms was maximum in two rural stations (Bellver de Cerdanya, - 63% and Begur, - 61%), presumably due to lower emissions from the ceasing hotel and ski resort activities during eastern holidays. In absolute terms and from an epidemiologic perspective, decrease in NO2, also reinforced by the high amount of rainfall registered in April 2020, was more relevant in the urban stations around Barcelona. O3 levels increased in the transited urban stations (Gràcia, + 42%, and Granollers, + 64%) due to the lower titration effect by NOx. PM10 lockdown levels decreased, mostly in Gràcia, Vall d'Hebron, and Granollers (- 35, - 39%, and - 39%, respectively) due to traffic depletion (- 90% in Barcelona's transport). Correlation among mobility index in Barcelona (- 100% in retail and recreation) and contamination was positive for NO2 and PM10 and negative for O3 (P < 0.001). Satellite images evidenced two hotspots of NO2 in Spain (Madrid and Barcelona) in April 2018 and 2019 that disappeared in 2020. Overall, the benefits of lockdown on air quality in Catalonia were evidenced with NO2, O3 and PM10 levels below WHOAQG values in most of stations opposed to the excess registered in previous years.


Fragile X Mental Retardation Protein Bidirectionally Controls Dendritic Ih in a Cell Type-Specific Manner between Mouse Hippocampus and Prefrontal Cortex.

Abstract: Channelopathies are implicated in Fragile X syndrome (FXS), yet the dysfunction of a particular ion channel varies with cell type. We previously showed that HCN channel function is elevated in CA1 dendrites of the fmr1 -/y mouse model of FXS, but reduced in L5 PFC dendrites. Using male mice, we tested whether Fragile X Mental Retardation Protein (FMRPO), the protein whose absence causes FXS, differentially modulates HCN channels in CA1 versus L5 PFC dendrites. Using a combination of viral tools, intracellular peptide, and dendritic electrophysiology, we found that FMRP regulates HCN channels via a cell-autonomous protein-protein interaction. Virally expressed FMRP restored WT HCN channel-related dendritic properties in both CA1 and L5 neurons. Rapid intracellular perfusion of the non-mRNA binding N-terminal fragment, FMRP1-298, similarly restored dendritic function. In support of a protein-protein interaction, we found that FMRP associated with HCN-TRIP8b complexes in both hippocampus and PFC. Finally, voltage-clamp recordings showed that FMRP modulated Ih by regulating the number of functional dendritic HCN channels rather than individual channel properties. Together, these represent three novel findings as to the nature of the changes in dendritic function in CA1 and PFC neurons based on the presence or absence of FMRP. Moreover, our findings provide evidence that FMRP can regulate its targets in opposite directions depending upon the cellular milieu.SIGNIFICANCE STATEMENT Changes in dendritic function, and voltage-gated ion channels in particular, are increasingly the focus of neurological disorders. We, and others, previously identified cell type-specific channelopathies in a mouse of model of Fragile X syndrome. The present study shows that replacing Fragile X Mental Retardation Protein, which is absent in Fragile X syndrome, in adult CA1 and L5 PFC neurons regulates the number of functional dendritic HCN channels in a cell type-specific manner. These results suggest that Fragile X Mental Retardation Protein regulates dendritic HCN channels via a cell-autonomous protein--protein mechanism.

Brandalise|Federico|F|
Kalmbach|Brian E|BE|0000-0003-3136-8097
Mehta|Preeti|P|
Thornton|Olivia|O|
Johnston|Daniel|D|0000-0002-9733-1011
Zemelman|Boris V|BV|0000-0003-2463-4887
Brager|Darrin H|DH|0000-0002-3736-0515

D051860:Fragile X Mental Retardation Protein


Enhanced 3-epi-25-hydroxyvitamin D3 signal leads to overestimation of its concentration and amplifies interference in 25-hydroxyvitamin D LC-MS/MS assays.

Abstract:
BACKGROUND
3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3) interferes in most liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for 25-hydroxyvitamin D (25OHD). The clinical significance of this is unclear, with concentrations from undetectable to 230 nmol/L reported. Many studies have quantified 3-epi-25OHD3 based on 25OHD3 calibrators or other indirect methods, and we speculated that this contributes to the observed variability in reported 3-epi-25OHD3 concentrations.

METHODS
We compared continuous MS/MS infusions of 3-epi-25OHD3 and 25OHD3 solutions, spiked both analytes into the same serum matrix and analysed patient samples to assess the effect of three different quantitation methods on 3-epi-25OHD3 concentration. Experiments were performed on an LC-MS/MS system using a phenyl column which does not resolve 3-epi-25OHD3, and a modified method utilizing a Zorbax SB-CN column that chromatographically resolves 3-epi-25OHD3 from 25OHD3.

RESULTS
A greater 3-epi-25OHD3 signal, compared with 25OHD3, was observed during equimolar post-column continuous infusion of analyte solutions, and following analysis of a serum pool spiked with both analytes. 3-epi-25OHD3 signal enhancement was dependent on mobile phase composition. Compared with 3-epi-25OHD3 calibrators, indirect quantitation methods resulted in up to 10 times as many samples having 3-epi-25OHD3 concentrations ≥ 10 nmol/L, and an approximately fourfold increase in the maximum observed 3-epi-25OHD3 concentration to 95 nmol/L.

CONCLUSIONS
Enhanced 3-epi-25OHD3 signal leads to overestimation of its concentrations in the indirect quantitation methods used in many previous studies. The enhanced signal may contribute to greater interference in some 25OHD LC-MS/MS assays than others. We highlight that equimolar responses cannot be assumed in LC-MS/MS systems, even if two molecules are structurally similar.

3-epi-25-hydroxyvitamin D3
25-hydroxyvitamin D
LC-MS/MS
epimer
ionization


Varying Associations Between Body Mass Index and Physical and Cognitive Function in Three Samples of Older Adults Living in Different Settings.

Abstract:
BACKGROUND
The study investigates variations in the associations between body mass index (BMI) and (a) physical and (b) cognitive function across three samples of older adults living in different settings, and moreover determines if the association between BMI and physical function is confounded by cognitive abilities.

METHODS
One hundred ninety-five patients of a geriatric day hospital, 322 persons receiving home care (HC), and 183 nursing home (NH) residents were examined regarding BMI, cognitive (Mini-Mental State Examination), and physical function (Barthel Index for activities of daily living). Differences in Mini-Mental State Examination and activities of daily living scores between BMI groups (<22, 22-<25, 25-<30, 30-<35, ≥35kg/m(2)) were tested by analysis of covariance considering relevant confounders.

RESULTS
Activities of daily living and Mini-Mental State Examination impairments increased from the geriatric day hospital over the HC to the NH sample, whereas prevalence rates of obesity and severe obesity (35%, 33%, 25%) decreased. In geriatric day hospital patients cognitive and physical function did not differ between BMI groups. In the HC and NH samples, cognitive abilities were highest in obese and severely obese subjects. Unadjusted mean activities of daily living scores differed between BMI groups in HC receivers (51.6±32.2, 61.8±26.1, 67.5±28.3, 72.0±23.4, 66.2±24.2, p = .002) and NH residents (35.6±28.6, 48.1±25.7, 39.9±28.7, 50.8±24.0, 57.1±28.2, p = .029). In both samples significance was lost after adjustment indicating cognitive function as dominant confounder.

CONCLUSIONS
In older adults the associations between BMI and physical and cognitive function were dependent on the health and care status corresponding to the setting. In the HC and the NH samples, cognitive status, as measured by the Mini-Mental State Examination, emerged as an important confounder within the association between BMI and physical function.

Kiesswetter|Eva|E|
Schrader|Eva|E|
Diekmann|Rebecca|R|
Sieber|Cornel Christian|CC|
Volkert|Dorothee|D|

D000203:Activities of Daily Living
D000368:Aged
D000369:Aged, 80 and over
D015992:Body Mass Index
D003072:Cognition Disorders
D003631:Day Care, Medical
D004185:Disability Evaluation
D005260:Female
D015577:Geriatric Assessment
D006699:Home Care Services
D006801:Humans
D008297:Male
D009735:Nursing Homes
D012111:Residence Characteristics

Body mass index
Cognition
Physical function


Active Surveillance in Metastatic Renal Cell Carcinoma: Results From the Canadian Kidney Cancer Information System.

Abstract:
BACKGROUND
Active surveillance (AS) is a commonly used strategy in patients with slow-growing disease. We aimed to assess the outcomes and safety of AS in patients with metastatic renal cell carcinoma (mRCC).

PATIENTS AND METHODS
We used the Canadian Kidney Cancer information system (CKCis) to identify patients with mRCC diagnosed between January 1, 2011, and December 31, 2016. The AS strategy was defined as (1) the start of systemic therapy ≥ 6 months after diagnosis of mRCC, or (2) never receiving systemic therapy for mRCC with an overall survival (OS) of ≥1 year. Patients starting systemic treatment <6 months after diagnosis of mRCC were defined as receiving immediate systemic treatment. OS and time until first-line treatment failure (TTF) were compared between the two cohorts.

RESULTS
A total of 853 patients met the criteria for AS (cohort A). Of these, 364 started treatment >6 months after their initial diagnosis (cohort A1) and 489 never started systemic therapy (cohort A2); 827 patients received immediate systemic treatment (cohort B). The 5-year OS probability was significantly greater for cohort A than for cohort B (70% vs. 33.6%; P < .0001). After adjusting for International Metastatic RCC Database Consortium risk criteria and age, both OS (hazard ratio [HR] = 0.58; 95% confidence interval [CI], 0.47-0.70; P < .0001) and TTF (HR = 0.72; 95% CI, 0.60-0.85; P = .0002) were greater in cohort A1 compared with B. For cohort A1, the median time on AS was 14.2 months (range, 6-71).

CONCLUSIONS
Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of patients may be safely observed without immediate initiation of systemic therapy.

Kushnir|Igal|I|
Basappa|Naveen S|NS|
Ghosh|Sunita|S|
Lalani|Aly-Khan A|AA|
Hansen|Aaron R|AR|
Wood|Lori|L|
Kollmannsberger|Christian K|CK|
Heng|Daniel Y C|DYC|
Bjarnason|Georg A|GA|
Soulières|Denis|D|
Dawe|David E|DE|
Tanguay|Simon|S|
Breau|Rodney H|RH|
Pouliot|Frédéric|F|
Kapoor|Anil|A|
Graham|Jeffrey|J|
Reaume|M Neil|MN|

Surveillance
Metastatic
Renal cell carcinoma
Systemic therapy
Toxicity


Predictors of Early Neurologic Deterioration in Acute Pontine Infarction.

Abstract: Background and Purpose- The relationship between infarct dimensions and neurological progression in patients with acute pontine infarctions remains unclear. This study aimed to investigate the morphometric predictive value of magnetic resonance imaging for early neurological deterioration (END) in acute pontine infarction. Methods- We included all patients admitted to our department having an acute ischemic stroke in the pons. The ventrodorsal length multiplied by thickness was measured as parameters of infarct size. END was defined as an incremental increase in the National Institutes of Health Stroke Scale score by ≥1 point in motor power, or ≥2 points in the total score within the first week after admission. Results- We enrolled 407 patients, and 114 (28.0%) patients were diagnosed with END. Adjusted logistic regression analyses showed the maximum length multiplied by thickness was independently associated with END (odds ratio, 4.580 [95% CI, 2.909-7.210]). The sensitivity, specificity, and area under the curve were 77.2%, 79.2%, and 0.843, respectively, in the receiver operating characteristic curve analysis of maximum length multiplied by thickness for predicting END. Conclusions- These results suggest that the maximum length multiplied by thickness may be a possible predictor in the evaluation of progression with isolated acute pontine infarction. The extent of the pontine infarction along the conduction tract may contribute to deterioration.

Li|Haiyan|H| Dai|Yongqiang|Y| Wu|Haotian|H| Luo|Lingyun|L| Wei|Lei|L| Zhou|Li|L| Lin|Yinyao|Y| Wang|Qiujing|Q| Lu|Zhengqi|Z|

D038524:Diffusion Magnetic Resonance Imaging

magnetic resonance imaging
brain stem stroke
prognosis
stroke in evolution


The matricellular protein periostin contributes to proper collagen function and is downregulated during skin aging.

Abstract:
BACKGROUND
Periostin is a secreted 90kDa matricellular protein, which is predominantly expressed in collagen-rich tissues. Collagen is the most abundant protein in mammals and has great tensile strength. Recent investigations have shown that periostin influences collagen fibrillogenesis and biomechanical properties of murine connective tissues.

OBJECTIVE
We investigated the function of periostin concerning collagen homeostasis during intrinsic and extrinsic skin aging. For this purpose, human skin samples of young and old donors as well as samples of photoaged and sun-protected skin areas were analyzed for periostin expression. Using in vitro models, we determined the cell types responsible for periostin expression and performed functional analyses with periostin knockdown cells.

METHODS
TaqMan Real-Time PCR, UV irradiation, knockdown experiments, immunostaining, electron microscopy, collagen degradation assay, collagen crosslink analysis.

RESULTS
Periostin expression is highest in the papillary dermis and downregulated during skin aging. Fibroblasts and non-follicular skin derived precursors were identified as main source for periostin expression in human skin. Periostin knockdown in fibroblasts has no effect on collagen expression, but results in an increased fibril diameter and aberrant collagen structure. This leads to an increased susceptibility of collagen toward proteases, whereas recombinant periostin protects collagen fibrils from degradation.

CONCLUSION
Our data show that periostin plays an important role for proper collagen assembly and homeostasis. During skin aging periostin expression decreases and contributes to the phenotype of aged skin.

Egbert|M|M|
Ruetze|M|M|
Sattler|M|M|
Wenck|H|H|
Gallinat|S|S|
Lucius|R|R|
Weise|J M|JM|

D053773:Transforming Growth Factor beta1

l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate

quantitative real-time polymerase chain reaction

P P P P P P U U U U U U U U U U U U U U U U U U M U M U U U U U U M R U U M U U


Five decades of research and theorization on clinical reasoning: a critical review.

Abstract: Clinical reasoning is a complex cognitive process that is essential to evaluate and manage a patient's medical problem. The aim of this paper was to provide a critical review of the research literature on clinical reasoning theories and models. To conduct our study, we applied the process of conducting a literature review in four stages in accordance with the approach of Carnwell and Daly. First, we defined the scope of the review as being limited to clinical reasoning theories and models in medical education. In the second stage, we conducted a search based on related words in PubMed, Google Scholar, PsycINFO, ERIC, ScienceDirect and Web of Science databases. In the third stage, we classified the results of the review into three categories, and in the fourth stage, we concluded and informed further studies. Based on the inclusion and exclusion criteria, 31 articles were eligible to be reviewed. Three theories and two models were recognized and classified into three categories. Several theories and models have been proposed in relation to clinical reasoning, but it seems that these theories and models could only explain part of this complex process and not the whole process. Therefore, to fulfill this gap, it may be helpful to build a Meta-model or Meta-theory, which unified all the models, and theories of clinical reasoning.

clinical reasoning
review
medical education


Discrimination between authentic and adulterated liquors by near-infrared spectroscopy and ensemble classification.

Abstract: Chinese liquor is one of the famous distilled spirits and counterfeit liquor is becoming a serious problem in the market. Especially, age liquor is facing the crisis of confidence because it is difficult for consumer to identify the marked age, which prompts unscrupulous traders to pose off low-grade liquors as high-grade liquors. An ideal method for authenticity confirmation of liquors should be non-invasive, non-destructive and timely. The combination of near-infrared spectroscopy with chemometrics proves to be a good way to reach these premises. A new strategy is proposed for classification and verification of the adulteration of liquors by using NIR spectroscopy and chemometric classification, i.e., ensemble support vector machines (SVM). Three measures, i.e., accuracy, sensitivity and specificity were used for performance evaluation. The results confirmed that the strategy can serve as a screening tool applied to verify adulteration of the liquor, that is, a prior step used to condition the sample to a deeper analysis only when a positive result for adulteration is obtained by the proposed methodology.

Chen|Hui|H| Tan|Chao|C| Wu|Tong|T| Wang|Li|L| Zhu|Wanping|W|

Authenticity
Liquor
Near-infrared
Support vector machines


Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets.

Abstract: The widely used lipid-lowering drug niacin is reported to induce hyperglycemia during chronic and high-dose treatments, but the mechanism is poorly understood. Recently, the niacin receptor [G-protein-coupled receptor, (GPR) 109a], has been localized to islet cells while its potential role therein remains unclear. We, therefore, aimed at investigating how GPR109a regulates islet beta-cell function and its downstream signaling using high-fat diet-induced obese mice and INS-1E beta cells. Eight-week niacin treatment elevated blood glucose concentration in obese mice with increased areas under the curve at oral glucose and intraperitoneal insulin tolerance tests. Additionally, niacin treatment significantly decreased glucose-stimulated insulin secretion (GSIS) but induced peroxisome proliferator-activated receptor gamma (Pparg) and GPR109a expression in isolated pancreatic islets; concomitantly, reactive oxygen species (ROS) were transiently increased, with decreases in GSIS, intracellular cyclic adenosine monophosphate (cAMP) accumulation and mitochondrial membrane potential (ΔΨm), but with increased expression of uncoupling protein 2 (Ucp2), Pparg and Gpr109a in INS-1E cells. Corroborating these findings, the decreases in GSIS, ΔΨm and cAMP production and increases in ROS, Pparg and GPR109a expression were abolished in INS-1E cells by GPR109a knockdown. Our data indicate that niacin-induced pancreatic islet dysfunction is probably modulated through activation of the islet beta-cell GPR109a-induced ROS-PPARγ-UCP2 pathways.

Chen|Lihua|L|
So|Wing Yan|WY|
Li|Stephen Y T|SY|
Cheng|Qianni|Q|
Boucher|Barbara J|BJ|
Leung|Po Sing|PS|

Insulin secretion
Reactive oxygen species
G-protein coupled receptor
Glucose homeostasis
Islet function
Pancreas


Biological Relativity Requires Circular Causality but Not Symmetry of Causation: So, Where, What and When Are the Boundaries?

Abstract: Since the Principle of Biological Relativity was formulated and developed there have been many implementations in a wide range of biological fields. The purpose of this article is to assess the status of the applications of the principle and to clarify some misunderstandings. The principle requires circular causality between levels of organization. But the forms of causality are also necessarily different. They contribute in asymmetric ways. Upward causation can be represented by the differential or similar equations describing the mechanics of lower level processes. Downward causation is then best represented as determining initial and boundary conditions. The questions tackled in this article are: (1) where and when do these boundaries exist? and (2) how do they convey the influences between levels? We show that not all boundary conditions arise from higher-level organization. It is important to distinguish those that do from those that don't. Both forms play functional roles in organisms, particularly in their responses to novel challenges. The forms of causation also change according to the levels concerned. These principles are illustrated with specific examples.

Noble|Raymond|R|
Tasaki|Kazuyo|K|
Noble|Penelope J|PJ|
Noble|Denis|D|

biological relativity
circular causality
downward causation
boundaries in physiology
entangled causation


Neuropeptides and breathing in health and disease.

Abstract: Regulatory neuropeptides control and regulate breathing in physiological and pathophysiological conditions. While they have been identified in the neurons of major respiratory areas, they can be active not only at the central level, but also at the periphery via chemoreceptors, vagal afferents, or locally within lungs and airways. Some neuropeptides, such as leptin or substance P, are respiratory stimulants; others, such as neurotensin, produce variable effects on respiration depending on the site of application. Some neuropeptides have been implicated in pathological states, such as obstructive sleep apnea or asthma. This article provides a concise review of the possible role and functions of several selected neuropeptides in the process of breathing in health and disease and in lung pathologies.

Kaczyńska|Katarzyna|K| Zając|Dominika|D| Wojciechowski|Piotr|P| Kogut|Ewelina|E| Szereda-Przestaszewska|Małgorzata|M|

Neuropeptides
Apnea
Asthma
Lung pathology
Control of breathing


Quantifying the Performance of Micro-Compartmentalized Directed Evolution Protocols.

Abstract: High-throughput, in vitro approaches for the evolution of enzymes rely on a random micro-encapsulation to link phenotypes to genotypes, followed by screening or selection steps. In order to optimise these approaches, or compare one to another, one needs a measure of their performance at extracting the best variants of a library. Here, we introduce a new metric, the Selection Quality Index (SQI), which can be computed from a simple mock experiment, performed with a known initial fraction of active variants. In contrast to previous approaches, our index integrates the effect of random co-encapsulation, and comes with a straightforward experimental interpretation. We further show how this new metric can be used to extract general protocol efficiency trends or reveal hidden selection mechanisms such as a counterintuitive form of beneficial poisoning in the compartmentalized self-replication protocol.

directed evolution
enrichment factor
self-selection


Pressure Equilibrium Time of a Cyclic-Olefin Copolymer.

Abstract: Integrative simulation techniques for predicting component properties, based on the conditions during processing, are becoming increasingly important. The calculation of orientations in injection molding, which, in addition to mechanical and optical properties, also affect the thermal shrinkage behavior, are modeled on the basis of measurements that cannot take into account the pressure driven flow processes, which cause the orientations during the holding pressure phase. Previous investigations with a high-pressure capillary rheometer (HPC) and closed counter pressure chamber (CPC) showed the significant effect of a dynamically applied pressure on the flow behavior, depending on the temperature and the underlying compression rate. At a constant compression rate, an effective pressure difference between the measuring chamber and the CPC was observed, which resulted in a stop of flow through the capillary referred to as dynamic compression induced solidification. In order to extend the material understanding to the moment after dynamic solidification, an equilibrium time, which is needed until the pressure signals equalize, was evaluated and investigated in terms of a pressure, temperature and a possible compression rate dependency in this study. The findings show an exponential increase of the determined equilibrium time as a function of the holding pressure level and a decrease of the equilibrium time with increasing temperature. In case of supercritical compression in the area of a dynamic solidification, a compression rate dependency of the determined equilibrium times is also found. The measurement results show a temperature-invariant behavior, which allows the derivation of a master curve, according to the superposition principle, to calculate the pressure equilibrium time as a function of the holding pressure and the temperature.

equilibrium time
cyclic-olefin copolymers
high-pressure capillary rheometer
counter pressure chamber
compression induced solidification


Left Atrial Localized Low-Voltage Areas Indicate Whole Left Atrial Electrophysiological Degeneration in Atrial Fibrillation Patients.

Abstract:
BACKGROUND
The efficacy of ablation targeting low-voltage areas (LVAs) is controversial, although LVA presence is well known to be associated with atrial fibrillation (AF) recurrence after ablation. AF substrate may not localize within LVAs.Methods and Results:This observational study enrolled 405 consecutive patients who underwent an initial AF ablation procedure. The left atrial (LA) voltage map was obtained after pulmonary vein isolation. LVAs were defined as areas with voltage <0.5 mV. To estimate whole LA electrophysiological degeneration, mean regional voltage at each of the 6 regions and LA total conduction velocity were measured. LVAs existed in 143 of 405 (35.3%) patients. Patients with LVAs demonstrated lower mean regional voltages throughout all 6 regions compared to those without LVAs (1.3 [1.8, 0.8] vs. 0.6 [1.0, 0.2] mV for the anterior wall, P<0.001). In contrast, LA conduction velocity was lower in patients with LVAs than in those without (0.89 [1.01, 0.74] vs. 0.93 [1.03, 0.87] m/s, P<0.001). Multivariate analysis revealed that low LA total conduction velocity and a higher number of regions with mean voltage reduction were independently associated with AF recurrence, although LVA presence was not.

CONCLUSIONS
Patients with localized LA LVAs were characterized by whole LA electrophysiological degeneration as assessed by mean regional voltage and conduction velocity. In addition, whole LA electrophysiological degeneration parameters were well associated with AF recurrence.

Kurata|Naoya|N| Masuda|Masaharu|M| Kanda|Takashi|T| Asai|Mitsutoshi|M| Iida|Osamu|O| Okamoto|Shin|S| Ishihara|Takayuki|T| Nanto|Kiyonori|K| Tsujimura|Takuya|T| Matsuda|Yasuhiro|Y| Hata|Yosuke|Y| Uematsu|Hiroyuki|H| Mano|Toshiaki|T|

Low-voltage areas
Atrial fibrillation
Ablation
Regional voltage
Conduction velocity


Photophobia and disability glare in adult patients with Marfan syndrome: a case-control study.

Abstract:
PURPOSE
The aim of the present study was to investigate photophobia and disability glare in adult patients with Marfan syndrome (MFS).

METHODS
In this case-control study, 44 patients with MFS (87 eyes) were compared to 44 controls (88 eyes), who were matched for age and sex. The subjects were asked to grade their photophobia and glare using 10-cm visual analogue scales (VAS), which were marked with 'never' at zero and 'always' at 10 -cm. In addition, disability glare was measured with C-Quant straylight meter.

RESULTS
The patients with MFS had significantly higher VAS scores than the controls in four out of seven statements related to photophobia and glare. When including cataract, spherical equivalent, iris colour, axial length and corneal curvature, three of the seven statements were still significantly different between the two groups. The mean straylight values were 1.29 ± 0.03 log(s) in the MFS group and 1.01 ± 0.03 log(s) in the control group (p < 0.001, mixed model). These differences remained significant after adjusting for cataract, spherical equivalent, iris colour, axial length and corneal curvature.

CONCLUSION
Patients with MFS reported more photophobia and had a higher straylight value than the control group. Awareness of these findings of more photophobia and glare in the MFS patients is important when counselling and treating these patients.

photophobia
disability glare
Marfan syndrome
ocular straylight


Primary congenital sacrococcygeal neuroblastoma: A case report with immunohistochemical study and review of literature.

Abstract: Primary localized congenital sacrococcygeal neuroblastomas (SCNs) are rare. Diagnosis is based on histological and immunohistochemical evaluation, which is indispensable not only for determining tumor type but also for predicting biological behavior. We report a rare case of congenital SCN in a 9-month-old baby girl. Based on clinical and radiological findings, a provisional diagnosis of solid variant of sacrococcygeal teratoma (SCT) was made. The swelling was entirely excised. On histopathological examination, diagnosis of neuroblastoma, differentiating type in the sacrococcygeal region was considered. On immunohistochemistry, the tumor cells showed immunoreactivity for markers such as neuronspecific enolase, chromogranin-A, synaptophysin, and cyclin D1. S-100 showed positive cytoplasmic immunoreactivity. CD99, leucocyte common antigen, PanCK, and epidermal growth factor receptor were nonreactive. Cyclin D1 showed strong nuclear immunoreactivity. p53 was negative and Ki67 labelling index was less than 1%. The immunohistochemical markers studied, confirmed the histopathological diagnosis, and the cell proliferative index markers indicated it to be a very low grade lesion. Postoperatively, the child is disease-free and has achieved normal milestones for age for period of 6 months.

Khandeparkar|Siddhi Gaurish Sinai|SG|
Deshmukh|Sanjay Digambar|SD|
Naik|Ajay M|AM|
Naik|Pooja Suresh|PS|
Shinde|Jeevan|J|

sacrococcygeal neuroblastoma
neuroblastoma
Immunohistochemical markers


Intermittent electrical stimuli for guidance of human mesenchymal stem cell lineage commitment towards neural-like cells on electroconductive substrates.

Abstract: In the context of the role of multiple physical factors in dictating stem cell fate, the present paper demonstrates the effectiveness of the intermittently delivered external electric field stimulation towards switching the stem cell fate to specific lineage, when cultured in the absence of biochemical growth factors. In particular, our findings present the ability of human mesenchymal stem cells (hMSCs) to respond to the electric stimuli by adopting extended neural-like morphology on conducting polymeric substrates. Polyaniline (PANI) is selected as the model system to demonstrate this effect, as the electrical conductivity of the polymeric substrates can be systematically tailored over a broad range (10(-9) to 10 S/cm) from highly insulating to conducting by doping with varying concentrations (10(-5) to 1 m) of HCl. On the basis of the culture protocol involving the systematic delivery of intermittent electric field (dc) stimulation, the parametric window of substrate conductivity and electric field strength was established to promote significant morphological extensions, with minimal cellular damage. A time dependent morphological change in hMSCs with significant filopodial elongation was observed after 7 days of electrically stimulated culture. Concomitant with morphological changes, a commensurate increase in the expression of neural lineage commitment markers such as nestin and βIII tubulin was recorded from hMSCs grown on highly conducting substrates, as revealed from the mRNA expression analysis using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) as well as by immune-fluorescence imaging. Therefore, the present work establishes the key role of intermittent and systematic delivery of electric stimuli as guidance cues in promoting neural-like differentiation of hMSCs, when grown on electroconductive substrates.

Mesenchymal stem cells
Electric field
Polyaniline
Substrate conductivity
Neural-like differentiation


Particle Characterization for a Protein Drug Product Stored in Pre-Filled Syringes Using Micro-Flow Imaging, Archimedes, and Quartz Crystal Microbalance with Dissipation.

Abstract: Micro-flow imaging (MFI) has been used for formulation development for analyzing sub-visible particles. Archimedes, a novel technique for analyzing sub-micron particles, has been considered as an orthogonal method to currently existing techniques. This study utilized these two techniques to investigate the effectiveness of polysorbate (PS-80) in mitigating the particle formation of a therapeutic protein formulation stored in silicone oil-coated pre-filled syringes. The results indicated that PS-80 prevented the formation of both protein and silicone oil particles. In the case of protein particles, PS-80 might involve in the interactions with the hydrophobic patches of protein, air bubbles, and the stressed surfaces of silicone oil-coated pre-filled syringes. Such interactions played a role in mitigating the formation of protein particles. Subsequently, quartz crystal microbalance with dissipation (QCM-D) was utilized to characterize the interactions associated with silicone oil, protein, and PS-80 in the solutions. Based on QCM-D results, we proposed that PS-80 likely formed a layer on the interior surfaces of syringes. As a result, the adsorbed PS-80 might block the leakage of silicone oil from the surfaces to solution so that the silicone oil particles were mitigated at the presence of PS-80. Overall, this study demonstrated the necessary of utilizing these three techniques cooperatively in order to better understand the interfacial role of PS-80 in mitigating the formation of protein and silicone oil particles.

Zheng|Songyan|S| Puri|Aastha|A| Li|Jinjiang|J| Jaiswal|Archana|A| Adams|Monica|M|


Shellfish consumption and health: A comprehensive review of human studies and recommendations for enhanced public policy.

Abstract: Shellfish, including various species of mollusks (e.g., clams, oysters, and mussels) and crustaceans (e.g., shrimp and crab), have been a cornerstone of healthy dietary recommendations. However, beyond providing basic nutrition needs, their health-promoting effects have been suggested to include inflammation reduction and prevention of various chronic non-communicable diseases. Currently, studies on the association between shellfish consumption and health outcomes have reported conflicting results. The present comprehensive review summarized the latest studies on shellfish consumption and synthesized the available evidence on the potential health benefits or risks of shellfish consumption. The findings demonstrated that shellfish consumption may increase the risk of hyperuricemia and gout but may not increase the risk of type 2 diabetes, cardiovascular diseases, and thyroid cancer. Adequate evidence is lacking on the association between shellfish consumption and the risk of colorectal cancer, pancreatic cancer, oral cancer, endometriosis, hip fracture, cognitive function, wheeze, eczema and food allergy. Raw shellfish consumption may cause gastroenteritis and other diseases infected by bacteria or viruses. This review thus provides consumers and other relevant stakeholders with the latest evidence-based information on the potential benefits and risks of shellfish consumption.

Xu|Lei|L| Cai|Jing|J| Gao|Tianlin|T| Ma|Aiguo|A|

shellfish
health
review
shrimp
Seafood
chronic diseases


The Imperative for Diversity and Inclusion in Interventional Radiology.

Abstract: OBJECTIVE. The purpose of our study was to review key social justice and competitive advantage arguments for diversity in interventional radiology (IR) to substantiate the need for a more inclusive workforce. CONCLUSION. As a specialty based on innovation and flexibility of thought, IR is well positioned to be a driver of diversity and inclusion in medicine. The status quo is far from ideal. Social justice and business advantage arguments provide us with the imperative for change.

Higgins|Mikhail C S S|MCSS|
Beeram|Indeevar R|IR|

D018864:Cultural Diversity
D054625:Healthcare Disparities
D006801:Humans
D015642:Radiology, Interventional
D012935:Social Justice
D014481:United States
D000078329:Workforce

diversity and inclusion
interventional radiology
social justice
competitive advantage
equity
performance excellence


Synthesis methods influence characteristics, behaviour and toxicity of bare CuO NPs compared to bulk CuO and ionic Cu after in vitro exposure of Ruditapes philippinarum hemocytes.

Abstract: Copper oxide (CuO) nanoparticles (NPs) are increasingly investigated, developed and produced for a wide range of industrial and consumer products. Notwithstanding their promising novel applications, concern has been raised that their increased use and disposal could consequently increase their release into marine systems and potentially affect species within. To date the understanding of factors and mechanisms of CuO (nano-) toxicity to marine invertebrates is still limited. Hence, we studied the characteristics and behaviour of two commercially available CuO NPs of similar size, but produced employing distinct synthesis methods, under various environmentally and experimentally relevant conditions. In addition, cell viability and DNA damage, as well as gene expression of detoxification, oxidative stress, inflammatory response, DNA damage repair and cell death mediator markers were studied in primary cultures of hemocytes from the marine clam Ruditapes philippinarum and, where applicable, compared to bulk CuO and ionic Cu (as CuSO4) behaviour and effects. We found that the synthesis method can influence particle characteristics and behaviour, as well as the toxicity of CuO NPs to Ruditapes philippinarum hemocytes. Our results further indicate that under the tested conditions aggregating behaviour influences the toxicity of CuO NPs by influencing their rate of extra- and intracellular dissolution. In addition, gene expression analysis identified similar transcriptional de-regulation for all tested copper treatments for the here measured suite of genes. Finally, our work highlights various differences in the aggregation and dissolution kinetics of CuO particles under environmental (marine) and cell culture exposure conditions that need consideration when extrapolating in vitro findings.

Volland|Moritz|M|
Hampel|Miriam|M|
Katsumiti|Alberto|A|
Yeste|María Pilar|MP|
Gatica|José Manuel|JM|
Cajaraville|Miren|M|
Blasco|Julián|J|

Synthesis method
Toxicity
Hemocytes
Clams
CuO nanoparticles
Ionic copper


Lack of adverse health effects following 30-weeks of dietary exposure to acrylamide at low doses in male F344 rats.

Abstract: Understanding the health hazards following exposure to food-borne acrylamide, especially at low levels typified by human diets, is an ongoing food safety issue. We recently published results from a study that aimed to understand the effects of acrylamide short-term exposure at doses known to cause tumors in rodents, demonstrating that a number of key toxicological end points were altered by acrylamide exposure. Additionally, we reported that at much lower doses for 30 weeks of exposure, dietary acrylamide was 'not a complete carcinogen' to the colon in an organ-specific rodent carcinogenesis study but acted as a co-carcinogen along with azoxymethane (AOM, a colon-specific carcinogen). Here, we present toxicological data from a sub-set of this long-term exposure study from animals that received saline (instead of AOM). Briefly, male F344 rats were randomized to receive acrylamide at 0.5, 1.0 and 2.0 mg/kg diet (∼0.02, 0.04, and 0.09 mg/kg BW/day, respectively) or no acrylamide (control), for 30 weeks; all rats were then euthanized and their tissues harvested and processed for toxicological evaluation. We report that at the doses tested, acrylamide did not cause any changes in general well-being, body weight or food intake. Similarly, acrylamide did not cause any biologically relevant change in parameters associated with immunophenotyping, serum biochemistry or hematology. Histopathology assessment of tissues showed no changes except in the testis, where non-specific mild lesions were observed in all the groups, inclusive of the controls. No neuropathological effects of acrylamide were observed in the brain and nerve tissues. Together, these results suggest that acrylamide administered to rats through the diet at low doses for 30 weeks did not cause any toxicologically relevant changes. Given that the doses of acrylamide in the current study are low and are comparable to human dietary exposure, this null-effect study provides data that contribute to the body of scientific evidence relevant to understanding the health effects of acrylamide.

Raju|Jayadev|J| Kocmarek|Andrea|A| Roberts|Jennifer|J| Taylor|Marnie|M| Patry|Dominique|D| Chomyshyn|Emily|E| Caldwell|Don|D| Cooke|Gerard|G| Mehta|Rekha|R|

Acrylamide
F344 rats
Diet
Hematology
Clinical biochemistry
Pathology
Testosterone
Toxicity