Blood flow in intracranial aneurysms treated with Pipeline embolization devices: computational simulation and verification with Doppler ultrasonography on phantom models.

Abstract:
PURPOSE
The aim of this study was to validate a computational fluid dynamics (CFD) simulation of flow-diverter treatment through Doppler ultrasonography measurements in patient-specific models of intracranial bifurcation and side-wall aneurysms.

METHODS
Computational and physical models of patient-specific bifurcation and sidewall aneurysms were constructed from computed tomography angiography with use of stereolithography, a three-dimensional printing technology. Flow dynamics parameters before and after flow-diverter treatment were measured with pulse-wave and color Doppler ultrasonography, and then compared with CFD simulations.

RESULTS
CFD simulations showed drastic flow reduction after flow-diverter treatment in both aneurysms. The mean volume flow rate decreased by 90% and 85% for the bifurcation aneurysm and the side-wall aneurysm, respectively. Velocity contour plots from computer simulations before and after flow diversion closely resembled the patterns obtained by color Doppler ultrasonography.

CONCLUSION
The CFD estimation of flow reduction in aneurysms treated with a flow-diverting stent was verified by Doppler ultrasonography in patient-specific phantom models of bifurcation and side-wall aneurysms. The combination of CFD and ultrasonography may constitute a feasible and reliable technique in studying the treatment of intracranial aneurysms with flow-diverting stents.

Intracranial aneurysm
Ultrasonography
Endovascular procedures
Flow diverter
Printing, three-dimensional


Modulatory effect of zingerone against cisplatin or γ-irradiation induced hepatotoxicity by molecular targeting regulation.

Abstract: Zingerone (ZO) is an ingredient of ginger (Zingiber officinale) which has different pharmacological properties. The objective of this research was to evaluate the protective effect of ZO against Cisplatin (Cis) or γ-Irradiation (IR)-induced hepatotoxicity in rats. ZO was given orally for consecutive 14 days prior to the treatment with Cis or exposure to IR at 15th day. Animals were sacrificed at the 23rd day. Cis or IR induced a marked increase in MAPK signal transduction as evidenced by increased p38 MAPK, JNK and ErK1/2. CYP2E1 and NADPH oxidase were significantly up-regulated. Inflammatory markers (TLR4, iNOS, COX-2 and MPO) and liver enzymes (AST, ALT and ALP) activities were also increased. Administration of ZO significantly ameliorated the above mentioned parameters.

Mohamed|Hebatallah E|HE|
Badawy|Monda M M|MMM|

Zingerone Cisplatin γ-Irradiation Hepatotoxicity MAPK CYP2E1 TLR4


Chrysanthemum Morifolium Extract And Ascorbic Acid-2-Glucoside (AA2G) Blend Inhibits UVA-Induced Delayed Cyclobutane Pyrimidine Dimer (CPD) Production In Melanocytes.

Abstract:
Background
Solar ultraviolet radiation (UV) induces DNA damages in skin via direct absorption of UVB or indirectly by photosensitization mediated through UVA. Recent findings have revealed that UVA induces cyclobutane pyrimidine dimer (CPD) generation via chemiexcitation in melanocytes hours after the exposure. This UVA-induced delayed CPD (dark CPD) constitutes the majority of CPD in melanocytes. These findings indicate that sun light can damage the skin hours after the exposure, suggesting the need for skin care products post sun exposure. The main objective of this study was to investigate whether a blend of Chrysanthemum Morifolium flower extract (Chrys) and vitamin C derivative, Ascorbic Acid-2-Glucoside (AA2G), can provide protective effects against reactive oxygen species, melanin formation and UVA-induced dark CPD.

Methods
Intracellular ROS levels were measured in epidermal keratinocytes using DHR123 dye. Melanogenesis inhibition efficacy was determined using B16 cells. As for the dark CPD measurement, Melan-a cells were treated with or without actives for 6 days, then irradiated with UVA at various doses. Cells were exposed with anti-CPD mAb followed by secondary Ab. CPD levels were determined by measuring fluorescent intensity using a high content imaging analysis.

Results
Chrys, AA2G and their blend at various concentrations demonstrated ROS scavenging activity. Though Chrys alone did not show significant melanogenesis inhibition in B16 assay, the blend of Chrys with AA2G demonstrated additive effects in comparison with AA2G alone. The blend of AA2G and Chrys at various concentrations exhibited enhanced efficacy for inhibiting dark CPD compared to AA2G alone.

Conclusion
The results from this study indicate that the use of natural antioxidant, Chrys in combination with AA2G, provides protection against UVA-induced delayed CPD formation by enhancing ROS scavenging activity and melanogenesis inhibition. These findings could potentially be applied for formulating post-sun exposure skin care products, possibly extending to evening-after care products.

Yim|Sunghan|S|0000-0002-2525-6235
Lee|Jeesun|J|0000-0002-1702-7459
Jo|Hae|H|
Scholten|Jeff|J|
Willingham|Ryan|R|
Nicoll|Jim|J|
Baswan|Sudhir M|SM|0000-0003-4828-6856

chrysanthemum morifolium extract
ascorbic acid-2-glucoside
AA2G
cyclobutane pyrimidine dimers
CPD
melanocytes
DNA damage
dark CPD
cellular DNA photodamage


A macroscopic and histological analysis of radiographically well-defined deep and extremely deep carious lesions: carious lesion characteristics as indicators of the level of bacterial penetration and pulp response.

Abstract:
AIM
To investigate the relationship between radiographically and macroscopically well-defined carious lesions and the dentine-pulp complex with regard to: (i) level of bacterial penetration; (ii) inflammatory status including the presence of hyperplastic pulp stroma; and (iii) formation of hard and/or ectopic connective tissue.

METHODOLOGY
The material comprised 68 untreated cavitated permanent teeth divided into well-defined radiographic categories based on the lesion penetration depth: (i) deep lesions ( ≥3/4 of the dentine thickness with a radio-dense zone separating the lesion from the pulp) and (ii) extremely deep lesions (the carious lesion penetrated the entire thickness of the dentine, without a radio-dense zone). After extraction, the teeth were processed for histology. The material was scored with regard to coronal breakdown, macroscopic variables describing caries activity and histological variables describing the dentine-pulp complex (bacteria, inflammatory infiltrate, partial pulp necrosis, hyperplastic changes and hard tissue/ectopic presence of connective tissue). Interrater agreement was assessed using Cohen's kappa. Associations between variables were assessed using Pearson's chi-squared or Fisher's exact test. The effect size was reported by odds ratio (OR) and associated 95% confidence interval (CI). Level of significance was set to 5%.

RESULTS
There were significant associations between a closed environment (1-2 surfaces involved) and the presence of biofilm, retrograde demineralization and light-coloured demineralized dentine. Whereas radiographically defined deep lesions tended to have bacteria only in the primary dentine (P < 0.001, OR = 20.55, 95% CI [4.44, 107.89]), extremely deep carious lesions tended to have bacteria in contact with the pulpal tissue (P = 0.007, OR = 6.84, 95% CI [2.00, 62.83]), presence of an inflammatory infiltrate (Fisher's exact; P < 0.001) and partial pulp necrosis. Hyperplastic pulps were seen only in extremely deep lesions.

CONCLUSIONS
Unlike deep lesions, extremely deep carious lesions were often associated with severe pulp inflammation and infection. A radiographic threshold between deep and extremely deep lesions is suggested as indicator of the bacterial penetration level and the severity of the pulpal response prior to intervention.

caries
inflammation
dental pulp
lesion activity
polyps


Phytochemistry, Pharmacology, and Toxicology of Datura Species-A Review.

Abstract: Datura, a genus of medicinal herb from the Solanaceae family, is credited with toxic as well as medicinal properties. The different plant parts of Datura sp., mainly D. stramonium L., commonly known as Datura or Jimson Weed, exhibit potent analgesic, antiviral, anti-diarrheal, and anti-inflammatory activities, owing to the wide range of bioactive constituents. With these pharmacological activities, D. stramonium is potentially used to treat numerous human diseases, including ulcers, inflammation, wounds, rheumatism, gout, bruises and swellings, sciatica, fever, toothache, asthma, and bronchitis. The primary phytochemicals investigation on plant extract of Datura showed alkaloids, carbohydrates, cardiac glycosides, tannins, flavonoids, amino acids, and phenolic compounds. It also contains toxic tropane alkaloids, including atropine, scopolamine, and hyoscamine. Although some studies on D. stramonium have reported potential pharmacological effects, information about the toxicity remains almost uncertain. Moreover, the frequent abuse of D. stramonium for recreational purposes has led to toxic syndromes. Therefore, it becomes necessary to be aware of the toxic aspects and the potential risks accompanying its use. The present review aims to summarize the phytochemical composition and pharmacological and toxicological aspects of the plant Datura.

Sharma|Meenakshi|M|
Dhaliwal|Inderpreet|I|
Rana|Kusum|K|0000-0003-4061-224X
Delta|Anil Kumar|AK|
Kaushik|Prashant|P|

alkaloids
cardiac glycosides
atropine
hyoscamine
Ayurveda
Datura stramonium


Epigenetic regulation of Newborns' imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status.

Abstract:
BACKGROUND
Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood.

METHODS
We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010-2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences.

RESULTS
Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education.

CONCLUSIONS
Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers.

D001724:Birth Weight
D015331:Cohort Studies
D019175:DNA Methylation
D044127:Epigenesis, Genetic
D005006:Ethnicity
D005312:Fetal Blood
D047109:Fetal Development
D018392:Genomic Imprinting
D006801:Humans
D007231:Infant, Newborn
D009657:North Carolina
D009765:Obesity
D010290:Parents
D012044:Regression Analysis
D012923:Social Class
D013995:Time

GENETICS
PERINATAL EPIDEMIOLOGY
Social and life-course epidemiology


Insulin effects on honeybee appetitive behaviour.

Abstract: Worker honeybees (Apis mellifera) carry out multiple tasks throughout their adult lifespan. It has been suggested that the insulin/insulin-like signalling pathway participates in regulating behavioural maturation in eusocial insects. Insulin signalling increases as the honeybee worker transitions from nurse to food processor to forager. As behavioural shifts require differential usage of sensory modalities, our aim was to assess insulin effects on olfactory and gustatory responsiveness as well as on olfactory learning in preforaging honeybee workers of different ages. Adults were reared in the laboratory or in the hive. Immediately after being injected with insulin or vehicle (control), and focusing on the proboscis extension response, bees were tested for their spontaneous response to odours, sucrose responsiveness and ability to discriminate odours through olfactory conditioning. Bees injected with insulin have higher spontaneous odour responses. Sucrose responsiveness and odour discrimination are differentially affected by treatment according to age: whereas insulin increases gustatory responsiveness and diminishes learning abilities of younger workers, it has the opposite effect on older bees. In summary, insulin can improve chemosensory responsiveness in young workers, but also worsens their learning abilities to discriminate odours. The insulin signalling pathway is responsive in young workers, although they are not yet initiating outdoor activities. Our results show strong age-dependent effects of insulin on appetitive behaviour, which uncover differences in insulin signalling regulation throughout the honeybee worker's adulthood.

Mengoni Goñalons|Carolina|C|
Guiraud|Marie|M|
de Brito Sanchez|María Gabriela|MG|
Farina|Walter M|WM|0000-0001-6411-489X

Insulin
Apis mellifera
Sucrose
Odour discrimination
Associative learning
Chemosensory perception


Validity and reliability of smartphone-based pelvic rotation evaluations of children with cerebral palsy while sitting, standing, and standing on one leg.

Abstract:
PURPOSE
We explored the test-retest reliability of pelvic rotation measured using a smartphone and established criterion-related validity by analyzing simple linear regression between pelvic rotation data obtained using the smartphone and those measured by a palpation meter.

METHODS
We recruited 12 children with cerebral palsy (CP) (7 boys and 5 girls) and measured pelvic rotation using a smartphone application and a palpation meter in the sitting, standing, and one-leg standing positions. Test-retest reliability was evaluated by calculating intraclass correlation coefficients (ICCs); simple linear regression was analyzed to explore the relationships between smartphone and palpation meter data.

RESULTS
In terms of the test-retest reliability of pelvic rotation measured by the smartphone, the ICCs ranged from 0.85 to 0.95. A positive linear correlation was found between smartphone and palpation meter data.

CONCLUSIONS
We confirmed that measurement of pelvic rotation using a smartphone was reliable when children with CP were in the sitting, standing, and one-leg standing positions. In addition, pelvic rotation measured using the smartphone correlated significantly with that measured using a palpation meter.

pelvic rotation
Cerebral palsy
palpation meter


Stiffness reconstruction methods for MR elastography.

Abstract: Assessment of tissue stiffness is desirable for clinicians and researchers, as it is well established that pathophysiological mechanisms often alter the structural properties of tissue. Magnetic resonance elastography (MRE) provides an avenue for measuring tissue stiffness and has a long history of clinical application, including staging liver fibrosis and stratifying breast cancer malignancy. A vital component of MRE consists of the reconstruction algorithms used to derive stiffness from wave-motion images by solving inverse problems. A large range of reconstruction methods have been presented in the literature, with differing computational expense, required user input, underlying physical assumptions, and techniques for numerical evaluation. These differences, in turn, have led to varying accuracy, robustness, and ease of use. While most reconstruction techniques have been validated against in silico or in vitro phantoms, performance with real data is often more challenging, stressing the robustness and assumptions of these algorithms. This article reviews many current MRE reconstruction methods and discusses the aforementioned differences. The material assumptions underlying the methods are developed and various approaches for noise reduction, regularization, and numerical discretization are discussed. Reconstruction methods are categorized by inversion type, underlying assumptions, and their use in human and animal studies. Future directions, such as alternative material assumptions, are also discussed.

reconstruction
MR elastography
inverse problem
review
shear-modulus tissue stiffness


Intensity and clinical morbidities of tungiasis in an impoverished south-west Nigerian community.

Abstract: Sand fleas infestation, Tunga penetrans, remains a neglected tropical disease of public-health concern in many countries. Tungiasis can lead to destruction of the feet causing serious discomfort and deformities. This study aim was to determine the intensity rate and clinical morbidities of tungiasis among the people living in Igbokoda, Ondo State, Nigeria. A community-based cross-sectional survey was conducted among households in three villages in Igbokoda. Hands and feet of selected household members were examined, while fleas on different floor types of houses were sampled by soil collection and extraction by tullgren funnel method. Sand fleas were equally sampled from legs of infested individuals by hand picking. Intensity was determined in terms of number of lesions and fleas in different floor-types. Tungiasis-associated morbidities was assessed using acute and chronic lesions severity scores. The study revealed that moderate infestation was observed in 173 infested individuals and severe infestation in 16 infested individuals. A total of 5293 lesions was observed out of which 3098 were viable. The flea burdens on sampled floors and legs were 127 and 146 fleas respectively occurring mostly in unpaved veranda and rooms (65 and 62 fleas respectively). Tungiasis lesions observed in males were more intense compared to females. Flea lesions and burdens with respect to age stratification and location were significant P < 0.0001. Difficulty in walking, pain upon pressure and deformation of the feet were the most common tungiasis-associated morbidity recorded. Also, tungiasis-associated morbidities, and flea number sampled on legs and on floor of environment were reportedly intense. Therefore, scaling up an appropriate and affordable intervention approach targeted at the fleas would serve as a relief to the scourge of tungiasis in Igbokoda community.

Enwemiwe|Victor N|VN|
Ojianwuna|Cynthia C|CC|
Anyaele|Okorie O|OO|

Intensity
Clinical morbidity
Tungiasis
Tunga penetrans
Igbokoda


A Systematic Review of Health Promotion Programs to Improve Nutrition for People with Intellectual Disability.

Abstract:
PURPOSE OF REVIEW
To investigate the type and effectiveness of health promotion programs designed to improve nutrition for people with intellectual disability. This review also sought to highlight gaps in the evidence by mapping interventions to the socio-ecological model.

RECENT FINDINGS
To date, reviews on health promotion programs for people with intellectual disability have focused on individualised weight management interventions and behaviour change techniques. No reviews have focused solely on nutrition or considered a broader range of interventions and policies targeted beyond the individual. This review found that health promotion interventions to date were predominantly at the individual level of the socio-ecological model and of varying effectiveness. Of the non-individually focused interventions, those targeting the physical environment or considering multiple socio-ecological levels achieved the greatest improvements in nutrition outcomes. Nutrition and obesity prevention research and policy need to include intellectual disability as part of equity considerations, while intellectual disability policy needs to consider the broader food environment.

Health promotion
Nutrition
Intellectual disability
Socio-ecological model
Obesity
Equity


Long-term maintenance of limbal epithelial progenitor cells using rho kinase inhibitor and keratinocyte growth factor.

Abstract: Corneal epithelial stem cells are located in the limbus, the junction between the cornea and the conjunctiva. A limbal epithelium model in vitro would be useful for the study of epithelial stem cells, as well as improving the quality of cultivated epithelial sheets for the treatment of limbal stem cell deficiency. In this study, we succeeded in constructing a limbal epithelium-like structure that could be maintained for at least 5 months in vitro. We modified conventional medium by replacing epidermal growth factor with keratinocyte growth factor (KGF) and adding Y-27632, a rho kinase inhibitor. Using this medium, epithelial cells freshly isolated from human limbus were cocultured with human mesenchymal stem cell-derived feeder cells. Cells formed a stratified layer without air exposure, and both basal and suprabasal layers maintained their unique morphologies for up to 5 months. Basal layers expressed the progenitor marker p63 uniformly and K15 heterogeneously. Expressions of PAX6, K3, and K12 indicated that cell sheets underwent normal differentiation in the corneal epithelium lineage. Although medium was changed daily after day 7, cell debris was observed every day, suggesting that cell sheets underwent turnover. Furthermore, secondary colonies were observed from cells dissociated from 1-month and 3-month cultured sheets. In conclusion, human limbal epithelial cell sheet cultures with KGF and Y-27632 maintained stratification, high expression of both stem/progenitor markers and differentiation markers, and colony-forming cells long-term. This protocol may be useful as an in vitro limbal epithelial model for basic studies.

Miyashita|Hideyuki|H| Yokoo|Seiichi|S| Yoshida|Satoru|S| Kawakita|Tetsuya|T| Yamagami|Satoru|S| Tsubota|Kazuo|K| Shimmura|Shigeto|S|

D018929:Cell Culture Techniques
D018920:Coculture Techniques
D004847:Epithelial Cells
D051523:Fibroblast Growth Factor 7
D006801:Humans
D007150:Immunohistochemistry
D016850:Limbus Corneae
D059630:Mesenchymal Stem Cells
D013234:Stem Cells
D054460:rho-Associated Kinases

Differentiation
Adult stem cells
Cell culture
Colony formation
Experimental models
Long-term repopulation
Stem cell culture


Esthetic rehabilitation of discolored anterior teeth with porcelain veneers.

Abstract: The common man is bombarded by the media extolling the virtues of "the perfect smile." In the 21(st) century of esthetic dentistry, fractured, malformed, malposed, and discolored teeth can be changed and restored to highly desirable form due to introduction of wide range of esthetic materials and techniques. Porcelain veneers is a conservative method of restoring the appearance of discolored, pitted teeth, and teeth with diastemas that provide extremely good esthetic results. A 21-year-old female patient with staining in anterior teeth had reported to the Department of Prosthodontics for esthetic rehabilitation. The patient was treated with porcelain veneers on maxillary anterior teeth. The patient was satisfied with the enhanced esthetic appearance.

Kamble|Vaibhav D|VD|
Parkhedkar|Rambhau D|RD|

Esthetics
porcelain veneers
pitted teeth
fluorosis


Field effectiveness evaluation of advanced driver assistance systems.

Abstract:
OBJECTIVE
Advanced driver assistance systems (ADAS) are a class of vehicle technologies designed to increase safety by providing drivers with timely warnings and autonomously intervening to avoid hazardous situations. Though laboratory testing suggests that ADAS technologies will greatly impact crash involvement rates, real-world evidence that characterizes their effectiveness is still limited. This study evaluates and quantifies the association of ADAS technologies with the likelihood of a moderate or severe crash for new-model BMWs in the United States.

METHODS
Vehicle ADAS option information for the cohort of model year 2014 and later BMW passenger vehicles sold after January 1, 2014 (n = 1,063,503), was coded using VIN-identified options data. ADAS technologies of interest include frontal collision warning with autonomous emergency braking, lane departure warning, and blind spot detection. BMW Automated Crash Notification system data (from January 2014 to November 2017) were merged with vehicle data by VIN to identify crashed vehicles (n = 15,507), including date, crash severity (delta V), and area of impact. Using Cox proportional hazards regression modeling, the study calculates the adjusted hazard ratio for crashing among BMW passenger vehicles with versus without ADAS technologies. The adjusted percentage reduction in moderate and severe crashes associated with ADAS is interpreted as one minus the hazard ratio.

RESULTS
Vehicles equipped with both autonomous emergency braking and lane departure warning were 23% less likely to crash than those not equipped (hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.73-0.81), controlling for model year, vehicle size and body type. Autonomous emergency braking and lane departure warning generally occur together, making it difficult to tease apart their individual effects. Blind spot detection was associated with a 14% reduction in crashes after controlling for the presence of autonomous emergency braking and lane departure warning (HR =0.86; 95% CI, 0.744-0.99). Differences were observed by vehicle type and crash type. The combined effect of autonomous emergency braking and lane departure warning was greater in newer model vehicles: Equipped vehicles were 13% less likely to crash (HR =0.87; 95% CI, 0.79-0.95) among 2014 model year vehicles versus 34% less likely to crash (HR =0.66; 95% CI, 0.57-0.77) among 2017 model year vehicles.

CONCLUSION
This robust cohort study contributes to the growing evidence on the effectiveness of ADAS technologies.

Spicer|Rebecca|R|
Vahabaghaie|Amin|A|
Bahouth|George|G|
Drees|Ludwig|L|
Martinez von Bülow|Robert|R|
Baur|Peter|P|

D000063:Accidents, Traffic
D001334:Automobile Driving
D001336:Automobiles
D015331:Cohort Studies
D006801:Humans
D011482:Protective Devices
D012189:Retrospective Studies
D016019:Survival Analysis
D014481:United States


Preterm Infant Feeding: A Mechanistic Comparison between a Vacuum Triggered Novel Teat and Breastfeeding.

Abstract: The goal for preterm infants is to achieve full oral feeds quickly and ultimately progress to full breastfeeding. Supplementary oral feeds are often given when the mother is not available to breastfeed. Bottles typically deliver milk in a different fashion compared to breastfeeding, which is thought to hamper transition to full breastfeeding. The aim of this study was to compare the sucking dynamics of preterm infants fed at the breast to feeding with an experimental novel teat (NT) designed to release milk only upon the application of vacuum. Simultaneous ultrasound imaging of the infant oral cavity and measurement of intra-oral vacuum was performed during a breastfeed and a feed with the NT. Test weighs were used to measure milk intake. Linear mixed effects models were performed to investigate differences by feed type, and simultaneous linear regression was performed to investigate individual patterns. Tongue movement was not different between breastfeeding and the NT. Intra-oral vacuums (median (interquartile range: IQR)) were significantly lower with the NT (Baseline vacuum: -5.8 mmHg (-11.0, 0.1); Peak: 40.0 mmHg (-54.6, -27.1)) compared to breastfeeding (Baseline: -31.1 mmHg (-60.0, -12.7); Peak: -106.2 mmHg (-153.0, -65.5)). Milk intake was significantly higher with the NT (33 mL (22.5, 42.5)) compared to the breastfeed (12 mL (3, 15.5)). The novel teat encouraged a similar tongue action to breastfeeding, and infants transferred a greater volume of milk with the novel teat. Intra-oral vacuums were lower in strength with the novel teat compared to the breast. Use of the novel teat for the training of sucking dynamics in preterm infants has the potential to improve breastfeeding success and requires further investigation.

Geddes|Donna|D| Kok|Chooi|C| Nancarrow|Kathryn|K| Hepworth|Anna|A| Simmer|Karen|K|

D000367:Age Factors
D001724:Birth Weight
D001903:Bottle Feeding
D001942:Breast Feeding
D004867:Equipment Design
D005247:Feeding Behavior
D005260:Female
D005865:Gestational Age
D006801:Humans
D007223:Infant
D018730:Infant Behavior
D007230:Infant, Low Birth Weight
D007231:Infant, Newborn
D007234:Infant, Premature
D016014:Linear Models
D008297:Male
D013391:Sucking Behavior
D013997:Time Factors
D014061:Tongue Habits
D014618:Vacuum

preterm
infant
infant feeding
feeding
breastfeeding
bottle
human milk
nipple shield
premature


A practitioner's guide for exploring water quality patterns using principal components analysis and Procrustes.

Abstract: To design sustainable water quality monitoring programs, practitioners must choose meaningful variables, justify the temporal and spatial extent of measurements, and demonstrate that program objectives are successfully achieved after implementation. Consequently, data must be analyzed across several variables and often from multiple sites and seasons. Multivariate techniques such as ordination are common throughout the water quality literature, but methods vary widely and could benefit from greater standardization. We have found little clear guidance and open source code for efficiently conducting ordination to explore water quality patterns. Practitioners unfamiliar with techniques such as principal components analysis (PCA) are faced with a steep learning curve to summarize expansive data sets in periodic reports and manuscripts. Here, we present a seven-step framework for conducting PCA and associated tests. The last step is dedicated to conducting Procrustes analysis, a valuable but rarely used test within the water quality field that describes the degree of concordance between separate multivariate data matrices and provides residual values for similar points across each matrix. We illustrate the utility of these tools using three increasingly complex water quality case studies in US parklands. The case studies demonstrate how PCA and Procrustes analysis answer common applied monitoring questions such as (1) do data from separate monitoring locations describe similar water quality regimes, and (2) what time periods exhibit the greatest water quality regime variability? We provide data sets and annotated R code for recreating case study results and as a base for crafting new code for similar monitoring applications.

Sergeant|C J|CJ|
Starkey|E N|EN|
Bartz|K K|KK|
Wilson|M H|MH|
Mueter|F J|FJ|

Water quality
Principal components analysis
Procrustes
Monitoring
Guidance
Open source code


Probing the impact of sex steroids and menopause-related sex steroid deprivation on modulation of immune senescence.

Abstract: Immune senescence denotes the general decline in immune system function, characterized by a reduced immune response and an increased inflammatory state. Menopause is a natural change in a women's life, the menopause-related low estrogen levels affecting many body functions, among them the immune system. Numerous human studies with menopausal women and animal models with surgically induced menopause show a clear impact of sex steroids in immune responses. Female superiority in vaccination response and predisposition to infections are eliminated after menopause, while during menopause inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukins-1β, 6, 8 and 13 (IL-1β, IL-6, IL-8, IL-13) and Monocyte Chemoattractant Protein-1 (MCP-1) are increased, implying a molecular connection of sex steroid loss with immune senescence. Moreover, immune cells modify their number and function after the menopausal transition, this offering another explanation for immune senescence. Until now most of the existing studies have concluded that menopause plays an additional role to aging in immune senescence. While it is clear that we are as yet far from thoroughly understanding the molecular pathways connecting sex steroids and menopause with immune senescence, such knowledge is highly likely to enable future targeted interventions in treatment and prevention of age-related diseases in women.

Vrachnis|Nikolaos|N| Zygouris|Dimitrios|D| Iliodromiti|Zoe|Z| Daniilidis|Angelos|A| Valsamakis|Georgios|G| Kalantaridou|Sophia|S|

Sex steroids
Immune senescence
Menopause
Cytokines
Inflammatory molecules


Psychology, Science, and Knowledge Construction: Broadening Perspectives from the Replication Crisis.

Abstract: Psychology advances knowledge by testing statistical hypotheses using empirical observations and data. The expectation is that most statistically significant findings can be replicated in new data and in new laboratories, but in practice many findings have replicated less often than expected, leading to claims of a replication crisis. We review recent methodological literature on questionable research practices, meta-analysis, and power analysis to explain the apparently high rates of failure to replicate. Psychologists can improve research practices to advance knowledge in ways that improve replicability. We recommend that researchers adopt open science conventions of preregi-stration and full disclosure and that replication efforts be based on multiple studies rather than on a single replication attempt. We call for more sophisticated power analyses, careful consideration of the various influences on effect sizes, and more complete disclosure of nonsignificant as well as statistically significant findings.

Shrout|Patrick E|PE|
Rodgers|Joseph L|JL|


Anti-mouse CD52 monoclonal antibody ameliorates intestinal epithelial barrier function in interleukin-10 knockout mice with spontaneous chronic colitis.

Abstract: Intestinal inflammation causes tight junction changes and death of epithelial cells, and plays an important role in the development of Crohn's disease (CD). CD52 monoclonal antibody (CD52 mAb) directly targets the cell surface CD52 and is effective in depleting mature lymphocytes by cytolytic effects in vivo, leading to long-lasting changes in adaptive immunity. The aim of this study was to investigate the therapeutic effect of CD52 mAb on epithelial barrier function in animal models of IBD. Interleukin-10 knockout mice (IL-10(-/-) ) of 16 weeks with established colitis were treated with CD52 mAb once a week for 2 weeks. Severity of colitis, CD4(+) lymphocytes and cytokines in the lamina propria, epithelial expression of tight junction proteins, morphology of tight junctions, tumour necrosis factor-α (TNF-α)/TNF receptor 2 (TNFR2) mRNA expression, myosin light chain kinase (MLCK) expression and activity, as well as epithelial apoptosis in proximal colon were measured at the end of the experiment. CD52 mAb treatment effectively attenuated colitis associated with decreased lamina propria CD4(+) lymphocytes and interferon-γ/IL-17 responses in colonic mucosa in IL-10(-/-) mice. After CD52 mAb treatment, attenuation of colonic permeability, increased epithelial expression and correct localization of tight junction proteins (occludin and zona occludens protein-1), as well as ameliorated tight junction morphology were observed in IL-10(-/-) mice. CD52 mAb treatment also effectively suppressed the epithelial apoptosis, mucosa TNF-α mRNA expression, epithelial expression of long MLCK, TNFR2 and phosphorylation of MLC. Our results indicated that anti-CD52 therapy may inhibit TNF-α/TNFR2-mediated epithelial apoptosis and MLCK-dependent tight junction permeability by depleting activated T cells in the gut mucosa.

Wang|Honggang|H| Dong|Jianning|J| Shi|Peiliang|P| Liu|Jianhui|J| Zuo|Lugen|L| Li|Yi|Y| Gong|Jianfeng|J| Gu|Lili|L| Zhao|Jie|J| Zhang|Liang|L| Zhang|Wei|W| Zhu|Weiming|W| Li|Ning|N| Li|Jieshou|J|

D047889:Receptors, Tumor Necrosis Factor, Type II

CD52 monoclonal antibody
barrier function
interleukin-10 knockout
tight junction
Crohn's disease
apoptosis


Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation.

Abstract:
BACKGROUND
Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy.

METHODS
To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies.

RESULTS
Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal.

CONCLUSIONS
In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.

Friedman|Deborah M|DM|
Kim|Mimi|M|
Costedoat-Chalumeau|Nathalie|N|
Clancy|Robert|R|
Copel|Joshua|J|
Phoon|Colin K|CK|
Cuneo|Bettina F|BF|
Cohen|Rebecca|R|
Masson|Mala|M|
Wainwright|Benjamin J|BJ|
Zahr|Noel|N|
Saxena|Amit|A|
Izmirly|Peter M|PM|
Buyon|Jill P|JP|

hydroxychloroquine
COVID-19
pregnancy
heart block
incidence


EIQ: EEG based IQ test using wavelet packet transform and hierarchical extreme learning machine.

Abstract:
BACKGROUND
The use of electroencephalography has been perpetually incrementing and has numerous applications such as clinical and psychiatric studies, social interactions, brain computer interface etc. Intelligence has baffled us for centuries, and we have attempted to quantify using EEG signals.

NEW METHOD
This paper aims at devising a novel non-invasive method of measuring human intelligence. A newly devised scoring scheme is used to ultimately generate a score for the subjects. Wavelet packet transform approach for feature extraction is applied to 5 channel EEG data. This approach uses db-8 as the mother wavelet. Hierarchical extreme learning machine is used for classification of the EEG signals.

RESULT
80.00% training accuracy and 73.33% testing accuracy was measured for the classifier. The average sensitivity and specificity across all three classes was measured to be 0.8133 and 0.8923 respectively. An aggregate score was determined from the classification of EEG data. The power spectral analysis of the EEG data was conducted and regions of the brain responsible for various activities was confirmed. In the memory test, theta and beta bands exhibit high power, for arithmetic test, alpha and beta bands are strong, whereas in linguistic test, theta, alpha and beta bands are equally strong.

COMPARISON
The traditional IQ test determines intelligence indirectly, based on the score obtained from Wechsler test. In this paper an attempt is made to measure intelligence based on various brain activities - memory, arithmetic, linguistic.

CONCLUSION
A new method to measure intelligence using direct approach by classifying the EEG signals is proposed.

Kadam|Shashikant T|ST|
Dhaimodker|Vineet M N|VMN|
Patil|Milind M|MM|
Reddy Edla|Damodar|D|
Kuppili|Venkatanareshbabu|V|

Wavelet packet transform
Hierarchical extreme learning machine
Electroencephalography
Brain computer interface
Human intelligence


Surrogacy and uterus transplantation using live donors: Examining the options from the perspective of 'womb-givers'.

Abstract: For females without a functioning womb, the only way to become a biological parent is via assisted gestation-either surrogacy or uterus transplantation (UTx). This paper examines the comparative impact of these options on two types of putative 'womb-givers': people who provide gestational surrogacy and those who donate their uterus for live donation. The surrogate 'leases' their womb for the gestational period, while the UTx donor donates their womb permanently via hysterectomy. Both enterprises involve a significant degree of self-sacrifice and medical risk in order to enable another person(s) to become a parent by either providing gestational labour or enabling the other person to undertake gestation themselves. In this paper, we explore the burdens and the benefits from the perspective of the womb-giver in order to inform ethical debate about assisted gestation. This is a perspective that is often neglected in the bioethical discourse. With both surrogacy and UTx, when success follows the womb-giver's sacrifice, the key benefit is delivered to the intending parent(s), but as this article examines, the womb-giver may also enjoy some unique (relational) benefits as a result of their sacrifice. Ultimately, the choice of how a womb-giver lends assistance in gestation will impact on their bodily autonomy; some will prefer to carry a pregnancy and others to donate their uterus. We argue that the perspective of the womb-giver is crucial and thus far has not been afforded sufficient consideration in ethical discussion.

surrogacy
assisted gestation
live uterus donation


Development of Quality Management Systems for Clinical Practice Guidelines in Korea.

Abstract: This study introduces the Clinical practice guidelines (CPGs) appraisal system by the Korean Academy of Medical Sciences (KAMS). Quality management policies for CPGs vary among different countries, which have their own cultures and health care systems. However, supporting developers in guideline development and appraisals using standardized tools are common practices. KAMS, an organization representing the various medical societies of Korea, has been striving to establish a quality management system for CPGs, and has established a CPGs quality management system that reflects the characteristics of the Korean healthcare environment and the needs of its users. KAMS created a foundation for the development of CPGs, set up an independent appraisal organization, enacted regulations related to the appraisals, and trained appraisers. These efforts could enhance the ability of each individual medical society to develop CPGs, to increase the quality of the CPGs, and to ultimately improve the quality of the information available to decision-makers.

Jo|Heui-Sug|HS|
Kim|Dong Ik|DI|
Chang|Sung-Goo|SG|
Shin|Ein-Soon|ES|
Oh|Moo-Kyung|MK|

D019983:Guideline Adherence
D017146:Models, Organizational
D017410:Practice Guidelines as Topic
D011785:Quality Assurance, Health Care
D056910:Republic of Korea

Korea, Korean Academy of Medical Sciences


Midbody of the medial meniscus as a reference of preservation in partial meniscectomy for complete discoid lateral meniscus.

Abstract:
PURPOSE
To evaluate the postoperative size of discoid lateral meniscus using magnetic resonance imaging (MRI) after partial meniscectomy relative to the size of medial meniscus midbody.

METHODS
This study included 48 patients who underwent arthroscopic partial meniscectomy with or without repair for symptomatic complete discoid meniscus. The intraoperative size of midbody of medial meniscus was used as a reference for partial meniscectomy. MRIs were performed pre- and postoperatively. Quantitative evaluations of the height, width, extrusion of the meniscus, and relative percentage of extrusion in the coronal and sagittal planes were completed. Demographic data, preoperative shift, type of shift, and operative technique were analyzed while considering the remaining meniscus. Logistic regression analyses were used.

RESULTS
The mean remaining discoid meniscal width in the coronal plane of MRI was not significantly different from the width of midbody of medial meniscus (9.1 ± 4.2 mm vs. 9.4 ± 1.4 mm, n.s.) Absolute meniscal extrusion and relative percentage of extrusion in the coronal plane and the ratio of t meniscus in sagittal plane of the final MRI were significantly increased as compared with the preoperative MRI. Preoperative shift was a risk factor for the reduction of remaining meniscal width (odds ratio 11.997, p = 0.016, 95% CI 1.586-90.737).

CONCLUSION
The size of midbody of medial meniscus could be a reference for partial meniscectomy in symptomatic complete discoid meniscus. Preoperative shift represents a risk factor for decreased remaining meniscal width. These findings could be helpful in ensuring appropriate surgical planning and explaining poor prognostic factors.

LEVEL OF EVIDENCE
Prospective cohort study, Level II.

Medial meniscus
Partial meniscectomy
Discoid lateral meniscus
Magnetic resonance imaging
Extrusion


Physical fitness and cardiovascular risk factors in the novel diabetes subgroups.

Abstract:
CONTEXT
Physical inactivity promotes insulin resistance and increases the risk of diabetes and cardiovascular disease. Recently introduced clustering based on simple clinical measures identified diabetes subgroups (clusters) with different risks of diabetes-related comorbidities and complications.

OBJECTIVE
This study aims to determine differences in physical fitness and cardiovascular risk between diabetes subgroups and a glucose-tolerant control group (CON). We hypothesized that the severe insulin-resistant diabetes (SIRD) subgroup associates with lower physical fitness and increased cardiovascular risk.

METHODS
Physical fitness and cardiovascular risk of 746 participants with recent-onset diabetes (diabetes duration of <12 months, aged 18-69 years) and 74 CON of the German Diabetes Study (GDS), a prospective longitudinal cohort study, were analyzed. Main outcome measures included physical fitness (VO2max from spiroerogometry), endothelial function (flow- and nitroglycerin-mediated dilation) and cardiovascular risk scores (Framingham Risk Scores for Coronary Heart Disease (FRS-CHD) and Atherosclerotic CardioVascular Disease (ASCVD) risk score).

RESULTS
VO2max was lower in SIRD than in CON, severe autoimmune diabetes (SAID) (both p<0.001) and mild age-related diabetes (MARD) (p<0.01) subgroups, but not different compared to severe insulin-deficient diabetes (SIDD) (p=0.98) and moderate obesity-related diabetes (MOD) subgroups (p=0.07) after adjustment for age, sex and BMI. Endothelial function was similar among all groups, whereas SAID had lower FRS-CHD and ASCVD than SIRD, MOD and MARD (all p<0.001).

CONCLUSIONS
Despite comparable endothelial function across all groups, SIRD showed the lowest physical fitness. Of note, SAID had the lowest cardiovascular risk within the first year after diabetes diagnosis compared to the other diabetes subgroups.

physical fitness
cardiovascular risk factors
diabetes subgroups
endothelial function
physical activity


Concise, Simple, and Not Wrong: In Search of a Short-Hand Interpretation of Statistical Significance.

Abstract: One challenge when communicating science to practitioners and the general public is accurately representing statistical results. In particular, describing the meaning of statistical significance to a non-scientific audience is especially difficult given the technical nature of a correct definition. Correct interpretations of statistical significance can be unintuitive, nuanced, and use unfamiliar technical language. As a result, when researchers are tasked with providing short and understandable interpretations of statistical significance it can be tempting to default to convenient but incorrect interpretations. In the current paper, we offer a concise, simple, and correct interpretation of statistical significance that is suitable for communications targeting a general audience.

Spence|Jeffrey R|JR|
Stanley|David J|DJ|

evidence – based practice
p-value
science communication
science practice
significance tests


Co-Designing an eHealth Service for the Co-Care of Parkinson Disease: Explorative Study of Values and Challenges.

Abstract:
BACKGROUND
The need for services to support patient self-care and patient education has been emphasized for patients with chronic conditions. People with chronic conditions may spend many hours per year in health and social care services, but the majority of time is spent in self-care. This has implications in how health care is best organized. The term co-care specifically stresses the combination of health care professionals' and patients' resources, supported by appropriate (digital) tools for information exchange, to achieve the best possible health outcomes for patients. Developers of electronic health (eHealth) services need to consider both parties' specific needs for the service to be successful. Research on participants' experiences of participating in co-design sessions is scarce.

OBJECTIVE
The aim of this study was to describe different stakeholders' (people with chronic conditions, health care professionals, and facilitators) overall experiences of participating in co-design workshops aimed at designing an eHealth service for co-care for Parkinson disease, with a particular focus on the perceptions of values and challenges of co-design as well as improvement suggestions.

METHODS
We conducted 4 half-day co-design workshops with 7 people with Parkinson disease and 9 health care professionals. Data were collected during the workshop series using formative evaluations with participants and facilitators after each workshop, researchers' diary notes throughout the co-design process, and a Web-based questionnaire after the final workshop. Quantitative data from the questionnaire were analyzed using descriptive statistics. Qualitative data were triangulated and analyzed inductively using qualitative content analysis.

RESULTS
Quantitative ratings showed that most participants had a positive general experience of the co-design workshops. Qualitative analysis resulted in 6 categories and 30 subcategories describing respondents' perceptions of the values and challenges of co-design and their improvement suggestions. The categories concerned (1) desire for more stakeholder variation; (2) imbalance in the collaboration between stakeholders; (3) time investment and commitment paradox; (4) desire for both flexibility and guidance; (5) relevant workshop content, but concerns about goal achievement; and (6) hopes and doubts about future care.

CONCLUSIONS
Based on the identified values and challenges, some paradoxical experiences were revealed, including (1) a desire to involve more stakeholders in co-design, while preferring to work in separate groups; (2) a desire for more preparation and discussions, while the required time investment was a concern; and (3) the experience that co-design is valuable for improving care, while there are doubts about the realization of co-care in practice. The value of co-design is not mainly about creating new services; it is about improving current practices to shape better care. The choice of methods needs to be adjusted to the stakeholder group and context, which will influence how they experience the process and outcomes of co-design.

co-design
eHealth
Parkinson disease
self-care
chronic conditions
health care
questionnaire
mobile phone
qualitative research
user involvement


Cisplatin-resistant A549 non-small cell lung cancer cells can be identified by increased mitochondrial mass and are sensitive to pemetrexed treatment.

Abstract:
Background
Cisplatin plus pemetrexed combination therapy is considered the standard treatment for patients with advanced, non-squamous, non-small-cell lung cancer (NSCLC). However, advanced NSCLC has a 5-year survival rate of below 10%, which is mainly due to therapy resistance. We previously showed that the NSCLC cell line A549 harbors different subpopulations including a mesenchymal-like subpopulation characterized by increased chemo- and radiotherapy resistance. Recently, therapy resistance in hematological and solid tumors has been associated with increased mitochondrial activity. Thus, the aim of this study was to investigate the role of the mitochondrial activity in NSCLC chemotherapy resistance.

Methods
Based on MitoTracker staining, subpopulations characterized by the highest 10% (Mito-High) or lowest 10% (Mito-Low) mitochondrial mass content were sorted by FACS (Fluorescence-Activated Cell Sorting) from paraclonal cultures of the NSCLC A549 cell line . Mitochondrial DNA copy numbers were quantified by real-time PCR whereas basal cellular respiration was measured by high-resolution respirometry. Cisplatin and pemetrexed response were quantified by proliferation and colony formation assay.

Results
Pemetrexed treatment of parental A549 cells increased mitochondrial mass over time. FACS-sorted paraclonal Mito-High cells featured increased mitochondrial mass and mitochondrial DNA copy number compared to the Mito-Low cells. Paraclonal Mito-High cells featured an increased proliferation rate and were significantly more resistant to cisplatin treatment than Mito-Low cells. Interestingly, cisplatin-resistant, paraclonal Mito-High cells were significantly more sensitive to pemetrexed treatment than Mito-Low cells. We provide a working model explaining the molecular mechanism underlying the increased cisplatin- and decreased pemetrexed resistance of a distinct subpopulation characterized by high mitochondrial mass.

Conclusions
This study revealed that cisplatin resistant A549 lung cancer cells can be identified by their increased levels of mitochondrial mass. However, Mito-High cells feature an increased sensitivity to pemetrexed treatment. Thus, pemetrexed and cisplatin target reciprocal lung cancer subpopulations, which could explain the increased efficacy of the combination therapy in the clinical setting.

Gao|Yanyun|Y|
Dorn|Patrick|P|
Liu|Shengchen|S|
Deng|Haibin|H|
Hall|Sean R R|SRR|
Peng|Ren-Wang|RW|
Schmid|Ralph A|RA|
Marti|Thomas M|TM|0000-0003-3005-220X

Lung cancer
Mitochondrial mass
Pemetrexed
Cisplatin
NSCLC
Resistance
Mitochondrial activity
Chemotherapy


A Protocol for the Pharmacokinetics of Enteric Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN): an open-label, randomised controlled trial.

Abstract:
INTRODUCTION
Mycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN) and have fewer side effects than pulsed intravenous cyclophosphamide. Blood concentrations of mycophenolic acid (MPA), the active metabolite of EC-MPS, vary between participants despite fixed dosing. Interpatient variability has been studied in transplantation, but not well documented in LN. The relationship between MPA concentration and its clinical effect on LN has not been described.

METHODS AND ANALYSIS
This is a prospective, open-label, randomised controlled trial. -32 participants with LN who meet the inclusion and exclusion criteria will be randomised into two groups: one receiving a fixed dose of EC-MPS and the second, a dosing regimen that is titrated with therapeutic drug monitoring. Included participants will have blood sampled over a period of 8-12 h on three different occasions. Pharmacokinetic parameters will be calculated using non-compartmental methods.

ETHICS AND DISSEMINATION
The Human Research and Ethics Committee of the Royal Brisbane Women's Hospital have approved this study. The study is registered with Australian and New Zealand Clinical Trials Registry-ACTRN12611000798965 We planned to present the de-identified information at conferences and publish the results in medical journals.

TRIAL REGISTRATION
ACTRN12611000798965.

Ranganathan|Dwarakanathan|D|
John|George T|GT|
Healy|Helen|H|
Roberts|Matthew J|MJ|
Fassett|Robert G|RG|
Lipman|Jeffrey|J|
Kubler|Paul|P|
Ungerer|Jacobus|J|
McWhinney|Brett C|BC|
Lim|Aaron|A|
Purvey|Megan|M|
Reyaldeen|Reza|R|
Roberts|Jason A|JA|

Pharmacokinetics
Mycophenolate Sodium
Lupus Nephritis


Imaging cAMP nanodomains in the heart.

Abstract: 3'-5'-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that modulates multiple cellular functions. It is now well established that cAMP can mediate a plethora of functional effects via a complex system of local regulatory mechanisms that result in compartmentalized signalling. The use of fluorescent probes to monitor cAMP in intact, living cells have been instrumental in furthering our appreciation of this ancestral and ubiquitous pathway and unexpected details of the nano-architecture of the cAMP signalling network are starting to emerge. Recent evidence shows that sympathetic control of cardiac contraction and relaxation is achieved via generation of multiple, distinct pools of cAMP that lead to differential phosphorylation of target proteins localized only tens of nanometres apart. The specific local control at these nanodomains is enabled by a distinct signalosome where effectors, targets, and regulators of the cAMP signal are clustered. In this review, we focus on recent advances using targeted fluorescent reporters for cAMP and how they have contributed to our current understanding of nanodomain cAMP signalling in the heart. We briefly discuss how this information can be exploited to design novel therapies and we highlight some of the questions that remain unanswered.

Chao|Ying-Chi|YC|
Surdo|Nicoletta C|NC|
Pantano|Sergio|S|
Zaccolo|Manuela|M|

D031541:Fluorescence Resonance Energy Transfer

cAMP
nanodomain
compartmentalization
FRET imaging


Split cord malformation combined with tethered cord syndrome in an adult.

Abstract: Split cord malformations (SCMs) usually present in childhood, and are rarely reported in adults. And also, a cervicothoracic SCM associated with tethered cord syndrome has very rarely been reported in the literature. We report a case of SCM associated with tethered cord and spina bifida in an adult. This report describes the case of a 34-year-old woman who presented for evaluation of neck pain, back pain, and intermittent paraparesis of several months duration. The MRI and CT showed a SCM at the cervicothoracic level and a fibrous septum at the thoracic level. She underwent surgery for the SCM and tethered cord syndrome, and was followed for 7 years. Patient presented complete recovery in the follow-up. The authors discuss this unusual lesion and describe the anatomical relationship of the level of cord duplication and fibrous septum.

Kim|Young Deok|YD|
Sung|Ji Hoon|JH|
Hong|Jae Taek|JT|
Lee|Sang Won|SW|

Split cord malformation
Tethered cord syndrome
Adult


Patient ergonomics: 10-year mapping review of patient-centered human factors.

Abstract: Patient ergonomics is the application of human factors or related disciplines to study and improve patients' and other non-professionals' performance of effortful work activities in pursuit of health goals. We performed a mapping review of 212 full-text patient ergonomics publications in two conference proceedings, 2007-2017. The review revealed a robust and growing body of literature on patient ergonomics, particularly in the areas of aging and chronic disease, tools and technologies, and evaluations of patient-centered interventions on outcomes such as usability, user acceptance, and performance. Findings highlighted gaps deserving future research, including research with understudied populations such as children, informal caregivers, networks and collectives (groups), and marginalized populations; on topics such as health promotion and transitions of care; and using longitudinal and experimental study designs. The growth of patient-centeredness in general and of patient ergonomics in particular compel other more focused reviews, new primary research, and developing a roadmap for future patient ergonomics research.

Holden|Richard J|RJ|
Cornet|Victor P|VP|
Valdez|Rupa S|RS|

Patient-centered human factors and ergonomics


Age-specific prevalence of TB infection among household contacts of pulmonary TB: Is it time for TB preventive therapy?

Abstract:
BACKGROUND
Household contacts (HHCs) of TB patients are at high risk of developing evidence of latent TB infection (LTBI) and active disease from the index patient. We estimated the age-specific prevalence of LTBI and the force of infection (FI), as a measure of recent transmission, among HHCs of active TB patients.

METHODS
A cross-sectional analysis of HHCs of pulmonary TB patients enrolled in a prospective study, 'CTRIUMPh', was conducted at two sites in India. LTBI was defined as either a positive tuberculin skin test (induration ≥5 mm) or QuantiFERON-Gold in tube test (value ≥0.35 IU/ml) and was stratified by age. FI, which is a measure of recent transmission of infection and calculated using changes in age-specific prevalence rates at specific ages, was calculated. Factors associated with LTBI were determined by logistic regression models.

RESULTS
Of 1020 HHCs of 441 adult pulmonary TB cases, there were 566 (55%) females and 289 (28%) children aged ≤15 y. While screening for the study 3% of HHC were diagnosed with active TB. LTBI prevalence among HHCs of pulmonary TB was 47% at <6 y, 53% between 6-14 y and 78% between 15-45 y. FI increased significantly with age, from 0.4 to 1.15 in the HHCs cohort (p=0.05).

CONCLUSION
This study observed an increased prevalence of LTBI and FI among older children and young adults recently exposed to infectious TB in the household. In addition to awareness of coughing etiquette and general hygiene, expanding access to TB preventive therapy to all HHCs, including older children, may be beneficial to achieve TB elimination by 2035.

Shivakumar|Shri Vijay Bala Yogendra|SVBY|

latent TB
force of infection
transmission
close contacts


Psychological Distress Amongst Health Workers and the General Public During the COVID-19 Pandemic in Saudi Arabia.

Abstract:
Background
The rapid spread of COVID-19 worldwide has confined millions of people to their homes and has caused a substantial degree of psychological distress. This study aims to investigate the psychological distress impact of the COVID-19 pandemic among the Saudi population.

Methods
This is a cross-sectional study, using data collected from 3036 participants via an online self-reported questionnaire. The psychological distress was constructed using the COVID-19 Peritraumatic Distress Index to classify individuals in the sample as having normal, mild or severe distress levels. The study used descriptive analysis and multinomial logistic regressions to examine the sociodemographic factors associated with psychological distress levels during the COVID-19 pandemic.

Results
The evidence showed that 40% of the Saudi population are distressed due to COVID-19, of whom approximately 33% are mildly distressed, while 7% are severely distressed. The distress levels are particularly high amongst the young, females, private sector employees and health workers, especially those working on the frontline.

Conclusion
The COVID-19 pandemic is associated with increased distress amongst people living in Saudi Arabia. In support of evidence found in other countries, the study has established that the distress levels vary across different sociodemographic characteristics. Therefore, limiting people's psychological damage demands both medium- and long-term policy strategies, which include mapping the rates of stress and anxiety for effective psychological treatment allocation and establishing innovative online methods of heightening people's mental wellbeing.

psychological
distress
health workers
public
COVID-19
Saudi Arabia


Influenza A virus shedding reduction observed at 12 weeks post-vaccination when newborn pigs are administered live-attenuated influenza virus vaccine.

Abstract:
BACKGROUND
Influenza A virus in swine (IAV-S) causes an acute respiratory disease of swine which results in great economic losses. A bivalent H1N1 and H3N2, NS1-truncated live-attenuated IAV-S vaccine (LAIV, Ingelvac Provenza™ ) has recently become available.

OBJECTIVE
Reduction of shedding during an outbreak in the nursery or finisher is an important parameter from an epidemiological control strategy; therefore, a laboratory efficacy study was conducted to evaluate nasal virus shedding when vaccinated pigs were challenged with either heterologous H1N2 or H3N2 strains 12 weeks post-vaccination.

METHODS
Between 1 and 5 days of age, pigs born to IAV-S seronegative dams were intranasally administered 1 mL of vaccine or saline. At 30 days post-vaccination, pigs were weaned and randomized into two different challenge groups consisting of vaccinated pigs and control pigs commingled within pens for the two challenge groups. At 85 days post-vaccination, pigs in the first group were challenged with A/Swine/North Carolina/001169/2006 H1N2 challenge strain, and the second group was challenged with A/Swine/Nebraska/97901-10/2008 H3N2. Nasal swabs were collected daily for five days and tested by virus isolation.

RESULTS AND CONCLUSION
This study showed significant reduction in nasal virus shedding with regard to both frequency and duration. A 1 mL intranasal dose of Ingelvac Provenza™ given as early as 1 day of age showed protection for at least 12 weeks later as evidenced by the reduction of shedding live, viable virus after challenge with either a heterologous H1N2 strain or a heterologous H3N2 strain.

Kaiser|Troy J|TJ|
Smiley|Rex A|RA|
Fergen|Brian|B|
Eichmeyer|Marc|M|
Genzow|Marika|M|0000-0001-8368-4812

D032761:Animal Experimentation
D000818:Animals
D005260:Female
D057221:Influenza A Virus, H1N2 Subtype
D053122:Influenza A Virus, H3N2 Subtype
D007252:Influenza Vaccines
D008297:Male
D009297:Nasal Mucosa
D009329:Nebraska
D009976:Orthomyxoviridae Infections
D013552:Swine
D013553:Swine Diseases
D013997:Time Factors
D014613:Vaccines, Attenuated
D017201:Virus Shedding

influenza A
shedding
pig
vaccination
influenza A virus in swine
LAIV


Associations between maternal helminth and malaria infections in pregnancy and clinical malaria in the offspring: a birth cohort in entebbe, Uganda.

Abstract:
BACKGROUND
Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood.

METHODS
In a birth cohort of 2345 mother-child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring.

RESULTS
Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10-1.41; aHR, 1.20, 95% CI, 1.05-1.38, respectively). S. mansoni infection had no consistent association with childhood malaria.

CONCLUSIONS
This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.

Ndibazza|Juliet|J|
Webb|Emily L|EL|
Lule|Swaib|S|
Mpairwe|Harriet|H|
Akello|Miriam|M|
Oduru|Gloria|G|
Kizza|Moses|M|
Akurut|Helen|H|
Muhangi|Lawrence|L|
Magnussen|Pascal|P|
Vennervald|Birgitte|B|
Elliott|Alison|A|

helminths malaria pregnancy coinfections childhood


Fragmented QRS as a Predictor of Appropriate Implantable Cardioverter-defibrillator Therapy.

Abstract:
BACKGROUND
Fragmented QRS (fQRS) has been shown to be a marker of local myocardial conduction abnormalities and a predictor of cardiac events in selected populations. We hypothesized that the presence of a fQRS might predict arrhythmic events in patients who received an implantable cardioverter-defibrillator (ICD), regardless of the indications for implantation.

METHODS AND RESULTS
A cohort of 107 consecutive patients (mean age, 53 years; 82% male) who underwent an ICD implantation was studied. We defined fQRS, on a routine 12-lead ECG, as the presence of an additional R wave or notching in the nadir of the S wave in 2 consecutive leads corresponding to a major coronary artery territory. In the presence of bundle branch block, more than 2 notches in the R or S waves in 2 consecutive leads were required to characterize fQRS. Patients were followed for 21.3±23 months for appropriate ICD therapy (antitachycardia pacing and/or shock). ICDs were implanted predominantly in patients with ischemic cardiomyopathy (N=45, 42.1%), followed by Brugada syndrome (N=26, 24.3%). fQRS presented in 42 patients (39.3%). During follow-up, patients with fQRS received more appropriate ICD therapy than those without fQRS (45.2% vs. 10.8%, P<0.0001). After adjustment for covariates, fQRS remained an independent predictor for appropriate ICD therapy (hazard ratio=5.32, 95% confidence interval=2.11-13.37, P<0.0001).

CONCLUSION
The presence of fQRS appeared to be directly associated with appropriate ICD therapy.

Apiyasawat|Sirin|S| Sahasthas|Dujdao|D| Ngarmukos|Tachapong|T| Chandanamattha|Pakorn|P| Likittanasombat|Khanchit|K|

Fragmented QRS
Implantable cardioverter-defibrillator
electrocardiography
tachyarrhythmia


Mantodea (Insecta) of Uruguay: diversity and distribution.

Abstract: Praying mantises (Order Mantodea) are charismatic insects thanks to their diverse and peculiar appearance and surprising behaviors. However, studies on this order are scarce, particularly in the Southern Neotropical Region. Here we present the first catalogue of praying mantises from Uruguay. We revised Mantodea specimens deposited at Colección de Entomología, Facultad de Ciencias (FCE-MN), Universidad de la República, Montevideo, Uruguay. We recorded information about distribution and notes on the biology of the species. Nineteen species are reported for Uruguay, including new family, genera or species for the country. We report the presence of six taxa for first time: the family Mantoididae, genus Pseudovates, Musoniella and Metaphotina, the species Mantoida beieri, Eumusonia livida, Musoniella argentina, Metaphotina brevipennis, Parastagmatoptera theresopolitana and Pseudovates iheringi. We could confirm four species previously reported for the country, but eight species are based on dubious records or species and we cannot confirm their current occurrence in this work. More studies are needed in the country for further investigations of Mantodea in the country and the region.

Trillo|Mariana C|MC|
Agudelo|Antonio A|AA|
Guerrero|José C|JC|
Miguel|Lucía|L|
Lorier|Estrellita|E|

biodiversity, Neotropical region, praying mantises, taxonomy, Insecta


Axillary lymph node metastasis status prediction of early-stage breast cancer using convolutional neural networks.

Abstract: Deep learning (DL) algorithms have been proven to be very effective in a wide range of computer vision applications, such as segmentation, classification, and detection. DL models can automatically assess complex medical image scenes without human intervention and can be applied as a second reader to provide an additional opinion for the physician. To predict the axillary lymph node (ALN) metastatic status in patients with early-stage breast cancer, a deep learning-based computer-aided prediction system for ultrasound (US) images was proposed. A total of 153 women with breast tumor US images were involved in this study; there were 59 patients with metastasis and 94 patients without ALN metastasis. A deep learning-based computer-aided prediction (CAP) system using the tumor region and peritumoral tissue in ultrasound (US) images were employed to determine the ALN status in breast cancer. First, we adopted Mask R-CNN as our tumor detection and segmentation model to obtain the tumor localization and region. Second, the peritumoral tissue was extracted from the US image, which reflects metastatic progression. Third, we used the DL model to predict ALN metastasis. Finally, the simple linear iterative clustering (SLIC) superpixel segmentation method and the LIME explanation algorithm were employed to explain how the model makes decisions. The experimental results indicated that the DL model had the best prediction performance on tumor regions with 3 mm thick peritumoral tissue, and the accuracy, sensitivity, specificity, and AUC were 81.05% (124/153), 81.36% (48/59), 80.85% (76/94), and 0.8054, respectively. The results indicated that the proposed CAP system could help determine the ALN status in patients with early-stage breast cancer. The results reveal that the proposed CAP model, which combines primary tumor and peritumoral tissue, is an effective method to predict the ALN status in patients with early-stage breast cancer.

Lee|Yan-Wei|YW| Huang|Chiun-Sheng|CS| Shih|Chung-Chih|CC| Chang|Ruey-Feng|RF|

D001943:Breast Neoplasms
D005260:Female
D006801:Humans
D008198:Lymph Nodes
D008207:Lymphatic Metastasis
D016571:Neural Networks, Computer
D012189:Retrospective Studies

Breast cancer
Convolutional neural network
Deep learning
Computer-aided prediction
Axillary lymph node status
Breast ultrasound


Green synthesis of copper nanoparticles using Celastrus paniculatus Willd. leaf extract and their photocatalytic and antifungal properties.

Abstract: This research aimed to explore the eco-friendly green synthesis of copper nanoparticles (CuNPs) using Celastrus paniculatus leaves extract. Primarily, the biosynthesized CuNPs characterized by UV-vis spectroscopy showed an absorption peak at 269 nm. Further, The SEM and TEM studies revealed the spherical shape of particles with size ranged between 2-10 nm with an average particle diameter of 5 nm. FT-IR analysis confirmed the presence of functional groups -OH, C[bond, double bond]C and C-H triggers the synthesis of CuNPs. The negative zeta potential -22.2 mV indicated the stability of CuNPs was confirmed by DLS and the composition and purity by EDS studies. Further, the photocatalytic property of the CuNPs was divulged by their methylene blue dye degradation potential. The reaction kinetics followed pseudo-first-order with k-values (rate constant) 0.0172 min-1. In addition, this material was found to be a good antifungal agent against plant pathogenic fungi Fusarium oxysporum showed 76.29 ± 1.52 maximum mycelial inhibition.

Mali|Suresh Chand|SC|
Dhaka|Anita|A|
Githala|Chanda Kumari|CK|
Trivedi|Rohini|R|

Green synthesis
Copper nanoparticles
Photocatalytic
Antifungal
Methylene blue


Orai1 forms a signal complex with BKCa channel in mesenteric artery smooth muscle cells.

Abstract: Orai1, a specific nonvoltage-gated Ca(2+) channel, has been found to be one of key molecules involved in store-operated Ca(2+) entry (SOCE). Orai1 may associate with other proteins to form a signaling complex, which is essential for regulating a variety of physiological functions. In this study, we studied the possible interaction between Orai1 and large conductance Ca(2+)-activated potassium channel (BKC a). Using RNA interference technique, we demonstrated that the SOCE and its associated membrane hyperpolarization were markedly suppressed after knockdown of Orai1 with a specific Orai1 siRNA in rat mesenteric artery smooth muscle. Moreover, isometric tension measurements showed that agonist-induced vasocontraction was increased after Orai1 was knocked down or the tissue was incubated with BKC a blocker iberiotoxin. Coimmunoprecipitation data revealed that BKC a and Orai1 could reciprocally pull down each other. In situ proximity ligation assay further demonstrated that Orai1 and BKC a are in close proximity. Taken together, these results indicate that Orai1 physically associates with BKC a to form a signaling complex in the rat mesenteric artery smooth muscle. Ca(2+) influx via Orai1 stimulates BKC a, leading to membrane hyperpolarization. This hyperpolarizing effect of Orai1-BKC a coupling could contribute to reduce agonist-induced membrane depolarization, therefore preventing excessive contraction of the rat mesenteric artery smooth muscle in response to contractile agonists.

Chen|Meihua|M| Li|Jie|J| Jiang|Feifei|F| Fu|Jie|J| Xia|Xianming|X| Du|Juan|J| Hu|Min|M| Huang|Junhao|J| Shen|Bing|B|

D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits


External Lumbar Drainage following Traumatic Intracranial Hypertension: A Systematic Review and Meta-Analysis.

Abstract:
BACKGROUND
Traumatic brain injury (TBI) often results in elevations in intracranial pressure (ICP) that are refractory to standard therapies. Several studies have investigated the utility of external lumbar drainage (ELD) in this setting.

OBJECTIVE
To evaluate the safety and efficacy of ELD or lumbar puncture with regard to immediate effect on ICP, durability of the effect on ICP, complications, and neurological outcomes in adults with refractory traumatic intracranial hypertension.

METHODS
A systematic review and meta-analysis were conducted beginning with a comprehensive search of PubMed/EMBASE. Two investigators reviewed studies for eligibility and extracted data. The strength of evidence was evaluated using GRADE methodology. Random-effects meta-analyses were performed to calculate pooled estimates.

RESULTS
Nine articles detailing 6 studies (N = 110) were included. There was moderate evidence that ELD has a significant immediate effect on ICP; the pooled effect size was -19.5 mmHg (95% CI -21.0 to -17.9 mmHg). There was low evidence to indicate a durable effect of ELD on ICP up to at least 24 h following ELD. There was low evidence to indicate that ELD was safe and associated with a low rate of clinical cerebral herniation or meningitis. There was very low evidence pertaining to neurological outcomes.

CONCLUSION
Given preliminary data indicating potential safety and feasibility in highly selected cases, the use of ELD in adults with severe TBI and refractory intracranial hypertension in the presence of open basal cisterns and absence of large focal hematoma merits further high-quality investigation; the ideal conditions for potential application remain to be determined.

Lumbar drainage
Intracranial hypertension
Systematic review
Meta-analysis
Traumatic brain injury
Intracranial pressure
Lumbar puncture
Cerebrospinal fluid
Head injury


Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation.

Abstract: Donation after circulatory death (DCD) is being used to increase the number of transplantable organs. The role and timing of steroids in DCD donation and ex vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study, we investigated the effect of steroids on warm ischemic injury in a porcine model (n = 6/group). Following cardiac arrest, grafts were left untouched in the donor (90-min warm ischemia). Graft function was assessed after 6 h of EVLP. In the MP group, 500 mg methylprednisolone was given prior to cardiac arrest and during EVLP. In the CONTR group, no steroids were added. Median lung compliance (13 ml/cmH2 0) was significantly better preserved in the CONTR group than in the MP group (30.5 ml/cmH2 0). Also, median wet-to-dry weight (6.11 vs. 6.94) and CT density (182.5 vs. 352.9 g/l) were significantly better in the MP group than in the CONTR group, respectively. There was no difference in oxygenation and pulmonary vascular resistance. Perfusate cytokine analysis showed a significant reduction in IL-1β, IL-8, IFN-α, IL-10, TNF-α, and IFN-γ in MP. Cytokines in bronchoalveolar lavage were not decreased except for IFN-gamma. We demonstrated that warm ischemic injury in DCD donation can be attenuated by steroids when given prior to warm ischemia and during EVLP. Ethical context of donor preconditioning should be discussed further.

Martens|An|A|
Boada|Marc|M|
Vanaudenaerde|Bart M|BM|
Verleden|Stijn E|SE|
Vos|Robin|R|
Verleden|Geert M|GM|
Verbeken|Eric K|EK|
Van Raemdonck|Dirk|D|
Schols|Dominique|D|
Claes|Sandra|S|
Neyrinck|Arne P|AP|

donation
donation after circulatory death
ex vivo lung perfusion
animal models
donor management
experimental transplantation
extended donor pool
ischemia reperfusion injury
organ preservation and procurement


Clinical characteristics of lichen and dysplasia vs lichen planus cases and dysplasia cases.

Abstract:
OBJECTIVES
To compare the clinical characteristics of lichen planus with dysplasia (LD) cases with oral dysplasia (DYS), and LP/lichenoid reaction (LP/LR).

METHODS
Patients treated at the Department of Oral Medicine with a histological diagnosis were included. Patient information (age, gender, ethnicity, smoking habits, and medical status) and parameters of oral manifestation (lesions' distribution, site, and type) were compared.

RESULTS
Two hundred and thirty five patients were included. 54% were never smokers and 25% were current smokers. The LD group (n = 79) had more bilateral cases when compared to the DYS group (n = 30), 70% to 40.7%, respectively (P = 0.008), and a lower average age [56-62, respectively (P = 0.043)]. All other parameters were similar. When compared to LR patients, the LD group had a higher percentage of men [41.8-27.9%, respectively (P = 0.08)] while all other parameters were similar.

CONCLUSIONS
As clinical characteristics of LD are more similar to the LP and LR group than to dysplasia, these findings may indicate that LD should be considered as part of the lichen planus disorder spectrum rather than a separate entity, although further analysis of larger groups is warranted. These results support the need for clinical follow-up among patients diagnosed with lichenoid changes.

Czerninski|R|R| Zeituni|S|S| Maly|A|A| Basile|J|J|

lichen planus
mucosal diseases
oncology
pre-cancer


A short-term risk-benefit analysis of occasional and regular use of low-dose aspirin in primary prevention of vascular diseases: a nationwide population-based study.

Abstract:
OBJECTIVE
To calculate the short-term risk-benefit effect of occasional and regular use of low-dose aspirin (≤100 mg/day) in primary prevention.

STUDY DESIGN
Two retrospective cohort studies.

SETTING
Taiwan.

PARTICIPANTS
63 788 and 24 910 patients of two nationwide population-based studies were examined.

METHODS
Two databases of 1 000 000 patients were randomly sampled from data of Taiwan's National Health Insurance (NHI) for years 1997-2000 (NHI 2000) and 2005 (NHI 2005). In NHI 2000, 63 788 patients 30-95 years of age were found not to have previously been prescribed aspirin before 1 January 2000, but to have first been prescribed low-dose aspirin after that date. They were also found to be at risk of first hospitalisation for any major vascular diseases including haemorrhage (major gastrointestinal haemorrhage or cerebral haemorrhage) and ischaemia (acute myocardial infarction or ischaemic stroke) after their first prescription. We also applied it to NHI 2005, and the number of eligible patients was 24 910. Patients prescribed low-dose aspirin for <20% of the days of a 60-day follow-up period were considered to be occasional users, and those prescribed low-dose aspirin for ≥80% of the days were considered to be regular users. Differences in rate of haemorrhage and ischaemia between these users were used to calculate their net clinical risk.

PRIMARY OUTCOME
Vascular diseases.

RESULTS
In NHI 2000, the overall unadjusted rates of haemorrhage and ischaemia were 0.09% and 0.21%, respectively, for occasional users and 0.32% and 2.30%, respectively, for regular users. Adjusted net clinical risk of low-dose aspirin use between the two groups was 2.24% (95% CI 2.03% to 2.48%; p<0.001). Similar results were also found in NHI 2005.

CONCLUSIONS
Short-term regular use of low-dose aspirin might not be better than occasional use for preventing major vascular diseases in primary prevention. Prescribing regular low-dose aspirin for primary prevention should be done with caution. Future studies should explore the risk-benefit effect of long-term low-dose aspirin use in primary prevention.

EPIDEMIOLOGY
PREVENTIVE MEDICINE
PRIMARY CARE


A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living.

Abstract: The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities.

Semenza|Carlo|C| Meneghello|Francesca|F| Arcara|Giorgio|G| Burgio|Francesca|F| Gnoato|Francesca|F| Facchini|Silvia|S| Benavides-Varela|Silvia|S| Clementi|Maurizio|M| Butterworth|Brian|B|

neurological diseases
activities of daily living
acalculia
mathematical cognition
neuropsychological assessment


Metabolomics and the Microbiome as Biomarkers in Sepsis.

Abstract: Metabolomics is an emerging field of research interest in sepsis. Metabolomics provides new ways of exploring the diagnosis, mechanism, and prognosis of sepsis. Advancements in technologies have enabled significant improvements in identifying novel biomarkers associated with the disease progress of sepsis. The use of metabolomics in the critically ill may provide new approaches to enable precision medicine. Furthermore, the dynamic interactions of the host and its microbiome can lead to further progression of sepsis. Understanding these interactions and the changes in the host's genomics and the microbiome can provide novel preventive and therapeutic strategies against sepsis.

Metabolomics
Microbiome
Dysbiosis
Gut microbiota
Personalized medicine
Pharmaco-metabonomics


myo-Inositol Oxygenase is Required for Responses to Low Energy Conditions in Arabidopsis thaliana.

Abstract: myo-Inositol is a precursor for cell wall components, is used as a backbone of myo-inositol trisphosphate (Ins(1,4,5)P(3)) and phosphatidylinositol phosphate signaling molecules, and is debated about whether it is also a precursor in an alternate ascorbic acid synthesis pathway. Plants control inositol homeostasis by regulation of key enzymes involved in myo-inositol synthesis and catabolism. Recent transcriptional profiling data indicate up-regulation of the myo-inositol oxygenase (MIOX) genes under conditions in which energy or nutrients are limited. To test whether the MIOX genes are required for responses to low energy, we first examined MIOX2 and MIOX4 gene expression regulation by energy/nutrient conditions. We found that both MIOX2 and MIOX4 expression are suppressed by exogenous glucose addition in the shoot, but not in the root. Both genes were abundantly expressed during low energy/nutrient conditions. Loss-of-function mutants in MIOX genes contain alterations in myo-inositol levels and growth changes in the root. Miox2 mutants can be complemented with a MIOX2:green fluorescent protein fusion. Further we show here that MIOX2 is a cytoplasmic protein, while MIOX4 is present mostly in the cytoplasm, but also occasionally in the nucleus. Together, these data suggest that MIOX catabolism in the shoot may influence root growth responses during low energy/nutrient conditions.

Alford|Shannon R|SR|
Rangarajan|Padma|P|
Williams|Phoebe|P|
Gillaspy|Glenda E|GE|

myo-inositol
energy
ascorbic acid
nutrient response


Morphogenesis of lingual papillae of one-humped camel (Camelus dromedarius) during prenatal life: A light and scanning electron microscopic study.

Abstract: This study was made on 24 camel fetuses of crown-rump vertebral length (CVRL) ranging from 10.5 cm to 105 cm CVRL (94-352 days old). These camel fetuses were classified into three groups representing the three trimesters of prenatal life. During the first trimester (94-142 days), lingual papillae (circumvallate and lentiform papillae) were demonstrated on the lingual root, but lingual body and the apex were almost free of papillae except for some scattered epithelial projections especially near the lateral borders of the body. In the second trimester (152-229 days), the lentiform papillae covered the entire root of the tongue except for areas occupied by the circumvallate papillae. Taste buds with clear pores were observed for the first time in areas between the circumvallate gustatory furrow and surface epithelium of the tongue. In addition, short numerous filiform papillae were observed on the rostral part of the lingual body and the lateral parts of the apex. Fungiform papillae, however, were demonstrated amidst the filiform papillae. In this trimester, taste buds were also seen on the top of the fungiform papillae. In the third trimester (256-352 days), all lingual papillae were clearly demonstrated on the dorsum of the root, body and apex of the tongue. Both types of gustatory papillae (circumvallate and fungiform) had well-developed taste buds. Mechanical papillae (filiform and lentiform) were well developed. Lentiform papillae occupied most of the dorsal aspect of the Torus linguae; they were larger in size with semicircular apices. Filiform papillae, however, were numerous and demonstrated heavily on the lateral and rostral parts of the body as well as on the apex of the tongue.

Abou-Elhamd|A S|AS|
Abd-Elkareem|M|M|
El-Zuhry Zayed|A|A|

lingual papillae
camel
prenatal development


A standardized extract of the fruit of Hovenia dulcis alleviated alcohol-induced hangover in healthy subjects with heterozygous ALDH2: A randomized, controlled, crossover trial.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Hovenia dulcis, known as the oriental raisin tree, is mainly found in East Asia. It has long been used as traditional folk remedies for alcohol intoxication.

AIM OF THE STUDY
To examine the anti-hangover effect of Hovenia dulcis Thunb. fruit extract (HDE) in a randomized controlled crossover trial.

MATERIALS AND METHODS
Twenty-six eligible male adults with heterozygous ALDH2 (23.7±0.3 years old) consumed 360mL of Korean Soju (50g alcohol) together with HDE (2460mg) or matched placebo with subsequent crossover. The blood samples were taken at baseline and 1, 4, and 12h post-treatment.

RESULTS
Blood alcohol, acetaldehyde, and total hangover scores were highest at 1h post-treatment with no difference between groups, but declines in hangover symptom scores were significant in the HDE group compared to the placebo group. Significant differences between groups were also observed on interleukin (IL)-6, IL-10, IL-10/IL-6 ratio, and aspartate aminotransferase levels, but not on endotoxins. Pearson correlation analysis revealed a positive correlation between total hangover symptom scores and IL-6 and IL-10 level. Further analyses by CYP2E1 polymorphism at rs10776687, rs2031920, rs3813867, and rs4838767 alleles showed a reversed association, suggesting that CYP2E1 polymorphism might be an effect modifier.

CONCLUSIONS
The results suggest that a favorable effect of HDE on alcohol hangovers might be associated with enhancing homeostatic regulation of inflammatory response. The magnitude of impact might be different in the presence of CYP2E1 polymorphism.

Kim|Hoejin|H|
Kim|You Jin|YJ|
Jeong|Hye Yun|HY|
Kim|Ji Yeon|JY|
Choi|Eun-Kyung|EK|
Chae|Soo Wan|SW|
Kwon|Oran|O|

D020022:Genetic Predisposition to Disease

Hangover
Alcohol
Fruit of Hovenia dulcis Thunb
Genetic polymorphism
Inflammation


First isolation of Leishmania infantum by blood culture in bovines from endemic area for canine visceral leishmaniasis.

Abstract: Leishmaniasis is considered a parasitic disease that still causes serious consequences for mankind, because it presents a high mortality rate worldwide. Considered multi-hosts, the parasites of the genus Leishmania are able of infecting a wide variety of animal species. The dog was considered the main source of infection of visceral leishmaniasis (VL), in the urban area. However, the role of other animal species in the epidemiological cycle of the disease, such as cattle, remains unclear. Therefore, the aim of the present study was to evaluate the occurrence of Leishmania spp. in 100 bovines (Bos taurus) from an area endemic for canine VL, using blood culture and molecular analysis. By the sequencing analysis, one sample showed 100% similarity with Leishmania infantum. The results provide the first case of L. infantum isolation in one bovine from the periurban areas of Bauru, state of São Paulo, Brazil.

Leishmania infantum
Blood culture
bovine
Brazil
polymerase chain reaction


Adverse childhood experiences are associated with illicit drug use among pregnant women with middle to high socioeconomic status: findings from the All Our Families Cohort.

Abstract:
BACKGROUND
Adverse childhood experiences (ACEs) are associated with illicit drug use among pregnant women who are socioeconomically vulnerable. While it is assumed that the impact of ACEs on illicit drug use in pregnancy is reduced among women with higher socioeconomic status (SES), this assumption is not well tested in the literature. The objective of this study was to examine the impact of maternal ACEs on illicit drug use in a community-based sample of pregnant women with middle to high SES.

METHODS
This study is a secondary analysis of a prospective cohort study that collected data from 1660 women during and after pregnancy in Calgary, Canada between 2008 and 2011 using mailed surveys. Illicit drug use in pregnancy was self-reported by women at 34-36 weeks gestation. An established scale examined maternal ACEs before 18 years. Logistic regression models and 95% confidence intervals tested associations between maternal ACE scores and illicit drug use in pregnancy.

RESULTS
Overall, 3.1% of women in this predominantly married, well-educated, middle and upper middle income sample reported illicit drug use in pregnancy. Women with 2-3 ACEs had more than a two-fold increase, and women with 4 or more ACEs had almost a four-fold increase in illicit drug use in pregnancy, relative to women with 0-1 ACEs after adjustment for confounders. Exposure to child abuse was more consistently associated with illicit drug use in pregnancy than exposure to household dysfunction in childhood.

CONCLUSIONS
Maternal ACEs were common and associated with a moderate increase in the odds of illicit drug use in pregnancy among Canadian women with middle to high SES.

Adverse childhood experiences
Illicit drug use
All our families
Pregnancy


Metabolic engineering to expand the substrate spectrum of Pseudomonas putida toward sucrose.

Abstract: Sucrose is an important disaccharide used as a substrate in many industrial applications. It is a major component of molasses, a cheap by-product of the sugar industry. Unfortunately, not all industrially relevant organisms, among them Pseudomonas putida, are capable of metabolizing sucrose. We chose a metabolic engineering approach to circumvent this blockage and equip P. putida with the activities necessary to consume sucrose. Therefore, we constructed a pair of broad-host range mini-transposons (pSST - sucrose splitting transposon), carrying either cscA, encoding an invertase able to split sucrose into glucose and fructose, or additionally cscB, encoding a sucrose permease. Introduction of cscA was sufficient to convey sucrose consumption and the additional presence of cscB had no further effect, though the sucrose permease was built and localized to the membrane. Sucrose was split extracellularly by the activity of the invertase CscA leaking out of the cell. The transposons were also used to confer sucrose consumption to Cupriavidus necator. Interestingly, in this strain, CscB acted as a glucose transporter, such that C. necator also gained the ability to grow on glucose. Thus, the pSST transposons are functional tools to extend the substrate spectrum of Gram-negative bacterial strains toward sucrose.

D003470:Culture Media
D020118:Cupriavidus necator
D004251:DNA Transposable Elements
D026901:Membrane Transport Proteins
D060847:Metabolic Engineering
D016254:Mutagenesis, Insertional
D016958:Pseudomonas putida
D011994:Recombinant Proteins
D013395:Sucrose
D013549:Sweetening Agents
D043324:beta-Fructofuranosidase

metabolic engineering
Pseudomonas putida
sucrose metabolism


Iatrogenic retinal detachment secondary to inadvertent subretinal injection during posterior sub-Tenon triamcinolone injection.

Abstract: Objective: To report a case of iatrogenic retinal detachment due to inadvertent globe penetration during posterior sub-Tenon injection Methods: A 65-year-old female was given posterior sub-Tenon injection of triamcinolone acetonide for pseudophakic cystoid macular oedema. The globe was inadvertently perforated with superior macula off retinal detachment. Results: She underwent immediate pars plana vitrectomy but failed to regain significant vision improvement. Conclusion: According to the literature, retinal detachment as a complication of posterior sub-Tenon injection is rare. This complication may be prevented by adhering to the standard practice of injecting slowly avoiding any undue pressure.

retinal detachment
triamcinolone acetonide
cystoid macular oedema
pars plana vitrectomy