Comparison of Loading Efficiency between Hyperbranched Polymers and Cross-Linked Nanogels at Various Branching Densities.

Abstract: The effect of branching point structures and densities is studied between azido-containing hyperbranched polymers and cross-linked nanogels on their loading efficiency of alkynyl-containing dendron molecules. Hyperbranched polymers that contained "T"-shaped branching linkage from which three chains radiated out and cross-linked nanogels that contained "X"-shaped branching linkage with four radiating chains are synthesized in microemulsion using either atom transfer radical polymerization (ATRP) or conventional radical polymerization (RP) technique. Both polymers have similar density of azido groups in the structure and exhibit similar hydrodynamic diameter in latexes before purification. Subsequent copper-catalyzed azide-alkyne cycloaddition reactions between these polymers and alkynyl-containing dendrons in various sizes (G1-G3) demonstrate an order of dendron loading efficiencies (i.e., final conversion of alkynyl-containing dendron) as hyperbranched polymers > nanogels synthesized by ATRP > nanogels synthesized by RP. Decreasing the branching density or using smaller dendron molecules increases the click efficiency of both polymers. When G2 dendrons with a molecular weight of 627 Da are used to click with the hyperbranched polymers composed of 100% inimer, a maximum loading efficiency of G2 in the loaded hyperbranched polymer is 58% of G2 by weight. These results represent the first comparison between hyperbranched polymers and cross-linked nanogels to explore the effect of branching structures on their loading efficiencies.

Graff|Robert W|RW|
Shi|Yi|Y|
Wang|Xiaofeng|X|
Gao|Haifeng|H|

hyperbranched polymer
nanogels
microemulsion
click reactions
encapsulation


Psychometric properties of the Turkish version of the Diabetes Family Impact Scale.

Abstract:
PURPOSE
The objective of this study was to examine the psychometric properties of the Turkish version of the Diabetes Family Impact Scale (DFIS).

METHODS AND DESIGN
The study was carried out methodologically with 121 parents who have 6-18 year-old children with type 1 diabetes (n = 121). The collected data were analyzed by conducting confirmatory factor analysis, t test, and Pearson's correlation analysis and by computing Cronbach's α and intraclass correlation coefficients (ICCs).

RESULTS
The linguistic validity of the scale was ensured by undertaking translation and back-translation. Expert opinions were analyzed and all the content validity indices were found to be ≥0.80. The factor loadings of all the items ranged from 0.47 to 0.89, and the model fit indices were as follows: χ²/df = 1.21 and RMSEA = 0.04. Scores that were obtained across two temporally separated administrations were not significantly different (p > .05), and there was a strong correlation between the two sets of scores (ICC = 0.892; p < .001). The Cronbach's α of the scale was .881. The item-total correlation coefficients of the scale items ranged from .34 to .72.

CONCLUSIONS
Similar to the original assessment, the Turkish version of the DFIS consists of 14 items and 4 subscales. It is a valid and reliable measure that is suitable for use with Turkish samples. Researchers can use this scale to assess the effect of type 1 diabetes mellitus on the family of an affected child.

family impact
scale
validity
reliability
diabetes mellitus


Sharing patient-generated data with healthcare providers: findings from a 2019 national survey.

Abstract:
OBJECTIVE
Our study estimates the prevalence and predictors of wearable device adoption and data sharing with healthcare providers in a nationally representative sample.

MATERIALS AND METHODS
Data were obtained from the 2019 Health Information National Trend Survey. We conducted multivariable logistic regression to examine predictors of device adoption and data sharing.

RESULTS
The sample contained 4159 individuals, 29.9% of whom had adopted a wearable device in 2019. Among adopters, 46.3% had shared data with their provider. Individuals with diabetes (odds ratio [OR], 2.39; 95% CI, 1.66-3.45; P < .0001), hypertension (OR, 2.80; 95% CI, 2.12-3.70; P < .0001), and multiple chronic conditions (OR, 1.55; 95% CI, 1.03-2.32; P < .0001) had significantly higher odds of wearable device adoption. Individuals with a usual source of care (OR, 2.44; 95% CI, 1.95-3.04; P < .0001), diabetes (OR, 1.66; 95% CI, 1.32-2.08; P < .0001), and hypertension (OR, 1.78; 95% CI, 1.44-2.20; P < .0001) had significantly higher odds of sharing data with providers.

DISCUSSION
A third of individuals adopted a wearable medical device and nearly 50% of individuals who owned a device shared data with a provider in 2019. Patients with certain conditions, such as diabetes and hypertension, were more likely to adopt devices and share data with providers. Social determinants of health, such as income and usual source of care, negatively affected wearable device adoption and data sharing, similarly to other consumer health technologies.

CONCLUSIONS
Wearable device adoption and data sharing with providers may be more common than prior studies have reported; however, digital disparities were noted. Studies are needed that test implementation strategies to expand wearable device use and data sharing into care delivery.

Turner|Kea|K|
Jo|Ara|A|
Wei|Grace|G|
Tabriz|Amir Alishahi|AA|
Clary|Alecia|A|
Jim|Heather S L|HSL|

D000076206:Patient Generated Health Data

patient-generated data
wearable device
patient-generated health data
wearable technology


Sensory processing disorders in children with hearing impairment: Implications for multidisciplinary approach and early intervention.

Abstract:
OBJECTIVE
To explore the differences in sensory processing between children with hearing impairments and children with normal hearing and the variables that influence sensory processing disorder (SPD).

METHODS
The sensory processing abilities of 90 children were compared in three age-matched groups of 30, with cochlear implants (CIs), hearing aids (HAs), and normal hearing (NH). The Arabic Sensory Profile (Arabic_SP) was used.

RESULTS
Findings were presented in the Arabic_SP section and factor levels. Sections: The NH group performed better (p < .05) than the CI group in 57% of the sections and better than the HA group in 14%. The CI group exhibited more signs of SPD than the HA group with vestibular processing, multisensory processing, and emotional-social responses.

FACTORS
The NH group differed from the CI group on all the factors that showed significance and from the HA group with inattention/distractibility and poor registration. There were great differences between the CI and the HA groups on all the factors except with poor registration and fine motor/perceptual. Hearing loss variables that most affected results in the Arabic_SP were the age at receiving a hearing device and type of hearing loss onset.

CONCLUSION
Along with speech and language problems, children with hearing impairment are especially vulnerable to SPD. Children with CIs and HAs are increasingly susceptible to auditory processing disorders. Higher risks of balance, multisensory processing, social-emotional, and fine motor problems are in children with CIs. Increased SPD risks came with a higher age at implantation. Findings indicate the importance of a multidisciplinary approach for early detection and intervention for children with hearing impairment, especially those with CIs.

Alkhamra|Rana A|RA|
Abu-Dahab|Sana M N|SMN|

Sensory processing disorders
Children
Hearing impairment
Cochlear implants
Hearing aids


Pancreatic fistula rates after internal and external stenting of the pancreatojejunostomy anastomosis following pancreatoduodenectomy.

Abstract: Background: This retrospective comparative case series study aims to analyze the pancreatic fistula rates of internal and external stenting of the pancreatojejunostomy (PJ) anastomosis in patients who underwent pancreatoduodenectomy (PD) for periampullary tumors.Methods: Ninety-eight patients with periampullary tumors who were operated between 2010 and 2017 were enrolled in this study. A classic open PD with Roux-en-Y PJ reconstruction was performed in all cases.Results: The PJ anastomosis of 53 patients (54%) were stented internally whereas in 45 patients (46%) external stenting was preferred. Pancreatic fistula was observed in 29 patients (29.6%). Internal stenting and soft pancreatic tissue were found to be related to higher pancreatic fistula rates with odds ratios of 3.27 (p = .024) and 3.4 (p = .017), respectively. When only grade B and grade C fistulas were taken into account, the type of stenting has lost its significance but the texture of the remnant pancreas was still associated with 'clinically important' pancreatic fistula.Conclusions: We concluded that the external stenting of the PJ anastomosis may be considered as an effective approach for reducing postoperative pancreatic leaks in PD-planned patients for periampullary tumors. Although our study was retrospectively designed, we used standard charts to gather patient data and compared two stenting methods among homogeneous patient groups.

pancreatic fistula
stents
pancreatojejunostomy
Pancreatoduodenectomy


Artifactual Stratum Corneum Calcification of the Beagle Dog Tongue.

Abstract: Examination of H&E-stained tongue samples from a 26-week intravenous infusion study of Beagle dogs, utilizing a compound with no recognized effect on mineral metabolism, exhibited superficial stratum corneum calcification in both treated and control animals. This resulted in the search for possible causes of the finding to help clarify confounding issues. Retrospective examination of 11 studies performed before the signal case indicated that the problem existed in the testing facility but was not recognized. Prior to 2008, this finding was not observed, perhaps indicating the requirement for a change in procedures or suppliers. Based on the hypothesis that the calcium salts were deposited from bone during processing, a series of tests was performed by fixing tongue and femur along with different tissues, processed routinely to slide, and stained with H&E and von Kossa stains. We conclude that the presence of superficial stratum corneum calcification of the tongue in dogs demonstrated in toxicology studies is an artifactual change related to the processing of tissues, specifically the fixation of tongue in the same container as bone and stomach. This change should not be confused with compound-related effects, even when the incidence varies between controls and treated animals.

calcification
digestive system
dog pathology
toxicologic pathology


Current standing and future directions in pediatric oncofertility: a narrative review.

Abstract: In this narrative review, we discuss the epidemiology and pathophysiology of infertility in childhood and adolescent cancer. We also review the current guidelines and ethical issues related to pediatric oncofertility. Finally, we present recent advances in basic science and translational research in pediatric fertility preservation (FP).

pediatric oncofertility Childhood adolescent fertility preservation


Metabolomics Reveals Inflammatory-Linked Pulmonary Metabolic Alterations in a Murine Model of House Dust Mite-Induced Allergic Asthma.

Abstract: Although the house dust mite (HDM) is a major environmental aeroallergen that promotes the pathogenesis and severity of allergic asthma, it remains elusive if HDM exposures can induce global metabolism aberrations during allergic airway inflammation. Using an integrated gas and liquid chromatography mass spectrometry-based metabolomics and multiplex cytokine profile analysis, metabolic alterations and cytokine changes were investigated in the bronchoalveolar lavage fluid (BALF), serum, and lung tissues in experimental HDM-induced allergic asthma. Allergic pulmonary HDM exposures lead to pronounced eosinophilia, neutrophilia, and increases in inflammatory cytokines. Metabolomics analysis of the BALF, serum, and lung tissues revealed distinctive compartmental metabolic signatures, which included depleted carbohydrates, increased energy metabolites, and consistent losses of sterols and phosphatidylcholines. Pearson correlation analysis uncovered strong associations between specific metabolic alterations and inflammatory cells and cytokines, linking altered pulmonary metabolism to allergic airway inflammation. The clinically prescribed glucocorticoid prednisolone could modulate airway inflammation but was ineffective against the reversal of many HDM-induced metabolic alterations. Collectively, metabolomics reveal comprehensive pulmonary metabolic signatures in HDM-induced allergic asthma, with specific alterations in carbohydrates, lipids, sterols, and energy metabolic pathways. Altered pulmonary metabolism may be a major underlying molecular feature involved during HDM-induced allergic airway inflammation, linked to inflammatory cells and cytokines changes.

Ho|Wanxing Eugene|WE|
Xu|Yong-Jiang|YJ|
Cheng|Chang|C|
Peh|Hong Yong|HY|
Tannenbaum|Steven R|SR|
Wong|W S Fred|WSF|
Ong|Choon Nam|CN|

metabolome
inflammation
liquid chromatography
allergy
corticosteroids
gas chromatography
mass spectrometry


Health-seeking behaviours in the homeless population: A concept analysis.

Abstract: This concept analysis aims to define the concept of health-seeking behaviour in relation to the homeless population. The altered experiences of individuals who are homeless suggest that the concept of health-seeking behaviours has distinct attributes and therefore, a new definition of this concept is needed when compared with other populations. The framework outlined by Walker and Avant was used for this analysis with model, borderline and contrary cases. Databases searched were: CINAHL, Sociological Abstracts, PsycInfo, Google Scholar and PubMed. Because of the limited literature on the overall health-seeking behaviours of the homeless population, the most relevant 15 sources were selected from these databases for the literature review. Critical attributes derived from the literature were: (a) distrust in healthcare services, emerging from feelings of judgement or stigma from healthcare providers; (b) prioritising physiological needs such as food, shelter and clothing over the safety needs of health; (c) delaying seeking care until physical symptoms are severe; and (d) having decreased access to healthcare because of being uninsured or having no money, requiring transportation, experiencing long wait times for appointments, or lacking knowledge of available healthcare services. We define health-seeking behaviours in the homeless population as a complex process where a homeless individual seeks out healthcare for a problem or illness, but must first meet his or her physiological needs and then deem current symptoms severe enough to seek medical treatment despite his or her distrust in the healthcare system and barriers to accessing healthcare. Homeless individuals may face unique physiological hardships and emotional stressors compared to the general population, which results in distinct attributes surrounding health-seeking behaviours. Healthcare providers need to be aware of current barriers to care and perceived access to care in order to reduce the barriers to care that the homeless population faces.

health-seeking
homeless
concept analysis


Evaluation of different lead types and implantation techniques in pediatric populations with permanent pacemakers: Single-center with 10 years' experience.

Abstract:
BACKGROUND
Permanent pacemaker (PM) implantation is performed for various indications and by different techniques in children; however, many problems with lead performance are encountered during follow-up. This study aims to evaluate the possible effects of different lead types and implantation techniques on pacing at early and midterm in children with a permanent PM.

PATIENTS AND METHODS
Pediatric patients who underwent permanent PM system implantation at our tertiary cardiac surgery center between January 1, 2010 and January 1, 2020 were evaluated retrospectively. Patients were categorized in the epicardial pacing lead (EP), transvenous pacing lead (TP), and transvenous bipolar lumenless (Select Secure [SS]) lead groups according to the lead implantation technique and lead type with the same manufacturer. Groups were evaluated statistically for demographic features, pacing type and indication for implantation, lead electrical performance, lead failure, complications, and outcome.

RESULTS
Over 10 years, 323 lead implantations were performed on 167 patients (96 males, median age 68 months [5 days-18 years]). Of 323 leads, 213 (66%) were EP, 64 (20%) were TP, and 46 (14%) were SS. Of the total, 136 of the leads were implanted in atria, and 187 were implanted in ventricles. Primary pacing indications were postoperative complete atrioventricular (AV) block (n = 95), congenital AV block (n = 71), sinus node dysfunction (n = 13), and acquired complete AV block (n = 1). Additional cardiac diseases were present in 115 patients (69%). No statistically significant difference was observed in gender, syndrome, or pacing indication (P > .05). Atrial and ventricular capture, threshold, sensing, and lead impedance measurements were not significantly different at the initial and follow-up periods (P > .05). The median follow-up duration was 3.3 years (6 months-10 years). Twenty lead failures were determined in 15 patients (EP: 14 lead failures in 10 patients; TP: two lead failures in two patients; and SS: four lead failures in three patients) during follow-up, and no statistically significant difference was found between groups (P = .466). The 5-year lead survival was 98% for TP, 95% for EP, and 90% for SS; the 10-year lead survival was 90% for TP, 70% for EP, and 70% for SS. There was no mortality related to chronic pacing or due to the procedure of implantation.

CONCLUSIONS
Despite improvements in technology, lead failure is still one of the most critical problems during these patients' follow-up. Early to midterm lead survival rates of all three lead types were satisfactory.

Ergul|Yakup|Y|0000-0001-8814-0435
Yukcu|Bekir|B|
Ozturk|Erkut|E|0000-0002-1762-3269
Kafali|Hasan Candas|HC|
Ayyildiz|Pelin|P|
Ergun|Servet|S|
Onan|Ismihan Selen|IS|
Haydin|Sertac|S|
Guzeltas|Alper|A|

pediatric
lead failure
cardiac pacing
congenital heart disease


Systematic Review and Meta-Analysis: Risk of Hospitalization in Patients with Ulcerative Colitis and Crohn's Disease in Population-Based Cohort Studies.

Abstract:
BACKGROUND AND AIMS
Inflammatory bowel diseases (IBD) lead to high morbidity and unplanned healthcare utilization. We conducted a systematic review with meta-analysis to estimate the cumulative incidence of IBD-related (and all-cause) hospitalization in patients with ulcerative colitis (UC) and Crohn's disease (CD).

METHODS
Through a systematic review to September 3, 2019, we identified population-based inception cohort studies in patients with IBD that reported patient-level cumulative incidence of hospitalization at 1, 3 and 5 years after diagnosis. Hospitalization risk was pooled using random effects meta-analysis, and risk factors analyzed through mixed-effects meta-regression and qualitative synthesis.

RESULTS
In patients with UC (6 cohorts), 1-, 3- and 5-year risk of UC-related hospitalization was 10.4% (95% CI 8.2-13.2), 17.0% (95% CI 14.0-20.4) and 21.5% (95% CI 18.0-25.4), respectively, with considerable heterogeneity. In patients with CD (6 cohorts), 1-, 3- and 5-year risk of CD-related hospitalization was 29.3% (95% CI 20.0-40.8), 38.5% (95% CI 26.8-51.7) and 44.3% (95% CI 32.7-56.5), respectively, with considerable heterogeneity. On meta-regression, steady decline in risk of hospitalization was observed in patients diagnosed in a more contemporary era. Younger age at onset (both UC and CD), extensive colitis (UC), ileal-dominant CD, perianal CD and penetrating and/or stricturing behavior (CD) and early need for corticosteroids and immunosuppressive therapy (both UC and CD) were associated with increased risk of hospitalization.

CONCLUSION
Approximately one in five and one in two patients with UC and CD are hospitalized within 5 years of diagnosis, respectively. Population health management strategies are required to mitigate unplanned healthcare utilization.

Inflammatory bowel diseases
Biologics
Complications
Inpatient
Natural history


Intensifying Functional Task Practice to Meet Aerobic Training Guidelines in Stroke Survivors.

Abstract: Objective: To determine whether stroke survivors could maintain workloads during functional task practice that can reach moderate levels of cardiometabolic stress (i.e., ≥40% oxygen uptake reserve ([Formula: see text]O2R) for ≥20 min) without the use of ergometer-based exercise. Design: Cross-sectional study using convenience sampling. Setting: Research laboratory in a tertiary rehabilitation hospital. Participants: Chronic hemiparetic stroke survivors (>6-months) who could provide consent and walk with or without assistance. Intervention: A single bout of intermittent functional training (IFT). The IFT protocol lasted 30 min and involved performing impairment specific multi-joint task-oriented movements structured into circuits lasting ~3 min and allowing 30-45 s recovery between circuits. The aim was to achieve an average heart rate (HR) 30-50 beats above resting without using traditional ergometer-based aerobic exercise. Outcome measures: Attainment of indicators for moderate intensity aerobic exercise. Oxygen uptake ([Formula: see text]O2), carbon dioxide production ([Formula: see text]CO2), and HR were recorded throughout the 30 min IFT protocol. Values were reported as percentage of [Formula: see text]O2R, HR reserve (HRR) and HRR calculated from predicted maximum HR (HRRpred), which were determined from a prior maximal graded exercise test. Results: Ten (3-female) chronic (38 ± 33 months) stroke survivors (70% ischemic) with significant residual impairments (NIHSS: 3 ± 2) and a high prevalence of comorbid conditions (80% ≥ 1) participated. IFT significantly increased all measures of exercise intensity compared to resting levels: [Formula: see text]O2 (Δ 820 ± 290 ml min-1, p < 0.001), HR (Δ 42 ± 14 bpm, p < 0.001), and energy expenditure (EE; Δ 4.0 ± 1.4 kcal min-1, p < 0.001). Also, mean values for percentage of [Formula: see text]O2R (62 ± 19), HRR (55 ± 14), and HRRpred (52 ± 18) were significantly higher than the minimum threshold (40%) indicating achievement of moderate intensity aerobic exercise (p = 0.004, 0.016, and 0.043, respectively). Conclusion: Sufficient workloads to achieve moderate levels of cardiometabolic stress can be maintained in chronic stroke survivors using impairment-focused functional movements that are not dependent on ergometers or other specialized equipment.

Kelly|Liam P|LP|
Devasahayam|Augustine J|AJ|
Chaves|Arthur R|AR|
Wallack|Elizabeth M|EM|
McCarthy|Jason|J|
Basset|Fabien A|FA|
Ploughman|Michelle|M|

cardiometabolic stress
aerobic exercise
physical exertion
physical therapy modalities
stroke rehabilitation


Urinary hydration biomarkers and water sources in free-living elderly.

Abstract:
INTRODUCTION
Accurate estimates of water intake and hydration status in populations are essential to identify populations at risk of dehydration and define strategies to improve standards of water intake.

OBJECTIVE
To evaluate the hydration status and the contribution of food and beverages to the total water intake in a sample of free-living physically active Portuguese elderly.

METHODS
A sample of 74 individuals (28 men), aged 60 to 83 years, were included in this study. A 24 h urine sample was collected; 24 h urine volume and osmolality were quantifi ed in order to estimate the free water reserve (FWR) used to assess the hydration status. A 24 h food recall corresponding to the day of urine collection was obtained. Food and beverages were grouped according to their nutritional composition, namely water content. The contribution of those groups to total water intake and its association with the hydration status were estimated. Urinary markers and food groups' contribution to total water intake were compared between sexes and according to the median FWR, using the t-test and Mann Whitney test.

RESULTS
Less than 10% of the participants were classifi ed as hypohydrated/at hypohydration risk. Water from food was nearly half of the total water intake (47% in females and 48% in males, p = 0.757). "Water" (22%) and "foods with reduced water content" (19%) were the groups that contributed the most to the total water intake in women and men, respectively. In men, the contribution of "alcoholic beverages" was signifi cantly higher than that of women (10.5% vs 1.7%, p < 0.001).

CONCLUSIONS
Even though most of the study participants were classified as euhydrated, the contribution of water-rich and nutritionally dense food, and non-alcoholic beverages, particularly in men, should be promoted.

Gonçalves|Alexandra|A| Silva|Joana|J| Moreira|Pedro|P| Padrao|Patrícia|P|

Hydration status. Water sources. Elderly. Free water reserve.


Quality Evaluation of Juniperus rigida Sieb. et Zucc. Based on Phenolic Profiles, Bioactivity, and HPLC Fingerprint Combined with Chemometrics.

Abstract: Juniperus rigida (J. rigida) which is endemic to East Asia, has traditionally been used as an ethnomedicinal plant in China. This study was undertaken to evaluate the quality of J. rigida samples derived from 11 primary regions in China. Ten phenolic compounds were simultaneously quantified using reversed-phase high-performance liquid chromatography (RP-HPLC), and chlorogenic acid, catechin, podophyllotoxin, and amentoflavone were found to be the main compounds in J. rigida needles, with the highest contents detected for catechin and podophyllotoxin. J. rigida from Jilin (S9, S10) and Liaoning (S11) exhibited the highest contents of phenolic profiles (total phenolics, total flavonoids and 10 phenolic compounds) and the strongest antioxidant and antibacterial activities, followed by Shaanxi (S2, S3). A similarity analysis (SA) demonstrated substantial similarities in fingerprint chromatograms, from which 14 common peaks were selected. The similarity values varied from 0.85 to 0.98. Chemometrics techniques, including hierarchical cluster analysis (HCA), principal component analysis (PCA), and discriminant analysis (DA), were further applied to facilitate accurate classification and quantification of the J. rigida samples derived from the 11 regions. The results supported HPLC data showing that all J. rigida samples exhibit considerable variations in phenolic profiles, and the samples were further clustered into three major groups coincident with their geographical regions of origin. In addition, two discriminant functions with a 100% discrimination ratio were constructed to further distinguish and classify samples with unknown membership on the basis of eigenvalues to allow optimal discrimination among the groups. Our comprehensive findings on matching phenolic profiles and bioactivities along with data from fingerprint chromatograms with chemometrics provide an effective tool for screening and quality evaluation of J. rigida and related medicinal preparations.

Liu|Zehua|Z| Wang|Dongmei|D| Li|Dengwu|D| Zhang|Shuai|S|

Juniperus rigida
phenolic profiles
bioactivities
HPLC fingerprint
chemometrics


The effectiveness of influenza vaccination against medically-attended illnesses in Hong Kong across three years with different degrees of vaccine match, 2014-17.

Abstract:
BACKGROUND
Influenza vaccination is the most effective intervention to prevent influenza virus infections. Vaccine effectiveness (VE) can vary due to factors such as matching between vaccine strains and prevailing strains, age and other characteristics of the vaccine recipients.

OBJECTIVE
To evaluate influenza VE against medically-attended illness in different age groups and against specific influenza types/subtypes in Hong Kong.

METHODS
A test-negative study was conducted from December 2014 through August 2017 in 20 outpatient clinics. Patients at least 6 months of age presenting with at least two symptoms of acute respiratory illness, ARI (fever ≥37.8 °C, cough, sore throat, runny nose, headache, myalgia and phlegm) within 72 h of onset were tested for influenza virus by reverse transcription polymerase chain reaction (PCR). Vaccination history was assessed by self-report or medical records at the clinics. VE against medically-attended illness was estimated using conditional logistic regression for influenza PCR result versus vaccination history, matching by calendar time and adjusting for age, age-squared, sex, and chronic medical illness. Additional analyses examined VE by age group and by influenza type/subtype.

RESULTS
We enrolled 2566 patients, of whom 1118 (43.6%) tested positive for influenza A or B virus by PCR. Test-positive subjects were generally older, more likely to present with one of the symptoms of ARI, and less likely to receive vaccination against influenza. VE estimates for influenza A(H1N1), A(H3N2), B/Yamagata and B/Victoria were 61.6% (95% confidence interval, CI: 21.8%, 81.1%), 26.4% (95% CI: -1.3%, 46.6%), 67.0% (95% CI: 25.9%, 85.3%), 60.4% (95% CI: 0.3%, 84.3%), respectively. Estimates of VE by age group were generally higher in adults aged 50-64 and lower among children and older adults.

CONCLUSIONS
VE against medically-attended influenza was moderate in Hong Kong, confirming the impact of influenza vaccination in reducing disease burden. The reduced VE for influenza A(H3N2) is a continuing concern.

Tam|Yat Hung|YH|
Ng|Tiffany W Y|TWY|
Chu|Daniel K W|DKW|
Fang|Vicky J|VJ|
Cowling|Benjamin J|BJ|
Malik Peiris|J S|JS|
Ip|Dennis K M|DKM|

Influenza
Hong Kong
Vaccine match
Vaccine effectiveness


Towards Phenotyping of Clinical Trial Eligibility Criteria.

Abstract:
BACKGROUND
Medical plaintext documents contain important facts about patients, but they are rarely available for structured queries. The provision of structured information from natural language texts in addition to the existing structured data can significantly speed up the search for fulfilled inclusion criteria and thus improve the recruitment rate.

OBJECTIVES
This work is aimed at supporting clinical trial recruitment with text mining techniques to identify suitable subjects in hospitals.

METHOD
Based on the inclusion/exclusion criteria of 5 sample studies and a text corpus consisting of 212 doctor's letters and medical follow-up documentation from a university cancer center, a prototype was developed and technically evaluated using NLP procedures (UIMA) for the extraction of facts from medical free texts.

RESULTS
It was found that although the extracted entities are not always correct (precision between 23% and 96%), they provide a decisive indication as to which patient file should be read preferentially.

CONCLUSION
The prototype presented here demonstrates the technical feasibility. In order to find available, lucrative phenotypes, an in-depth evaluation is required.

Löbe|Matthias|M| Stäubert|Sebastian|S| Goldberg|Colleen|C| Haffner|Ivonne|I| Winter|Alfred|A|

D002986:Clinical Trials as Topic
D057225:Data Mining
D004608:Eligibility Determination
D006801:Humans
D007802:Language
D009323:Natural Language Processing
D012107:Research Design

Phenotyping
Clinical Trials
Recruitment
Text Mining
NLP
Apache UIMA
cTAKES


Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction.

Abstract:
INTRODUCTION
To better understand the mechanisms underlying the beneficial effects of the intravaginal administration of dehydroepiandrosterone (DHEA) observed in postmenopausal women on sexual dysfunction.

AIMS
To identify the distribution of the androgen-synthesizing enzymes as well as androgen receptor (AR) and measure steroid levels in the monkey vagina.

METHODS
The cynomolgus monkey (Macaca fascicularis), the closest model to the human, has been used to measure the expression levels of steroidogenic enzymes and androgen receptor by quantitative reverse transcription polymerase chain reaction (n=4), confirmed by immunohistochemistry, and immunofluorescence (n=3). DHEA and its androgenic metabolites were quantified by LC-MS/MS (n=4).

MAIN OUTCOME MEASURES
The presence of SRD5A1, SRD5A2, HSD17B3, AR as well as nerve fibers (PGP 9.5) was investigated, and steroid levels were measured.

RESULTS
AR is widely distributed within the vaginal epithelium and also in the lamina propria with a lower expression in the muscularis layer and blood vessel walls. Androgen-forming enzymes, on the other hand, are expressed in the vaginal stratified squamous epithelium at a relatively high level where they are uniformly distributed from the basal membrane up to the superficial keratinized cells. The enzymes are at a lower level in blood vessel walls and zona muscularis where nerve fibers are localized. DHEA and its androgen metabolites are present at biologically significant concentrations in the monkey vagina.

CONCLUSION
The enzymes responsible for androgen formation as well as AR are at the highest level in the superficial layer of the stratified epithelium and muscularis layers of the vagina. These data provide a potential explanation for the described role of androgens in regulating vaginal lubrication, smooth muscle activity, blood flow, and the neuronal activity potentially involved in the correction of sexual dysfunction.

Bertin|Jonathan|J|
Dury|Alain Y|AY|
Ouellet|Johanne|J|
Pelletier|Georges|G|
Labrie|Fernand|F|

Androgens
Vagina
Sexual Dysfunction
DHEA
Vulvovaginal Atrophy


Tribological Properties of Aluminium Alloy Composites Reinforced with Multi-Layer Graphene-The Influence of Spark Plasma Texturing Process.

Abstract: Self-lubricating composites are designed to obtain materials that reduce energy consumption, improve heat dissipation between moving bodies, and eliminate the need for external lubricants. The use of a solid lubricant in bulk composite material always involves a significant reduction in its mechanical properties, which is usually not an optimal solution. The growing interest in multilayer graphene (MLG), characterised by interesting properties as a component of composites, encouraged the authors to use it as an alternative solid lubricant in aluminium matrix composites instead of graphite. Aluminium alloy 6061 matrix composite reinforced with 2-15 vol % of MLG were synthesised by the spark plasma sintering process (SPS) and its modification, spark plasma texturing (SPT), involving deformation of the pre-sintered body in a larger diameter matrix. It was found that the application of the SPT method improves the density and hardness of the composites, resulting in improved tribological properties, particularly in the higher load regime.

Kostecki|Marek|M| Woźniak|Jarosław|J| Cygan|Tomasz|T| Petrus|Mateusz|M| Olszyna|Andrzej|A|

tribological properties
multilayer graphene
aluminium matrix composites
SPS sintering


Gitelman's syndrome: Rare presentation with growth retardation.

Abstract: Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypokalemia, hypomagnesaemia, hypocalciuria, hyperreninemia and without hypertension. Gitelman's syndrome is caused by mutations of the SLC12A3 gene, which encodes the Na/Cl co-transporter (NCCT) in the distal convoluted tubule. Majority of cases manifest during adolescence or adulthood and growth retardation is not the common feature. We report a rare presentation of Gitelman's syndrome in a four-year-old boy with growth retardation.

Gitelman's syndrome
metabolic alkalosis
hypokalemia
hypomagnesaemia
hypocalciuria


Child sexual abuse - Initial suspicion and legal outcome.

Abstract:
OBJECTIVES
To evaluate the association of primary reason to suspect child sexual abuse with the legal end-point in medically examined, police reported cases.

STUDY DESIGN
Observational post hoc analysis of retrospective review of records of 155 medically examined, police reported alleged child sexual abuse (CSA) cases during 2001-2009. Primary referral indications for medical examinations or criminal investigations were analyzed with an end-point in the legal process. The data consists of official investigation documents from University Hospital records, police, crime laboratories, state prosecutor, and courts of Law.

RESULTS
The median age of the children was 7.1 years (range 11 months-17.5 years) at the time when suspicion of sexual abuse was reported to police. Conviction of the alleged perpetrator was significantly more likely in cases where the child's disclosure was the reason for the initial suspicion of CSA, compared to cases with referrals for "suspicious circumstances" (39/92, 42.4% vs. 7/37, 19%, p<0.001). In 92 (59.5%) cases the initial suspicion of CSA arose from child's disclosure. The forensic interviewer's report supported more likely CSA allegations where the suspicion of CSA arose by child's clear, detailed and credible disclosure of what had happened, compared to the other initial reasons of suspicion (35/61, 57.4% vs. 13/42, 31.0%, p=0.001). In child's age category of 4-9 years conviction was significantly more likely where the initial suspicion of CSA arose with child's disclosure, compared to other reasons of suspicion (21.45, 46.7% vs. 5/27, 16.7%, p=0.001). No association was found regarding to whom the initial suspicion of CSA arose and legal outcome. Forensic interviewer's report supported the allegation of CSA more often if the suspicion was arose first to a neutral person (p=0.019). Legal outcome of conviction was associated with child's disclosure of perpetrator's physical contact regardless of how the suspicion arose (45/99, 45.5% vs. 10/46, 21.7%, p<0.001).

CONCLUSION
The reason which initially arise a suspicion of child sexual abuse plays an important role in the criminal investigation. Initial suspicion of CSA by child's disclosure, an eyewitness or objective material may lead to higher conviction rates. If a concerning physical symptom or finding arise the suspicion of CSA, referral to expert consultation is recommended to prevent unnecessary allegations and investigations. Other possible differential diagnostic medical conditions need to be evaluated. Furthermore, when child's disclosure arise a suspicion of CSA, it needs to be thoroughly investigated, regardless to whom the child discloses to.

Child sexual abuse
Legal outcome
Referral indications
Consultation
Child’s disclosure


Analysis of nontypeable haemophilus influenzae phase-variable genes during experimental human nasopharyngeal colonization.

Abstract:
BACKGROUND
Studies of nontypeable Haemophilus influenzae (NTHi) have demonstrated that a number of genes associated with infectivity have long repeat regions associated with phase variation in expression of the respective gene. The purpose of this study was to determine the genes that underwent phase variation during a 6-day period of experimental human nasopharyngeal colonization.

METHODS
Strain NTHi 2019Str(R)1 was used to colonize the nasopharynx of human subjects in a study of experimental colonization. Thirteen phase-variable genes were analyzed in NTHi 2019Str(R)1. Samples of NTHi 2019Str(R)1 were cultured from subjects during the 6-day colonization period. We used capillary electrophoresis and Roche 454 pyrosequencing to determine the number of repeats in each gene from each sample.

RESULTS
A significant number of samples switched licA and igaB from phase off in the inoculated strain to phase on during the 4-day period of observation. lex2A also showed variability as compared to baseline, but the differences were not significant. The remaining genes showed no evidence of phase variation.

CONCLUSIONS
Our studies suggest that the phase-on genotypes of licA and igaB are important for early human nasopharynx colonization. lex2A showed a trend from phase off to phase on, suggesting a potentially important role in the colonization process.

Poole|Jessica|J|
Foster|Eric|E|
Chaloner|Kathryn|K|
Hunt|Jason|J|
Jennings|Michael P|MP|
Bair|Thomas|T|
Knudtson|Kevin|K|
Christensen|Erik|E|
Munson|Robert S|RS|
Winokur|Patricia L|PL|
Apicella|Michael A|MA|

D000940:Antigenic Variation
D000942:Antigens, Bacterial
D002353:Carrier State
D019075:Electrophoresis, Capillary
D020869:Gene Expression Profiling
D006192:Haemophilus Infections
D006193:Haemophilus influenzae
D006801:Humans
D008962:Models, Theoretical
D009305:Nasopharynx
D017422:Sequence Analysis, DNA

Haemophilus influenzae
phase variation
licA
igaB
lex2A nasopharyngeal colonization


Fostering quality experiences: Qualitative perspectives from program members and providers in a community-based exercise program for adults with physical disabilities.

Abstract:
BACKGROUND
Opportunities to be physically active within one's community need to be available and accessible to individuals with physical disabilities in order to increase participation; however, what constitutes quality participation within these opportunities and how exercise programs can foster quality experiences for this population have yet to be explored.

OBJECTIVES
(1) To explore the participation experiences of adults with physical disabilities in a community-based exercise program from two perspectives; (2) To establish whether the participants' experiences could be understood through an existing quality participation framework.

METHODS
Participants were thirteen members and ten providers (i.e., coordinators, trainers, and supervisors) recruited from a community-based exercise program for adults with physical disabilities. Six focus groups (three with program members and three with each distinct group of program providers) were carried out, audio recorded and transcribed. Following an initial inductive thematic analysis, themes were deductively mapped to Martin Ginis and colleagues' (2017) conceptualization of the experiential aspects of participation.

RESULTS
Six themes (autonomy, belongingness, challenge, engagement, mastery and meaning) important for experiencing quality participation were identified and were in line with Martin Ginis and colleagues' (2017) framework.

CONCLUSION
Findings support the use of Martin Ginis and colleagues' (2017) conceptualization of quality participation within the context of community-based exercise programs for adults with physical disabilities. Practitioners and researchers can use the findings as a starting point for designing, implementing and evaluating programs with the goal of optimizing quality participation.

Jackson|Julia|J|
Williams|Toni L|TL|
McEachern|Brittany M|BM|
Latimer-Cheung|Amy E|AE|
Tomasone|Jennifer R|JR|

Community-based
Exercise program
Physical disability
Quality participation


Quantitative Analysis of Protein S-Acylation Site Dynamics Using Site-Specific Acyl-Biotin Exchange (ssABE).

Abstract: Protein S-acylation (palmitoylation) is a reversible lipid modification that is increasingly recognized as an important regulator of protein function, including membrane association, trafficking, and subcellular localization. Most proteomic methods to study palmitoylation allow characterization of putative palmitoylated proteins but do not permit identification of individual sites of palmitoylation. We have recently adapted the Acyl-Biotin Exchange (ABE) method that is routinely used for palmitoyl-proteome characterization, to permit global S-acylation site analysis. This site-specific ABE (ssABE) protocol, when combined with SILAC-based quantification, allows both the large-scale identification of palmitoylation sites and quantitative profiling of palmitoylation site changes. This approach enables palmitoylation to be studied at a systems level comparable to other more intensively studied post-translational modifications.

Quantitative
Protein
S-Acylation
Palmitoylation
Membrane
Proteomic
Mass spectrometry


Determination of pterins in urine by HPLC with UV and fluorescent detection using different types of chromatographic stationary phases (HILIC, RP C8, RP C18).

Abstract: Pterins are a class of potential cancer biomarkers. New methods involving hydrophilic interaction liquid chromatography (HILIC) and reversed phase (RP) high-performance liquid chromatography have been developed for analysis of eight pterin compounds: 6,7-dimethylpterin, pterin, 6-OH-methylpterin, biopterin, isoxanthopterin, neopterin, xanthopterin, and pterin-6-carboxylic acid. The effect of mobile phase composition, buffer type, pH and concentration on retention using HILIC, C8 and C18 RP stationary phases were examined. Separation of pterins on RP and HILIC stationary phase was performed and optimized. Eight pterins were successfully separated on HILIC Luna diol-bonded phases, Aquasil C18 RP column and LiChrospher C8 RP column. Determination and separation of the pterins from urine samples were performed on HILIC Luna and LiChrospher C8 RP columns which were chosen as the most appropriate ones. Finally, LiChrospher C8 RP column with fluorescence detection was selected for further validation of the method. The optimum chromatographic condition was mobile phase methanol (A)/phosphoric buffer pH 7, 10mM (B), isocratic elution 0-15min 5% A flow=0.5ml/min 15-17min. 5% A, flow=0.5-1ml/min the linearity (R(2)>0.997) and retention time repeatability (RSD%<1) were at satisfactory level. The precision of peak areas expressed as RSD in % was between 0.55 and 14. Pterins detection limits varied from 0.041ng/ml to 2.9ng/ml. Finally, HPLC method was used for the analysis of pterins in urine samples with two different oxidation procedures. Concentration levels of pterin compounds in bladder cancer patients and healthy subjects were compared.

Kośliński|Piotr|P|
Jarzemski|Piotr|P|
Markuszewski|Michał J|MJ|
Kaliszan|Roman|R|

D002851:Chromatography, High Pressure Liquid

Pterin
HILIC
Biomarkers
Bladder cancer
Reversed phase HPLC


Behavioral and brain asymmetries in primates: a preliminary evaluation of two evolutionary hypotheses.

Abstract: Contrary to many historical views, recent evidence suggests that species-level behavioral and brain asymmetries are evident in nonhuman species. Here, we briefly present evidence of behavioral, perceptual, cognitive, functional, and neuroanatomical asymmetries in nonhuman primates. In addition, we describe two historical accounts of the evolutionary origins of hemispheric specialization and present data from nonhuman primates that address these specific theories. Specifically, we first discuss the evidence that genes play specific roles in determining left-right differences in anatomical and functional asymmetries in primates. We next consider and present data on the hypothesis that hemispheric specialization evolved as a by-product of increasing brain size relative to the surface area of the corpus callosum in different primate species. Last, we discuss some of the challenges in the study of hemispheric specialization in primates and offer some suggestions on how to advance the field.

Hopkins|William D|WD|
Misiura|Maria|M|
Pope|Sarah M|SM|
Latash|Elitaveta M|EM|

brain asymmetry
primates
hemispheric specialization
corpus callosum
handedness


Incidence of Successful Pregnancy After Weight Loss Interventions in Infertile Women: a Systematic Review and Meta-Analysis of the Literature.

Abstract: Little is known about the impact of weight loss interventions on pregnancy rate. A systematic review with meta-analysis of literature has been performed to evaluate the incidence of successful pregnancy after bariatric interventions in infertile women. By pooling together data from 589 infertile obese women, we have been able to provide an aggregate estimation of successful pregnancy after weight loss interventions. Our results showed an impressive high incidence (58%) of infertile women who become spontaneously pregnant after surgery. Based on our results, bariatric interventions could be included in the treatment of obesity-related infertility. However, the results must be interpreted with caution owning to the quality of the data provided by included studies. Further ad hoc studies are needed to validate the effectiveness of bariatric interventions on reproductive function.

Milone|Marco|M|
De Placido|Giuseppe|G|
Musella|Mario|M|
Sosa Fernandez|Loredana Maria|LM|
Sosa Fernandez|Laura Virginia|LV|
Campana|Gabriele|G|
Di Minno|Matteo Nicola Dario|MN|
Milone|Francesco|F|

Infertility Bariatric Obesity BMI Fertility


Protocol of single cells preparation for time of flight secondary ion mass spectrometry.

Abstract: There are several techniques like time of flight secondary ion mass spectrometry (ToF SIMS) that require a special protocol for preparation of biological samples, in particular, those containing single cells due to high vacuum conditions that must be kept during the experiment. Frequently, preparation methodology involves liquid nitrogen freezing what is not always convenient. In our studies, we propose and validate a protocol for preparation of single cells. It consists of four steps: (i) paraformaldehyde fixation, (ii) salt removal, (iii) dehydrating, and (iv) sample drying under ambient conditions. The protocol was applied to samples with single melanoma cells i.e. WM115 and WM266-4 characterized by similar morphology. The surface and internal structures of cells were monitored using atomic force, scanning electron and fluorescent microscopes, used to follow any potential protocol-induced alterations. To validate the proposed methodology for sample preparation, ToF SIMS experiments were carried out using C60(+) cluster ion beam. The applied principal component analysis (PCA) revealed that chemical changes on cell surface of melanoma cells were large enough to differentiate between primary and secondary tumor sites. Subject category: Mass spectrometry.

Bobrowska|Justyna|J|
Pabijan|Joanna|J|
Wiltowska-Zuber|Joanna|J|
Jany|Benedykt R|BR|
Krok|Franciszek|F|
Awsiuk|Kamil|K|
Rysz|Jakub|J|
Budkowski|Andrzej|A|
Lekka|Malgorzata|M|

D018629:Spectrometry, Mass, Secondary Ion

ToF SIMS
Melanoma cells
AFM
ESEM
Sample preparation protocol


Innate immune responses play a key role in controlling infection of the intestinal epithelium by Cryptosporidium.

Abstract: Cryptosporidium infection leads to acute diarrhea worldwide. The development of cryptosporidiosis is closely related to the immune status of its host, affecting primarily young ruminants, infants, and immunocompromised individuals. In recent years, several studies have improved our knowledge on the immune mechanisms responsible for the control of the acute phase of the infection and have highlighted the importance of innate immunity. The parasite develops in the apical side of intestinal epithelial cells, giving these cells a central role, as they are both the exclusive host cell for replication of the parasite and participate in the protective immune response. Epithelial cells signal the infection by producing chemokines, attracting immune cells to the infected area. They also actively participate in host defense by inducing apoptosis and releasing antimicrobial peptides, free or incorporated into luminal exosomes, with parasiticidal activity. The parasite has developed several escape mechanisms to slow down these protective mechanisms. Recent development of several three-dimensional culture models and the ability to genetically manipulate Cryptosporidium will greatly help to further investigate host-pathogen interactions and identify virulence factors. Intestinal epithelial cells require the help of immune cells to clear the infection. Intestinal dendritic cells, well known for their ability to induce and orchestrate adaptive immunity, play a key role in controlling the very early steps of Cryptosporidium parvum infection by acting as immunological sentinels and active effectors. However, inflammatory monocytes, which are quickly and massively recruited to the infected mucosa, seem to participate in the loss of epithelial integrity. In addition to new promising chemotherapies, we must consider stimulating the innate immunity of neonates to strengthen their ability to control Cryptosporidium development. The microbiota plays a fundamental role in the development of intestinal immunity and may be considered to be a third actor in host-pathogen interactions. There is an urgent need to reduce the incidence of this yet poorly controlled disease in the populations of developing countries, and decrease economic losses due to infected livestock.

Innate immunity
Cryptosporidium
Epithelial cell
Immunostimulation
Mononuclear phagocytes


Effects of Inhaled Nitrous Oxide on the Induction Dose and Time Requirements of Propofol: A Prospective, Randomized, Double-blind Study.

Abstract:
CONTEXT
Propofol is a commonly used induction agent during general anesthesia. As a sole agent, it does not provide any strong analgesic effect. The nitrous oxide (N2O) used along with propofol for induction of anesthesia augments the induction characteristics and reduces the dose of propofol.

AIMS
To study the effects of inhaled N2O on the induction dose and time of propofol during general anesthesia and also its hemodynamic response and adverse effects.

SETTINGS AND DESIGN
The present research is a prospective, randomized, double-blind comparative study.

SUBJECTS AND METHODS
The study population consisted of eighty patients aged 18-60 years from either sex, American Society of Anesthesiologists physical status 1 and 2 which were scheduled for various elective surgical procedures under general anesthesia. The patients were randomly allocated into two groups comprising forty patients in each group. All patients were premedicated with glycopyrrolate 0.2 mg, ondansetron 4 mg, and fentanyl 1 μg/kg intravenously. Group FN received breathing mixture of gases (67% N2O @ 4 L/min and 33% O2 @ 2 L/min), and propofol and Group FO received 100% O2 @ 6 L/min and propofol. The different hemodynamic parameters (heart rate, mean arterial pressure, systolic blood pressure, diastolic blood pressure, and SpO2) were measured.

STATISTICAL ANALYSIS
All observations were analyzed using Chi-square test, Student's t-test, and analysis of variance.

RESULTS
The mean induction time and dose were significantly less in Group FN as compared to Group FO (P < 0.05). The mean induction time was 172 ± 32 s in Group FN as compared to 242 ± 43 s in Group FO (P < 001), whereas the mean induction dose was 56.10 ± 13.92 mg in Group FN as compared to 81.67 ± 17.64 mg in Group FO (P < 0.05). The hemodynamic parameters remained stable with no complications.

CONCLUSION
The coadministration of N2O during induction of anesthesia with propofol not only reduced the induction dose of propofol but also reduced induction time significantly. Furthermore, it provided stable hemodynamics without any complications.

Jain|Kavita|K|
Sethi|Surendra Kumar|SK|
Damor|Mamta|M|
Jain|Neena|N|

nitrous oxide
induction
Dose
propofol
hemodynamics


Chondrosarcomas of the small bones: analysis of 44 patients.

Abstract:
BACKGROUND
Chondrosarcomas of the small bones of the hands and feet are uncommon and account for less than 2% of all chondrosarcomas in the skeleton; a 4.2% rate of malignant degeneration of enchondromas to secondary chondrosarcomas has been reported. We performed this study to assess the outcome of the patients with chondrosarcomas of the small bones. We hypothesized that the presumed better prognosis of chondrosarcomas in these locations could be biased as the majority of these tumors tend to be of lower grades and are removed when still small sized, and that less aggressive surgery has an adverse effect on local control MATERIALS AND METHODS: We retrospectively studied the files of 44 patients with chondrosarcomas of the small bones of the hands and feet. There were 23 female and 21 male patients with a mean age of 50.9 years (range, 6-86 years). The mean follow-up was 13 years (range, 5-40 years). We recorded the patients' details including gender and age at diagnosis, type and duration of symptoms, tumor location and histology, type of surgery and complications, and outcome (local recurrences and metastases).

RESULTS
The most common anatomical location for chondrosarcomas of the hands was the metacarpals and proximal phalanges. The most common presenting symptom was a slowly enlarging palpable mass. Overall, 36 chondrosarcomas were secondary to a pre-existing cartilaginous tumor. Patients with syndromes were affected in younger age compared to the others. The mean age at diagnosis was higher for higher grade chondrosarcomas. Overall, 13 patients (29.5%) experienced a local recurrence; the rate of local recurrence was higher after curettage regardless the histological grade of the tumors. After wide resection of the first local recurrence, five patients experienced local re-recurrence. Five patients (11.4%) experienced lung metastases, two patients at presentation. All these patients had a high grade chondrosarcomas. At the last follow-up, one patient with lung metastases died from disease, and another patient died from unrelated cause.

CONCLUSIONS
The patients with chondrosarcomas of the small bones of the hands and feet may have a dismal outcome if treated improperly. A careful treatment planning is required to avoid unnecessary amputations. Curettage is associated with a high rate for local recurrence that should be treated with a more aggressive surgical resection to avoid re-recurrences. Although the risk is low, the patients may develop lung metastases, especially those with higher grade chondrosarcomas, therefore, they should be staged and followed closely.

Chondrosarcoma
Hand
Outcome
Local recurrence
Foot
Metastasis


Antral follicular count and its relationship with ovarian volume, preantral follicle population and survival, oocyte meiotic progression and ultrastructure of in vitro matured bovine cumulus-oocyte complexes.

Abstract: This study aimed to evaluate the relationship between antral follicular count (AFC) and ovarian volume (OV), preantral follicular population and survival, meiotic progression and ultrastructure of cumulus-oocyte complexes (COCs) after in vitro maturation. In experiment 1, the relationship between AFC and preantral follicle population and survival was evaluated by classical histology. In experiment 2, the relationship among AFC, OV, ability of oocytes to resume meiosis and ultrastructure of in vitro matured bovine COCs was studied. A positive correlation (P < 0.05) between AFC and the numbers of healthy primordial, degenerate and total follicles was observed, as well as with healthy secondary follicles and total follicles. The numbers of grades I and II oocytes in ovaries of high AFC class were higher compared with those with intermediate or lower AFC. After in vitro maturation, COCs from ovaries of high AFC had a higher percentage of oocytes in metaphase II compared with those of intermediate and low AFC (P < 0.0001). Ovaries of intermediate AFC had a higher percentage of oocytes in metaphase II compared with ovaries with low AFC (P < 0.0001). The proportion of oocytes in metaphase I, telophase I and anaphase I in COCs from ovaries of intermediate AFC (26.04%) was higher (P < 0.05) compared with that seen in COCs of ovaries with high (8.55%) and low (14.15%) AFC. No differences in the ultrastructure of oocytes were seen. In conclusion, after in vitro maturation, cow ovaries with high AFC have higher numbers of oocytes that reach in metaphase II (MII), but they also have higher numbers of degenerated primordial and primary follicles.

In vitro maturation
Cattle
Morphology
Oocyte quality
Ovarian follicular reserve


The heparan sulfate mimetic PG545 interferes with Wnt/β-catenin signaling and significantly suppresses pancreatic tumorigenesis alone and in combination with gemcitabine.

Abstract: The heparan sulfate mimetic PG545 has been shown to exert anti-angiogenic and anti-metastatic activity in vitro and in vivo cancer models. Although much of this activity has been attributed to inhibition of heparanase and heparan sulfate-binding growth factors, it was hypothesized that PG545 may additionally disrupt Wnt signaling, an important pathway underlying the malignancy of pancreatic cancer. We show that PG545, by directly interacting with Wnt3a and Wnt7a, inhibits Wnt/β-catenin signaling leading to inhibition of proliferation in pancreatic tumor cell lines. Additionally, we demonstrate for the first time that the combination of PG545 with gemcitabine has strong synergistic effects on viability, motility and apoptosis induction in several pancreatic cell lines. In an orthotopic xenograft mouse model, combination of PG545 with gemcitabine efficiently inhibited tumor growth and metastasis compared to single treatment alone. Also, PG545 treatment alone decreased the levels of β-catenin and its downstream targets, cyclin D1, MMP-7 and VEGF which is consistent with our in vitro data. Collectively, our findings suggest that PG545 exerts anti-tumor activity by disrupting Wnt/β-catenin signaling and combination with gemcitabine should be considered as a novel therapeutic strategy for pancreatic cancer treatment.

Jung|Deok-Beom|DB|
Yun|Miyong|M|
Kim|Eun-Ok|EO|
Kim|Jaekwang|J|
Kim|Bonglee|B|
Jung|Ji Hoon|JH|
Wang|Enfeng|E|
Mukhopadhyay|Debabrata|D|
Hammond|Edward|E|
Dredge|Keith|K|
Shridhar|Viji|V|
Kim|Sung-Hoon|SH|

D000971:Antineoplastic Combined Chemotherapy Protocols

D023041:Xenograft Model Antitumor Assays

heparan sulfate mimetic
PG545
Wnt/β-catenin
gemcitabine
pancreatic cancer


Frequent avoidable admissions amongst Aboriginal and non-Aboriginal people with chronic conditions in New South Wales, Australia: a historical cohort study.

Abstract:
BACKGROUND
Aboriginal and Torres Strait Islander people have high rates of avoidable hospital admissions for chronic conditions, however little is known about the frequency of avoidable admissions for this population. This study examined trends in avoidable admissions among Aboriginal and non-Aboriginal people with chronic conditions in New South Wales (NSW), Australia.

METHODS
A historical cohort analysis using de-identified linked administrative data of Aboriginal patients and an equal number of randomly sampled non-Aboriginal patients between 2005/06 to 2013/14. Eligible patients were admitted to a NSW public hospital and who had one or more of the following ambulatory care sensitive chronic conditions as a principal diagnosis: diabetic complications, asthma, angina, hypertension, congestive heart failure and/or chronic obstructive pulmonary disease. The primary outcomes were the number of avoidable admissions for an individual in each financial year, and whether an individual had three or more admissions compared with one to two avoidable admissions in each financial year. Poisson and logistic regression models and a test for differences in yearly trends were used to assess the frequency of avoidable admissions over time, adjusting for sociodemographic variables and restricted to those aged ≤75 years.

RESULTS
Once eligibility criteria had been applied, there were 27,467 avoidable admissions corresponding to 19,025 patients between 2005/06 to 2013/14 (71.2% Aboriginal; 28.8% non-Aboriginal). Aboriginal patients were 15% more likely than non-Aboriginal patients to have a higher number of avoidable admissions per financial year (IRR = 1.15; 95% CI: 1.11, 1.20). Aboriginal patients were almost twice as likely as non-Aboriginal patients to experience three or more avoidable admissions per financial year (OR = 1.90; 95% CI = 1.60, 2.26). There were no significant differences between Aboriginal and non-Aboriginal people in yearly trends for either the number of avoidable admissions, or whether or not an individual experienced three or more avoidable admissions per financial year (p = 0.859; 0.860 respectively).

CONCLUSION
Aboriginal people were significantly more likely to experience frequent avoidable admissions over a nine-year period compared to non-Aboriginal people. These high rates reflect the need for further research into which interventions are able to successfully reduce avoidable admissions among Aboriginal people, and the importance of culturally appropriate community health care.

D044468:Native Hawaiian or Other Pacific Islander

Aboriginal health
Chronic disease
Data linkage
Frequent admissions
Health services research


Tailoring of a Potential Nanoformulated Form of Gibberellic Acid: Synthesis, Characterization, and Field Applications on Vegetation and Flowering.

Abstract: Nanoformulation of agrochemicals has become a potential choice to improve the physicochemical properties, enhance the utilization efficiency, and reduce the side effects and ecotoxicity of many hazardous chemicals. Here, we tailored a new formulation platform for gibberellic acid (GA) using the layered double hydroxides (LDH) as a potential carrier. Typically, we synthesized, characterized, and potentially applied the newly nanoformulated form of GA on the quantity and quality properties of Dendranthema grandiflorum cultivar. We also evaluated the synergetic effect of the carrier LDH on the release behavior of GA, showing a remarkable impact on the utilization efficiency of GA. The nanohybrid structure of GA also showed an enhanced thermal stability and safe preservation for the incorporated moieties. Taking into account the hazardous effect of free GA on the environment and human health, the hybrid technique of GA is one of the best choices among all of the studied protocols.

nanoformulation
gibberellic acid
agrochemicals
layered double hydroxides
hybrids


Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders.

Abstract: Immunotherapy is an important armamentarium for cancer treatment nowadays. Apart from their significant effectiveness in controlling disease they also generate potential severe immune related adverse effects. Preexistence of immune related conditions may eventually predispose to the development of more severe complication and extreme caution have been taken in treating these patients. We performed a literature review searching for case reports and case series in order to offer evidence-based data for clinical management of these patients. Preexisting serological-only immune abnormalities or presence of a predisposing genetic background does not seem to confer significant risk but existing data is scarce. Most patients with preexistent autoimmune diseases can probably treated with checkpoint inhibitors as they seem to have at least the same response rate as the general cancer population. Under treatment, a significant part of them (at least 30%) can experience a flare of their baseline disease which can sometime be severe. Life-threatening cases seems rare and disease flare can be generally managed with steroids. The volume of available data is more important for rheumatologic diseases than for inflammatory bowel diseases were more caution should be observed. However, it has to be kept in mind that new immune related adverse effects (IrAE) are seen with a similar frequency as the flare of the baseline disease. Both flare-up's and newly developed IrAE are generally manageable with a careful clinical follow-up and prompt therapy.

Coureau|Michelle|M| Meert|Anne-Pascale|AP| Berghmans|Thierry|T| Grigoriu|Bogdan|B|

autoimmunity immunotherapy cancer flare-up side-effect


The prognostic impact of abnormally expressed, long noncoding RNAs in acute myeloid leukemia: a meta-analysis.

Abstract: Objectives: A growing number of studies demonstrate that long noncoding RNAs (lncRNAs) could act as biomarkers to determine the prognosis of acute myeloid leukemia (AML) patients. Nonetheless, the significance of lncRNAs in AML prognosis remains unclear. We conducted a meta-analysis to assess the prognostic indicators of abnormally expressed lncRNAs in AML. Methods: Literature was searched using PubMed, EMBASE, and Web of Science databases up to November 10, 2018. Results: Thirteen studies with 2755 individuals were included. The abnormal expression of lncRNAs was associated with worse overall survival (OS) in AML patients, especially in cytogenetically normal AML (CN-AML), and was associated with shorter disease-free survival and event-free survival. Subgroup analysis showed that high levels of HOTAIR and TUG1 were associated with poor OS. Discussion: Overexpression of lncRNA HOTAIR and TUG1 were reported in two separate studies, and correlated with worse AML prognoses. Conclusion: Abnormally expressed lncRNAs are significantly related to worse prognoses of AML patients and might serve as potential prognostic markers to predict the prognosis of AML patients.

D015973:Gene Expression Regulation, Leukemic

acute myeloid leukemia
meta-analysis
LncRNA
prognosis
cytogenetics
diagnostics
gene expression


Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation.

Abstract: Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of >50μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu(2+)-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent.

Chen|Jing-Hsien|JH| Tsai|Chia-Wen|CW| Wang|Chi-Ping|CP| Lin|Hui-Hsuan|HH|

D024202:Electrophoretic Mobility Shift Assay

D017392:Thiobarbituric Acid Reactive Substances

sodium dodecyl sulfate polyacrylamide gel electrophoresis

P P P P P P P P P P P P P P P P P U M U U U M U U U U U M M U M U U


Moniliformediquinone induces in vitro and in vivo antitumor activity through glutathione involved DNA damage response and mitochondrial stress in human hormone refractory prostate cancer.

Abstract:
PURPOSE
Hormone refractory metastatic prostate cancer is a major obstacle in clinical treatment. The key focus of this study was the discovery and development of a potential agent for this disease.

MATERIALS AND METHODS
Several pharmacological and biochemical assays were used to characterize the apoptotic signaling pathways of moniliformediquinone, a natural product, in hormone refractory metastatic prostate cancer.

RESULTS
Moniliformediquinone induced cell cycle arrest at the S-phase and subsequent apoptosis in the hormone refractory metastatic prostate cancer cell lines PC-3 and DU-145. Further examination showed that moniliformediquinone induced a DNA damage response associated with Chk1, Chk2, c-Jun and JNK activation. Mitochondrial apoptosis pathways were also activated, including loss of mitochondrial membrane potential, cytochrome c release, and activation of caspase-9 and 3. The antioxidant and glutathione precursor N-acetylcysteine, and the antioxidant Trolox™ completely abolished moniliformediquinone induced generation of reactive oxygen species. However, N-acetylcysteine but not Trolox blocked moniliformediquinone mediated apoptosis and related signaling cascades. Further identification showed that moniliformediquinone alone did not conjugate glutathione but significantly decreased cellular glutathione levels. The in vivo study revealed that moniliformediquinone completely inhibited tumor growth with no weight loss.

CONCLUSIONS
Our data suggest that moniliformediquinone is a potential anticancer agent for hormone refractory metastatic prostate cancer by decreasing cellular glutathione, leading to a DNA damage response and cell cycle arrest at the S-phase. Mitochondrial stress also occurs due to moniliformediquinone action through loss of mitochondrial membrane potential and cytochrome c release, which in turn induce the activation of caspase cascades and apoptotic cell death.

Hsu|Jui-Ling|JL| Lee|Yean-Jang|YJ| Leu|Wohn-Jenn|WJ| Dong|Yu-Shun|YS| Pan|Shiow-Lin|SL| Uang|Biing-Jiun|BJ| Guh|Jih-Hwa|JH|

D004354:Drug Screening Assays, Antitumor

glutathione
apoptosis
Dendrobium
castration-resistant
mitochondria
prostatic neoplasms


Caesarean delivery rate and indications at a secondary healthcare Facility in Ibadan, South Western Nigeria: a five-year review.

Abstract:
Background
Caesarean delivery is an essential surgical skill within the primary care setting aimed at reducing maternal morbidity and mortality.

Objectives
To determine the rate and indications for caesarean deliveries with a view to improving on the service delivery in the study area.

Methods
A retrospective review of all caesarean deliveries over a five-year period, January 1st, 2012 to December 31st, 2016.

Results
A total of 2321 deliveries were recorded during the study duration and 481 of them were through caesarean section (CS) giving a caesarean section rate of 20.4%. The rate was higher in the multigravida 255 (53.1%). The commonest indication for caesarean section was previous caesarean section 131 (27.2%). Emergency caesarean delivery accounted for 278 (57.8%). Only 16 (3.3%) stayed more than five days postoperatively while the rest, 465 (96.7%), stayed less than five days. There was a gradual yearly increase in rate from 12.1% in 2012 to 19.5% in 2016.

Conclusion
The rate of CS in this study has shown a gradual yearly increase with emergency CS having a higher percentage. Early diagnosis and referral of high-risk pregnancies from peripheral hospitals could reduce emergency CS among the study population.

Ismail|Waheed O|WO|
Bello|Ibrahim S|IS|
Olowookere|Samuel A|SA|
Ibrahim|Azeez O|AO|
Agbesanwa|Tosin A|TA|
Adekunle|Wulaimat A|WA|

rate
secondary healthcare
Nigeria
Caesarean section


Evaluation of bacterial contamination in raw milk, ultra-high temperature milk and infant formula using single molecule, real-time sequencing technology.

Abstract: The Pacific Biosciences (Menlo Park, CA) single molecule, real-time sequencing technology (SMRT) was reported to have some advantages in analyzing the bacterial profile of environmental samples. In this study, the presence of bacterial contaminants in raw milk, UHT milk, and infant formula was determined by SMRT sequencing of the full length 16S rRNA gene. The bacterial profiles obtained at different taxonomic levels revealed clear differences in bacterial community structure across the 16 analyzed dairy samples. No indicative pathogenic bacteria were found in any of these tested samples. However, some of the detected bacterial species (e.g., Bacillus cereus, Enterococcus casseliflavus, and Enterococcus gallinarum) might potentially relate with product quality defects and bacterial antibiotic gene transfer. Although only a limited number of dairy samples were analyzed here, our data have demonstrated for the first time the feasibility of using the SMRT sequencing platform in detecting bacterial contamination. Our paper also provides interesting reference information for future development of new precautionary strategies for controlling the dairy safety in large-scale industrialized production lines.

Hou|Qiangchuan|Q| Xu|Haiyan|H| Zheng|Yi|Y| Xi|Xiaoxia|X| Kwok|Lai-Yu|LY| Sun|Zhihong|Z| Zhang|Heping|H| Zhang|Wenyi|W|

real-time sequencing technology sequencing


Migraine Treatment in Emergency Departments of Brazil: A Retrospective Study of 2 Regions.

Abstract:
OBJECTIVE
This study describes the approaches, medications used, and time of care for migraineurs, who have been in emergency departments (ED) from 2 different regions of Brazil.

METHODS
Retrospective, cross-sectional, observational, non-randomized study of migraine patients seen at 2 headache centers in Brazil.

RESULTS
Eighty-four migraine patients (15 men and 69 women) were divided into 2 groups: chronic (19%, n = 16) and episodic migraineurs (81%, n = 68). In the ED, medications were used in the following order of frequency: dipyrone or metamizole (89.3%, 75/84), nonsteroidal anti-inflammatory drugs (57.1%; 48/84) opioids (51.1%; 43/84), metoclopramide (29.8%; 25/84), dexamethasone (28.6%; 24/84), chlorpromazine (13.1%; 11/84), and subcutaneous sumatriptan (7.1%; 6/84). The average time in the care center was 8.2 hours, but only 23 patients (27.4%) left the hospital with greater than 50% relief in headache severity.

CONCLUSIONS
Dipyrone and nonsteroidal anti-inflammatories were the most used drugs, but nearly half received opioids. More efficient drugs were poorly used. Considering the number of patients leaving the hospital with headache relief, a changing treatment paradigm should be carried out in Brazil.

D065127:Dopamine D2 Receptor Antagonists

migraine
Brazil
opioids
sumatriptan
headache relief
emergency treatments


Prescriber practices and patient adherence to artemisinin-based combination therapy for the treatment of uncomplicated malaria in Guinea, 2016.

Abstract:
BACKGROUND
The World Health Organization recommends the use of artemisinin-based combination therapy (ACT) to treat uncomplicated malaria for the control of malaria across the world. There are several types of ACT used across malaria-endemic countries, yet there is little information about preferences and adherence practices regarding different types of ACT. The objective of this study was to evaluate levels of adherence to two types of ACT, artemether-lumefantrine (AL) and artesunate + amodiaquine (ASAQ), for the treatment of uncomplicated malaria among prescribers and patients in Guinea in 2016.

METHODS
The study included a review of records of malaria patients and three health-facility, cross-sectional surveys. Patients diagnosed with uncomplicated malaria and prescribed ACT (n = 1830) were recruited and visited in their home after receiving the medication and administered a questionnaire regarding ACT adherence. Prescribers (n = 115) and drug dispensers (n = 43) were recruited at the same public health facilities and administered questionnaires regarding prescribing practices and opinions regarding the national treatment policies and protocols.

RESULTS
According to the registry review, 35.8% of all-cause consultations were recorded as malaria. Of these, 26.6% were diagnosed clinically without documentation of laboratory confirmation. The diagnosis of uncomplicated malaria represented 64.1% of malaria cases among children under 5 years and 74.9% of those 5 years of age and older. An ACT was prescribed for 83.5% of cases of uncomplicated malaria. Among participants in the study, ACT adherence was 95.4% (95% CI 94.4, 96.3). Overall, about one in four patients (23.4%; 95% CI 21.5, 25.3) reported experiencing adverse events. While patients prescribed ASAQ were significantly more likely to report experiencing adverse effects than patients on AL (p < 0.001), given the overall high adherence, there was no evidence of a statistically significant difference in adherence between AL and ASAQ. Patients 5 years or older who reported experiencing adverse events were more likely to be non-adherent.

CONCLUSION
Although there were more reported adverse events associated with ASAQ when compared with AL, both prescribers and patients were found to be mostly adherent to ACT for the treatment of malaria, regardless of ACT type.

Camara|Alioune|A|
Moriarty|Leah F|LF|
Guilavogui|Timothée|T|
Diakité|Papa Sambou|PS|
Zoumanigui|Joseph Souba|JS|
Sidibé|Sidikiba|S|
Bah|Ibrahima|I|
Kaba|Ibrahima|I|
Kourouma|Djebory|D|
Zoumanigui|Koho|K|
Plucinski|Mateusz|M|

D000077611:Artemether, Lumefantrine Drug Combination

Adherence
Malaria
Guinea
ACT
Amodiaquine
Drug intake
Lumefantrine


Some peculiarities of turbulent mixing growth and perturbations at hydrodynamic instabilities.

Abstract: The author presents a review of some experimental works devoted to the research of evolution of large-scale perturbations and turbulent mixing (TM) in liquid and gaseous media during the growth of hydrodynamic instabilities. In particular, it is shown that growth of perturbations and TM in gases is sensitive to the Mach number of shock wave; character of gas front penetration into liquid is not changed as the Reynolds number of flow increases from 5×10(5) to 10(7); and change of the Atwood number sign from positive to negative causes stopping of gas front penetration into liquid, but mixing zone width is expanded under inertia.

turbulent mixing
Mach number
shock wave
Reynolds number


Humanized mice in infectious diseases.

Abstract: The pathogenesis of infectious agents with human tropism can only be properly studied in an in vivo model featuring human cells or tissue. Humanized mice represent a small animal model featuring human cells or tissue that can be infected by human-specific viruses, bacteria, and parasites and also providing a functional human immune system. This makes the analysis of a human immune response to infection possible and allows for preclinical testing of new vaccines and therapeutic agents. Results of various studies using humanized mice to investigate pathogens with human tropism are presented in this review. In addition, the limitations of humanized mice and methods to improve this valuable animal model are discussed.

Humanized mice
Infectious diseases
Review
Human specific pathogens


Hepatic Artery Pseudoaneurysm Presenting as Gastrointestinal Hemorrhage.

Abstract: A hepatic artery pseudoaneurysm (HAP) is a rare complication of laparoscopic cholecystectomy. It can vary in its clinical presentation; however, given its severe nature, prompt assessment and management are crucial. We report a case of a 73-year-old male who underwent a laparoscopic cholecystectomy complicated by a right hepatic artery injury. This subsequently presented as a life-threatening case of upper gastrointestinal bleeding from HAP, with presumable hemobilia and septic shock from multiple liver abscesses. The diagnosis was made with computed tomography angiography (CTA) of the abdomen and pelvis followed by visceral angiography. The patient ultimately underwent a right hepatectomy for definitive treatment. The primary objective of this case is to highlight a less novel, though rare, case presentation and define a spectrum of treatment options available based on severity.

Singh|Pratishtha|P|
Scibelli|Nicolina|N|
Gosal|Kiranpreet|K|
Bostick|Adam|A|
Morgan|Dylan C|DC|

hepatic artery pseudoaneurysm
gastrointestinal bleeding
right hepatectomy
hepatectomy


Heredity of interocular similarities in components of refraction: a population-based twin study among 66- to 79-year-old female twins.

Abstract:
PURPOSE
To examine genetic influences on interocular similarities in ocular refraction and components of refraction among elderly female twins.

METHODS
Refraction was assessed in 94 monozygotic (MZ) and 74 dizygotic (DZ) female twins aged 66-78 years. Absolute values of interocular differences (Aniso variables) in spherical refraction (SR), refractive astigmatism (AST), spherical equivalent (SE), corneal refractive power (CR), corneal astigmatism (CAST), anterior chamber depth (ACD) and axial length (AL) were calculated. The differences between sisters in each of the Aniso variables were calculated and graded into two categories, best differentiating the groups, here isometropic and anisometropic values. The cut-offs for grading as isometropic were AnisoSR < 0.75 D, AnisoAST < 0.5 D, AnisoSE < 1.0 D, AnisoCR < 0.5 D, AnisoCAST < 0.50 D, AnisoACD < 0.1 mm and AniosAL < 0.1 mm. Genetic influences on these traits were investigated by comparing the prevalence of isometropic and anisometropic differences between the MZ and DZ pairs in the Aniso variables and the interrelationships between the Aniso variables.

RESULTS
When the Aniso variables were treated as continuous, no significant differences were found between the MZ and DZ subjects. When the proportions of isometropic intratwinpair interocular differences in the Aniso variables in the MZ and DZ cotwins were compared, the prevalences (MZ/DZ) were AnisoSR: 68%/60%; AnisoAST: 66%/57%; AnisoSE: 87%/68%; AnisoCR: 83%/78%; AnisoCAST: 69%/35%; AnisoACD: 77%/63%; and AnisoAL: 76%/60%. The differences were statistically significant for Aniso SE (p = 0.035, Fisher's exact test) and CAST (p = 0.007). The greater homogeneity in the interocular differences between the MZ sisters supports the assumption that isometropia of different elements of refraction is genetically influenced and tending to continue up to older ages. In cases where AnisoSE was <1.0 D, higher CR in one eye was associated with shorter AL (r = -0.398, p < 0.001), thereby contributing to emmetropization, irrespective of zygosity. In the cases of AnisoSE ≥1 D, no similar influence on emmetropization was observed. The difference between sisters in AnisoSE was associated with the intratwinpair difference in Aniso AL, but not with the intratwinpair differences in AnisoCR, irrespective of zygosity.

CONCLUSION
The higher prevalence of similarities in isometropia of the spherical equivalent and corneal astigmatism between the MZ pairs compared to DZ pairs is consistent with the view that genetic influences on the refractive elements of the eye, tending to isometropia, continue into older age. The interrelation between CR and AL tends to maintain isometropia of SE irrespective of zygosity.

D020022:Genetic Predisposition to Disease

astigmatism
spherical equivalent
corneal refraction
isometropia
ansiometropia
emmetropia


Predicting Factors of Pain Duration in Patients with Chronic Pain: A Large Population-based Study.

Abstract:
Background
Chronic pain is the third main problem of global health and the most common cause of long-term disabilities. The duration that patients suffer from chronic pain is directly proportional to the extent of the suffering and to the amount of health care resources allocated to this problem. There is no research that has studied the risk factors associated with the long pain duration in chronic pain patients.

Methods
We investigated the potential risk factors associated with long pain duration in a population with diverse pain conditions in a cross-sectional study. We used a questionnaire that included a number of potential risk factors including sex, age, marital status, household condition, number of children, employment, education, body mass index (BMI), pain intensity, and the level of anxiety/depression. The data were analyzed by univariable and multivariable linear regression models.

Results
We recruited 780 patients. The analyses showed that age and abnormal BMI had a positive correlation with pain duration.

Conclusions
The risk factors that might be associated with longer pain duration include older age and abnormal BMI.

Pain Duration Chronic Sex Age BMI Gender Management Obesity Treatment


Intermittent parathyroid hormone administration attenuates endothelial dysfunction in old rats.

Abstract:
Aging is an independent risk factor for cardiovascular disease and is characterized by a decline in endothelial function. Parathyroid hormone (PTH) administration has been shown to increase endothelial nitric oxide synthase (eNOS) expression. The purpose of this investigation was to determine the effect of intermittent PTH administration on aortic endothelial function in old rodents. We hypothesized that intermittent PTH administration would improve endothelial function in older rodents. Old (24-mo-old) and young (4-mo-old) Fischer-344 rats were given 10 injections of PTH 1-34 (43 μg·kg-1·day-1) or phosphate-buffered saline (100 μl/day) over 15 days. Endothelium-dependent relaxation of aortic rings in response to acetylcholine (10-9 to 10-5 M) was significantly impaired in old control (OC) compared with young control (YC) as indicated by a reduced area under the curve (AUC, 100 ± 6.28 vs. 54.08 ± 8.3%; P < 0.05) and impaired maximal relaxation (Emax, 70.1 ± 4.48 vs. 92.9 ± 4.38%; P < 0.05). Emax was improved in old animals treated with PTH (OPTH) (OC, 70.1 ± 4.48 vs. OPTH, 85 ± 7.48%; P < 0.05) as well as AUC (OC, 54.08 ± 8.3 vs. OPTH, 82.5 ± 5.7%; P < 0.05) while logEC50 was not different. Endothelial-independent relaxation in response to sodium nitroprusside was not different among groups. Aortic eNOS protein expression was significantly decreased in OC compared with YC (P < 0.05). PTH treatment restored eNOS expression in OPTH animals (P < 0.05). These data suggest that PTH may play a role in attenuating age-related impairments in aortic endothelial function.

NEW & NOTEWORTHY
We have demonstrated that intermittent parathyroid hormone administration can rescue age-related vascular dysfunction by improving endothelial-dependent dilation in the aorta of older rodents. This demonstrates a novel potential benefit of parathyroid hormone administration in aging.

Guers|John J|JJ|
Prisby|Rhonda D|RD|
Edwards|David G|DG|
Lennon-Edwards|Shannon|S|

parathyroid hormone
endothelial
aging
nitric oxide


Identification of Foxl2 in freshwater mussel Hyriopsis cumingii and its involvement in sex differentiation.

Abstract: The freshwater mussel Hyriopsis cumingii, is the most important species for pearl culture in China. At present, the mechanisms underlying sex differentiation and determination remain unclear in this species. Herein the open reading frame (ORF) of Foxl2 from H. cumingii (Hc-Foxl2) was cloned, and Hc-Foxl2 expression levels in six tissues (the gonad, gill, adductor muscle, foot, mantle, and kidney) were determined. Further, we performed quantitative real-time PCR to compare expressions levels between 1 and 8 months of age and 1-, 2-, and 3-year-old H. cumingii. The localization of Hc-Foxl2 expression in the ovary was analyzed by in situ hybridization, and its function was explored using RNA interference. We found that the ORF region of Hc-Foxl2 was 1215 bp in length, encoded 404 amino acids, and contained conserved FH domains. Hc-Foxl2 was expressed in the male and female tissues, with the expression levels being significantly higher in the ovary than in the testis. In 1-8-month-old H. cumingii, Hc-Foxl2 was expressed at the highest level at 5 months of age, and the gonads began to differentiate at the same time. Moreover, in 1-, 2-, and 3-year-old individuals, Hc-Foxl2 expression levels in the ovaries gradually decreased, but they were higher than those in the testis. Strong hybridization signals for Hc-Foxl2 were detected on the oocyte membrane in 3-year-old female mussels. We also performed double-stranded RNA (dsRNA) interference experiments using three dsRNA strands, which were injected into 5-month-old H. cumingii; the interference effects were the best at 12 h and 48 h post-injection. After interference with Hc-Foxl2, the expression levels of Wnt4, which has an antagonistic relationship with Foxl2 during ovarian development, were slightly increased. Thus, we speculate that Hc-Foxl2 is a female-related gene in H. cumingii and that it is involved in sex differentiation and ovarian development.

Wang|Guiling|G| Dong|Saisai|S| Guo|Pengfei|P| Cui|Xiaoyu|X| Duan|Shenghua|S| Li|Jiale|J|

D000595:Amino Acid Sequence
D000818:Animals
D001483:Base Sequence
D049872:Bivalvia
D003001:Cloning, Molecular
D000074842:Forkhead Box Protein L2
D005618:Fresh Water
D005786:Gene Expression Regulation
D010802:Phylogeny
D017385:Sequence Homology
D012733:Sex Differentiation

Foxl2
Hyriopsis cumingii
Sex differentiation
In situ hybridization
RNAi
qRT-PCR


Micro-anatomical structure of the first spine of the dorsal fin of Atlantic bluefin tuna, Thunnus thynnus (Osteichthyes: Scombridae).

Abstract: The first spine of the first dorsal fin (FS) of the Atlantic bluefin tuna (ABFT), Thunnus thynnus, is customarily used in age determination research because its transverse sections display well-defined growth marks. In this paper the FS structure was studied to explain its known dramatic age- and season-related morphological modifications, which are evidently caused by bone remodeling. Cross sections of samples from six adult ABFT were in part decalcified to be stained with histological, histochemical and immunohistochemical methods, and in part embedded in methyl-methacrylate to be either observed under a linear polarized light or microradiographed. FS showed an external compact bone zone and an inner trabecular bone zone. The compact bone zone consisted of an outer non-osteonic primary bone layer (C1) and an inner osteonic bone layer (C2). C1 was in turn characterized by alternate translucent and opaque bands. Evidence of spine bone remodeling was shown by the presence of osteoclasts and osteoblasts as well as by tartrate-resistant acid phosphatase (TRAP) positive bands at the boundary between old and newly formed bone. The examination of plain, i.e. not-fixed and not-decalcified, FS from 28 ABFT showed that the average thickness of C1 remained fairly constant during fish growth, whereas C2 increased significantly, indicating that the periosteal primary bone apposition is counterbalanced by the parallel bone remodeling occurring inside the compact bone zone. The present study revealed the structure of the ABFT FS and the pattern of its bone remodeling. Both of them underlay phenomena, never examined in detail before, such as the appearance followed by the progressive disappearance of growth bands.

Santamaria|Nicoletta|N|
Bello|Giambattista|G|
Passantino|Letizia|L|
Di Comite|Mariasevera|M|
Zupa|Rosa|R|
Pousis|Chrysovalentinos|C|
Vassallo-Agius|Robert|R|
Cicirelli|Vincenzo|V|
Basilone|Gualtiero|G|
Mangano|Salvatore|S|
Corriero|Aldo|A|

Atlantic bluefin tuna
Bone remodeling
Dorsal fin spine
Fish bone


Targeting Resident Memory T Cells for Cancer Immunotherapy.

Abstract: A novel population of memory CD8+ T cells called resident memory T cells (TRM) has been identified based on their phenotype (CD103, CD69) and on their local tissue residency without recirculating in the blood. These cells have been implicated in protective immune response against pathogens in both animal models and humans. Their role in cancer is just emerging as a key player in tumor immunosurveillance. Many properties of these cells suggest that they could control tumor growth: (i) they respond much faster to reexposure to cognate antigen than circulating memory cells, (ii) they express high levels of cytotoxic molecules, and (iii) they are enriched in tumor-specific T cells in close contact with tumor cells. TRM are present in many human cancers and are associated with a good clinical outcome independently of the infiltration of CD8+ T cells. It has been recently shown that the efficacy of cancer vaccines depends on their ability to elicit TRM. In adoptive cell therapy, the transfer of cells with the ability to establish TRM at the tumor site correlates with the potency of this approach. Interestingly, TRM express immune checkpoint molecules and preliminary data showed that they could expand early during anti-PD-1 treatment, and thus be considered as a surrogate marker of response to immunotherapy. Some cues to better expand these cells in vivo and improve the success of cancer immunotherapy include using mucosal routes of immunization, targeting subpopulations of dendritic cells as well as local signal at the mucosal site to recruit them in mucosal tissue.

Blanc|Charlotte|C| Hans|Sophie|S| Tran|Thi|T| Granier|Clemence|C| Saldman|Antonin|A| Anson|Marie|M| Oudard|Stephane|S| Tartour|Eric|E|

resident memory T cells
immunotherapy
cancer vaccine
immune checkpoint molecule
mucosal route of vaccination


Establishment of human trabecular meshwork cell cultures using nontransplantable corneoscleral rims.

Abstract: Human trabecular meshwork (hTM) cell isolation in academic settings utilizes the motile nature of these cells, allowing them to migrate away from the explant and proliferate on distal regions of the culture substrate. Corneoscleral rims used for transplantation are a potential source of explants for the establishment of hTM cell cultures. However, cell isolation and the initiation of primary cell cultures from ocular tissues stored in Optisol-GS medium for an extended period of time (>6 days) has proven difficult, since Optisol-GS remarkably reduces cell viability and cellularity. Therefore, explants obtained from ocular tissues stored in Optisol-GS do not often provide adequate cell yield to initiate primary cell cultures if conventional culture techniques are used. Therefore, the majority of the research on primary hTM cell isolation has been accomplished using donor tissue obtained within 72 h postmortem. The goal of this study was to develop an hTM cell isolation procedure from nontransplantable ocular materials, utilizing the anchorage dependency of TM cells. This procedure yielded functionally viable cells, eficiently dissociated from the trabecular meshwork. Isolated cells demonstrated typical hTM cell characteristics including monolayer formation, contact inhibition, phagocytosis, and responses to glucocorticoid exposure. To the best of our knowledge, this is the first time an expired explant has been utilized in the successful isolation of hTM cells. Our results clearly demonstrate the advantage of increasing the anchor points of hTM cells for enhanced cell migration out from the explants, which have limited cell proliferative capacity.

Trabecular meshwork
primary cell culture
Optisol-GS
phagocytosis
dexamethasone