Risk of inferior alveolar nerve injury with coronectomy vs surgical extraction of mandibular third molars-A comparison of two techniques and review of the literature.

Abstract: The removal of mandibular third molar teeth is one of the most common oral surgical procedures. In a significant number of patients, it carries a degree of associated morbidity, including damage to the inferior alveolar nerve (IAN). For this reason, practitioners desire the most up-to-date guidance on the most appropriate technique, informed by the best available evidence that will produce the lowest incidence of iatrogenic complications. The aim of this study was to perform a systematic review comparing the effect of coronectomy vs complete surgical extraction of mandibular third molar teeth on the risk of IAN injury and other complications in adults. Studies were identified through Embase (1980-2016) and Ovid MEDLINE (1946-2016) database searches. Search terms included coronectomy, partial root removal, deliberate vital root retention, odontectomy, surgical removal, surgical extraction, complete tooth extraction and extract. Limits of the study included humans, English language and randomised controlled trials (RCTs). Only RCTs comparing IAN damage associated with surgical extraction of mandibular third molars vs coronectomy were included. From our database searches, we identified two unique RCTs matching the inclusion criteria. Both evaluated patients who had specific radiographic signs of intimate relationships with the IAN. Upon detailed analysis, the studies were noted to exhibit a high risk of bias in many categories, thereby rendering their results inconclusive. Although evidence from two RCTs suggests that coronectomy can reduce the risk of IAN injury compared to surgical removal of high-risk mandibular third molars, the quality of evidence is insufficient to provide definitive conclusions regarding the preferred technique.

nerve injury
coronectomy
third molars
surgical removal
wisdom teeth


Transcriptome Analysis of Cardiac Hypertrophic Growth in MYBPC3-Null Mice Suggests Early Responders in Hypertrophic Remodeling.

Abstract: Rationale: With a prevalence of 1 in 200 individuals, hypertrophic cardiomyopathy (HCM) is thought to be the most common genetic cardiac disease, with potential outcomes that include severe hypertrophy, heart failure, and sudden cardiac death (SCD). Though much research has furthered our understanding of how HCM-causing mutations in genes such as cardiac myosin-binding protein C (MYBPC3) impair contractile function, it remains unclear how such dysfunction leads to hypertrophy and/or arrhythmias, which comprise the HCM phenotype. Identification of early response mediators could provide rational therapeutic targets to reduce disease severity. Our goal was to differentiate physiologic and pathophysiologic hypertrophic growth responses and identify early genetic mediators in the development of cardiomegaly in the cardiac myosin-binding protein C-null (cMyBP-C-/-) mouse model of HCM. Methods and Results: We performed microarray analysis on left ventricles of wild-type (WT) and cMyBPC-/- mice (n = 7 each) at postnatal day (PND) 1 and PND 9, before and after the appearance of an overt HCM phenotype. Applying the criteria of ≥2-fold change, we identified genes whose change was exclusive to pathophysiologic growth (n = 61), physiologic growth (n = 30), and genes whose expression changed ≥2-fold in both WT and cMyBP-C-/- hearts (n = 130). Furthermore, we identified genes that were dysregulated in PND1 cMyBP-C-/- hearts prior to hypertrophy, including genes in mechanosensing pathways and potassium channels linked to arrhythmias. One gene of interest, Xirp2, and its protein product, are regulated during growth but also show early, robust prehypertrophic upregulation in cMyBP-C-/- hearts. Additionally, the transcription factor Zbtb16 also shows prehypertrophic upregulation at both gene and protein levels. Conclusion: Our transcriptome analysis generated a comprehensive data set comparing physiologic vs. hypertrophic growth in mice lacking cMyBP-C. It highlights the importance of extracellular matrix pathways in hypertrophic growth and early dysregulation of potassium channels. Prehypertrophic upregulation of Xirp2 in cMyBP-C-/- hearts supports a growing body of evidence suggesting Xirp2 has the capacity to elicit both hypertrophy and arrhythmias in HCM. Dysregulation of Xirp2, as well as Zbtb16, along with other genes associated with mechanosensing regions of the cardiomyocyte implicate stress-sensing in these regions as a potentially important early response in HCM.

Farrell|Emily|E|
Armstrong|Annie E|AE|
Grimes|Adrian C|AC|
Naya|Francisco J|FJ|
de Lange|Willem J|WJ|
Ralphe|J Carter|JC|


Trends and changes in the knowledge of mother-to-child transmission means of HIV among Vietnamese women aged 15-49 years and its associated factors: findings from the Multiple Indicator Cluster Surveys, 2000-2014.

Abstract: This study aims to characterize trends and changes in the prevalence of knowledge of mother-to-child transmission (MTCT) means of HIV as well as to identify its associated socioeconomic factors among Vietnamese women. This is a repeated cross-sectional study using data from the Vietnam Multiple Indicator Cluster Surveys 2000, 2006, 2011 and 2014. We found that a slow increase was found in the trend of adequate knowledge of HIV transmission means from mother to child among women between 2000 and 2014 (41.81% in 2000, 45.66% in 2006, 49.58% in 2011, and 46.83% in 2014). Most women knew that HIV could be transmitted during pregnancy, however, more than half of women did not know all three ways of MTCT. Socioeconomic factors including age, ethnicity, education level, and economic status as factors that affected full knowledge of MTCT means. The study helps to design public health programs to raise 15-49-year-old women's knowledge in HIV transmission means from mother to child as well as can provide a quite strong case for policy adaptation to improve women's health in the time to come.

Vo Hoang|Long|L|0000-0001-5992-875X
Nguyen Si Anh|Hao|H|0000-0002-3287-4808
Tran Minh|Hien|H|
Tran Nhu|Phong|P|
Nguyen|Huyen-Trang|HT|
Affarah|Wahyu Sulistya|WS|
Van|Huy Nguyen|HN|

D007722:Health Knowledge, Attitudes, Practice

D018445:Infectious Disease Transmission, Vertical

Knowledge
mother-to-child transmission means
HIV
Vietnamese women
socioeconomic factors


A synergetic analysis method for antifouling behavior investigation on PES ultrafiltration membrane with self-assembled TiO2 nanoparticles.

Abstract: Fouling of ultrafiltration (UF) membranes is a major impediment for their use in drinking water production. Mixed matrix membranes (MMMs) may have great opportunities in dealing with this challenge due to their hierarchical structures and multiple functionalities. In this study, a synergetic analysis method based on intermolecular adhesion force measurement and fouling process simulation was applied to investigate the fouling mechanism of polyethersulfone (PES) UF membranes containing in situ self-assembled TiO2 nanoparticles (NPs). The fouling resistance behavior and antifouling mechanism of the newly developed composite membranes were investigated with sodium alginate (SA), bovine serum albumin (BSA) and humic acid (HA) as model organic foulants. An improved antifouling effect was conspicuously observed for the composite membranes, expressed by a lower flux decline and significantly better cleaning efficiency. A strong correlation between the self-assembled structure of TiO2 NPs and the antifouling behavior of the composite membrane was observed. A lower magnitude and a narrower distribution of adhesion forces for the composite membrane suggest the effective suppression of foulants adsorption on the clean or fouled membrane. The simulation analysis indicates that the main fouling mechanism was standard blocking and cake filtration, further confirming the superiority of the NPs self-assembled structure in mitigating membrane fouling. This dual analysis method may provide a promising technological support for the application of modified UF membranes with self-assembled NPs in drinking water production.

Li|Xin|X|
Li|Jiansheng|J|
Fang|Xiaofeng|X|
Bakzhan|Kariboz|K|
Wang|Lianjun|L|
Van der Bruggen|Bart|B|

Antifouling
Antifouling mechanism
Fouling behavior
Self-assembly membrane


Structural Stability of N-Alkyl-Functionalized Titanium Metal-Organic Frameworks in Aqueous and Humid Environments.

Abstract: We demonstrate that the highly photoredox active metal-organic framework (MOF) MIL-125-NHCyp exhibits crystalline and porosity stability in humid environments for more than 30 days as well as increased hydrophobicity compared to the unfunctionalized framework. This improved stability, in synergy with its high photocatalytic activity, makes this MOF a very promising candidate for large-scale applications in CO2 photoreduction.

functional materials
metal−organic frameworks
photocatalysis
porous coordination polymers
porous materials
water adsorption


Prediction of the output factor using machine and deep learning approach in uniform scanning proton therapy.

Abstract:
PURPOSE
The purpose of this work is to develop machine and deep learning-based models to predict output and MU based on measured patient quality assurance (QA) data in uniform scanning proton therapy (USPT).

METHODS
This study involves 4,231 patient QA measurements conducted over the last 6 years. In the current approach, output and MU are predicted by an empirical model (EM) based on patient treatment plan parameters. In this study, two MATLAB-based machine and deep learning algorithms - Gaussian process regression (GPR) and shallow neural network (SNN) - were developed. The four parameters from patient QA (range, modulation, field size, and measured output factor) were used to train these algorithms. The data were randomized with a training set containing 90% and a testing set containing remaining 10% of the data. The model performance during training was accessed using root mean square error (RMSE) and R-squared values. The trained model was used to predict output based on the three input parameters: range, modulation, and field size. The percent difference was calculated between the predicted and measured output factors. The number of data sets required to make prediction accuracy of GPR and SNN models' invariable was also evaluated.

RESULTS
The prediction accuracy of machine and deep learning algorithms is higher than the EM. The output predictions with [GPR, SNN, and EM] within ± 2% and ± 3% difference were [97.16%, 97.64%, and 92.95%] and [99.76%, 99.29%, and 97.18%], respectively. The GPR model outperformed the SNN with a smaller number of training data sets.

CONCLUSION
The GPR and SNN models outperformed the EM in terms of prediction accuracy. Machine and deep learning algorithms predicted the output factor and MU for USPT with higher predictive accuracy than EM. In our clinic, these models have been adopted as a secondary check of MU or output factors.

Grewal|Hardev S|HS|
Chacko|Michael S|MS|
Ahmad|Salahuddin|S|
Jin|Hosang|H|

D000465:Algorithms
D000077321:Deep Learning
D006801:Humans
D016571:Neural Networks, Computer
D016011:Normal Distribution
D061766:Proton Therapy

machine and deep learning
proton therapy
gaussian process regression
shallow neural network


Intermittent Hypoxia and Unsaturated Aldehydes: Effects on Oral Epithelial Wound Healing.

Abstract: Obstructive sleep apnea (OSA) is a highly prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), leading to blood hypoxemia, hypercapnia, and sleep fragmentation. Studies on the effects of OSA on oral epithelial tissue healing are limited. Smoking is considered a risk factor for OSA through the exposure to chemically active toxins, present in the smoke. Acrolein is the most chemically active unsaturated aldehyde, impairing a variety of biological processes. The aim of this study was to determine the effect of IH on oral epithelial tissue healing, with and without acrolein. HaCaT cells were wounded by a cross-scratch made in the cell cultures, considered as time zero. Then, cells were exposed to 28 IH cycles (5-20% oxygen) during 12 h using the BioSpherix OxyCycler-C42 system. Control cells were maintained in normoxic conditions or in sustained hypoxia (SH) (5% oxygen) for the same durations, after which all cells were maintained for additional 12 h in normoxia. The migrating abilities of cells were measured after 24 h by calculating the percent of the residual cross-scratch area. In parallel experiments, 25 μM acrolein were added to each treatment. We found that the scratch closure was the slowest under IH. After 24 h, the residual scratch area in the IH treated cells was 29.5 ± 13.4% of the initial area, while in normoxia and SH it was 9.2 ± 5.8% and 10.3 ± 11.3%, respectively (p < 0.01 for both vs. IH). Adding acrolein further attenuated the migratory ability in IH as compared to normoxia and SH. We conclude that IH delays the healing process of oral epithelial tissue by slowing the cells' migratory abilities. The healing might be further attenuated by chemically active unsaturated aldehydes such as acrolein.

Hypoxia
Obstructive sleep apnea
Sleep fragmentation
Oral epithelial tissue
Smoking
Acrolein
Healing process


Predicting Intensive Care Unit Admissions for COVID-19 Patients in the Emergency Department.

Abstract:
OBJECTIVE
Determining the parameters that can predict the requirement of intensive care unit (ICU) admissions among the coronavirus disease 2019 (COVID-19) patients presented to the emergency departments (EDs).

METHODS
In adult consecutive patients admitted (March 15 - April 15, 2020) to the ED of a state hospital for COVID-19, we retrospectively analyzed demographic data, symptoms, laboratory tests, and chest computed tomography (CT) on arrival.

RESULTS
We included 458 patients [213 (46.5%) females, median age 48 y]. Body temperature, respiration rate, C-reactive protein (CRP), D-dimer, ferritin values, and the number of comorbidities were significantly higher in patients admitted to the ICU than others. Also, diffuse infiltration in chest CT is more common in patients who need ICU follow-up. As a result of the binary regression analysis, a statistically significant correlation was found between the presence of dyspnea (odds ratio [OR]: 12.55), tachypnea (relative risk [RR] ≥ 18) (OR: 14.54), multiple comorbidities (≥2) (OR: 23.39), diffuse infiltration in CT (OR: 14.52), and CRP (≥45 mg/L) (OR: 4.71); and the need for ICU admission.

CONCLUSION
It has been concluded that the presence of dyspnea and tachypnea, elevated CRP, presence of multiple comorbidities, and diffuse infiltration in CT may predict the need for ICU admissions of the patients, who presented to the EDs.

intensive care units
COVID-19
emergency departments
C-reactive protein
comorbidity


Paclitaxel delivery system based on poly(lactide-co-glycolide) microparticles and chitosan thermo-sensitive gel for mammary adenocarcinoma treatment.

Abstract:
OBJECTIVES
To evaluate the combination of more than one release system in the same formulation as a useful strategy to achieve paclitaxel delivery in a more sustained and controlled manner.

METHODS
The present study deals with the preparation of poly(lactide-co-glycolide) microparticles loaded with paclitaxel and included in a chitosan thermo-sensitive gelling solution. The microparticles were characterized by their size, shape and drug loading. The formulation was characterized by scanning electron microscopy, in vitro release experiments and was evaluated in mice bearing mammary adenocarcinoma.

KEY FINDINGS
The formation of paclitaxel crystals in a pharmaceutical formulation reduces its efficacy. In this work, the use of microparticles avoided this phenomenon. Combining more than one delivery system allowed delivering paclitaxel in a more sustained and controlled manner leading to a long-term effect in the site of action. The formulation showed an inhibition in tumour volume of 63.0% in comparison with the control group.

CONCLUSIONS
One intratumour injection of gelling solution containing the microparticles was at least as efficacious as four intraperitoneal injections of a commercial formulation. In addition, the delivery system was nontoxic, and the treated mice presented the highest percentage of tumour regression and median survival time.

paclitaxel
poly(lactide-co-glycolide)
microparticle
chitosan
hydrogel
mammary cancer


Influence of Chromophoric Electron-Donating Groups on Photoinduced Solid-to-Liquid Transitions of Azopolymers.

Abstract: The photoinduced solid-to-liquid transitions property of azobenzene-containing polymers (azopolymers) enables azopolymers with various promising applications. However, a general lack of knowledge regarding the influence of structure of the azobenzene derivatives on the photoinduced liquefaction hinders the design of novel azopolymers. In the present study, a series of azopolymers with side chains containing azobenzene unit bearing alkyl electron-donating groups were synthesized. The photoisomerization and photoinduced liquefaction properties of newly synthesized azopolymers were investigated. Alkyl-based electron-donating group significantly facilitate the photoisomerization process of azopolymers in solution, as the electron-donating ability of substituents increased, the time required for photoisomerization of azopolymers continually deceased. Meanwhile, the electron-donating group can drastically accelerate photoinduced solid-to-liquid transitions of azopolymers, the liquefaction rate of obtained azopolymers gradually getting quicker as the electron-donating ability of substituents increased. This study clearly demonstrates that the electron-donating group that bearing in the azobenzene group of polymer side chain play an essential role on the photoinduced solid-to-liquid transitions of azopolymers, and hence, gives an insight into how to design novel azopolymers for practical applications.

Xu|Jian|J| Niu|Bin|B| Guo|Song|S| Zhao|Xiaolei|X| Li|Xiaoli|X| Peng|Jinwen|J| Deng|Weixing|W| Wu|Si|S| Liu|Yuanli|Y|

electron-donating groups
azopolymer
photoisomerization
solid–liquid transitions


Phenological overlap of interacting species in a changing climate: an assessment of available approaches.

Abstract: Concern regarding the biological effects of climate change has led to a recent surge in research to understand the consequences of phenological change for species interactions. This rapidly expanding research program is centered on three lines of inquiry: (1) how the phenological overlap of interacting species is changing, (2) why the phenological overlap of interacting species is changing, and (3) how the phenological overlap of interacting species will change under future climate scenarios. We synthesize the widely disparate approaches currently being used to investigate these questions: (1) interpretation of long-term phenological data, (2) field observations, (3) experimental manipulations, (4) simulations and nonmechanistic models, and (5) mechanistic models. We present a conceptual framework for selecting approaches that are best matched to the question of interest. We weigh the merits and limitations of each approach, survey the recent literature from diverse systems to quantify their use, and characterize the types of interactions being studied by each of them. We highlight the value of combining approaches and the importance of long-term data for establishing a baseline of phenological synchrony. Future work that scales up from pairwise species interactions to communities and ecosystems, emphasizing the use of predictive approaches, will be particularly valuable for reaching a broader understanding of the complex effects of climate change on the phenological overlap of interacting species. It will also be important to study a broader range of interactions: to date, most of the research on climate-induced phenological shifts has focused on terrestrial pairwise resource-consumer interactions, especially those between plants and insects.

Rafferty|Nicole E|NE|
Caradonna|Paul J|PJ|
Burkle|Laura A|LA|
Iler|Amy M|AM|
Bronstein|Judith L|JL|

phenology
Climate change
observation
simulation
models
long-term data
community
demography
experiment
life history


aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

Abstract: Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms.

Kato|Shingo|S| Akimoto|Kazunori|K| Nagashima|Yoji|Y| Ishiguro|Hitoshi|H| Kubota|Kensuke|K| Kobayashi|Noritoshi|N| Hosono|Kunihiro|K| Watanabe|Seitaro|S| Sekino|Yusuke|Y| Sato|Takamitsu|T| Sasaki|Kazunori|K| Nakaigawa|Noboru|N| Kubota|Yoshinobu|Y| Inayama|Yoshiaki|Y| Endo|Itaru|I| Ohno|Shigeo|S| Maeda|Shin|S| Nakajima|Atsushi|A|

Intraductal papillary mucinous neoplasms


Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial.

Abstract: The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n=51) or spironolactone 12.5 mg (n=27), 25 mg (n=26), or 50 mg (n=25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to explore cardiovascular efficacy. The primary safety endpoints were hyperkalemia (potassium > 6.5 mEq/L) and hypotension requiring emergency department visit or hospitalization. Diastolic function was assessed by Doppler echocardiography. 125 participants (97%) completed dose escalation, with no significant difference in permanent study drug discontinuation between the groups (27.5% in placebo versus 16.7% in the combined spironolactone groups and 28% in the 50 mg group). Hyperkalemia frequency was similar between spironolactone and placebo (0.49 versus 0.50 events per patient-year) but demonstrated a significant linear trend due primarily to an increased event rate at the 50 mg dose (0.89 events per patient-year). The primary hypotension outcome was infrequent and similar with spironolactone and placebo (0.11 versus 0 events per patient-year). Gynecomastia was rare and did not differ significantly between groups. Change in diastolic function was similar with spironolactone and placebo. Spironolactone appears safe in carefully monitored maintenance hemodialysis patients, but did not affect cardiovascular parameters in this small study. Hyperkalemia occurs more frequently as dosage increases to 50 mg daily.

Charytan|David M|DM|
Himmelfarb|Jonathan|J|
Ikizler|T Alp|TA|
Raj|Dominic S|DS|
Hsu|Jesse Y|JY|
Landis|J Richard|JR|
Anderson|Amanda H|AH|
Hung|Adriana M|AM|
Mehrotra|Rajnish|R|
Sharma|Shailendra|S|
Weiner|Daniel E|DE|
Williams|Mark|M|
DiCarli|Marcelo|M|
Skali|Hicham|H|
Kimmel|Paul L|PL|
Kliger|Alan S|AS|
Dember|Laura M|LM|
|||

multiple dosage
hemodialysis
mineralocorticoid blockade
randomized controlled trial


A Novel Image Analysis Approach Reveals a Role for Complement Receptors 1 and 2 in Follicular Dendritic Cell Organization in Germinal Centers.

Abstract: Follicular dendritic cells (FDCs) are rare and enigmatic cells that mainly reside in germinal centers (GCs). They are capable of capturing immune complexes, via their Fc (FcRs) and complement receptors (CRs) and storing them for long periods in non-degradative vesicles. Presentation of ICs on FDCs to B cells is believed to drive affinity maturation. CR1 and CR2 are expressed on B cells and FDCs. Cr2 knock out (KO) mice, lacking both receptors, have impaired antibody and GC responses. Utilizing a novel ImageJ macro to analyze confocal fluorescence microscopy images of spleen sections, we here investigate how FDCs in wild type (WT) and Cr2 KO mice behave during the first two weeks after immunization with sheep red blood cells (SRBC). Mice were immunized with SRBC i.v. and spleen and serum samples harvested at various time points. As expected, antibody and GC responses in Cr2 KO mice were impaired in comparison to WT mice. Fewer FDCs were identified in Cr2 KO mice, and these exhibited differential localization and organization in comparison to WT mice. WT FDCs were primarily located within GCs at the light zone/dark zone border. FDCs from WT but not Cr2 KO mice were actively dispersed in GCs, i.e. tended to move away from each other, presumably to increase their surface area for B cell interaction. FDCs from Cr2 KO mice were more often found on follicles outside of the GCs and those within the GCs were closer to the periphery in comparison to WT FDCs. Expression of CR1 and CR2, FcγRIIB, and FcµR increased in FDCs from WT mice during the course of immunization. The results suggest that decreased ability to capture ICs by FDCs lacking CR1 and CR2 may not be the only explanation for the impaired GC and antibody responses in Cr2 KO mice. Poor FDC organization in GCs and failure to increase receptor expression after immunization may further contribute to the inefficient immune responses observed.

Anania|Jessica C|JC|
Westin|Annika|A|
Adler|Jeremy|J|
Heyman|Birgitta|B|

complement receptor
follicular dendritic cell (FDC)
germinal center (GC)
ImageJ macro
Fc receptor
IgM receptor
immune complex (IC)


Microtubule inhibitor, SP-6-27 inhibits angiogenesis and induces apoptosis in ovarian cancer cells.

Abstract: In ovarian cancer (OVCA), treatment failure due to chemo-resistance is a serious challenge. It is therefore critical to identify new therapies that are effective against resistant tumors and have reduced side effects. We recently identified 4-H-chromenes as tubulin depolymerizing agents that bind to colchicine site of beta-tubulin. Here, we screened a chemical library of substituted 4-H-chromenes and identified SP-6-27 to exhibit most potent anti-proliferative activity towards a panel of human cisplatin sensitive and resistant OVCA cell lines with 50% inhibitory concentration (IC50; mean ± SD) ranging from 0.10 ± 0.01 to 0.84 ± 0.20 μM. SP-6-27 exhibited minimum cytotoxicity to normal ovarian epithelia. A pronounced decrease in microtubule density as well as G2/M cell cycle arrest was observed in SP-6-27 treated cisplatin sensitive/resistant OVCA cells. The molecular mechanism of SP-6-27 induced cell death revealed modulation in cell-cycle regulation by upregulation of growth arrest and DNA damage inducible alpha transcripts (GADD45). An enhanced intrinsic apoptosis was observed in OVCA cells through upregulation of Bax, Apaf-1, caspase-6, -9, and caspase-3. In vitro wound healing assay revealed reduced OVCA cell migration upon SP-6-27 treatment. Additionally, SP-6-27 and cisplatin combinatorial treatment showed enhanced cytotoxicity in chemo-sensitive/resistant OVCA cells. Besides effect on cancer cells, SP-6-27 further restrained angiogenesis by inhibiting capillary tube formation by human umbilical vein endothelial cells (HUVEC). Together, these findings show that the chromene analog SP-6-27 is a novel chemotherapeutic agent that offers important advantages for the treatment of ovarian cancer.

Kulshrestha|Arpita|A|
Katara|Gajendra K|GK|
Ibrahim|Safaa A|SA|
Patil|Renukadevi|R|
Patil|Shivaputra A|SA|
Beaman|Kenneth D|KD|

microtubule inhibitor
ovarian cancer
chromene
cisplatin resistance


Plastic with personality: Increasing student engagement with manikins.

Abstract:
BACKGROUND
Simulation allows students to practice key psychomotor skills and gain technical proficiency, fostering the development of clinical reasoning and student confidence in a low risk environment. Manikins are a valuable learning tool; yet there is a distinct lack of empirical research investigating how to enhance engagement between nursing students and manikins.

OBJECTIVE
To describe student perspectives of a layered, technology enhanced approach to improve the simulation learning experience.

EDUCATIONAL FRAMEWORK
Tanner's Model of Clinical Judgment underpins the entire curriculum. This study additionally drew on the principles of narrative pedagogy.

INTERVENTION
Across ten teaching weeks, five separate case studies were introduced to students through short vignettes. Students viewed the vignettes prior to their laboratory class. In the labs, manikins were dressed in the props used in the vignettes.

SETTING
The innovation was trialed in a second year core subject of a Bachelor of Nursing program in a large urban university in the autumn semester of 2014.

DATA COLLECTION AND ANALYSIS
Following ethics approval, students were emailed a participant information sheet. A focus group of nine students was held. The discussion was digitally recorded and transcribed verbatim prior to being subject to thematic analysis. Students' comments (143) about the vignettes in their standard subject specific student feedback surveys were also considered as data.

RESULTS
Four themes were identified: Getting past the plastic; knowing what to say; connecting and caring; and, embracing diversity. The feedback indicated that these measures increased students ability to suspend disbelief, feel connected to, and approach the manikins in a more understanding and empathetic fashion.

CONCLUSIONS
In addition to achieving increased engagement with manikins, other advantages such as students reflecting on their own values and pre-conceived notions of people from diverse backgrounds were realized.

Power|Tamara|T| Virdun|Claudia|C| White|Haidee|H| Hayes|Carolyn|C| Parker|Nicola|N| Kelly|Michelle|M| Disler|Rebecca|R| Cottle|Amanda|A|

Student engagement
Manikins
Simulation
Nursing students
Nursing education


Factors Affecting the Outcomes of Arthroscopic Capsular Release for Idiopathic Adhesive Capsulitis.

Abstract:
Background
Arthroscopic capsular release has been shown to provide excellent short- and long-term outcomes in patients with idiopathic frozen shoulder. Some surgeons delay surgery in the belief that operating in the early stages of adhesive capsulitis results in a poorer prognosis. However, it is unclear which factors, particularly the stage of the disorder, affect the surgical outcome of this procedure.

Hypothesis
Patients who undergo capsular release during the early symptomatic stage of idiopathic adhesive capsulitis would have less improvement in range of motion compared with those who undergo surgery at a later stage.

Study Design
Cohort study; Level of evidence, 3.

Methods
A total of 189 shoulders with idiopathic adhesive capsulitis that underwent arthroscopic capsular release were evaluated. All patients completed a L'Insalata questionnaire and had their range of motion and strength tested prior to surgery and at 1, 6, and 12 weeks and 6 months post-capsular release. Post hoc, patients were grouped by whether they had symptoms lasting <10 months (shorter symptoms group; n = 131) or ≥10 months (longer symptoms group; n = 38). Multiple linear regression analysis was performed to determine which preoperative factors were independently associated with a favorable outcome.

Results
Patients in the shorter symptoms group were more restricted prior to surgery than were those in the longer symptoms group (mean ± SEM: external rotation, 17° ± 2° vs 27° ± 4° [P = .04]; abduction, 78° ± 3° vs 92° ± 6° [P = .04]; internal rotation, S3 ± 1 vs S1 ± 1 [P = .03]). The shorter symptoms group had greater postoperative improvement in internal rotation (from S3 ± 1 preoperatively to T12 ± 1 vertebral levels) compared with the longer symptoms cohort (from S1 ± 1 to L2 ± 1) (P = .02).

Conclusion
Patients with a frozen shoulder and a duration of symptoms <10 months made greater improvements in internal rotation and had similar final results for flexion, abduction, and external rotation following arthroscopic capsular release when compared with patients who had a longer duration of symptoms, so there is no reason to delay surgery.

Rizvi|Syed M|SM|
Harisha|Ahmed J|AJ|
Lam|Patrick H|PH|
Murrell|George A C|GAC|

arthroscopic capsular release
idiopathic adhesive capsulitis
frozen shoulder
freezing phase
frozen phase
stiffness


School health for migrant children: a myth or a must?

Abstract:
Background
School health plays a vital role in lifelong health outcomes. Migrant children are a vulnerable population that seem to have inadequate health promotion interventions, and limited studies have assessed their health status and personal hygiene at schools. This study aimed to evaluate school health promotion and health outcomes of migrant children in Thai public schools (TPSs) and migrant learning centers (MLCs).

Methods
A cross-sectional study was applied. Data were collected from questionnaires focusing on health care access, nutritional status, and personal hygiene of migrant children in two MLCs and four TPSs, along with Thai children in the same TPSs. Descriptive analysis and logistic regression model were used to compare access to health promotion and the health status of migrant children with the Thai counterparts.

Results
Blended school health services were generally found in TPSs, which led to indifferent vaccination rates between Thai and migrant children in TPSs (odds ratio [OR] 0.457 (0.186-1.120)). However, vaccination rates of migrant children in MLCs are noticeably around fourfold lower. Overall, migrant children received fewer dental health services than Thai children, both in TPSs (OR 0.198 (0.076,0.517)) and MLCs (OR 0.156 (0.004,0.055)). Other personal hygiene behaviors and nutritional statuses saw no significant difference between Thai children and migrant children in either TPSs or MLCs. The uninsured status among migrant children posed another challenge to health care access, as 81.7% of the migrant children in MLCs and 56.6% in TPSs were uninsured.

Conclusion
Migrant children in MLCs received a lower rate of essential vaccinations compared to those in TPSs. Dental services appeared to be the most neglected area of care in migrant children. The findings indicate the necessity of supportive policy for MLCs, while regulating quality and standards concurrently. Multisectoral collaboration is critically needed for sustainably improving the quality of life of migrant children.

Tuangratananon|Titiporn|T| Julchoo|Sataporn|S| Wanwong|Yaowaluk|Y| Sinam|Pigunkaew|P| Suphanchaimat|Rapeepong|R|

migrant children
school health promotion
migrants learning center
education


Physicochemical properties of whole fruit plum powders obtained using different drying technologies.

Abstract: Physicochemical quality parameters of plum powders obtained by applying conventional drying methods and their combination devised to process plums were evaluated. The effect of freeze-drying (FD), vacuum drying (VD), convective drying (CD), microwave-vacuum drying (MVD) and combination of convective pre-drying and microwave finish-drying (CPD-MVFD) affected physical (bulk density, porosity, colour, solubility) and chemical (polyphenolic compounds determined by UPLC and antioxidant capacity by TEAC ABTS and FRAP methods) properties of plum powders. The MVD at 1.2 W g(-1) and a novel combination for plum powders production - CPD-MVFD at 70 °C/1.2 W g(-1) allowed the best preservation of phenolic compounds and increased the efficiency of production. Results obtained support the use of MVD and its combination for better quality of dried plum products. The study proved that the determination of the browning index and HMF level (formed via Maillard reaction) might be good tool for monitoring the thermal processing of plum powders.

Michalska|Anna|A|
Wojdyło|Aneta|A|
Lech|Krzysztof|K|
Łysiak|Grzegorz P|GP|
Figiel|Adam|A|

Convective drying
Combined drying
Hydroxymethylfurfural
Microwave drying
Prunus domestica L.


Harnessing the Topography of 3D Spongy-Like Electrospun Bundled Fibrous Scaffold via a Sharply Inclined Array Collector.

Abstract: To date, many researchers have studied a considerable number of three-dimensional (3D) cotton-like electrospun scaffolds for tissue engineering, including the generation of bone, cartilage, and skin tissue. Although numerous 3D electrospun fibrous matrixes have been successfully developed, additional research is needed to produce 3D patterned and sophisticated structures. The development of 3D fibrous matrixes with patterned and sophisticated structures (FM-PSS) capable of mimicking the extracellular matrix (ECM) is important for advancing tissue engineering. Because modulating nano to microscale features of the 3D fibrous scaffold to control the ambient microenvironment of target tissue cells can play a pivotal role in inducing tissue morphogenesis after transplantation in a living system. To achieve this objective, the 3D FM-PSSs were successfully generated by the electrospinning using a directional change of the sharply inclined array collector. The 3D FM-PSSs overcome the current limitations of conventional electrospun cotton-type 3D matrixes of random fibers.

Cho|Sun Hee|SH|
Kim|Jeong In|JI|
Kim|Cheol Sang|CS|
Park|Chan Hee|CH|
Kim|In Gi|IG|

electrospinning
3D aligned fibers
3D electrospun scaffolds
cottony fibers
fiber topography


Protective Effects of Pyruvic Acid Salt Against Lithium Toxicity and Oxidative Damage in Human Blood Mononuclear Cells.

Abstract: Aim of present work was to study cytoprotective properties of lithium pyruvate, as a prospective pharmacological agent. Pyruvate has a lot of potential benefits due to positive influence on cell metabolism. Lithium is "gold-standard" mood-stabilizer. Combination of both may lead advantages.  Lithium pyruvate was tested as cytoprotector on human blood mononuclears under induced oxidative stress. Cells were obtained from healthy donors and patients with alcoholism. The detection of cell viability, apoptosis and determination of oxidative stress level were conducted by flow cytometry.  Lithium pyruvate showed excellent cytoprotective properties in normal and oxidation conditions. This effect was independent from cell donor health status. It was shown on cells from healthy donors and alcoholics patients.  Obtained results allow considering lithium pyruvate as potential normothymic agents (mood stabilizer) with excellent cytoprotective properties.

Cytoprotection
Lithium pyruvate
Mood-stabilizer
Oxidative stress
Apoptosis
Antioxidant


Characterization of cytochrome P450 isoforms involved in sequential two-step bioactivation of diclofenac to reactive p-benzoquinone imines.

Abstract: Idiosyncratic drug-induced lever injury (IDILI) is a rare but severe side effect of diclofenac (DF). Several mechanisms have been proposed as cause of DF-induced toxicity including the formation of protein-reactive diclofenac-1',4'-quinone imine (DF-1',4'-QI) and diclofenac-2,5-quinone imine (DF-2,5-QI). Formation of these p-benzoquinone imines result from two-step oxidative metabolism involving aromatic hydroxylation to 4'-hydroxydiclofenac and 5-hydroxydiclofenac followed by dehydrogenation to DF-1',4'-QI and DF-2,5-QI, respectively. Although the contribution of individual cytochrome P450s (CYPs) in aromatic hydroxylation of DF is well studied, the enzymes involved in the dehydrogenation reactions have been poorly characterized. The results of the present study show that both formation of 4'-hydroxydiclofenac and it subsequent bioactivation to DF-1',4'-QI is selectively catalyzed by CYP2C9. However, the two-step bioactivation to DF-2,5-QI appears to be catalyzed with highest activity by two different CYPs: 5-hydroxylation of DF is predominantly catalyzed by CYP3A4, whereas its subsequent bioactivation to DF-2,5-QI is catalyzed with 14-fold higher intrinsic clearance by CYP2C9. The fact that both CYPs involved in two-step bioactivation of DF show large interindividual variability may play a role in different susceptibility of patients to DF-induced IDILI. Furthermore, expression levels of these enzymes and protective enzymes might be important factors determining sensitivity of in vitro models for hepatotoxicity.

den Braver|Michiel W|MW|
den Braver-Sewradj|Shalenie P|SP|
Vermeulen|Nico P E|NP|
Commandeur|Jan N M|JN|

Cytochrome P450
Bioactivation
Diclofenac
Glutathione conjugates
Idiosyncratic liver injury
Reactive intermediates


Short telomeres increase the risk of severe COVID-19.

Abstract: Telomeres are non-coding DNA sequences that protect chromosome ends and shorten with age. Short telomere length (TL) is associated with chronic diseases and immunosenescence. The main risk factor for mortality of coronavirus disease 2019 (COVID-19) is older age, but outcome is very heterogeneous among individuals of the same age group. Therefore, we hypothesized that TL influences COVID-19-related outcomes. In a prospective study, we measured TL by Flow-FISH in 70 hospitalized COVID-19 patients and compared TL distribution with our reference cohort of 491 healthy volunteers. We also correlated TL with baseline clinical and biological parameters. We stained autopsy lung tissue from six non-survivor COVID-19 patients to detect senescence-associated β-galactosidase activity, a marker of cellular aging. We found a significantly higher proportion of patients with short telomeres (<10th percentile) in the COVID-19 patients as compared to the reference cohort (P<0.001). Short telomeres were associated with a higher risk of critical disease, defined as admission to intensive care unit (ICU) or death without ICU. TL was negatively correlated with C-reactive protein and neutrophil-to-lymphocyte ratio. Finally, lung tissue from patients with very short telomeres exhibit signs of senescence in structural and immune cells. Our results suggest that TL influences the severity of the disease.

Froidure|Antoine|A|
Mahieu|Manon|M|
Hoton|Delphine|D|
Laterre|Pierre-François|PF|
Yombi|Jean Cyr|JC|
Koenig|Sandra|S|
Ghaye|Benoit|B|
Defour|Jean-Philippe|JP|
Decottignies|Anabelle|A|


Individual Development and Adaptation (IDA): A Life-Span Longitudinal Program Suited for Person-Oriented Research.

Abstract: In this article, we give a presentation of the longitudinal research program Individual Development and Adaptation (IDA) that can be helpful as a template for researchers considering to launch their own longitudinal studies, and that opens the door to IDA for researchers looking for suitable data to be analyzed within their own project or in collaboration with IDA. We also introduce the holistic-interactionistic theoretical framework of IDA and the associated person-oriented approach - an approach that is especially suited for analyzing the rich IDA data set with its broad coverage of different areas of adjustment and related factors. The paper provides an overview of the essential features of the IDA database, as well as of ongoing and planned IDA research.

Bergman|Lars R|LR|
Andershed|Anna-Karin|AK|
Meehan|Anna|A|
Andershed|Henrik|H|

development adaptation IDA longitudinal person-oriented prospective


Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the brain with positron emission tomography.

Abstract: Exploration of the living human brain in real-time and in a noninvasive way was for centuries only a dream, made, however, possible today with the remarkable development during the four last decades of powerful molecular imaging techniques, and especially positron emission tomography (PET). Molecular PET imaging relies, from a chemical point of view, on the use and preparation of a positron-emitting radiolabelled probe or radiotracer, notably compounds incorporating one of two short-lived radionuclides fluorine-18 (T1/2 : 109.8 min) and carbon-11 (T1/2 : 20.38 min). The growing availability and interest for the radiohalogen fluorine-18 in radiopharmaceutical chemistry undoubtedly results from its convenient half-life and the successful use in clinical oncology of 2-[(18) F]fluoro-2-deoxy-d-glucose ([(18) F]FDG). The special interest of carbon-11 is not only that carbon is present in virtually all biomolecules and drugs allowing therefore for isotopic labelling of their chemical structures but also that a given molecule could be radiolabelled at different functions or sites, permitting to explore (or to take advantage of) in vivo metabolic pathways. PET chemistry includes production of these short-lived radioactive isotopes via nuclear transmutation reactions using a cyclotron, and is directed towards the development of rapid synthetic methods, at the trace level, for the introduction of these nuclides into a molecule, as well as the use of fast purification, analysis and formulation techniques. PET chemistry is the driving force in molecular PET imaging, and this special issue of the Journal of Labelled Compounds and Radiopharmaceuticals, which is strongly chemistry and radiochemistry-oriented, aims at illustrating, be it in part only, the state-of-the-art arsenal of reactions currently available and its potential for the research and development of specific molecular probes labelled with the positron emitters carbon-11 and fluorine-18, with optimal imaging properties for PET exploration of the brain.

carbon-11
fluorine-18
brain
PET
PET chemistry
CNS
radiochemistry


Interaction between hypoviral-regulated fungal virulence factor laccase3 and small heat shock protein Hsp24 from the chestnut blight fungus Cryphonectria parasitica.

Abstract: Laccase3 is an important virulence factor of the fungus Cryphonectria parasitica. Laccase3 gene (lac3) transcription is induced by tannic acid, a group of phenolic compounds found in chestnut trees, and its induction is regulated by the hypovirus CHV1 infection. CpHsp24, a small heat shock protein gene of C. parasitica, plays a determinative role in stress adaptation and pathogen virulence. Having uncovered in our previous study that transcriptional regulation of the CpHsp24 gene in response to tannic acid supplementation and CHV1 infection was similar to that of the lac3, and that conserved phenotypic changes of reduced virulence were observed in mutants of both genes, we inferred that both genes were implicated in a common pathway. Building on this finding, in this paper we examined whether the CpHsp24 protein (CpHSP24) was a molecular chaperone for the lac3 protein (LAC3). Our pull-down experiment indicated that the protein products of the two genes directly interacted with each other. Heterologous co-expression of CpHsp24 and lac3 genes using Saccharomyces cerevisiae resulted in more laccase activity in the cotransformant than in a parental lac3-expresssing yeast strain. These findings suggest that CpHSP24 is, in fact, a molecular chaperone for the LAC3, which is critical component of fungal pathogenesis.

laccase3
Cryphonectria parasitica
hypovirulence
small heat shock protein 24


Mitigation of Membrane Fouling Using an Electroactive Polyether Sulfone Membrane.

Abstract: Membrane fouling is the bottleneck limiting the wide application of membrane processes. Herein, we adopted an electroactive polyether sulfone (PES) membrane capable of mitigating fouling by various negatively charged foulants. To evaluate anti-fouling performance and the underlying mechanism of this electroactive PES membrane, three types of model foulants were selected rationally (e.g., bovine serum albumin (BSA) and sodium alginate (SA) as non-migratory foulants, yeast as a proliferative foulant and emulsified oil as a spreadable foulant). Water flux and total organic carbon (TOC) removal efficiency in the filtering process of various foulants were tested under an electric field. Results suggest that under electrochemical assistance, the electroactive PES membrane has an enhanced anti-fouling efficacy. Furthermore, a low electrical field was also effective in mitigating the membrane fouling caused by a mixture of various foulants (containing BSA, SA, yeast and emulsified oil). This result can be attributed to the presence of electrostatic repulsion, which keeps foulants away from the membrane surface. Thereby it hinders the formation of a cake layer and mitigates membrane pore blocking. This work implies that an electrochemical control might provide a promising way to mitigate membrane fouling.

Ma|Chunyan|C| Yi|Chao|C| Li|Fang|F| Shen|Chensi|C| Wang|Zhiwei|Z| Sand|Wolfgang|W| Liu|Yanbiao|Y|

low electrical field
electrostatic repulsion
fouling mitigation
membrane separation


Methods, accuracy and clinical implications of atrial fibrillation detection by cardiac implantable electronic devices.

Abstract: Atrial fibrillation (AF) is the most common arrhythmia in the developed countries and is associated with an increased risk of thromboembolic events and heart failure. Episodes of AF are often asymptomatic and intermittent, eluding diagnosis with non-continuous monitoring techniques. Cardiac implantable electronic devices (CIEDs) represent the gold standard for detecting asymptomatic AF. Improper CIED programming may however increase the risk of false-positive detection of atrial tachyarrhythmias, leading to inappropriate clinical management of patients. A faster rate and a longer duration of the tachyarrhythmic episodes, in addition to a greater AT/AF burden, have been proposed as potential criteria for differentiating between CIED-detected atrial tachyarrhythmias and true AF. Nonetheless, manual overreading of intracardiac electrograms recorded by the CIED remains crucial for a correct diagnosis. Asymptomatic atrial tachyarrhythmias may carry a higher risk of systemic thromboembolism, though clinical thromboembolic risk factors seem to play a greater if not absolute role in prognostication. In addition, there is no clear temporal relationship between CIED-detected atrial tachyarrhythmias and stroke, and the anticoagulation strategy to be pursued in these patients is still a matter of debate and the focus of current prospective randomized studies.

Solari|Diana|D| Bertero|Edoardo|E| Miceli|Roberta|R| Brunelli|Claudio|C| Ameri|Pietro|P| Canepa|Marco|M|

D058409:Cardiac Resynchronization Therapy Devices

D016032:Randomized Controlled Trials as Topic

Atrial fibrillation
Cardiac implantable electronic device
Atrial tachyarrhythmias
Thromboembolic risk
Stroke
Automatic mode switch


A new genus of oonopid spiders from Myanmar (Araneae, Oonopidae).

Abstract: A new genus, Kachinia Tong & Li, gen. n., including two new species, K.putao Tong & Li, sp. n., and K.mahmolae Tong & Li, sp. n., is described from Myanmar. The new genus belonging to the subfamily Oonopinae Simon, 1890, currently is the only member of the Brignolia-Opopaea clade with leg spines.

New species
Oonopinae
Southeast Asia
Taxonomy


Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery.

Abstract: Hereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affecting the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous. Finding treatments for the HSPs is a daunting task: a rare disease made rarer by so many causative genes and many potential mutations in those genes in individual patients. Personalized medicine through genetic correction may be possible, but impractical as a generalized treatment strategy. The ideal treatments would be small molecules that are effective for people with different causative mutations. This requires identification of disease-associated cell dysfunctions shared across genotypes despite the large number of HSP genes that suggest a wide diversity of molecular and cellular mechanisms. This review highlights the shared dysfunctional phenotypes in patient-derived cells from patients with different causative mutations and uses bioinformatic analyses of the HSP genes to identify novel cell functions as potential targets for future drug treatments for multiple genotypes.

spastic paraplegia
endoplasmic reticulum
motor neuron disease
neurodegeneration
protein-protein interaction network


Applications of Bacteriophages in the Treatment of Localized Infections in Humans.

Abstract: In the recent years, multidrug-resistant bacteria have become a global threat, and phage therapy may to be used as an alternative to antibiotics or, at least, as a supplementary approach to treatment of some bacterial infections. Here, we describe the results of bacteriophage application in clinical practice for the treatment of localized infections in wounds, burns, and trophic ulcers, including diabetic foot ulcers. This mini-review includes data from various studies available in English, as well as serial case reports published in Russian scientific literature (with, at least, abstracts accessible in English). Since, it would be impossible to describe all historical Russian publications; we focused on publications included clear data on dosage and rout of phage administration.

Morozova|Vera V|VV|
Vlassov|Valentin V|VV|
Tikunova|Nina V|NV|

phage therapy
clinical practice
wounds
burns
trophic ulcers
diabetic foot ulcers
therapeutic bacteriophage


Differential Methylation Patterns in Apomictic vs. Sexual Genotypes of the Diplosporous Grass Eragrostis curvula.

Abstract: DNA methylation is an epigenetic mechanism by which a methyl group is added to a cytosine or an adenine. When located in a gene/regulatory sequence it may repress or de-repress genes, depending on the context and species. Eragrostis curvula is an apomictic grass in which facultative genotypes increases the frequency of sexual pistils triggered by epigenetic mechanisms. The aim of the present study was to look for correlations between the reproductive mode and specific methylated genes or genomic regions. To do so, plants with contrasting reproductive modes were investigated through MCSeEd (Methylation Context Sensitive Enzyme ddRad) showing higher levels of DNA methylation in apomictic genotypes. Moreover, an increased proportion of differentially methylated positions over the regulatory regions were observed, suggesting its possible role in regulation of gene expression. Interestingly, the methylation pathway was also found to be self-regulated since two of the main genes (ROS1 and ROS4), involved in de-methylation, were found differentially methylated between genotypes with different reproductive behavior. Moreover, this work allowed us to detect several genes regulated by methylation that were previously found as differentially expressed in the comparisons between apomictic and sexual genotypes, linking DNA methylation to differences in reproductive mode.

Carballo|Jose|J|
Zappacosta|Diego|D|
Marconi|Gianpiero|G|0000-0003-2669-0399
Gallardo|Jimena|J|
Di Marsico|Marco|M|
Gallo|Cristian A|CA|0000-0001-9339-1802
Caccamo|Mario|M|
Albertini|Emidio|E|0000-0003-2585-5649
Echenique|Viviana|V|0000-0003-3755-9062

eragrostis
DNA methylation
epigenetics
apomixis
diplospory


Head and body/tail pancreatic neuroendocrine tumors have different biological characteristics and clinical outcomes.

Abstract:
PURPOSE
The incidence of pancreatic neuroendocrine tumors (pNETs) has continued to increase, but for pNETs, there is still no distinction between treatments based on anatomical location. We aim to determine whether NETs located at the head and body/tail of the pancreas are different.

PATIENTS AND METHODS
Within the Surveillance, Epidemiology, and End Results database (2004-2016), we focused on pNETs patients with comprehensive information. The patients were divided into two groups based on tumors' location. We compared the characteristics of the two groups and assessed the risk factors for lymphatic metastasis. Survival analysis was performed based on the biological characteristics of the tumor.

RESULTS
In all 3011 patients, pNETs were more common in the body/tail (62.94%) than in the head (37.06%) of the pancreas. The risk factors for lymph node metastasis in the two groups were different. Nonmetastatic, low-grade pancreatic body/tail NETs had the best prognosis (p < 0.001). For low-grade tumors (G1-G2), lymphatic metastasis did not significantly affect the prognosis of patients with pancreatic head NETs (p = 0.098) but affected the overall survival of patients with pancreatic body/tail NETs (p < 0.001). The tumors at the pancreatic head were larger (p = 0.001), more likely to have positive lymph nodes (p < 0.001) and more prone to locally advanced and distant invasion (p < 0.001). The prognosis of pancreatic head NETs 21-40 mm was worse than that of body/tail pNETs (p < 0.001). For non-functional NETs, the overall survival of pancreatic body/tail tumors was better (p < 0.001).

CONCLUSION
The pancreatic head and pancreatic body/tail NETs have different biological characteristics and clinical outcomes and they should be treated differently.

D000368:Aged
D005260:Female
D006801:Humans
D008207:Lymphatic Metastasis
D008297:Male
D008875:Middle Aged
D018358:Neuroendocrine Tumors
D010190:Pancreatic Neoplasms
D012189:Retrospective Studies
D012307:Risk Factors
D018426:SEER Program
D016019:Survival Analysis

Pancreatic neuroendocrine tumors
Clinical outcomes
Prognosis
Tumor biological characteristics


The complete mitochondrial genome of Yunnan black goat (Capra hircus).

Abstract: Yunnan black goat (Capra hircus) is one of the famous native goat breed in China. In this study, the complete nucleotide sequence of Yunnan black goat mitochondrial genome was determined for the first time. Sequence analysis showed that the genome structure was in typical with other vertebra animals. It contained 22 tRNA genes, 2 ribosomal RNA genes, 13 protein-coding genes and 1 control region (D-loop region). The base composition was A (33.6%), G (13.1%), C (26.0%) and T (27.3%), so the percentage of A and T (60.9%) was higher than that of G and C.

Tang|Yan-Xia|YX| Liu|Fang|F| Tang|Hong-Xia|HX| Yang|Shao-Kun|SK| Zhang|Xiao-Yan|XY|

D000818:Animals
D020459:Genes, rRNA
D054629:Genome, Mitochondrial
D006041:Goats
D058977:Molecular Sequence Annotation
D008969:Molecular Sequence Data
D016366:Open Reading Frames
D012343:RNA, Transfer
D017422:Sequence Analysis, DNA

Genome
Yunnan black goat (Capra hircus)
mitochondrion


Infection of Helicobacter pylori and Atrophic Gastritis Influence Lactobacillus in Gut Microbiota in a Japanese Population.

Abstract:
Background
Suppression of gastric acid by proton pump inhibitors is associated with the increase of Lactobacillus in human gut microbiota. Gastric acid secretion is also suppressed by Helicobacter pylori infection and following atrophic gastritis. However, few studies have examined the association between H. pylori infection and Lactobacillus species in gut microbiota particularly in Japan.

Methods
A total of 1,123 adult subjects who participated in a health survey in Hirosaki City were studied. Infection of H. pylori was defined by both serum antibody and stool antigen test. The presence and the severity of atrophic gastritis were defined by the serum level of serum pepsinogens. Using 16S ribosomal RNA amplification from fecal samples, the relative abundance of Lactobacillus was calculated, and the composition ratio of each Lactobacillus species was surveyed.

Results
The relative abundance of the Lactobacillus in H. pylori-infected subjects with severe atrophic gastritis was higher comparing with those in subjects with mild atrophic gastritis and without atrophic gastritis (0.591 vs 0.068% and 0.033%, respectively; p < 0.001) and also that of non-infected subjects (0.033%; p < 0.001). In H. pylori non-infected subjects, both gender and age were not associated with the relative abundance of Lactobacillus in fecal samples. The proportion of Lactobacillus salivarius was high in H. pylori-infected subjects while that of Lactobacillus acidophilus was high in non-infected subjects.

Conclusion
Lactobacillus in human gut microbiota could be influenced by H. pylori infection and severity of atrophic gastritis in Japanese subjects.

Iino|Chikara|C| Shimoyama|Tadashi|T| Chinda|Daisuke|D| Arai|Tetsu|T| Chiba|Daisuke|D| Nakaji|Shigeyuki|S| Fukuda|Shinsaku|S|

Helicobacter pylori
atrophic gastritis
Lactobacillus
gut microbiota
pepsinogen


Probabilistic frames for non-Boolean phenomena.

Abstract: Classical probability theory, as axiomatized in 1933 by Andrey Kolmogorov, has provided a useful and almost universally accepted theory for describing and quantifying uncertainty in scientific applications outside quantum mechanics. Recently, cognitive psychologists and mathematical economists have provided examples where classical probability theory appears inadequate but the probability theory underlying quantum mechanics appears effective. Formally, quantum probability theory is a generalization of classical probability. This article explores relationships between generalized probability theories, in particular quantum-like probability theories and those that do not have full complementation operators (e.g. event spaces based on intuitionistic logic), and discusses how these generalizations bear on important issues in the foundations of probability and the development of non-classical probability theories for the behavioural sciences.

quantum probability
intuitionistic probability theory
orthomodular lattices
quantum logic


Structural characterization of resistant starch isolated from Laird lentils (Lens culinaris) seeds subjected to different processing treatments.

Abstract: This work focused on the structural characterization of resistant starch from untreated (UL-RS), germinated (GL-RS), fermented (FL-RS), microwaved (ML-RS), conventionally cooked (CL-RS), and autoclaved (AL-RS) lentil seeds. The size exclusion chromatography (SEC) results showed that UL-RS, RL-RS, and GL-RS (Group A samples) exhibited higher values of Mw and Rh¯ than FL-RS, ML-RS, AL-RS (Group C samples), and CL-RS (Group B sample). In parallel with the SEC result, other structural characteristics followed similar trends, where Group C samples exhibited the lowest values of double helix content and crystallinity by 13C NMR, and degree of order/double helix by FT-IR. Comparatively, Group A samples exhibited the opposite trends, and displayed large amorphous aggregates on their micrograph. The results are expected to provide information for better understanding the mechanism of resistant starch formation during different processing of lentil and to lay a theoretical foundation for the future study of their structure-function relationship.

Ma|Zhen|Z|
Yin|Xiuxiu|X|
Hu|Xinzhong|X|
Li|Xiaoping|X|
Liu|Liu|L|
Boye|Joyce I|JI|

D017550:Spectroscopy, Fourier Transform Infrared

Structural characterization
Resistant starch
Processing treatments
Lentil seeds (Lens culinaris)


Comparative persistence on β-blockers versus calcium channel blockers for ventricular rate control in nonelderly patients with atrial fibrillation.

Abstract:
BACKGROUND
For patients with atrial fibrillation (AF), early treatment is essential to prevent serious complications such as stroke. Several randomized clinical trials have shown that rate-control may be as effective as rhythm-control medications, whereas the latter have serious side effects. Little evidence exists, however, about which class of rate-control medication-β-blockers (BBs) or calcium channel blockers (CCBs)-may be superior.

OBJECTIVE
The objective was to compare the long-term persistence on BBs versus CCBs in nonelderly adult patients with AF.

METHODS
A longitudinal retrospective cohort study for patients 40 to 60 years old with newly diagnosed AF (identified by ICD-9 code 427.31) was performed using data from Ohio Medicaid physician, institutional, and pharmacy claims from January 2006 through June 2011. A Cox proportional hazard regression, with time to change out of rate-control therapy as the dependent variable, was estimated to compare persistence on (proxy for effectiveness of) rate-control medication across drug classes. A propensity-score analysis was used to control for selection bias. Additional covariates included age, development of heart failure, and medication adherence.

RESULTS
Out of 1239 patients included in the cohort, 1016 received a BB; 223 received a CCB. Over time, patients on CCBs were significantly more likely to switch out of rate-control therapy (hazard ratio = 1.89; 95% CI = 1.14-3.09) than patients on BBs.

CONCLUSIONS
Evidence suggests that nonelderly AF patients, when prescribed rate-control therapy, persist longer on BBs than CCBs. Because this is the first long-term study comparing the 2 drug classes in the nonelderly population, further research is suggested.

Desai|Vibha C A|VC|
Kelton|Christina M L|CM|
Metzger|Anne H|AH|
Cavanaugh|Teresa M|TM|
Guo|Jeff J|JJ|
Heaton|Pamela C|PC|

persistence
β-blockers
calcium channel blockers
atrial fibrillation
rhythm-control medications
Medicaid claims data
comparative effectiveness
rate-control drugs


Measuring hand grip strength in rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease with a particular predilection for causing pain, deformity and functional limitation affecting the hands. Measures of the severity of RA, such as the disease activity score with 28 joint count may not fully reflect the regional impact of RA on the hands. Hand grip strength measurements are a form of objective assessment that focuses specifically on the hands in RA. This review explores what is currently known about the assessment of hand grip strength; what it may indicate, how it is measured, some of the practical aspects and challenges associated with performing these tests, and how this information can be applied in a clinical setting. It summarises the role that grip strength has in assessing patients with RA and finishes with some recommendations for how to use grip strength measurements in clinical practice, and what direction future research might take.

D001172:Arthritis, Rheumatoid
D006225:Hand
D018737:Hand Strength
D006801:Humans
D053581:Muscle Strength Dynamometer
D010808:Physical Examination
D011237:Predictive Value of Tests
D011379:Prognosis
D012720:Severity of Illness Index

Rheumatoid arthritis
Clinical protocols
Disease progression
Equipment design
Hand strength
Monitoring
Physical examination
Physiological
Rehabilitation


A Native Parasitic Plant Systemically Induces Resistance in Jack Pine to a Fungal Symbiont of Invasive Mountain Pine Beetle.

Abstract: Conifer trees resist pest and pathogen attacks by complex defense responses involving different classes of defense compounds. However, it is unknown whether prior infection by biotrophic pathogens can lead to subsequent resistance to necrotrophic pathogens in conifers. We used the infection of jack pine, Pinus banksiana, by a common biotrophic pathogen dwarf mistletoe, Arceuthobium americanum, to investigate induced resistance to a necrotrophic fungus, Grosmannia clavigera, associated with the mountain pine beetle, Dendroctonus ponderosae. Dwarf mistletoe infection had a non-linear, systemic effect on monoterpene production, with increasing concentrations at moderate infection levels and decreasing concentrations at high infection levels. Inoculation with G. clavigera resulted in 33 times higher monoterpene concentrations and half the level of phenolics in the necrotic lesions compared to uninoculated control trees. Monoterpene production following dwarf mistletoe infection seemed to result in systemic induced resistance, as trees with moderate disease severity were most resistant to G. clavigera, as evident from shorter lesion lengths. Furthermore, trees with moderate disease severity had the highest systemic but lowest local induction of α-pinene after G. clavigera inoculation, suggesting a possible tradeoff between systemically- and locally-induced defenses. The opposing effects to inoculation by G. clavigera on monoterpene and phenolic levels may indicate the potential for biosynthetic tradeoffs by the tree between these two major defense classes. Our results demonstrate that interactions between a biotrophic parasitic plant and a necrotrophic fungus may impact mountain pine beetle establishment in novel jack pine forests through systemic effects mediated by the coordination of jack pine defense chemicals.

Klutsch|Jennifer G|JG|
Najar|Ahmed|A|
Sherwood|Patrick|P|
Bonello|Pierluigi|P|
Erbilgin|Nadir|N|

D002851:Chromatography, High Pressure Liquid

Pinus banksiana
Dwarf mistletoe
Arceuthobium americanum
Grosmannia clavigera
Dendroctonus ponderosae
Monoterpenes
Phenolics
Defense tradeoffs
Plant-mediated interactions


Influence of Gender on Inhaler Technique.

Abstract:
BACKGROUND
This study was designed to evaluate the influence of gender on the inhaler technique of subjects on inhaler therapy and to determine the factors predicting the correct inhaler technique and a change of inhaler device.

METHODS
A total of 568 adult subjects (276 male, 292 female) on inhaler therapy were included in this cross-sectional, observational study. Data on sociodemographic characteristics, inhaler therapy, subject-reported difficulties, and technician-reported errors in inhaler technique were recorded.

RESULTS
A change of inhaler device was noted in 71.0% of male subjects and 77.4% of female subjects, and this was based on the physicians' decision in most cases (41.7% and 51.7%, respectively). A higher percentage of female subjects reported difficulties with using inhalers (63.7% vs 40.6%, P < .001). Overall, having received training on the inhaler technique was associated with a higher likelihood of correct inhaler technique (odds ratio 12.56, 95% CI 4.44-35.50, P < .001) and a lower risk of device change (odds ratio 0.46, 95% CI 0.27-0.77, P = .004).

CONCLUSIONS
Errors in the inhaler technique, including inhalation maneuvers and device handling, were common in subjects on inhaler therapy. Subject-reported difficulties with using inhalers were more prevalent among female subjects, whereas errors in the inhaler technique identified by direct observation were similarly high in both genders. Overall, a lack of training on the inhaler technique predicted a higher likelihood of errors in the inhaler technique and a change of inhaler device.

Ocakli|Birsen|B|
Ozmen|Ipek|I|
Tuncay|Eylem Acarturk|EA|
Gungor|Sinem|S|
Ozalp|Aylin|A|
Yasin|Yesim|Y|
Adiguzel|Nalan|N|
Gungor|Gokay|G|
Karakurt|Zuhal|Z|

D029424:Pulmonary Disease, Chronic Obstructive

gender
inhaler technique
inhaler therapy
dry powder inhalers
metered dose inhalers


DeepSV: accurate calling of genomic deletions from high-throughput sequencing data using deep convolutional neural network.

Abstract:
BACKGROUND
Calling genetic variations from sequence reads is an important problem in genomics. There are many existing methods for calling various types of variations. Recently, Google developed a method for calling single nucleotide polymorphisms (SNPs) based on deep learning. Their method visualizes sequence reads in the forms of images. These images are then used to train a deep neural network model, which is used to call SNPs. This raises a research question: can deep learning be used to call more complex genetic variations such as structural variations (SVs) from sequence data?

RESULTS
In this paper, we extend this high-level approach to the problem of calling structural variations. We present DeepSV, an approach based on deep learning for calling long deletions from sequence reads. DeepSV is based on a novel method of visualizing sequence reads. The visualization is designed to capture multiple sources of information in the sequence data that are relevant to long deletions. DeepSV also implements techniques for working with noisy training data. DeepSV trains a model from the visualized sequence reads and calls deletions based on this model. We demonstrate that DeepSV outperforms existing methods in terms of accuracy and efficiency of deletion calling on the data from the 1000 Genomes Project.

CONCLUSIONS
Our work shows that deep learning can potentially lead to effective calling of different types of genetic variations that are complex than SNPs.

High-throughput sequencing
Genetic variations
Deep learning
Visualization
Structural variations
Feature extraction


The Efficacy of Electron Beam Irradiated Bacterial Cellulose Membranes as Compared with Collagen Membranes on Guided Bone Regeneration in Peri-Implant Bone Defects.

Abstract: Bacterial cellulose (BC) is a natural polysaccharide produced by some bacteria, and consists of a linear polymer linked by β-(1,4) glycosidic bonds. BC has been developed as a material for tissue regeneration purposes. This study was conducted to evaluate the efficacy of resorbable electron beam irradiated BC membranes (EI-BCMs) for guided bone regeneration (GBR). The electron beam irradiation (EI) was introduced to control the biodegradability of BC for dental applications. EI-BCMs had higher porosity than collagen membranes (CMs), and had similar wet tensile strengths to CMs. NIH3T3 cell adhesion and proliferation on EI-BCMs were not significantly different from those on CMs (p > 0.05). Micro-computed tomography (μCT) and histometric analysis in peri-implant dehiscence defects of beagle dogs showed that EI-BCMs were non-significantly different from CMs in terms of new bone area (NBA; %), remaining bone substitute volume (RBA; %) and bone-to-implant contact (BIC; %) (p > 0.05). These results suggest resorbable EI-BCMs can be used as an alternative biomaterial for bone tissue regeneration.

Lee|So-Hyoun|SH| An|Sung-Jun|SJ| Lim|Youn-Mook|YM| Huh|Jung-Bo|JB|

guided bone regeneration (GBR)
electron beam irradiation (EI)
animal study
bacterial cellulose membrane (BCM)
resorbable barrier membrane


Organic additives stabilize RNA aptamer binding of malachite green.

Abstract: Aptamer-ligand binding has been utilized for biological applications due to its specific binding and synthetic nature. However, the applications will be limited if the binding or the ligand is unstable. Malachite green aptamer (MGA) and its labile ligand malachite green (MG) were found to have increasing apparent dissociation constants (Kd) as determined through the first order rate loss of emission intensity of the MGA-MG fluorescent complex. The fluorescent intensity loss was hypothesized to be from the hydrolysis of MG into malachite green carbinol base (MGOH). Random screening organic additives were found to reduce or retain the fluorescence emission and the calculated apparent Kd of MGA-MG binding. The protective effect became more apparent as the percentage of organic additives increased up to 10% v/v. The mechanism behind the organic additive protective effects was primarily from a ~5X increase in first order rate kinetics of MGOH→MG (kMGOH→MG), which significantly changed the equilibrium constant (Keq), favoring the generation of MG, versus MGOH without organic additives. A simple way has been developed to stabilize the apparent Kd of MGA-MG binding over 24h, which may be beneficial in stabilizing other triphenylmethane or carbocation ligand-aptamer interactions that are susceptible to SN1 hydrolysis.

Zhou|Yubin|Y|
Chi|Hong|H|
Wu|Yuanyuan|Y|
Marks|Robert S|RS|
Steele|Terry W J|TWJ|

Malachite green
Malachite green aptamer
Equilibrium
Adaptive binding
Ligand hydrolysis


Preparedness of dental clinics for medical emergencies in Riyadh, Saudi Arabia.

Abstract:
Aim
To assess knowledge, training of dental staff and the availability of emergency drugs and equipment in dental clinics, Riyadh, Saudi Arabia.

Methods
Cross-sectional survey was conducted in a random sample (N: 325) of governmental and private clinics in Riyadh, Saudi Arabia, between June-December 2016. Questions included Dentist's specialty, age, years of experience, knowledge and preparedness to handle ME (level of training, types of emergency drugs and equipment available).

Results
One dentist from each clinic filled the questionnaire (100% of the sample), 19% of whom were general dentists. Medical history is taken orally by 86% of respondents before dental treatment and 12% take vital signs every visit.Of the surveyed clinics, 30% didn't have emergency contact numbers available, 78% didn't have an emergency protocol and only 54% have a medical emergency plan with 11% performing periodic office emergency drills.The most available emergency drug and equipment were Aspirin (53%) and Sphygmomanometer (86%). Oxygen delivery device was not available in 90% of the surveyed clinics.

Conclusion
There is an alarming inadequacy of clinic/staff preparation to deal with ME. Efforts should be made to increase the awareness of dentists to take needed precautions and prepare their clinics.

Preparedness
Dental clinics
Medical emergencies


High prevalence of fatigue in adults with a 22q11.2 deletion syndrome.

Abstract: The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with high phenotypic variability, including somatic disorders like congenital heart disease and psychiatric disorders such as schizophrenia, anxiety disorders, and mood disorders. Clinical observations suggest that many patients with 22q11.2DS suffer from severe fatigue. However, to the best of our knowledge, no previous study has investigated the potential association between 22q11.2DS and fatigue. Twenty-nine patients (mean age 26.8, 18-38 y) with 22q11.2DS completed the multidimensional fatigue inventory (MFI) measuring severity of fatigue. The results of the study group were compared with published population norms. In addition, cross-sectional associations between fatigue, depression (Beck Depression Inventory-BDI), and a quality of life questionnaire (WHO) in patients with 22q11.2 DS were examined. Subscales and total MFI scores were significantly higher in adults with 22q11.2DS. Approximately 80% of the study group had a total MFI score above the mean of the norms. A significant correlation between depressive symptoms and fatigue was found. Fatigue was also significantly associated with quality of life scores, specifically the general score, psychological health, and environment. This is the first report of high levels of fatigue in adults with the 22q11.2DS. Fatigue is a frequent complaint in this age group and should get the necessary attention given its association with quality of life and depression severity. Taking into account the multisystem nature of the 22q11.2DS, we recommend a systematic clinical examination to exclude underlying somatic or psychiatric causes of fatigue. © 2017 Wiley Periodicals, Inc.

Vergaelen|Elfi|E| Claes|Stephan|S| Kempke|Stefan|S| Swillen|Ann|A|

fatigue
22q11.2 deletion syndrome
multidimensional fatigue inventory
quality of life
beck depression inventory


Non-inferiority versus superiority drug claims: the (not so) subtle distinction.

Abstract:
BACKGROUND
Current regulatory guidance and practice of non-inferiority trials are asymmetric in favor of the test treatment (Test) over the reference treatment (Control). These trials are designed to compare the relative efficacy of Test to Control by reference to a clinically important margin, M.

MAIN TEXT
Non-inferiority trials allow for the conclusion of: (a) non-inferiority of Test to Control if Test is slightly worse than Control but by no more than M; and (b) superiority if Test is slightly better than Control even if it is by less than M. From Control's perspective, (b) should lead to a conclusion of non-inferiority of Control to Test. The logical interpretation ought to be that, while Test is statistically better, it is not clinically superior to Control (since Control should be able to claim non-inferiority to Test). This article makes a distinction between statistical and clinical significance, providing for symmetry in the interpretation of results. Statistical superiority and clinical superiority are achieved, respectively, when the null and the non-inferiority margins are exceeded. We discuss a similar modification to placebo-controlled trials.

CONCLUSION
Rules for interpretation should not favor one treatment over another. Claims of statistical or clinical superiority should depend on whether or not the null margin or the clinically relevant margin is exceeded.

Non-inferiority
Superiority
Margin
Confidence interval
Trial design


Functional BCL-2 rs2279115 Promoter Noncoding Variant Contributes to Glioma Predisposition, Especially in Males.

Abstract: As a crucial oncogene, B cell lymphoma-2 (BCL-2) could promote cancer cell survival by inhibiting apoptosis via suppressing activation of proapoptotic proteins, such as BAX and BAK. There is a functional rs2279115 genetic polymorphism locating in BCL-2 promoter and deregulating BCL-2 expression. However, it is still largely undefined how BCL-2 rs2279115 promoter noncoding genetic variant is involved in glioma development. We examined the association between BCL-2 rs2279115 and glioma risk using a case-control approach. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression adjusted by age and sex. Our results demonstrated that BCL-2 rs2279115 was significantly associated with glioma risk. The odd of individuals harboring A allele (CA + AA genotype) was 0.50 (95% CI = 0.39-0.64, p = 1.0 × 10-7) compared with CC genotype carriers. Stratification analyses by sex elucidated that BCL-2 rs2279115 was significantly associated with glioma risk in males (OR = 0.41, 95% CI = 0.30-0.58, p = 1.0 × 10-7), but not in females (p > 0.05). In summary, our results indicate that the functional BCL-2 rs2279115 genetic variant contributes to glioma predisposition and suggest prevalent involvement of regulatory genetic variations in glioma development.

Qiu|Xiao-Guang|XG| Chen|Yi-Dong|YD| Yuan|Jupeng|J| Zhang|Nasha|N| Lei|Tianshui|T| Liu|Jie|J| Yang|Ming|M|

D020022:Genetic Predisposition to Disease

BCL-2
glioma
genetic polymorphism
Chinese
susceptibility


Understanding the aetiology and resolution of chronic otitis media from animal and human studies.

Abstract: Inflammation of the middle ear, known clinically as chronic otitis media, presents in different forms, such as chronic otitis media with effusion (COME; glue ear) and chronic suppurative otitis media (CSOM). These are highly prevalent diseases, especially in childhood, and lead to significant morbidity worldwide. However, much remains unclear about this disease, including its aetiology, initiation and perpetuation, and the relative roles of mucosal and leukocyte biology, pathogens, and Eustachian tube function. Chronic otitis media is commonly modelled in mice but most existing models only partially mimic human disease and many are syndromic. Nevertheless, these models have provided insights into potential disease mechanisms, and have implicated altered immune signalling, mucociliary function and Eustachian tube function as potential predisposing mechanisms. Clinical studies of chronic otitis media have yet to implicate a particular molecular pathway or mechanism, and current human genetic studies are underpowered. We also do not fully understand how existing interventions, such as tympanic membrane repair, work, nor how chronic otitis media spontaneously resolves. This Clinical Puzzle article describes our current knowledge of chronic otitis media and the existing research models for this condition. It also identifies unanswered questions about its pathogenesis and treatment, with the goal of advancing our understanding of this disease to aid the development of novel therapeutic interventions.

Bhutta|Mahmood F|MF|0000-0002-4688-1670
Thornton|Ruth B|RB|
Kirkham|Lea-Ann S|LS|
Kerschner|Joseph E|JE|
Cheeseman|Michael T|MT|

Chronic otitis media
Inflammation
Genetics
Animal models


Evaluation of proteome alterations induced by cadmium stress in sunflower (Helianthus annuus L.) cultures.

Abstract: The present study evaluates, at a proteomic level, changes in protein abundance in sunflower leaves in the absence or presence (at 50 or 700mg) of cadmium (as CdCl2). At the end of the cultivation period (45 days), proteins are extracted from leaves with phenol, separated by two-dimensional difference gel electrophoresis (2-D DIGE), and excised from the gels. The differential protein abundances (for proteins differing by more than 1.8 fold, which corresponds to 90% variation) are characterized using nESI-LC-MS/MS. The protein content decreases by approximately 41% in plants treated with 700mg Cd compared with control plants. By comparing all groups of plants evaluated in this study (Control vs. Cd-lower, Control vs. Cd-higher and Cd-lower vs. Cd-higher), 39 proteins are found differential and 18 accurately identified; the control vs. Cd-higher treatment is that presenting the most differential proteins. From identified proteins, those involved in energy and disease/defense (including stress), are the ribulose bisphosphate carboxylase large chain, transketolase, and heat shock proteins are the most differential abundant proteins. Thus, at the present study, photosynthesis is the main process affected by Cd in sunflowers, although these plants are highly tolerant to Cd.

Lopes Júnior|Cícero Alves|CA|
Barbosa|Herbert de Sousa|Hde S|
Moretto Galazzi|Rodrigo|R|
Ferreira Koolen|Hector Henrique|HH|
Gozzo|Fábio Cesar|FC|
Arruda|Marco Aurélio Zezzi|MA|

Proteomics
Cadmium
Sunflower
2-D DIGE
LC–MS/MS


Imaging biopsy composition at ACL reconstruction.

Abstract:
PURPOSE
Early-stage osteoarthritis (OA) includes glycosaminoglycan (GAG) loss and collagen disruption that cannot be seen on morphological magnetic resonance imaging (MRI). T1ρ MRI is a measurement that probes the low-frequency rate of exchange between protons of free water and those from water associated with macromolecules in the cartilage's extracellular matrix. While it has been hypothesized that increased water mobility resulting from early osteoarthritic changes cause elevated T1ρ MRI values, there remain several unknown mechanisms influencing T1ρ measurements in cartilage. The purpose of this work was to relate histological and biochemical metrics directly measured from osteochondral biopsies and fluid specimens with quantitative MRI-detected changes of in vivo cartilage composition.

PATIENTS AND METHODS
Six young patients were enrolled an average of 41 days after acute anterior cruciate ligament (ACL) rupture. Femoral trochlear groove osteochondral biopsies, serum, and synovial fluid were harvested during ACL reconstruction to complement a presurgery quantitative MRI study (T1ρ, T2, delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] relaxation times). A high-resolution MRI scan of the excised osteochondral biopsy was also collected. Analyses of in vivo T1ρ images were compared with ex vivo T1ρ imaging, GAG assays and histological GAG distribution in the osteochondral biopsies, and direct measures of bone and cartilage turnover markers and "OA marker" 3B3 in serum and synovial fluid samples.

CONCLUSION
T1ρ relaxation times in patients with a torn ACL were elevated from normal, indicating changes consistent with general fluid effusion after blunt joint trauma. Increased chondrogenic progenitor cell (CPC) production of chondroprotective lubricin may relate to cartilage surface disruption by blunt trauma and CPC amplification of joint inflammation. Disparity between ex vivo and matched in vivo MRI of trochlear cartilage suggests MRI signal differences that may be related to the synovial fluid environment. T1ρ is emerging as a promising MRI biomarker to relate noninvasive measures of whole-joint condition and cartilage composition to direct measures of cartilage changes in the acute phase of joint injuries.

Pedersen|Douglas R|DR|
Martin|James A|JA|
Thedens|Daniel R|DR|
Klocke|Noelle F|NF|
Roberts|Nathaniel H|NH|
Goetz|Jessica E|JE|
Amendola|Annunziato|A|

T1ρ
osteochondral biopsy
biomarker
proteoglycan


Calibration of a prototype NIRS oximeter against two commercial devices on a blood-lipid phantom.

Abstract: In a blood-lipid liquid phantom the prototype near-infrared spectroscopy oximeter OxyPrem was calibrated against the INVOS® 5100c adult sensor in respect to values of regional tissue oxygen haemoglobin saturation (rStO2) for possible inclusion in the randomised clinical trial - SafeBoosC. In addition different commercial NIRS oximeters were compared on changing haemoglobin oxygen saturation and compared against co-oximetry. The best calibration was achieved with a simple offset and a linear scaling of the OxyPrem rStO2 values. The INVOS adult and pediatric sensor gave systematically different values, while the difference between the NIRO® 300 and the two INVOS sensors were magnitude dependent. The co-oximetry proved unreliable on such low haemoglobin and high Intralipid levels.

Hyttel-Sorensen|Simon|S| Kleiser|Stefan|S| Wolf|Martin|M| Greisen|Gorm|G|

(170.1470) Blood or tissue constituent monitoring


Women, Infant and Children (WIC) peer counselor contact with first time breastfeeding mothers.

Abstract:
OBJECTIVE
This study was designed to determine whether singleton women who had not previously breastfed and who had a women, infant and children (WIC) peer counselor were more likely to initiate breastfeeding than women not exposed to the WIC peer counselor.

DESIGN AND SAMPLE
The retrospective cross-sectional study used data from the 2009 Texas Department of State Health Services (DSHS) WIC Infant Feeding Practices Survey (IFPS) administered through 73 local WIC agencies. Of the 5,427 responses to the 2009 Texas DSHS WIC IFP Survey, 56.6% (N = 3,070) were included in this study.

MEASURES
The Texas DSHS WIC IFPS, a 55-item survey with multiple-choice and two open-ended questions, was used to evaluate breastfeeding beliefs, attitudes, and practices among women receiving WIC services.

RESULTS
Women who had peer counselor contact during pregnancy, in the hospital, and after delivery were more likely to initiate breastfeeding than women without such contacts, OR = 1.36, 2.06, 1.85, respectively.

CONCLUSION
Women's decision to initiate breastfeeding is significantly associated with WIC peer counselor contacts. Continued WIC peer counselor program services may increase breastfeeding initiation rates among WIC participants.

Campbell|Lisa A|LA|
Wan|Jim|J|
Speck|Patricia M|PM|
Hartig|Margaret T|MT|

WIC
peer counselors
breastfeeding
initiation
first time mothers
infant health


Improved attitudes of interns versus undergraduate medical students towards patients with mental illness in Saudi Arabia.

Abstract:
Background
The attitudes of medical students towards mental illness are important since these students will be providing care to this group in the future.

Aims
To assess the beliefs and attitudes of undergraduate medical students regarding mental illness and to compare students at different levels.

Methods
This descriptive, cross-sectional study was conducted among undergraduate medical students in the College of Medicine, Majmaah University, Saudi Arabia, during the 2018-2019 academic years. Male students were included from Years 3-5 (25 from each year) and 25 male interns using the proportionate stratified random sampling method. The participants responded to the Beliefs about Mental Illness (BMI) Scale and the Attitudes towards Mental Illness Questionnaire (AMIQ).

Results
Bonferroni post hoc tests were used to conduct between-group comparisons of the year 3 group, who were at the beginning of their psychiatric training, with the other groups with more training. This revealed significant differences in scores for 11 of 21 items on the BMI Scale (P < 0.05). All questions regarding the 4 vignettes of the AMIQ (substance abuse, depression, psychosis, and obsessive compulsive disorders) showed a significant difference between students in year 3 and those in the other groups who had more psychiatric training (P < 0.05).

Conclusions
The current medical psychiatric training positively improved the beliefs and attitudes of medical students towards patients with mental illnesses.

D001291:Attitude of Health Personnel
D003430:Cross-Sectional Studies
D006801:Humans
D008297:Male
D001523:Mental Disorders
D011570:Psychiatry
D012529:Saudi Arabia
D057545:Social Stigma
D013337:Students, Medical
D011795:Surveys and Questionnaires

attitude
mental illness
impact of training
psychiatric care
social stigma


Potential role of aquaporin 3 in gastric intestinal metaplasia.

Abstract: Gastric intestinal metaplasia (GIM) is a pre-cancerous condition and a pivotal step in the formation of gastric cancer (GC). Aquaporin 3 (AQP3) has been found to be expressed in goblet cells rather than mucus-secreting glands. To investigate the characteristics of GIM in non-cancerous tissues adjacent to GC, as well as the expression and role of AQP3 in GIM tissues, 16 patients diagnosed with gastric adenocarcinoma of intestinal type located in the lesser curve of the antrum were consecutively enrolled in this study. A new pathological technology called "gastric mucosal sausage roll" was introduced. GIM was determined according to the updated Sydney system, and AQP3 expression in goblet cells was determined by immunohistochemistry. GIM was found in all stomach specimens, and its incidence increased with progression to GC (P < 0.001). GIM prevalence displayed remarkable association with the distance to GC in the anterior gastric wall tissues (P = 0.016) and tissues toward the cardia (P = 0.014), such that GIM was more common in the areas closer to GC (P < 0.001). AQP3 was found to be expressed in 67.71% of parts with GIM, and AQP3 immunoreactivity was identified more frequently in severe GIM areas (P < 0.001). In short, the incidence and severity of GIM correlated with the distance from GC, and AQP3 was differentially expressed in goblet cells, with most AQP3-positive goblet cells presenting in severe GIM. Together, this study suggests that AQP3 may play an important role in gastric carcinogenesis from GIM.

Zhao|Haijian|H| Yang|Xiaojun|X| Zhou|Yangchun|Y| Zhang|Weiming|W| Wang|Yao|Y| Wen|Jianfei|J| Zhang|Zhihong|Z| Shen|Lizong|L|

aquaporin 3
gastric intestinal metaplasia
gastric cancer
pathology


Asymmetric transfer efficiencies between fomites and fingers: Impact on model parameterization.

Abstract:
BACKGROUND
Healthcare-associated infections (HAIs) affect millions of patients every year. Pathogen transmission via fomites and healthcare workers (HCWs) contribute to the persistence of HAIs in hospitals. A critical parameter needed to assess risk of environmental transmission is the pathogen transfer efficiency between fomites and fingers. Recent studies have shown that pathogen transfer is not symmetric. In this study,we evaluated how the commonly used assumption of symmetry in transfer efficiency changes the dynamics of pathogen movement between patients and rooms and the exposures to uncolonized patients.

METHODS
We developed and analyzed a deterministic compartmental model of Acinetobacter baumannii describing the contact-mediated process among HCWs, patients, and the environment. We compared a system using measured asymmetrical transfer efficiency to 2 symmetrical transfer efficiency systems.

RESULTS
Symmetric models consistently overestimated contamination levels on fomites and underestimated contamination on patients and HCWs compared to the asymmetrical model. The magnitudes of these miscalculations can exceed 100%. Regardless of the model, relative percent reductions in contamination declined after hand hygiene compliance reached approximately 60% in the large fomite scenario and 70% in the small fomite scenario.

CONCLUSIONS
This study demonstrates how healthcare facility-specific data can be used for decision-making processes. We show that the incorrect use of transfer efficiency data leads to biased effectiveness estimates for intervention strategies. More accurate exposure models are needed for more informed infection prevention strategies.

Greene|Christine|C|
Ceron|Nancy Hernandez|NH|
Eisenberg|Marisa C|MC|
Koopman|James|J|
Miller|Jesse D|JD|
Xi|Chuanwu|C|
Eisenberg|Joseph N S|JNS|

Transfer efficiency
Fomite
Parameterization
Healthcare-associated infections
Environmental transmission
Acinetobacter baumannii
Hand hygiene
Hospital surfaces
Mathematical model