Two distinct cytokinesis pathways drive trypanosome cell division initiation from opposite cell ends.

Abstract: Cytokinesis in Trypanosoma brucei, an early branching protozoan, occurs along its longitudinal axis uni-directionally from the anterior tip of the new flagellum attachment zone filament toward the cell's posterior end. However, the underlying mechanisms remain elusive. Here we report that cytokinesis in T. brucei is regulated by a concerted action of Polo-like kinase, Aurora B kinase, and a trypanosome-specific protein CIF1. Phosphorylation of CIF1 by Polo-like kinase targets it to the anterior tip of the new flagellum attachment zone filament, where it subsequently recruits Aurora B kinase to initiate cytokinesis. Consistent with its role, CIF1 depletion inhibits cytokinesis initiation from the anterior end of the cell, but, surprisingly, triggers cytokinesis initiation from the posterior end of the cell, suggesting the activation of an alternative cytokinesis from the opposite cell end. Our results reveal the mechanistic roles of CIF1 and Polo-like kinase in cytokinesis initiation and elucidate the mechanism underlying the recruitment of Aurora B kinase to the cytokinesis initiation site at late anaphase. These findings also delineate a signaling cascade controlling cytokinesis initiation from the anterior end of the cell and uncover a backup cytokinesis that is initiated from the posterior end of the cell when the typical anterior-to-posterior cytokinesis is compromised.

Zhou|Qing|Q|
Gu|Jianhua|J|
Lun|Zhao-Rong|ZR|
Ayala|Francisco J|FJ|
Li|Ziyin|Z|

D002455:Cell Division
D048749:Cytokinesis
D010766:Phosphorylation
D015800:Protozoan Proteins
D013347:Subcellular Fractions
D014346:Trypanosoma brucei brucei

cytokinesis
Trypanosoma brucei
Polo-like kinase
Aurora B kinase
backup cytokinesis


Risk factors for progression of juvenile-onset non-radiographic axial spondyloarthritis to juvenile-onset ankylosing spondylitis: a nested case-control study.

Abstract:
OBJECTIVE
To evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS).

METHODS
A nested case-control study was conducted using the retrospectively collected data of 106 patients with juvenile-onset nr-axSpA (age at disease onset, <16 years) in the Clinical characteristic and Outcome in Chinese Axial Spondyloarthritis study cohort. Baseline demographic and clinical characteristics and prognosis were reviewed. Logistic regression analyses were performed to investigate risk factors associated with progression to JoAS.

RESULTS
Overall, 58.5% of patients with juvenile-onset nr-axSpA presented with peripheral symptoms at disease onset. In 82.1% of these patients, axial with peripheral involvement occurred during the disease course. The rate of disease onset at >12 years and disease duration of ≤10 years were significantly higher in those with progression to JoAS than in those without progression to JoAS (83.0% vs 52.8%, p=0.001; 92.5% vs 56.6%, p<0.001, respectively). Multivariable logistic regression analysis revealed that inflammatory back pain (IBP) (OR 13.359 (95% CI 2.549 to 70.013)), buttock pain (OR 10.171 (95% CI 2.197 to 47.085)), enthesitis (OR 7.113 (95% CI 1.670 to 30.305)), elevated baseline C reactive protein (CRP) levels (OR 7.295 (95% CI 1.984 to 26.820)) and sacroiliac joint-MRI (SIJ-MRI) positivity (OR 53.821 (95% CI 9.705 to 298.475)) were significantly associated with progression to JoAS.

CONCLUSION
Peripheral involvement was prevalent in juvenile-onset nr-axSpA. IBP, buttock pain, enthesitis, elevated baseline CRP levels and SIJ-MRI positivity in patients with the disease are associated with higher risk of progression to JoAS.

ankylosing
spondylitis
arthritis
autoimmune diseases
juvenile


Training doctors to manage patients with multimorbidity: a systematic review.

Abstract:
BACKGROUND
Patients with multimorbidity (two or more chronic conditions) are now the norm in clinical practice, and place an increasing burden on the healthcare system. Management of these patients is challenging, and requires doctors who are skilled in the complexity of multiple chronic diseases.

OBJECTIVE
To perform a systematic review of the literature to ascertain whether there are education and training formats which have been used to train postgraduate medical doctors in the management of patients with multimorbidity in primary and/or secondary care, and which have been shown to improve knowledge, skills, attitudes, and/or patient outcomes.

METHODS
Overall, 75,110 citations were screened, of which 65 full-text articles were then independently assessed for eligibility by two reviewers, and two studies met the inclusion criteria for the review.

RESULTS
The two included studies implemented and evaluated multimorbidity workshops, and highlight the need for further research addressing the learning needs of doctors tasked with managing patients with multimorbidity in their daily practice.

CONCLUSION
While much has been published about the challenges presented to medical staff by patients with multimorbidity, published research regarding education of doctors to manage these problems is lacking. Further research is required to determine whether there is a need for, or benefit from, specific training for doctors to manage patients with multimorbidity. PROSPERO registration number: CRD42013004010.

Lewis|Cliona|C|
Wallace|Emma|E|
Kyne|Lorraine|L|
Cullen|Walter|W|
Smith|Susan M|SM|

Multimorbidity
patient management
postgraduate education
postgraduate training


Internet gaming disorder and gaming disorder in the context of seeking and not seeking treatment for video-gaming.

Abstract: The aims of this study were to examine the relationship between Internet gaming disorder (IGD) and gaming disorder (GD) and the degree of concordance between treatment seeking for gaming and IGD/GD. One hundred gamers who sought treatment for their gaming were compared with one hundred gamers who never sought treatment and gamers who met IGD and/or GD criteria were compared with those who did not meet these criteria, regardless of their treatment-seeking status. These comparisons were made using semi-structured diagnostic interviews and self-report psychopathology and symptom measures. There was only a partial concordance between treatment seeking and IGD/GD because 61% of treatment-seeking gamers met the diagnostic criteria for IGD and 36% met the diagnostic criteria for GD. GD criteria were found to reflect a more intense, pathological pattern of gaming, associated with high rates of attention deficit/hyperactivity disorder (ADHD) and coping as the main reason for gaming. IGD criteria were found to refer to a broad, heterogeneous entity that encompasses a "spectrum" of gaming from risky/hazardous to pathological. These findings suggest that gamers may seek treatment for IGD/GD, a diagnostically subthreshold, risky gaming pattern (i.e., hazardous gaming) or for a gaming pattern that seems normal. A partial overlap between IGD and GD indicates that the two disorders as conceptualized by their respective criteria, should not be considered interchangeably. The relationship and extent of the conceptual overlap between ADHD and a gaming-related disorder, especially GD, merit further study.

Starcevic|Vladan|V|
Choi|Tae Young|TY|
Kim|Tae Ho|TH|
Yoo|Seo-Koo|SK|
Bae|Sujin|S|
Choi|Byung-Sun|BS|
Han|Doug Hyun|DH|

D007174:Disruptive, Impulse Control, and Conduct Disorders


Two Chlamydomonas OPR proteins stabilize chloroplast mRNAs encoding small subunits of photosystem II and cytochrome b6 f.

Abstract: In plants and algae, chloroplast gene expression is controlled by nucleus-encoded proteins that bind to mRNAs in a specific manner, stabilizing mRNAs or promoting their splicing, editing, or translation. Here, we present the characterization of two mRNA stabilization factors of the green alga Chlamydomonas reinhardtii, which both belong to the OctotricoPeptide Repeat (OPR) family. MCG1 is necessary to stabilize the petG mRNA, encoding a small subunit of the cytochrome b6 f complex, while MBI1 stabilizes the psbI mRNA, coding for a small subunit of photosystem II. In the mcg1 mutant, the small RNA footprint corresponding to the 5'-end of the petG transcript is reduced in abundance. In both cases, the absence of the small subunit perturbs assembly of the cognate complex. Whereas PetG is essential for formation of a functional cytochrome b6 f dimer, PsbI appears partly dispensable as a low level of PSII activity can still be measured in its absence. Thus, nuclear control of chloroplast gene expression is not only exerted on the major core subunits of the complexes, but also on small subunits with a single transmembrane helix. While OPR proteins have thus far been involved in translation or trans-splicing of plastid mRNAs, our results expand the potential roles of this repeat family to their stabilization.

Wang|Fei|F| Johnson|Xenie|X| Cavaiuolo|Marina|M| Bohne|Alexandra-Viola|AV| Nickelsen|Joerg|J| Vallon|Olivier|O|

D018506:Gene Expression Regulation, Plant

photosystem II
chloroplast gene expression
Chlamydomonas reinhardtii
OctotricoPeptide Repeat
petG
psbI
RNA footprint
RNA-binding protein
cytochrome b6f


Physiological and drug-induced changes in blood levels of adrenal steroids and their precursors in cynomolgus monkeys: An application of steroid profiling by LC-MS/MS for evaluation of the adrenal toxicity.

Abstract: The adrenal gland is the most common toxicological target of drugs within the endocrine system, and inhibition of adrenal steroidogenesis can be fatal in humans. However, methods to evaluate the adrenal toxicity are limited. The aim of the present study was to verify the usefulness of simultaneous measurement of blood levels of multiple adrenal steroids, including precursors, as a method to evaluate drug effects on adrenal steroidogenesis in cynomolgus monkeys. With this aim, physiological and drug-induced changes in blood levels of adrenal steroids, including cortisol, aldosterone, androgen, and their precursors were examined. First, for physiological changes, intraday and interday changes in blood steroid levels were examined in male and female cynomolgus monkeys. The animals showed circadian changes in steroid levels that are similar to those in humans, while interday changes were relatively small in males. Next, using males, changes in blood steroid levels induced by ketoconazole and metyrapone were examined, which suppress adrenal steroidogenesis via inhibition of CYP enzymes. Consistent with rats and humans, both ketoconazole and metyrapone increased the deoxycorticosterone and deoxycortisol levels, probably via CYP11B1 inhibition, and the increase was observed earlier and with greater dynamic range than the changes in cortisol level. Changes in other steroid levels reflecting the drug mechanisms were also observed. In conclusion, this study showed that in cynomolgus monkeys, simultaneous measurement of blood levels of adrenal steroids, including precursors, can be a valuable method to sensitively evaluate drug effects on adrenal steroidogenesis and to investigate the underlying mechanisms.

Tochitani|Tomoaki|T| Yamashita|Akihito|A| Matsumoto|Izumi|I| Kouchi|Mami|M| Fujii|Yuta|Y| Yamada|Toru|T| Miyawaki|Izuru|I|

Liquid chromatography-tandem mass spectrometry

Simultaneous measurement of multiple steroids


The influence of polishing techniques on pre-polymerized CAD\CAM acrylic resin denture bases.

Abstract:
Background
Lately, computer-aided design and computer-aided manufacturing (CAD/CAM) has broadly been successfully employed in dentistry. The CAD/CAM systems have recently become commercially available for fabrication of complete dentures, and are considered as an alternative technique to conventionally processed acrylic resin bases. However, they have not yet been fully investigated.

Objective
The purpose of this study was to inspect the effects of mechanical polishing and chemical polishing on the surface roughness (Ra) and contact angle (wettability) of heat-cured, auto-cured and CAD/CAM denture base acrylic resins.

Methods
This study was conducted at the Advanced Dental Research Laboratory Center of King Abdulaziz University from March to June 2017. Three denture base materials were selected: heat cure poly-methylmethacrylate resin, thermoplastic (polyamide resin) and (CAD\CAM) denture base resin. Sixty specimens were prepared and divided into three groups, twenty in each. Each group was divided according to the polishing techniques into (Mech P) and (Chem P), ten specimens in each; surface roughness and wettability were investigated. Data were analyzed by SPSS version 22, using one-way ANOVA and Pearson coefficient.

Results
One-way analysis of variance (ANOVA) and post hoc tests were used for comparing the surface roughness values between three groups which revealed a statistical significant difference between them (p1<0.001). Heat-cured denture base material of (Group I) in both methods, showed the highest mean surface roughness value (2.44±0.07, 2.72±0.09, Mech P and Chem P respectively); while CAD\CAM denture base material (group III) showed the least mean values (1.08±0.23, 1.39±0.31, Mech P and Chem P respectively). CAD/CAM showed the least contact angle in both polishing methods, which were statistically significant at 5% level (p=0.034 and p<0.001).

Conclusion
Mechanical polishing produced lower surface roughness of CAD\CAM denture base resin with superior smooth surface compared to chemical polishing. Mechanical polishing is considered the best effective polishing technique. CAD/CAM denture base material should be considered as the material of choice for complete denture construction in the near future, especially for older dental patients with changed salivary functions, because of its wettability.

Polishing
CAD\CAM acrylic resin
Surface roughness
Wettability
Acrylic denture base


Development of an emergency medical system model for resource-constrained settings.

Abstract:
OBJECTIVES
An emergency care system is an important aspect for healthcare organisations in low- and middle-income countries (LMICs) with a growing burden from emergency disease conditions. Evaluations of emergency care systems in LMICs in broader contexts are lacking. Thus, this study aimed to develop a comprehensive emergency medical system model appropriate for resource-constrained settings, based on expert opinions.

METHODS
We used the Delphi method, in which questionnaire surveys were administered three times to an expert panel (both emergency medical care providers and healthcare service researchers), from which opinions on the model's components were compiled. The panel members were mostly from Asian countries. In the first round, the questionnaire drew a list of model components developed through a literature review; the panel members then proposed new components to create a more comprehensive list. In the second and third rounds, the panel members rated the listed components to achieve consensus, as well as to remove components with low ratings. Finally, we rearranged the list to improve its usability.

RESULTS
In total, 32 experts from 12 countries participated. The final model totalled 177 components, categorised into 8 domains (leadership, community-based actions, emergency medical services, upward referral, definitive care, rehabilitation, downward referral, and evaluation and research). No components needed removal.

CONCLUSIONS
We developed a comprehensive emergency care system model, which could provide a basis to evaluate emergency care systems in resource-constrained LMICs; however, field-testing and validation of this system model remain to be done.

Nakahara|Shinji|S|
Hoang|Bui Hai|BH|
Mayxay|Mayfong|M|
Pattanarattanamolee|Ratrawee|R|
Jayatilleke|Achala Upendra|AU|
Ichikawa|Masao|M|
Sakamoto|Tetsuya|T|

system model
emergency care
low- and middle-income countries
modèle de système
pays à revenu faible ou intermédiaire
soins d'urgence


Retinal layer thickness in preclinical Alzheimer's disease.

Abstract:
PURPOSE
There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.

METHODS
One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BPND ) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ- individuals and associations between BPND and retinal thickness were analyzed.

RESULTS
No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ- individuals. A positive associations between BPND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068).

CONCLUSION
Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.

van de Kreeke|Jacoba A|JA|https://orcid.org/0000-0002-0165-1839

preclinical Alzheimer's disease
twins
OCT
ocular biomarkers
retina


Inhibition of in vitro Ebola infection by anti-parasitic quinoline derivatives.

Abstract: There continues to be no approved drugs for the treatment of Ebola virus disease (EVD). Despite a number of candidate drugs showing limited efficacy in vitro and/or in non-human primate studies, EVD continues to plaque certain areas of Africa without any efficacious treatments yet available. Recently, we have been exploring the potential for anti-malarial drugs to inhibit an in vitro model of Ebola Zaire replication using a transcription-competent virus-like particle (trVLP) assay. We examined the efficacy of chloroquine, amodiaquine and 36 novel anti-parasite quinoline derivatives at inhibiting Ebola virus replication. Drug efficacy was tested by trVLP assay and toxicity by MTT assay. Both chloroquine and amodiaquine were effective for inhibition of Ebola virus replication without significant toxicity. The half-maximal inhibitory concentration (IC 50) of chloroquine and amodiaquine to inhibit Ebola virus replication were IC 50, Chl = 3.95 µM and IC 50, Amo = 1.45 µM, respectively. Additionally, three novel quinoline derivatives were identified as having inhibitory activity and low toxicity for Ebola trVLP replication, with 2NH2Q being the most promising derivative, with an IC 50 of 4.66 µM. Quinoline compounds offer many advantages for disease treatment in tropical climates as they are cheap to produce, easy to synthesize and chemically stable. In this report, we have demonstrated the potential of anti-parasite quinolines for further investigation for use in EVD.

Ebola virus
antiparasitic drugs
antiviral activity


Impact of the size of the normal database on the performance of the specific binding ratio in dopamine transporter SPECT.

Abstract:
BACKGROUND
This study investigated the impact of the size of the normal database on the classification performance of the specific binding ratio (SBR) in dopamine transporter (DAT) SPECT with [123I]FP-CIT in different settings.

METHODS
The first subject sample comprised 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls (HC), and 438 Parkinson's disease (PD) patients. The second sample comprised 372 patients from clinical routine patient care, 186 with non-neurodegenerative parkinsonian syndrome (PS) and 186 with neurodegenerative PS. Single-photon emission computed tomography (SPECT) images of the clinical sample were reconstructed with two different reconstruction algorithms (filtered backprojection, iterative ordered subsets expectation maximization (OSEM) reconstruction with resolution recovery). The putaminal specific binding ratio (SBR) was computed using an anatomical region of interest (ROI) predefined in standard (MNI) space in the Automated Anatomic Labeling (AAL) atlas or using hottest voxels (HV) analysis in large predefined ROIs. SBR values were transformed to z-scores using mean and standard deviation of the SBR in a normal database of varying sizes (n = 5, 10, 15,…, 50) randomly selected from the HC subjects (PPMI sample) or the patients with non-neurodegenerative PS (clinical sample). Accuracy, sensitivity, and specificity for identifying patients with PD or neurodegenerative PS were determined as performance measures using a predefined fixed cutoff on the z-score. This was repeated for 10,000 randomly selected normal databases, separately for each size of the normal database. Mean and 5th percentile of the performance measures over the 10,000 realizations were computed. Accuracy, sensitivity, and specificity when using the whole set of HC or non-neurodegenerative PS subjects as normal database were used as benchmark.

RESULTS
Mean loss of accuracy of the putamen SBR z-score was below 1% when the normal database included at least 15 subjects, independent of subject sample (PPMI or clinical), reconstruction method (filtered backprojection or OSEM), and ROI method (AAL or HV). However, the variability of the accuracy of the putamen SBR z-score decreased monotonically with increasing size of normal database and was still considerable at size 15. In order to achieve less than 5% "maximum" loss of accuracy (defined by the 5th percentile) in all settings required at least 25 to 30 subjects in the normal database. Reduction of mean and "maximum" loss of accuracy of the putamen SBR z-score by further increasing the size of the normal database was very small beyond size 40.

CONCLUSIONS
The results of this study suggest that 25 to 30 is the minimum size of the normal database to reliably achieve good performance of semi-quantitative analysis in dopamine transporter (DAT) SPECT, independent of the algorithm used for image reconstruction and the ROI method used to estimate the putaminal SBR.

Normal database
Specific binding ratio
Dopamine transporter
SPECT
FP-CIT


Insecticidal Activity of a Destruxin-Containing Extract of Metarhizium brunneum Against Ceratitis capitata (Diptera: Tephritidae).

Abstract: Tephritid fruit flies are major pests that limit fruit production around the world; they cause important damages, increasing directly and indirectly annual costs, and their management is predominately based on the use of chemical insecticides. This research investigated the insecticidal activity of the crude extract obtained of Metarhizium brunneum Petch EAMb 09/01-Su strain and its capacity to secrete secondary metabolites including destruxins (dtx). Dtx A and A2 had insecticidal activity against Ceratitis capitata (Wiedemann) when administered per os. The crude extract of seven Metarhizium and one Beauveria isolates were evaluated per os against medfly adults. The crude extracts of the isolate EAMb 09/01-Su resulted in mortality ranging between 95 and 100% at 48 h. The high-pressure liquid chromatography profile showed two active peaks (F5B and F6 subfractions) related with dtx A2 and dtx A, which caused 70 and 100% mortality on C. capitata at 48 h postfeeding, respectively. The LC50 was 104.92 ppm of dtx A, contained in the F6 subfraction, and the LT50 was 4.16 h at a concentration of 400 ppm of dtx A contained in the F6 subfraction. Moreover, the average survival time of adults exposed to this subfraction was 12.6 h with only 1 h of exposure. The insecticide metabolites of the F6 subfraction of the EAMb 09/01-Su isolate retained >90% of its insecticidal activity after exposure to 60°C for 2 h and 120°C for 20 min. These results highlight the potential of this strain as a source of new insecticidal compounds of natural origin for fruit fly control.

Lozano-Tovar|M D|MD|
Garrido-Jurado|I|I|
Lafont|F|F|
Quesada-Moraga|E|E|

fruit fly
insecticidal compound
bioinsecticide
biological control


Characterization of Pathogenic Vibrio parahaemolyticus from the Chesapeake Bay, Maryland.

Abstract: Vibrio parahaemolyticus is the leading cause of bacterial gastroenteritis associated with seafood consumption in the United States. Here we investigated the presence of virulence factors and genetic diversity of V. parahaemolyticus isolated from water, oyster, and sediment samples from the Chesapeake Bay, Maryland. Of more than 2,350 presumptive Vibrio collected, more than half were confirmed through PCR as V. parahaemolyticus, with 10 encoding both tdh and trh and 6 encoding only trh. Potentially pathogenic V. parahaemolyticus were then serotyped with O1:KUT and O3:KUT predominant. Furthermore, pulsed-field gel electrophoresis was performed and the constructed dendrogram displayed high diversity, as did results from multiple-locus VNTR analysis. Vibrio parahaemolyticus was readily isolated from Chesapeake Bay waters but was less frequently isolated from oyster and sediment samples collected during this study. Potentially pathogenic V. parahaemolyticus was isolated in fewer numbers and the isolates displayed expansive diversity. Although characteristics of the pathogenic V. parahaemolyticus were highly variable and the percent of pathogenic V. parahaemolyticus detected was low, it is important to note that, pathogenic V. parahaemolyticus are present in the Chesapeake Bay, warranting seafood monitoring to minimize risk of disease for the public, and to reduce the economic burden of V. parahaemolyticus related illness.

Chen|Arlene J|AJ|
Hasan|Nur A|NA|
Haley|Bradd J|BJ|
Taviani|Elisa|E|
Tarnowski|Mitch|M|
Brohawn|Kathy|K|
Johnson|Crystal N|CN|
Colwell|Rita R|RR|
Huq|Anwar|A|

pathogenicity
Vibrio parahaemolyticus
Chesapeake Bay
virulence
environment


Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

Abstract: Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

Simpson|K|K|
Jones|R E|RE|
Grimstead|J W|JW|
Hills|R|R|
Pepper|C|C|
Baird|D M|DM|

Telomere
Breast cancer
Genome instability
Prognosis


Manufacturing custom-contoured wheelchair seating: A state-of-the-art review.

Abstract:
BACKGROUND
Custom-contoured wheelchair seating lowers risk of pressure injury and postural deterioration while custom-contoured wheelchair seating lowers risk of pressure injury and postural deterioration while increasing the stability and functional activity of the wheelchair occupant. Producing custom-contoured seating systems has historically been a labour-intensive process custom-contoured seating systems is historically labour-intensive.

OBJECTIVES
Evaluate the strengths and limitations of current manufacturing processes for custom-contoured wheelchair seating to suggest potential future manufacturing processes.

STUDY DESIGN
Literature review of the state of the art.

METHODS
Research conducted through a literature review focused on the performance of different types of custom-contoured wheelchair seating products and processes over the last 40 years. Recent literature in orthotics and prosthetics was also consulted to assess future trends in seating.

RESULTS
There are five main manufacturing processes currently used to produce custom-contoured wheelchair seating systems. No single process is yet suitable for all wheelchair users, but many manufacturers are transitioning to computer numerical controlled (CNC) milling to reduce manual labour. Adjustable micro-modular seating and moulded seat insert manufacturing are also prevalent and offer alternative seating to soft foam carving.

CONCLUSION
There is a need in the custom wheelchair seating sector for processes that are fast, cost-effective, produce little to no material waste, and that can effectively maintain a comfortable seating micro-climate. Additive manufacturing may meet these criteria, but further evaluation is required.

CLINICAL RELEVANCE
This review suggests that the custom-contoured wheelchair seating manufacturers are moving away from labour-intensive processes towards digital techniques, like CNC foam milling. Additive manufacturing is a potential new process that may reduce overall costs, the lead time in preparing seats and has the potential to better manage the seating micro-climate.

D017076:Computer-Aided Design
D004867:Equipment Design
D006801:Humans
D066330:Printing, Three-Dimensional
D000077708:Sitting Position
D014910:Wheelchairs


What are the chances for personalised treatment with antidepressants? Detection of patient-by-treatment interaction with a variance ratio meta-analysis.

Abstract:
OBJECTIVES
To investigate if the treatment effect of antidepressants in patients with depression substantially varies in each patient (patient-by-treatment interaction or treatment heterogeneity), a necessary but largely unexplored prerequisite of personalised antidepressant treatment.

DESIGN
Meta-analytic variance comparison of treatment outcome between drug arms and placebo arms of clinical trials, based on the assumption that patient-by-treatment interaction should lead to larger variances in drug arms than placebo arms. To put the results into context, we run simple simulations, assuming different definitions and rates of those who respond especially well to antidepressants.

DATA SOURCES
163 randomised, placebo-controlled trials (51 396 patients) with complete results for pre-post differences, selected from a recently published systematic review.

ANALYSIS
Variance ratios (VRs) and coefficients of variance ratios (CVRs) of individual trials were meta-analytically combined. The analysis was repeated for classes of antidepressants and specific antidepressants.

RESULTS
VRs (VR=1.01, CI 0.99 to 1.02) and CVRs (CVR=0.82, CI 0.80 to 0.84) of the antidepressant-treatment arms were comparable or smaller than in placebo arms. Similar results were observed for classes of antidepressants and for specific antidepressants. Our simulation analysis confirmed that equal VRs can only be obtained if they are not more than a few patients who respond slightly above average.

CONCLUSIONS
The lack of increased treatment-outcome variance in the antidepressants versus placebo groups in randomised controlled trials indicates that no or only very small subgroups of patients respond particularly well to antidepressants. Thus, the scope for personalised treatment with antidepressants seems to be limited.

D016032:Randomized Controlled Trials as Topic

depression and mood disorders
psychiatry
statistics and research methods


Prognostic impact of nutritional status and physical capacity in elderly patients with acute decompensated heart failure.

Abstract:
AIMS
Nutritional status as well as physical capacity is related to prognosis in patients with heart failure. The purpose of this study was to explore a simple prognostic indicator in patients with acute decompensated heart failure (ADHF) by including both nutritional status and physical capacity.

METHODS AND RESULTS
Patients hospitalized with ADHF (N = 203; mean age, 81 years) were enrolled. We evaluated the geriatric nutritional risk index (GNRI) on hospital admission and at discharge. A GNRI score < 92 was defined as malnutrition. Physical capacity was evaluated by simple walking test to determine if patients could walk 200 m, with a Borg scale score ≤ 13, without critical changes in vital signs. Primary endpoints were mortality and heart failure rehospitalization within 2 years. A total of 49% and 48% of patients showed malnutrition on admission and at discharge, respectively. Malnutrition at discharge was more strongly related to mortality [hazard ratio (HR) 3.382, 95% confidence interval (CI) 1.900-6.020, P < 0.0001)] than that on admission (HR 2.448, 95% CI 1.442-4.157, P = 0.001) by univariable analysis. Malnutrition at discharge was related to mortality (HR 2.370, 95% CI 1.166-4.814, P = 0.02), but malnutrition on admission was not related (HR 1.538, 95% CI 0.823-2.875, P = 0.18) by multivariable analysis. Almost half of patients (45%) could not walk 200 m, which was significantly related to mortality by univariable analysis (HR 3.303, 95% CI 1.905-5.727, P < 0.0001), but was not by multivariable analysis (HR 1.990, 95% CI 0.999-3.962, P = 0.05). The combined index including both GNRI and simple walking test was an independent and stronger predictor of mortality than either index alone by multivariable analysis (HR 2.249, 95% CI 1.362-3.716, P < 0.01). Neither malnutrition nor low physical capacity was related to heart failure rehospitalization by univariable analysis (HR 0.702, 95% CI 0.483-1.020, P = 0.06; HR 1.047, 95% CI 0.724-1.515, P = 0.81, respectively). Malnutrition at discharge significantly reduced heart failure rehospitalization by multivariable analysis (HR 0.431, 95% CI 0.266-0.698, P < 0.01). When patients were classified into Group G (both nutritional status and physical capacity at discharge were good), Group E (either was good), and Group B (both were bad), mortality rates were significantly different among the groups (log rank P < 0.0001).

CONCLUSION
A simple indicator including both nutritional status and physical capacity may predict 2 year mortality in elderly patients with ADHF.

Yasumura|Kaori|K| Abe|Haruhiko|H| Iida|Yoshinori|Y| Kato|Taishi|T| Nakamura|Masayuki|M| Toriyama|Chieko|C| Nishida|Hiroki|H| Idemoto|Akiko|A| Shinouchi|Kazuya|K| Mishima|Tsuyoshi|T| Awata|Masaki|M| Date|Motoo|M| Ueda|Yasunori|Y| Uematsu|Masaaki|M| Koretsune|Yukihiro|Y|

D000368:Aged
D000369:Aged, 80 and over
D015577:Geriatric Assessment
D006333:Heart Failure
D006801:Humans
D015596:Nutrition Assessment
D009752:Nutritional Status
D011379:Prognosis
D012307:Risk Factors

Elderly patients
Acute decompensated heart failure
Geriatric nutritional risk index
Simple walking test


Mental Objects in Working Memory: Development of Basic Capacity or of Cognitive Completion?

Abstract: Working memory is the small amount of information that we hold in mind and use to carry out cognitive processes such as language comprehension and production, problem solving, and decision making. In order to understand cognitive development, it would be helpful to know whether working memory increases in capacity with development and, if so, how and why. I will focus on two major stumbling blocks toward understanding working memory development, namely that (1) many potentially relevant aspects of the mind change in parallel during development, obscuring the role of any one change; and (2) one cannot use the same test procedure from infancy to adulthood, complicating comparisons across age groups. With regard to the first stumbling block, the parallel development of different aspects of the mind, we discuss research in which attempts were made to hold constant some factors (knowledge, strategies, direction of attention) to investigate whether developmental differences remain. With regard to the second stumbling block, procedural differences in tests for different age groups, I suggest ways in which the results might be reconciled across procedures. I highlight the value of pursuing research that could distinguish between two different key hypotheses that emerge: that there is a developmental increase in the number of working memory slots (or in a basic resource that holds items in working memory), and that there is a developmental increase in the amount of detail that each of these slots can hold.

Working memory
Capacity
Infancy
Childhood
Focus of attention
Short-term memory


Mean ADC values discriminate rectal mucinous carcinomafrom rectal nonmucinous adenocarcinoma

Abstract: Background/aim: This study aimed to differentiate rectal mucinous carcinoma (MC) from nonmucinous rectal adenocarcinoma (AC) using mean apparent diffusion coefficient (mADC) values obtained with diffusion-weighted imaging.Materials and methods: Sixty-two pathologically confirmed rectal AC (n = 44) and MC (n = 18) patients were included in this study. The two groups underwent pelvic MRI to determine the local staging baseline for rectal tumors. Once the region of interest (ROI) was determined, a border was drawn around each hyperintense tumor (b = 1000 s/mm2 images). Following a repeat of this procedure for each patient, the ROIs were recorded to apparent diffusion coefficient (ADC) maps, and mADC values were measured. The mADC was determined per slice, followed by a calculation of whole tumor volume ADC mean using the individual mADC values. The Mann?Whitney test was performed to compare mADCs for the two groups. A receiver operating characteristic (ROC) curve was generated to determine the differentiating capacity of ADCs from MC to AC. Results: The mADC was higher in MC (1.631 ± 0.375 x 10-3 mm2/s) (range: 0.95-2.36 x 10-3 mm2/s) than in AC (0.921 ± 0.157 x 10-3 mm2/s) (range: 0.6-1.48 x 10-3 mm2/s) (P < 0.001). mADCs were effective in distinguishing MC from AC (area under the ROC curve, 0.972 (95% CI : 0.928-1.00)). A threshold of 1.27 x 10-3 mm2/s was set that corresponded with high sensitivity (94.4%) and specificity (97.7%). Twelve MCs (67%) were predominantly hypointense, and 6 MCs (33%) were seen as mixed signal intensity lesions. Forty ACs (91%) were observed as hyperintense lesions, and 4 ACs (9%) had mixed signal intensity. There was a significant difference in the signal intensities between MC and AC (c2 = 54.7, P < 0.001).Conclusion: MCs and ACs show different diffusion characteristics, which can be distinguished with high sensitivity and specificity and can help to improve prognostic treatment options.

adenocarcinoma
apparent diffusion coefficient
diffusion-weighted imaging
Rectal cancer
mucinous adenocarcinoma


Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity.

Abstract: Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people that are diagnosed with insulin resistance. Regular physical activity in both healthy and insulin-resistant individuals is recognized as the single most effective intervention to increase whole-body insulin sensitivity and thereby positively affect glucose homeostasis. A single bout of exercise has long been known to increase glucose disposal in skeletal muscle in response to physiological insulin concentrations. While this effect is identified to be restricted to the previously exercised muscle, the molecular basis for an apparent convergence between exercise- and insulin-induced signaling pathways is incompletely known. In recent years, we and others have identified the Rab GTPase-activating protein, TBC1 domain family member 4 (TBC1D4) as a target of key protein kinases in the insulin- and exercise-activated signaling pathways. Our working hypothesis is that the AMP-activated protein kinase (AMPK) is important for the ability of exercise to insulin sensitize skeletal muscle through TBC1D4. Here, we aim to provide an overview of the current available evidence linking AMPK to post-exercise insulin sensitivity.

Kjøbsted|Rasmus|R|
Wojtaszewski|Jørgen F P|JF|
Treebak|Jonas T|JT|

D055372:AMP-Activated Protein Kinases
D000249:Adenosine Monophosphate
D000620:Aminoimidazole Carboxamide
D015444:Exercise
D020690:GTPase-Activating Proteins
D005786:Gene Expression Regulation
D005947:Glucose
D006003:Glycogen
D006801:Humans
D007333:Insulin Resistance
D009119:Muscle Contraction
D018482:Muscle, Skeletal
D055503:Protein Multimerization
D021122:Protein Subunits
D012265:Ribonucleotides
D015398:Signal Transduction

AMP-activated protein kinase
Insulin sensitivity
Skeletal muscle
Exercise
TBC1D4
AS160
Glucose uptake


Interconnected Network of Core-Shell CoP@CoBiPi for Efficient Water Oxidation Electrocatalysis under Near Neutral Conditions.

Abstract: Developing earth-abundant electrocatalysts for efficient and stable water oxidation under near neutral conditions is of great importance but still remains a key challenge. Herein, we demonstrate the development of an interconnected network of core-shell CoP@CoBiPi through anodic polarization of a CoP nanoarray in potassium borate aqueous electrolyte (KBi). This 3 D CoP@CoBiPi exhibits high catalytic activity for water oxidation at pH 9.2 and needs an overpotential (η) of only 410 mV to drive a geometrical catalytic current density of 10 mA cm-2 , with a high turnover frequency of 819 h-1 at an overpotential of 610 mV. Remarkably, this catalyst also demonstrates high long-term electrochemical stability with its activity being maintained for at least 27 h in KBi. This study provides us an attractive earth-abundant 3 D catalyst electrode for water-splitting devices toward efficient and stable water oxidation under benign conditions.

Cui|Liang|L|
Qu|Fengli|F|
Liu|Jingquan|J|
Du|Gu|G|
Asiri|Abdullah M|AM|
Sun|Xuping|X|

core-shell
anodic polarization
cobalt phosphide
electrolysis
oxygen evolution


Amides and neolignans from the aerial parts of Piper bonii.

Abstract: Six amides, piperbonamides A-F, three neolignans piperbonins A-C, and 11 known compounds were isolated from the aerial parts of Piper bonii (Piperaceae). The structures of piperbonamides A-F and piperbonins A-C were elucidated based on the analysis of 1D and 2D NMR and MS data. Piperbonin A, (+)-trans-acuminatin, (+)-cis-acuminatin, (+)-kadsurenone, and pipernonaline showed weak activity against platelet aggregation with IC50 values of 118.2, 108.5, 90.02, 107.3, and 116.3 μM, respectively, as compared with the positive control, tirofiban, with an IC50 value of 5.24 μM. Piperbonamides A-F were inactive against five tumor cell lines at concentrations up to 40 μM.

Ding|Duo-Duo|DD| Wang|Yue-Hu|YH| Chen|Ya-Hui|YH| Mei|Ren-Qiang|RQ| Yang|Jun|J| Luo|Ji-Feng|JF| Li|Yan|Y| Long|Chun-Lin|CL| Kong|Yi|Y|

D004354:Drug Screening Assays, Antitumor

Amides
Neolignans
Piper bonii
Piperaceae
Antiplatelet


Bifurcation theory and cardiac arrhythmias.

Abstract: In this paper we review two types of dynamic behaviors defined by the bifurcation theory that are found to be particularly useful in describing two forms of cardiac electrical instabilities that are of considerable importance in cardiac arrhythmogenesis. The first is action potential duration (APD) alternans with an underlying dynamics consistent with the period doubling bifurcation theory. This form of electrical instability could lead to spatially discordant APD alternans leading to wavebreak and reentrant form of tachyarrhythmias. Factors that modulate the APD alternans are discussed. The second form of bifurcation of importance to cardiac arrhythmogenesis is the Hopf-homoclinic bifurcation that adequately describes the dynamics of the onset of early afterdepolarization (EAD)-mediated triggered activity (Hopf) that may cause ventricular tachycardia and ventricular fibrillation (VT/VF respectively). The self-termination of the triggered activity is compatible with the homoclinic bifurcation. Ionic and intracellular calcium dynamics underlying these dynamics are discussed using available experimental and simulation data. The dynamic analysis provides novel insights into the mechanisms of VT/VF, a major cause of sudden cardiac death in the US.

Karagueuzian|Hrayr S|HS|
Stepanyan|Hayk|H|
Mandel|William J|WJ|

Hopf-homoclinic bifurcation
early afterdepolarization
triggered activity
ventricular tachycardia
ventricular fibrillation
Period-doubling bifurcation
action potential duration alternans
reentry
spatially-discordant alternans


Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?

Abstract: The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

He|Zhen|Z| Li|Min|M| Zheng|Dongmei|D| Chen|Qing|Q| Liu|Wenwen|W| Feng|Li|L|

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

D042461:Vascular Endothelial Growth Factor A

Adipose tissue
Hypoxia
Inflammation
Glucose intolerance
Ethanol


Application of the Trivex system in the treatment of primary severe superficial varicose veins of the lower extremity.

Abstract:
Purpose
The aim of this study was to evaluate the clinical effects of the Trivex system in the treatment of primary severe superficial varicose veins of the lower extremity and compare Trivex to the point-form-stripping combined with foam sclerotherapy (FS).

Methods
A total of 64 patients (35 females, 29 males; mean age, 57 ± 11 years [range, 29-79 years]) with primary severe superficial varicose veins of the lower extremity involving 64 legs were included between October 2015 and July 2019. The maximum diameter of the vein branches was >20 mm, which appeared to be cystic dilatation and forms large-scale in the crus or the thigh. All patients underwent high ligation and endovenous laser ablation or stripping of the trunk under general anesthesia. The surgical time, pain/phlebitis, number of incisions, amount of bleeding, recurrence of varicose vein, incidence of surgical site infections (SSIs), satisfaction score, and improvement in clinical symptoms were evaluated respectively with the patients in two groups: Group A, with patients who underwent treatment with the Trivex system, and Group B, patients who underwent treatment by point-form-stripping combined with FS.

Results
All procedures were performed successfully. The average operative time in Group A was 56 ± 11 min, whereas that of Group B was 90 ± 33 min, which was a significant difference (p < 0.05). Group A patients felt little pain after surgery, whereas in Group B the level of pain peaked on postoperative day 30, mostly due to thrombophlebitis after FS. There was no recurrence of varicose vein was observed in any patient, however, there were some residual effects in Group B, including the amount of bleeding volume, in-hospital stays, pain/phlebitis, and number of incisions (P < 0.05). There were no significant differences with respect to SSIs, improvement in clinical symptoms, and satisfaction scores observed (p>0.05).

Conclusions
This study shows that patients benefited from both treatment options. However, primary severe superficial varicose veins of the lower extremity treated with the Trivex system suffered less pain with fewer incisions than severe branches treated with the point-form-stripping combined with foam sclerotherapy (FS). In summary, the Trivex system is a suitable treatment prior to point-form-stripping combined with foam sclerotherapy (FS) for those who demand a high level of appearance, and especially for young patients, the Trivex system is recommended.

Yu|Wenshui|W| Liu|Jing|J| Yang|Hongwei|H| Wang|Zuhui|Z| Xia|Yongdi|Y| Liu|Peijuan|P| Zhu|Guoxian|G|

Trivex system
Varicose veins
Point-form-stripping
Foam sclerotherapy


Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16.

Abstract: Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.

Bonfim|Caroline Measso do|CMD|
Monteleoni|Letícia Figueiredo|LF|
Calmon|Marília de Freitas|MF|
Cândido|Natália Maria|NM|
Provazzi|Paola Jocelan Scarin|PJS|
Lino|Vanesca de Souza|VS|
Rabachini|Tatiana|T|
Sichero|Laura|L|
Villa|Luisa Lina|LL|
Quintana|Silvana Maria|SM|
Melli|Patrícia Pereira Dos Santos|PPDS|
Primo|Fernando Lucas|FL|
Amantino|Camila Fernanda|CF|
Tedesco|Antonio Claudio|AC|
Boccardo|Enrique|E|
Rahal|Paula|P|

Vulvar intraepithelial neoplasia
HPV
nanoemulsion
curcumin and photodynamic therapy


Population representation of visual information in areas V1 and V2 of amblyopic macaques.

Abstract: Amblyopia is a developmental disorder resulting in poor vision in one eye. The mechanism by which input to the affected eye is prevented from reaching the level of awareness remains poorly understood. We recorded simultaneously from large populations of neurons in the supragranular layers of areas V1 and V2 in 6 macaques that were made amblyopic by rearing with artificial strabismus or anisometropia, and 1 normally reared control. In agreement with previous reports, we found that cortical neuronal signals driven through the amblyopic eyes were reduced, and that cortical neurons were on average more strongly driven by the non-amblyopic than by the amblyopic eyes. We analyzed multiunit recordings using standard population decoding methods, and found that visual signals from the amblyopic eye, while weakened, were not degraded enough to explain the behavioral deficits. Thus additional losses must arise in downstream processing. We tested the idea that under monocular viewing conditions, only signals from neurons dominated by - rather than driven by - the open eye might be used. This reduces the proportion of neuronal signals available from the amblyopic eye, and amplifies the interocular difference observed at the level of single neurons. We conclude that amblyopia might arise in part from degradation in the neuronal signals from the amblyopic eye, and in part from a reduction in the number of signals processed by downstream areas.

Shooner|Christopher|C|
Hallum|Luke E|LE|
Kumbhani|Romesh D|RD|
Ziemba|Corey M|CM|
Garcia-Marin|Virginia|V|
Kelly|Jenna G|JG|
Majaj|Najib J|NJ|
Movshon|J Anthony|JA|
Kiorpes|Lynne|L|

Amblyopia
Contrast sensitivity
Ocular dominance
Visual cortex


APPLICATION OF INTELLECTUAL MONITORING INFORMATION TECHNOLOGY IN DETERMINING THE SEVERITY OF THE CONDITION OF PATIENTS WITH INFLAMMATORY BOWEL DISEASES.

Abstract:
OBJECTIVE
The aim: Was to evaluate the effectiveness of the use of information technology of intelligent monitoring in solving the problems of assessing the morbidity of a patient with IBD during treatment.

PATIENTS AND METHODS
Matherials and methods: 183 patients with IBD were observed. Among them 104(56.8%) patients suffered from Crohn's disease and 79(43.1%) patients had ulcerative colitis. For each patient and each disease, the formation of a list of signs, the extraction of information and knowledge will be carried out according to an individual method. At the lower level, tasks are performed: determination of the list of patient morbidity conditions, the formation of a list of indicators of the patient morbidity conditions, their identification as classes for machine learning models; formation of a list of signs, which identify the state of the patient's morbidity and whose characteristics obtained after results of medical tests.

RESULTS
Results: The number of correctly classified points reached 92%. An analysis of the conditions of patients characterized by incorrectly classified points revealed the information content of this fact. In those cases when the classification results did not coincide with the expert assessment of the patient's condition, additional factors were found that influenced his condition and whose characteristics were not taken into account in the structure of classifier models.

CONCLUSION
Conclusions: The results of the testing of classifier models indicate the effectiveness of the use of information technology of intelligent monitoring to assess the condition of patients with IBD.

Dorofeyev|Andriy E|AE|
Holub|Sergiy V|SV|
Babayeva|Gulustan H|GH|
Аnaniin|Оleg Е|ОЕ|

D003093:Colitis, Ulcerative
D003424:Crohn Disease
D006801:Humans
D015212:Inflammatory Bowel Diseases
D000073256:Information Technology

Intellectual monitoring
information technology
inflammatory bowel diseases


Hypermethylation of Auxin-Responsive Motifs in the Promoters of the Transcription Factor Genes Accompanies the Somatic Embryogenesis Induction in Arabidopsis.

Abstract: The auxin-induced embryogenic reprogramming of plant somatic cells is associated with extensive modulation of the gene expression in which epigenetic modifications, including DNA methylation, seem to play a crucial role. However, the function of DNA methylation, including the role of auxin in epigenetic regulation of the SE-controlling genes, remains poorly understood. Hence, in the present study, we analysed the expression and methylation of the TF genes that play a critical regulatory role during SE induction (LEC1, LEC2, BBM, WUS and AGL15) in auxin-treated explants of Arabidopsis. The results showed that auxin treatment substantially affected both the expression and methylation patterns of the SE-involved TF genes in a concentration-dependent manner. The auxin treatment differentially modulated the methylation of the promoter (P) and gene body (GB) sequences of the SE-involved genes. Relevantly, the SE-effective auxin treatment (5.0 µM of 2,4-D) was associated with the stable hypermethylation of the P regions of the SE-involved genes and a significantly higher methylation of the P than the GB fragments was a characteristic feature of the embryogenic culture. The presence of auxin-responsive (AuxRE) motifs in the hypermethylated P regions suggests that auxin might substantially contribute to the DNA methylation-mediated control of the SE-involved genes.

Grzybkowska|Daria|D|
Nowak|Katarzyna|K|
Gaj|Małgorzata D|MD|0000-0003-2995-4134

somatic embryogenesis
DNA methylation
SE-related genes


Effect on anxiety and depression of a multifactorial risk factor intervention program after stroke and TIA: a randomized controlled trial.

Abstract:
OBJECTIVES
Depression and anxiety related to stroke are caused by vascular lesions and psychological reactions. Treatment of vascular and modifiable behavioral risk factors reduces the risk of stroke and may also reduce the risk of emotional changes after stroke. We aimed to investigate whether a multifactorial risk factor intervention program in patients with first-ever stroke or transient ischemic attack (TIA) can influence post-stroke anxiety and depressive symptoms in patients one year post-stroke.

METHOD
The study population consisted of first-ever stroke and TIA patients allocated in a randomized, evaluator-blinded, controlled trial to care as usual or a structured and multidisciplinary follow-up including intensive treatment of vascular risk. The primary endpoint (cognition) has previously been reported. The secondary endpoint, reported here, was changes in the Hospital Anxiety and Depression Scale (HADS) from baseline to 12-month follow-up.

RESULTS
One hundred and ninety-five patients were randomized. The estimated difference between treatment groups, in changes in HADS, from baseline to 12 months was -1.32 (95% confidence interval: -2.61, -0.04; P = 0.044) in favor of the intervention group. One year post-stroke, 4/85 (4.7%) patients in the intervention group and 12/89 (13.5%) in the control group suffered from depression (P = 0.045), while 7/85 (8.2%) patients in the intervention group and 13/89 (14.6%) patients in the control group suffered from anxiety (P = 0.19).

CONCLUSION
A structured, multidisciplinary, multifactorial risk factor program including vascular risk factor management may be associated with reduced HADS scores and a lower prevalence of depressive symptoms one year after stroke.

Ihle-Hansen|Hege|H|
Thommessen|Bente|B|
Fagerland|Morten Wang|MW|
Oksengård|Anne Rita|AR|
Wyller|Torgeir Bruun|TB|
Engedal|Knut|K|
Fure|Brynjar|B|

D011569:Psychiatric Status Rating Scales

anxiety
depression
anxiety and trauma related disorders
mood disorders
psychosocial interventions
training and educational programs


Validation of the Health Literacy in Dentistry scale in Brazilian adults.

Abstract:
OBJECTIVES
To perform cross-cultural adaptation and validation of the Health Literacy Dental scale (HeLD) in Brazilian adults.

METHODS
The HeLD instrument was translated and cross-culturally adapted to the Brazilian Portuguese language to create longer (HeLD-29) and shorter (HeLD-14) versions. The reliability and validity of these versions were assessed in a sample of 603 adults living near six primary care units in the city of Piracicaba, São Paulo, Brazil.

RESULTS
Both versions of HeLD demonstrated high internal reliability, acceptable convergent validity and discriminant validity. However, the confirmatory factor analysis showed that only HeLD-14 demonstrated satisfactory goodness of fit. There were associations between HeLD-14 scores and social demographic characteristics, general and oral health and oral health-related behaviours. Higher scores were observed for the total HeLD-14 and/or individual components of HeLD-14 among women, ethnic white subjects, those with high educational attainment, those with higher income, those reporting toothbrushing twice or more daily, regular dental attenders, those who usually attended for dental care for a check-up, those with excellent or very good self-ratings of general health, those with excellent or very good self-ratings of oral health, and those without tooth extraction and oral health impact.

CONCLUSION
The Brazilian version of HeLD-14 was demonstrated to be a reliable and valid instrument for measuring broad aspects of oral health literacy in the adult Brazilian population.

validity
reliability
Oral health
oral health literacy


Partial sequencing of the VP2 capsid gene for direct enterovirus genotyping in clinical specimens.

Abstract: Typing of human enterovirus (EV) remains a major goal for diagnostic and epidemiological purposes. Whereas sequencing of the VP1 coding region is the reference standard for EV typing, a method relying on sequencing of the VP2 coding region has been proposed as an alternative; however, this has been validated only on cell culture supernatants. To avoid the selection of cultivable strains and to quicken the identification step, a new semi-nested PCR method targeting the VP2 region was developed by use of the CODEHOP strategy. After validation of the method on reference and clinical strains, a total of 352 clinical specimens found to be positive for EV RNA (138 with the GeneXpert EV kit and 214 with the Enterovirus R-gene kit) during a 3-year period (2010-2012) were analysed prospectively for VP2 genotyping. Overall, 204 (58%) specimens were typeable. A higher proportion of throat swab/stool specimens than of cerebrospinal fluid (CSF) specimens was found to be typeable (94 of 142 (66.2%) vs. 83 of 169 (49.1%), respectively, p <0.01 by the chi-square test). Moreover, the median Ct value obtained was lower for typeable specimens than for untypeable specimens (32.20 vs. 33.01, p <0.05, and 25.96 vs. 31.74, p <0.001, for the GeneXpert and R-gene tests, respectively, by the Mann-Whitney-Wilcoxon test). These results suggest that, in cases of EV meningitis, a peripheral specimen (i.e. throat swab or stool) that is susceptible to exhibiting a higher viral load should be used in preference to CSF for identifying the causative EV genotype by use of the VP2 typing method without cell culture isolation.

Ibrahim|W|W| Boukhadra|N|N| Nasri-Zoghlami|D|D| Berthelot|P|P| Omar|S|S| Bourlet|T|T| Pozzetto|B|B| Pillet|S|S|

D036022:Capsid Proteins
D002555:Cerebrospinal Fluid
D004770:Enterovirus
D004769:Enterovirus Infections
D005838:Genotype
D060005:Genotyping Techniques
D006801:Humans
D008969:Molecular Sequence Data
D010614:Pharynx
D016133:Polymerase Chain Reaction
D011446:Prospective Studies
D012367:RNA, Viral
D012680:Sensitivity and Specificity
D017422:Sequence Analysis, DNA

Clinical specimen
human enterovirus
viral load
typing method
VP2 capsid protein
molecular epidemiology


NavWell: A simplified virtual-reality platform for spatial navigation and memory experiments.

Abstract: Being able to navigate, recall important locations, and find the way home are critical skills, essential for survival for both humans and animals. These skills can be examined in the laboratory using the Morris water maze, often considered the gold standard test of animal navigation. In this task, animals are required to locate and recall the location of an escape platform hidden in a pool filled with water. Because animals can not see the platform directly, they must use various landmarks in the environment to escape. With recent advances in technology and virtual reality (VR), many tasks originally used in the animal literature can now be translated for human studies. The virtual water maze task is no exception. However, a number of issues are associated with these mazes, including cost, lack of flexibility, and lack of standardization in terms of experimental designs and procedures. Here we present a virtual water maze system (NavWell) that is readily downloadable and free to use. The system allows for the easy design of experiments and the testing of participants on a desktop computer or fully immersive VR environment. The data from four independent experiments are presented in order to validate the software. From these experiments, a set of procedures for use with a number of well-known memory tests is suggested. This potentially can help with the standardization of navigational research and with navigational testing in the clinic or in an educational environment. Finally, we discuss the limitations of the software and plans for its development and future use.

Commins|Sean|S|0000-0002-1161-1398 Duffin|Joseph|J| Chaves|Keylor|K| Leahy|Diarmuid|D| Corcoran|Kevin|K| Caffrey|Michelle|M| Keenan|Lisa|L| Finan|Deirdre|D| Thornberry|Conor|C|

Spatial
Navigation
Memory
Water maze
Virtual reality


Types of nasal delivery drugs and medications in Iranian traditional medicine to treatment of headache.

Abstract:
CONTEXT
Headache is a common symptom throughout the world. The main purpose of patient-centered approaches is the utilization of useful and simple treatment. Nowadays, there is a rising propensity toward herbal remedies. Nasal route is one of the ancient and topical prescriptions used in headache. In Iranian traditional medicine, physicians such as Avicenna were prescribing herbal drugs through the nose to treat a variety of central nervous system diseases like headache. In this review paper, authors have attempted to introduce different types of nasal administrations which were used in Iranian traditional medicine for the treatment of headaches.

EVIDENCE ACQUISITION
Initially, we studied two different types of Canon and separated all herbs used in the treatment of headache. Next, all plants were classified according to the method of prescription. Then, we pick out all the plants which were nasally utilized in the treatment of headache and divided them based on the method of administration. In order to find scientific names of herbs, we used two different botany references. Moreover, we conducted various researches in scientific databases with the aim of finding results concerning the analgesic and antinociceptive effects of herbs. Throughout the research, key terms were "analgesic" and "antinociceptive "with the scientific names of all herbs separately. The databases searched included PubMed, Scopus, Cochrane library and SID.

RESULTS
35 plants were prescribed for the treatment of headaches, which were all nasally used. These plants took either the form of powder, liquid or gas (steam). They were divided in to six categories according to the method of prescription. The Percentage of usage for each method was as follows: 62% Saoot (nasal drop), 25% Shamoom (smell), 17% Inkabab (vapor), 11% Nafookh (snuff), 11% Nashooq (inhaling) and 2% Bokhoor (smoke).

CONCLUSIONS
Medications that are used via nasal delivery have greater effect than oral medications. Iranian physicians were fully aware of systemic effects of topical medications, including prescription drugs through the nose. The study of ancient medical texts helps us in identification of herbal medicine and the investigation of new way for the preparation of drugs.

Ghorbanifar|Zahra|Z|
Delavar Kasmaei|Hosein|H|
Minaei|Bagher|B|
Rezaeizadeh|Hossein|H|
Zayeri|Farid|F|

Headache
Nose
Analgesics
Herbal Medicine


Using Salivary MMP-9 to Successfully Quantify Periodontal Inflammation during Orthodontic Treatment.

Abstract: Periodontitis is one of the most common immune-mediated inflammatory conditions resulting in progressive destruction of periodontium. Metalloproteinase-9 (MMP-9), an enzyme that is involved in the degradation of gelatin and collagen and present in the gingival crevicular fluid, is markedly increased in periodontitis. The aim of the study is to evaluate the effects of periodontal treatment either alone or in combination with orthodontic treatment on MMP-9 levels. In this study, 60 individuals were subjected to periodontal treatment (PD) or periodontal treatment combined with orthodontic treatment (POD). Both periodontal and periodontal plus orthodontic treatments significantly improved clinical parameters and lowered MMP-9 levels compared to control group. However, the combination of periodontal with orthodontic treatment further improved clinical parameters and enhanced the lowering effect on MMP-9 levels compared to periodontal or control groups alone. Finally, the degree of malocclusion significantly affected the effect of the treatment on MPP-9 levels with PD treatment having the most pronounced effect. We concluded that salivary MMP-9 can serve to accurately predict the level of inflammation in affected periodontal tissues during orthodontic treatment that is also associated with the type of malocclusion, making it a viable diagnosis tool in monitoring the progression of the periodontium during orthodontic treatment.

Luchian|Ionut|I| Moscalu|Mihaela|M|0000-0002-8899-8594 Goriuc|Ancuta|A| Nucci|Ludovica|L| Tatarciuc|Monica|M| Martu|Ioana|I| Covasa|Mihai|M|

periodontitis
matrix metalloproteinase
saliva


Carbides and possible hydrogen irreversible trapping sites in ultrahigh strength round steel.

Abstract: The carbides in ultrahigh strength round steel have been investigated by using laser-assisted atom probe tomography (APT) and high resolution transmission electron microscopy (HRTEM) in this paper. Two kinds of carbides are found and one is iron carbide M6C, where carbide formation elements Cr, Mn and Mo replace partial Fe, while the other is niobium carbide MC, where M includes V and Mo besides Nb. These two carbides, due to their different evaporation field, have various densities in reconstructed image of APT. After correction, the hydrogen content within these two carbides illustrates that M6C cannot trap hydrogen, while MC can. The different behaviors in trapping hydrogen between these two carbides may result from elements Fe or Cr in M6C carbide having weaker affinity for hydrogen than Nb and V have in MC.

Carbide
Hydrogen
Irreversible trapping site
Ultrahigh strength round steel
Atom probe tomography


Solitary castrate-resistant prostate cancer metastasis to adrenal gland with concordant intense avidity on PSMA and FDG PET.

Abstract: Isolated prostate cancer metastasis to the adrenal gland is rare. We report a case of concordant high uptake in a solitary adrenal metastasis on both prostate-specific membrane antigen and fluorodeoxyglucose positron-emission tomography in a patient with castrate-resistant prostate cancer. Good initial biochemical response was achieved with laparoscopic adrenalectomy. The patient developed lymph node recurrence 12 months later, although remains asymptomatic on hormonal treatment 22 months post-operatively, in keeping with prior results for metastasis-directed therapy which can delay time to additional treatment. Application of dual tracer PET can be valuable for prostate cancer staging and guidance of metastasis-directed treatment.

McGeorge|Stephen|S|
Phillips|Reece|R|
Rukin|Nicholas J|NJ|
Reynolds|Jamie|J|
Roberts|Matthew J|MJ|

Prostate cancer
PSMA
FDG
Fluorodeoxyglucose
Adrenalectomy
Prostate specific membrane antigen


Training Young Russian Physicians in Uganda: A Unique Program for Introducing Global Health Education in Russia.

Abstract:
BACKGROUND
Global health is a new concept in Russia. There has been an ongoing academic collaboration between the Yale School of Medicine in the United States and Makerere University College of Health Sciences in Uganda since 2010, and the US Western Connecticut Health Network/University of Vermont College of Medicine since 2012, to introduce global health concepts to Kazan State Medical University (KSMU) in Russia. The purpose was to educate Russian physicians and medical trainees about the practice of clinical medicine and medical education, as well as the general practice of global health in culturally diverse, resource-limited settings.

OBJECTIVES
The aim of this study was to evaluate the initial outcomes of this multi-institutional partnership and to assess the impact of the global health elective on the participants and on KSMU.

METHODS
Participants were selected to attend a 6-week elective in global health at Mulago Hospital in Kampala, Uganda. The elective consisted of clinical experience, education about Uganda's common diseases, and region-specific sociocultural classes. It included a predeparture orientation and, upon return, completion of a standard questionnaire to assess the program's impact.

RESULTS
Since 2010, there have been 20 KSMU members (4 medical students, 4 interns, 9 residents, 2 fellows, and 1 faculty member) who have participated in the program. As a result of the elective, the participants reported increased knowledge of tropical medicine (70%) and HIV/AIDS (75%), and 95% reported increased cultural sensitivity and desire to work with the underserved. The majority noted a very positive impact of their careers (90%) and personal life (80%). KSMU established the first successful collaborative program in global health education in Russia, leading to the integration of tropical medicine and global health courses in medical school curriculum.

CONCLUSION
This elective has proven highly effective in introducing the concept of global health to faculty, fellows, residents, and medical students at KSMU. It trained these participants to address the challenges faced by physicians in culturally diverse and resource-limited countries.

Ziganshin|Bulat A|BA|
Yausheva|Liliya M|LM|
Sadigh|Mitra|M|
Ziganshina|Anna P|AP|
Pichugin|Arseniy A|AA|
Ziganshin|Ayrat U|AU|
Sadigh|Majid|M|

individual and institutional effects on global health electives


Teaching Veterinary Histopathology: A Comparison of Microscopy and Digital Slides.

Abstract: Virtual microscopy using digitized slides has become more widespread in teaching in recent years. There have been no direct comparisons of the use of virtual microscopy and the use of microscopes and glass slides. Third-year veterinary students from two different schools completed a simple objective test, covering aspects of histology and histopathology, before and after a practical class covering relevant material presented as either glass slides viewed with a microscope or as digital slides. There was an overall improvement in performance by students at both veterinary schools using both practical formats. Neither format was consistently better than the other, and neither school consistently outperformed the other. In a comparison of student appraisal of use of digital slides and microscopes, the digital technology was identified as having many advantages.

Brown|Peter J|PJ|
Fews|Debra|D|
Bell|Nick J|NJ|

histology
assessment
clinical pathology
educational methods
pathology


Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells.

Abstract: The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigen-presenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS.

Rodríguez-Lorenzo|Sabela|S|
Konings|Julia|J|
van der Pol|Susanne|S|
Kamermans|Alwin|A|
Amor|Sandra|S|
van Horssen|Jack|J|
Witte|Maarten E|ME|
Kooij|Gijs|G|
de Vries|Helga E|HE|0000-0001-7904-7124

D020528:Multiple Sclerosis, Chronic Progressive

Choroid plexus
Granulocytes
T cells
Immune cells
Progressive MS
Blood-CSF barrier


Genome sequencing and analysis of a granulovirus isolated from the Asiatic rice leafroller, Cnaphalocrocis medinalis.

Abstract: The complete genome of Cnaphalocrocis medinalis granulovirus (CnmeGV) from a serious migratory rice pest, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), was sequenced using the Roche 454 Genome Sequencer FLX system (GS FLX) with shotgun strategy and assembled by Roche GS De Novo assembler software. Its circular double-stranded genome is 111,246 bp in size with a high A+T content of 64.8% and codes for 118 putative open reading frames (ORFs). It contains 37 conserved baculovirus core ORFs, 13 unique ORFs, 26 ORFs that were found in all Lepidoptera baculoviruses and 42 common ORFs. The analysis of nucleotide sequence repeats revealed that the CnmeGV genome differs from the rest of sequenced GVs by a 23 kb and a 17kb gene block inversions, and does not contain any typical homologous region (hr) except for a region of non-hr-like sequence. Chitinase and cathepsin genes, which are reported to have major roles in the liquefaction of the hosts, were not found in the CnmeGV genome, which explains why CnmeGV infected insects do not show the phenotype of typical liquefaction. Phylogenetic analysis, based on the 37 core baculovirus genes, indicates that CnmeGV is closely related to Adoxophyes orana granulovirus. The genome analysis would contribute to the functional research of CnmeGV, and would benefit to the utilization of CnmeGV as pest control reagent for rice production.

Zhang|Shan|S| Zhu|Zheng|Z| Sun|Shifeng|S| Chen|Qijin|Q| Deng|Fei|F| Yang|Kai|K|

D000595:Amino Acid Sequence
D000818:Animals
D001482:Base Composition
D001483:Base Sequence
D004261:DNA Replication
D005814:Genes, Viral
D016679:Genome, Viral
D025722:Granulovirus
D007915:Lepidoptera
D008969:Molecular Sequence Data
D016366:Open Reading Frames
D012275:Oryza
D016415:Sequence Alignment
D017422:Sequence Analysis, DNA
D014764:Viral Proteins


A guide to the external review of an academic radiology department.

Abstract: External reviews are used to evaluate a department on a routine basis or prior to reappointment or recruitment of a department chair. The Society of Chairs of Academic Radiology Departments (SCARD) developed a template that outlines important components of an external review report and a table that outlines the objective information that can be requested from the institution/department prior to the reviewer's site visit. The template is meant to facilitate a high-quality review and serve as a guide to a chair who is preparing for his/her first review, chairs who serve as external consultants, and institutional officials seeking review of a radiology department.

Collins|Jannette|J|
Amis|E Stephen|ES|
Beauchamp|Norman J|NJ|
Norbash|Alexander M|AM|
Meltzer|Carolyn C|CC|
|||

D000046:Academic Medical Centers
D000465:Algorithms
D010380:Peer Review
D015397:Program Evaluation
D011785:Quality Assurance, Health Care
D011872:Radiology Department, Hospital
D014481:United States

External Review
Radiology Department Review


Bilateral practice improves dominant leg performance in long jump.

Abstract: Benefits of bilateral practice both for the non-dominant and for the dominant body side have been shown in several studies. Thereby, most of the studies included movement tasks of the upper extremity or investigated sports games in which the ability of acting bilaterally is an essential basis for success and, thus, a bilateral practice is reasonable anyway. Individual unilaterally performed sports including movement tasks of the lower extremity are rarely investigated. Therefore, the aim of our study was to test if contralateral transfer due to bilateral practice can be found in an unilaterally performed sport including the lower extremity. We trained and tested 61 adolescent athletes in long jump to compare the jumping performance of the dominant leg after a 12-week practice period between two groups: a bilateral practice group that practiced specific long jump exercises with both the dominant and non-dominant leg and an unilateral practice group that practiced specific long jump exercises only with the dominant leg. Results showed a superior effect of bilateral practice compared to unilateral practice regarding the jumping performance of the dominant leg. The performance increase at post-test and retention-test for the dominant limb was significantly higher for the bilateral practice group (pre-to-post: 5.2%, pre-to-retention: 7.4%) compared to the unilateral practice group (pre-to-post: 3.4%, pre-to-retention: 4.5%). Thus, bilateral practice should be established in the early practice programmes of track and field athletes to improve the performance of the dominant take-off leg.

Focke|Anne|A| Spancken|Sina|S| Stockinger|Christian|C| Thürer|Benjamin|B| Stein|Thorsten|T|

lower extremity
contralateral transfer
Bilateral transfer
bilateral training
crosslimb education


The Association between State Policy Environments and Self-Rated Health Disparities for Sexual Minorities in the United States.

Abstract: A large body of research has documented disparities in health and access to care for lesbian, gay, and bisexual (LGB) people in the United States. Less research has examined how the level of legal protection afforded to LGB people (the state policy environment) affects health disparities for sexual minorities. This study used data on 14,687 sexual minority adults and 490,071 heterosexual adults from the 2014⁻2016 Behavioral Risk Factor Surveillance System to document differences in health. Unadjusted state-specific prevalence estimates and multivariable logistic regression models were used to compare poor/fair self-rated health by gender, sexual minority status, and state policy environments (comprehensive versus limited protections for LGB people). We found disparities in self-rated health between sexual minority adults and heterosexual adults in most states. On average, sexual minority men in states with limited protections and sexual minority women in states with either comprehensive or limited protections were more likely to report poor/fair self-rated health compared to their heterosexual counterparts. This study adds new findings on the association between state policy environments and self-rated health for sexual minorities and suggests differences in this relationship by gender. The associations and impacts of state-specific policies affecting LGB populations may vary by gender, as well as other intersectional identities.

D040343:Behavioral Risk Factor Surveillance System

state policy
health disparities
LGBT health
health policy


EFFECT OF BREASTFEEDING ON GASTROINTESTINAL INFECTION IN INFANTS: A TARGETED MAXIMUM LIKELIHOOD APPROACH FOR CLUSTERED LONGITUDINAL DATA.

Abstract: The PROmotion of Breastfeeding Intervention Trial (PROBIT) cluster-randomized a program encouraging breastfeeding to new mothers in hospital centers. The original studies indicated that this intervention successfully increased duration of breastfeeding and lowered rates of gastrointestinal tract infections in newborns. Additional scientific and popular interest lies in determining the causal effect of longer breastfeeding on gastrointestinal infection. In this study, we estimate the expected infection count under various lengths of breastfeeding in order to estimate the effect of breastfeeding duration on infection. Due to the presence of baseline and time-dependent confounding, specialized "causal" estimation methods are required. We demonstrate the double-robust method of Targeted Maximum Likelihood Estimation (TMLE) in the context of this application and review some related methods and the adjustments required to account for clustering. We compare TMLE (implemented both parametrically and using a data-adaptive algorithm) to other causal methods for this example. In addition, we conduct a simulation study to determine (1) the effectiveness of controlling for clustering indicators when cluster-specific confounders are unmeasured and (2) the importance of using data-adaptive TMLE.

Schnitzer|Mireille E|ME|
van der Laan|Mark J|MJ|
Moodie|Erica E M|EE|
Platt|Robert W|RW|

Causal inference
G-computation
inverse probability weighting
marginal effects
missing data
pediatrics


Hemicholinium-3 sensitive choline transport in human T lymphocytes: Evidence for use as a proxy for brain choline transporter (CHT) capacity.

Abstract: The synaptic uptake of choline via the high-affinity, hemicholinium-3-dependent choline transporter (CHT) strongly influences the capacity of cholinergic neurons to sustain acetylcholine (ACh) synthesis and release. To advance research on the impact of CHT capacity in humans, we established the presence of the neuronal CHT protein in human T lymphocytes. Next, we demonstrated CHT-mediated choline transport in human T cells. To address the validity of T cell-based choline uptake as a proxy for brain CHT capacity, we isolated T cells from the spleen, and synaptosomes from cortex and striatum, of wild type and CHT-overexpressing mice (CHT-OXP). Choline uptake capacity in T cells from CHT-OXP mice was two-fold higher than in wild type mice, mirroring the impact of CHT over-expression on synaptosomal CHT-mediated choline uptake. Monitoring T lymphocyte CHT protein and activity may be useful for estimating human CNS cholinergic capacity and for testing hypotheses concerning the contribution of CHT and, more generally, ACh signaling in cognition, neuroinflammation and disease.

Koshy Cherian|Ajeesh|A|
Parikh|Vinay|V|
Wu|Qi|Q|
Mao-Draayer|Yang|Y|
Wang|Qin|Q|
Blakely|Randy D|RD|
Sarter|Martin|M|

Choline transporter
T lymphocytes
Acetylcholine
Synaptosomes
Genetic CHT variants


Experience: developing an inpatient malnutrition checklist for children 6 to 59 months to improve WHO protocol adherence and facilitate quality improvement in a low-resource setting.

Abstract: In low-resource settings, inpatient case fatality for severe acute malnutrition (SAM) remains high despite evidenced-based protocols and resources to treat SAM. Key reasons include a combination of insufficiently trained staff, poor teamwork and inadequate compliance to WHO treatment guidelines which are proven to reduce mortality. Checklists have been used in surgery and obstetrics to ameliorate similarly complicated yet repetitive work processes and may be a key strategy to improving inpatient SAM protocol adherence and reducing unnecessary death. Here, we share our experience developing and piloting an inpatient malnutrition checklist (MLNC) for children 6 to 59 months and associated scoring system to coordinate care delivery, improve team documentation, strengthen WHO malnutrition protocol adherence and facilitate quality improvement in a district hospital in rural Rwanda. MLNC was developed after careful review of the 2009 Rwandan National Nutrition Protocol and 2013 WHO malnutrition guidelines. Critical steps were harmonized, extracted and designed into an initial MLNC with input from pediatric ward nurses, doctors, a locally based pediatrician and a registered dietitian. A scoring system was developed to facilitate quality improvement. Using the standard Plan-Do-Study-Act cycle, MLNC was modified and progress assessed on a monthly to bimonthly basis. Significant modifications occurred in the first 6 months of piloting including incorporation of treatment reminders and formatting improvements, as well as initiation of the MLNC from the emergency department. The MLNC is the first checklist to be developed that unifies WHO 10 steps of treatment of inpatient SAM with local standards. Anecdotally, MLNC was observed to identify gaps in key malnutrition care, promote protocol adherence and facilitate quality improvement. Data gathering on the MLNC local facility impact is underway. Collaborative international efforts are needed to create an inpatient malnutrition checklist for wider use to improve quality and reduce unnecessary, facility-based child mortality.

Malnutrition
checklists
quality improvement
low-resource setting
under-5 mortality


Failure of Traditional Risk Factors to Adequately Predict Cardiovascular Events in Older Populations.

Abstract:
BACKGROUND
Accurate assessment of atherosclerotic cardiovascular disease (ASCVD) risk across heterogeneous populations is needed for effective primary prevention. Little is known about the performance of standard cardiovascular risk factors in older adults.

OBJECTIVE
To evaluate the performance of the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) risk model, as well as the underlying cardiovascular risk factors, among adults older than 65 years.

DESIGN AND SETTING
Retrospective cohort derived from a regional referral system's electronic medical records.

PARTICIPANTS
A total of 25 349 patients who were 65 years or older at study baseline (date of the first outpatient lipid panel taken between 2007 and 2010).

MEASUREMENTS
Exposures of interest were traditional cardiovascular risk factors, as defined by inclusion in the PCE model. The primary outcome was major ASCVD events, defined as a composite of myocardial infarctions, stroke, and cardiovascular death.

RESULTS
The PCE and internally estimated models produced similar risk distributions for white men aged 65 to 74 years. For all other groups, PCE predictions were generally lower than those of the internal models, particularly for African Americans. Discrimination of the PCE was poor for all age groups, with concordance index (95% confidence interval) estimates of 0.62 (0.60-0.64), 0.56 (0.54-0.57), and 0.52 (0.49-0.54) among patients aged 65 to 74, 75 to 84, and 85 years and older, respectively. Reestimating relationships within these age groups resulted in better calibration but negligible improvements in discrimination. Blood pressure, total cholesterol, and diabetes either were not associated at all or had inverse associations in the older age groups.

CONCLUSION
Traditional clinical risk factors for cardiovascular disease failed to accurately characterize risk in a contemporary population of Medicare-aged patients. Among those aged 85 years and older, some traditional risk factors were not associated with ASCVD events. Better risk models are needed to appropriately inform treatment decision making for the growing population of older adults. J Am Geriatr Soc 68:754-761, 2020.

Dalton|Jarrod E|JE|0000-0001-8336-1212
Rothberg|Michael B|MB|
Dawson|Neal V|NV|
Krieger|Nikolas I|NI|
Zidar|David A|DA|
Perzynski|Adam T|AT|

older adults
model validation
risk heterogeneity
risk prediction


Postcesarean Section Skin-to-Skin Contact of Mother and Child.

Abstract: The first hour postpartum is critical for long-term, healthy development. At 12 de Octubre Hospital, Madrid, Spain, we developed and implemented a multidisciplinary strategy based on a consensual, participatory protocol for all health care professionals involved in cesarean deliveries. Our aims were 2-fold: the initiation of skin-to-skin (StS) contact with the newborn immediately after birth, regardless of the feeding method chosen, and the recognition of the importance of a companion present for support during the cesarean section (father or other designated by the mother). The objective of this article is to describe a policy developed to ensure timely postcesarean StS contact. Our protocol for neonatal StS contact with the mother is based on reported benefits found in literature, the World Health Organization's international recommendations, and deep respect for a process that is both natural and instinctive. We call it "humanizing the cesarean."

de Alba-Romero|Concepción|C|
Camaño-Gutiérrez|Isabel|I|
López-Hernández|Paloma|P|
de Castro-Fernández|Javier|J|
Barbero-Casado|Patricia|P|
Salcedo-Vázquez|Maria Luisa|ML|
Sánchez-López|Dolores|D|
Cantero-Arribas|Pilar|P|
Moral-Pumarega|Maria Teresa|MT|
Pallás-Alonso|Carmen Rosa|CR|

skin-to-skin
cesarean section
Baby-Friendly Hospital Initiative
bonding
breastfeeding
early StS contact


Ectopic thymus as a cause of Horner's syndrome.

Abstract: Ectopy of the thymus is a rare anomaly arising during fetal development, where the thymus does not make a complete decent into the thoracic cavity where it should involute in adolescence. The most common complications of an ectopic thymus include tracheal or esophageal compression presenting in childhood. This is a report of a single case of ectopic cervical thymus identified in a 2-month-old infant presenting with Horner's syndrome. Thymic ectopy should be on the differential when performing a radiologic evaluation of a neck mass when imaging characteristics are similar to thymic tissue.

Berroth|Margeaux L|ML|
Morozova|Lyudmila V|LV|
Pollock|Jeffery M|JM|

Ectopic
Thymus
Horner's syndrome
Pediatrics


An Investigation on the Effect of Extremely Low Frequency Pulsed Electromagnetic Fields on Human Electrocardiograms (ECGs).

Abstract: For this investigation, we studied the effects of extremely low frequency pulse electromagnetic fields (ELF-PEMF) on the human cardiac signal. Electrocardiograms (ECGs) of 22 healthy volunteers before and after a short duration of ELF-PEMF exposure were recorded. The experiment was conducted under single-blind conditions. The root mean square (RMS) value of the recorded data was considered as comparison criteria. We also measured and analysed four important ECG time intervals before and after ELF-PEMF exposure. Results revealed that the RMS value of the ECG recordings from 18 participants (81.8% of the total participants) increased with a mean value of 3.72%. The increase in ECG voltage levels was then verified by a second experimental protocol with a control exposure. In addition to this, we used hyperbolic T-distributions (HTD) in the analysis of ECG signals to verify the change in the RR interval. It was found that there were small shifts in the frequency-domain signal before and after EMF exposure. This shift has an influence on all frequency components of the ECG signals, as all spectrums were shifted. It is shown from this investigation that a short time exposure to ELF-PEMF can affect the properties of ECG signals. Further study is needed to consolidate this finding and discover more on the biological effects of ELF-PEMF on human physiological processes.

Fang|Qiang|Q|
Mahmoud|Seedahmed S|SS|
Yan|Jiayong|J|
Li|Hui|H|


Basic Accountability to Stop Ill-Treatment (BASI); Study Protocol for a Cluster Randomized Controlled Trial in Rural Tanzania.

Abstract: Background: Poor health system experiences negatively affect the lives of poor people throughout the world. In East Africa, there is a growing body of evidence of poor quality care that in some cases is so poor that it is disrespectful or abusive. This study will assess whether community feedback through report cards (with and without non-financial rewards) can improve patient experience, which includes aspects of patient dignity, autonomy, confidentiality, communication, timely attention, quality of basic amenities, and social support. Methods/Design: This cluster-randomized controlled study will randomize 75 primary health care facilities in rural Pwani Region, Tanzania to one of three arms: private feedback (intervention), social recognition reward through public reporting (intervention), or no feedback (control). Within both intervention arms, we will give the providers at the study facilities feedback on the quality of patient experience the facility provides (aggregate results from all providers) using data from patient surveys. The quality indicators that we report will address specific experiences, be observable by patients, fall into well-identified domains of patient experience, and be within the realm of action by healthcare providers. For example, we will measure the proportion of patients who report that providers definitely "explained things in a way that was easy to understand." This feedback will be delivered by a medical doctor to all the providers at the facility in a small group session. A formal discussion guide will be used. Facilities randomized to the social recognition intervention reward arm will have two additional opportunities for social recognition. First, a poster that displays their achieved level of patient experience will be publicly posted at the health facility and village government offices. Second, recognition from senior officials at the local NGO and/or the Ministry of Health will be given to the facility with the best or most-improved patient experience ratings at endline. We will use surveys with parents/guardians of sick children to measure patient experience, and surveys with healthcare providers to assess potential mechanisms of effect. Conclusion: Results from this study will provide evidence for whether, and through what mechanisms, patient reported feedback can affect interpersonal quality of care. Pan African Clinical Trials Registry (PACTR): 201710002649121 Protocol version 7, November 8, 2017.

Mbatia|Redempta|R| Cohen|Jessica|J| Zuakulu|Martin|M| Bukuku|Appolinary|A| Chandarana|Shikha|S| Eliakimu|Eliudi|E| Moshi|Sisty|S| Larson|Elysia|E|

accountability
report cards
patient experience
cluster randomized trials
quality of health care