A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita.

Abstract:
BACKGROUND
Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment.

RESULTS
A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle.

CONCLUSIONS
Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.

Phani|Victor|V|
Somvanshi|Vishal S|VS|
Shukla|Rohit N|RN|
Davies|Keith G|KG|
Rao|Uma|U|

Transcriptome
Pasteuria penetrans
Meloidogyne incognita
Root-knot nematode
Endospores


Short-term exposure to ambient air pollution and circulating biomarkers of endothelial cell activation: The Framingham Heart Study.

Abstract:
BACKGROUND
Short-term exposure to air pollution has been associated with cardiovascular events, potentially by promoting endothelial cell activation and inflammation. A few large-scale studies have examined the associations and have had mixed results.

METHODS
We included 3820 non-current smoking participants (mean age 56 years, 54% women) from the Framingham Offspring cohort examinations 7 (1998-2001) and 8 (2005-2008), and Third Generation cohort examination 1 (2002-2005), who lived within 50 km of a central monitoring station. We calculated the 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), and ozone before examination visits. We used linear mixed effect models for P-selectin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1, lipoprotein-associated phospholipase A2 activity and mass, and osteoprotegerin that were measured up to twice, and linear regression models for CD40 ligand and interleukin-18 that were measured once, adjusting for demographics, life style and clinical factors, socioeconomic position, time, and meteorology.

RESULTS
We found negative associations of PM2.5 and BC with P-selectin, of ozone with MCP-1, and of SO42- and NOx with osteoprotegerin. At the 5-day moving average, a 5 µg/m3 higher PM2.5 was associated with 1.6% (95% CI: - 2.8, - 0.3) lower levels of P-selectin; a 10 ppb higher ozone was associated with 1.7% (95% CI: - 3.2, - 0.1) lower levels of MCP-1; and a 20 ppb higher NOx was associated with 2.0% (95% CI: - 3.6, - 0.4) lower levels of osteoprotegerin.

CONCLUSIONS
We did not find evidence of positive associations between short-term air pollution exposure and endothelial cell activation. On the contrary, short-term exposure to higher levels of ambient pollutants were associated with lower levels of P-selectin, MCP-1, and osteoprotegerin in the Framingham Heart Study.

Li|Wenyuan|W|
Dorans|Kirsten S|KS|
Wilker|Elissa H|EH|
Rice|Mary B|MB|
Ljungman|Petter L|PL|
Schwartz|Joel D|JD|
Coull|Brent A|BA|
Koutrakis|Petros|P|
Gold|Diane R|DR|
Keaney|John F|JF|
Vasan|Ramachandran S|RS|
Benjamin|Emelia J|EJ|
Mittleman|Murray A|MA|

Air pollution
Biomarker
Inflammation
Endothelial dysfunction
Environment
Epidemiology


Wide Complex Tachycardia Differentiation: A Reappraisal of the State-of-the-Art.

Abstract: The primary goal of the initial ECG evaluation of every wide complex tachycardia is to determine whether the tachyarrhythmia has a ventricular or supraventricular origin. The answer to this question drives immediate patient care decisions, ensuing clinical workup, and long-term management strategies. Thus, the importance of arriving at the correct diagnosis cannot be understated and has naturally spurred rigorous research, which has brought forth an ever-expanding abundance of manually applied and automated methods to differentiate wide complex tachycardias. In this review, we provide an in-depth analysis of traditional and more contemporary methods to differentiate ventricular tachycardia and supraventricular wide complex tachycardia. In doing so, we: (1) review hallmark wide complex tachycardia differentiation criteria, (2) examine the conceptual and structural design of standard wide complex tachycardia differentiation methods, (3) discuss practical limitations of manually applied ECG interpretation approaches, and (4) highlight recently formulated methods designed to differentiate ventricular tachycardia and supraventricular wide complex tachycardia automatically.

Kashou|Anthony H|AH|
Noseworthy|Peter A|PA|
DeSimone|Christopher V|CV|
Deshmukh|Abhishek J|AJ|
Asirvatham|Samuel J|SJ|
May|Adam M|AM|

wide complex tachycardia
ECG
ventricular tachycardia
supraventricular tachycardia


Abstract:
OBJECTIVES
Modular junctions are ubiquitous in contemporary hip arthroplasty. The head-trunnion junction is implicated in the failure of large diameter metal-on-metal (MoM) hips which are the currently the topic of one the largest legal actions in the history of orthopaedics (estimated costs are stated to exceed $4 billion). Several factors are known to influence the strength of these press-fit modular connections. However, the influence of different head sizes has not previously been investigated. The aim of the study was to establish whether the choice of head size influences the initial strength of the trunnion-head connection.

MATERIALS AND METHODS
Ti-6Al-4V trunnions (n = 60) and two different sizes of cobalt-chromium (Co-Cr) heads (28 mm and 36 mm; 30 of each size) were used in the study. Three different levels of assembly force were considered: 4 kN; 5 kN; and 6 kN (n = 10 each). The strength of the press-fit connection was subsequently evaluated by measuring the pull-off force required to break the connection. The statistical differences in pull-off force were examined using a Kruskal-Wallis test and two-sample Mann-Whitney U test. Finite element and analytical models were developed to understand the reasons for the experimentally observed differences.

RESULTS
36 mm diameter heads had significantly lower pull-off forces than 28 mm heads when impacted at 4 kN and 5 kN (p < 0.001; p < 0.001), but not at 6 kN (p = 0.21). Mean pull-off forces at 4 kN and 5 kN impaction forces were approximately 20% larger for 28 mm heads compared with 36 mm heads. Finite element and analytical models demonstrate that the differences in pull-off strength can be explained by differences in structural rigidity and the resulting interface pressures.

CONCLUSION
This is the first study to show that 36 mm Co-Cr heads have up to 20% lower pull-off connection strength compared with 28 mm heads for equivalent assembly forces. This effect is likely to play a role in the high failure rates of large diameter MoM hips.Cite this article: A. R. MacLeod, N. P. T. Sullivan, M. R. Whitehouse, H. S. Gill. Large-diameter total hip arthroplasty modular heads require greater assembly forces for initial stability. Bone Joint Res 2016;5:338-346. DOI: 10.1302/2046-3758.58.BJR-2016-0044.R1.

MacLeod|A R|AR|
Sullivan|N P T|NP|
Whitehouse|M R|MR|
Gill|H S|HS|

Strength
Connection
Head Size
Trunnion
Pull-off
Taper


Surgical Experience of Posterior Fossa Meningioma in a Jehovah's Witnesses Patient.

Abstract: Unexpected bleeding is a common complication that can occur during surgery. This unexpected bleeding can be managed by checking the patients' preoperative hemodynamic state or by autologous transfusion of an appropriate volume during surgery depending on the amount of blood loss and hemodynamic condition. However, patients like Jehovah's Witnesses, who refuse autologous transfusions for religious reasons even in life-threatening situations, present a predicament for treating physicians. The author reports on a large meningioma on the posterior fossa of a Jehovah's Witness patient who underwent surgery without autologous blood transfusion. There were no major problems other than the fear of unexpected massive bleeding. The surgeon's attention and efforts to minimize bleeding during surgery seemed to be the most important factors for success.

Meningioma
Jehovah's Witnesses
Blood transfusion


Short QT Syndrome: A Comprehensive Genetic Interpretation and Clinical Translation of Rare Variants.

Abstract: Short QT syndrome, one of the most lethal entities associated with sudden cardiac death, is a rare genetic disease characterized by short QT intervals detected by electrocardiogram. Several genetic variants are causally linked to the disease, but there has yet to be a comprehensive analysis of variants among patients with short QT syndrome. To fill this gap, we performed an exhaustive study of variants currently catalogued as deleterious in short QT syndrome according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Analysis of the 32 variants described in the literature determined that only nine (28.12%) have a conclusive pathogenic role. All definitively pathogenic variants are located in KCNQ1, KCNH2, or KCNJ2; three genes encoding potassium channels. Other variants located in genes encoding calcium or sodium channels are associated with electrical alterations concomitant with shortened QT intervals but do not guarantee a diagnosis of short QT syndrome. We recommend caution regarding previously reported variants classified as pathogenic. An exhaustive re-analysis is necessary to clarify the role of each variant before routinely translating genetic findings to the clinical setting.

Campuzano|Oscar|O|0000-0001-5298-5276
Fernandez-Falgueras|Anna|A|
Lemus|Ximena|X|0000-0002-4661-8485
Sarquella-Brugada|Georgia|G|
Cesar|Sergi|S|0000-0002-2798-1756
Coll|Monica|M|
Mates|Jesus|J|
Arbelo|Elena|E|
Jordà|Paloma|P|
Perez-Serra|Alexandra|A|
Del Olmo|Bernat|B|
Ferrer-Costa|Carles|C|
Iglesias|Anna|A|
Fiol|Victoria|V|
Puigmulé|Marta|M|
Lopez|Laura|L|
Pico|Ferran|F|
Brugada|Josep|J|
Brugada|Ramon|R|0000-0001-6607-3032

short QT syndrome
genetics
sudden cardiac death
pathogenicity


SSBER: removing batch effect for single-cell RNA sequencing data.

Abstract:
BACKGROUND
With the continuous maturity of sequencing technology, different laboratories or different sequencing platforms have generated a large amount of single-cell transcriptome sequencing data for the same or different tissues. Due to batch effects and high dimensions of scRNA data, downstream analysis often faces challenges. Although a number of algorithms and tools have been proposed for removing batch effects, the current mainstream algorithms have faced the problem of data overcorrection when the cell type composition varies greatly between batches.

RESULTS
In this paper, we propose a novel method named SSBER by utilizing biological prior knowledge to guide the correction, aiming to solve the problem of poor batch-effect correction when the cell type composition differs greatly between batches.

CONCLUSIONS
SSBER effectively solves the above problems and outperforms other algorithms when the cell type structure among batches or distribution of cell population varies considerably, or some similar cell types exist across batches.

Batch effect
Data integration
Supervised cell type assignment
The shared cell type


Modeling arterial pulse waves in healthy aging: a database for in silico evaluation of hemodynamics and pulse wave indexes.

Abstract: The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25-75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.

arteries
pulse wave
aging
blood flow
database of virtual subjects


Kinship and cohabitation in relation to caregiver burden in the context of Alzheimer's disease: a 24-month longitudinal study.

Abstract:
OBJECTIVES
The aims of the study were to identify the clinical characteristics of three groups of caregivers: spouses, live-in adult-child or non-live-in adult-child, and their relation to the degree of perceived burden (Caregiver Burden Interview).

METHODS
The sample comprised 275 Alzheimer's disease primary caregivers, with a follow-up of 24 months. Cognitive, functional and behavioural characteristics were evaluated in persons with dementia, whilst sociodemographic data, use of socio-medical resources, physical and mental health and self-perceived burden were assessed in caregivers. Generalized estimating equations were used for longitudinal data analysis.

RESULTS
Spouse caregivers were 45.0% men, sole caregivers (>80%), used few external resources and had worse physical health. The number of female adult-child caregivers was higher (>75%). The live-in adult-child group, compared with the non-live-in adult-child group, was less likely to be married, had a lower level of education, was more commonly the sole caregiver and used fewer external resources. The greatest burden was observed in live-in adult-child caregivers, and the lowest in the non-live-in adult-child group, with no significant variation in the follow-up for both groups. Spouses had an intermediate level of perceived burden, which rose significantly during follow-up (p < 0.001).

CONCLUSIONS
Kinship and cohabitation with the persons with dementia were associated with different scores and evolution of the burden, with an increase in the follow-up of the spouses, and with more or less burden, depending on cohabitation, in the adult-child groups. Interventions to reduce the level of burden on caregivers should consider these differences. Copyright © 2017 John Wiley & Sons, Ltd.

Viñas-Diez|Vanesa|V|
Turró-Garriga|Oriol|O|
Portellano-Ortiz|Cristina|C|
Gascón-Bayarri|Jordi|J|
Reñé-Ramírez|Ramón|R|
Garre-Olmo|Josep|J|
Conde-Sala|Josep Lluís|JL|

kinship
cohabitation
burden
Alzheimer's disease
family caregivers


Atraumatic normal vaginal delivery: how many women get what they want?

Abstract:
BACKGROUND
Trauma to the perineum, levator ani complex, and anal sphincter is common during vaginal childbirth, but often clinically underdiagnosed, and many women are unaware of the potential for long-term damage.

OBJECTIVE
In this study we use transperineal ultrasound to identify how many women will achieve a normal vaginal delivery without substantial damage to the levator ani or anal sphincter muscles, and to create a model to predict patient characteristics associated with successful atraumatic normal vaginal delivery.

STUDY DESIGN
This is a retrospective, secondary analysis of data sets gathered in the context of an interventional perinatal imaging study. A total of 660 primiparas, carrying an uncomplicated singleton pregnancy, underwent an antepartum and postpartum interview, vaginal exam (Pelvic Organ Prolapse Quantification), and 4-dimensional translabial ultrasound. Ultrasound data were analyzed for levator trauma and/or overdistention and residual sphincter defects. Postprocessing analysis of ultrasound volumes was performed blinded against clinical data and analyzed against obstetric data retrieved from the local maternity database. Levator avulsion was diagnosed if the muscle insertion at the inferior pubic ramus at the plane of minimal hiatal dimensions and within 5 mm above this plane on tomographic ultrasound imaging was abnormal, ie the muscle was disconnected from the inferior pubic ramus. Hiatal overdistensibility (microtrauma) was diagnosed if there was a peripartum increase in hiatal area on Valsalva by >20% with the resultant area ≥25 cm2. A sphincter defect was diagnosed if a gap of >30 degrees was seen in ≥4 of 6 tomographic ultrasound imaging slices bracketing the external anal sphincter. Two models were tested: a first model that defines severe pelvic floor trauma as either obstetric anal sphincter injury or levator avulsion, and a second, more conservative model, that also included microtrauma.

RESULTS
A total of 504/660 women (76%) returned for postpartum follow-up as described previously. In all, 21 patients were excluded due to inadequate data or intercurrent pregnancy, leaving 483 women for analysis. Model 1 defined nontraumatic vaginal delivery as excluding operative delivery, obstetric anal sphincter injuries, and sonographic evidence of levator avulsion or residual sphincter defect. Model 2 also excluded microtrauma. Of 483 women, 112 (23%) had a cesarean delivery, 103 (21%) had an operative vaginal delivery, and 17 (4%) had a third-/fourth-degree tear, leaving 251 women who could be said to have had a normal vaginal delivery. On ultrasound, in model 1, 27 women (6%) had an avulsion and 31 (6%) had a residual defect, leaving 193/483 (40%) who met the criteria for atraumatic normal vaginal delivery. In model 2, an additional 33 women (7%) had microtrauma, leaving only 160/483 (33%) women who met the criteria for atraumatic normal vaginal delivery. On multivariate analysis, younger age and earlier gestation at time of delivery remained highly significant as predictors of atraumatic normal vaginal delivery in both models, with increased hiatal area on Valsalva also significant in model 2 (all P ≤ .035).

CONCLUSION
The prevalence of significant pelvic floor trauma after vaginal child birth is much higher than generally assumed. Rates of obstetric anal sphincter injury are often underestimated and levator avulsion is not included as a consequence of vaginal birth in most obstetric text books. In this study less than half (33-40%) of primiparous women achieved an atraumatic normal vaginal delivery.

Caudwell-Hall|Jessica|J|
Kamisan Atan|Ixora|I|
Guzman Rojas|Rodrigo|R|
Langer|Susanne|S|
Shek|Ka Lai|KL|
Dietz|Hans Peter|HP|

D000328:Adult
D000367:Age Factors
D001003:Anal Canal
D036861:Delivery, Obstetric
D005260:Female
D005865:Gestational Age
D006801:Humans
D008962:Models, Theoretical
D009517:New South Wales
D007744:Obstetric Labor Complications
D017773:Pelvic Floor
D011247:Pregnancy
D015995:Prevalence
D011644:Puerperal Disorders
D012189:Retrospective Studies
D012307:Risk Factors
D055815:Young Adult

ultrasound
pelvic organ prolapse
levator avulsion
obstetric anal sphincter injury
birth trauma


FAST MRI breast screening revisited.

Abstract:
INTRODUCTION
Screening for breast cancer in high-risk women takes about 40 minutes to acquire an MRI scan and is time-intensive to report. There is recent interest in the performance of an abbreviated MRI protocol (FAST) in the screening setting. FAST scans have a reported negative predictive value of 99.8%. This study evaluates the false positive rates (FPR) and recall rates for FAST scans as compared to full diagnostic studies (FD).

METHODS
A database of all screening breast MRI scans performed at our institution between 30 June 2013 and 1 July 2014 (n = 591) was created by one of the researchers, who did not subsequently analyse the MRI scans. The T1W and first post-contrast and subtracted images from each of these scans (FAST protocol) were assessed by experienced breast MRI radiologists, blinded to the final diagnosis. The findings were then compared with the FD result.

RESULTS
The recall rates were 6.6% for FAST scans and 5.8% for FD scans. FPR rates were 4.7% and 3.9% respectively. There is no statistically significant difference in the recall rates or FPR of FAST scans in comparison with full diagnostic studies.

CONCLUSIONS
Given the absence of statistically significant difference in the FPR and recall rates in comparison with FD, FAST scans can replace FD for screening of breast cancer.

Jain|Manish|M|
Jain|Arushi|A|
Hyzy|Marek D|MD|
Werth|Graziella|G|


Allergy to cooked, but not raw, peas: a case series and review.

Abstract: Allergic reactions to legumes are common.Food allergy to cooked, but not raw, pea has been rarely reported in the literature. This case series describes five children who had various IgE-mediated symptoms upon consumption of cooked pea, but tolerated raw pea. Skin testing then confirmed positive responses to cooked, but not raw, peas. It is important to consider allergy to cooked legumes, even in the context of raw legume tolerance.

Abrams|Elissa M|EM|
Gerstner|Thomas V|TV|


Formaldehyde Vapor Characteristics in Varied Decontamination Environments.

Abstract:
Introduction
This effort investigated formaldehyde vapor characteristics under various environmental conditions by the analyses of air samples collected over a time-course. This knowledge will help responders achieve desired formaldehyde exposure parameters for decontamination of affected spaces after a biological contamination incident.

Methods
Prescribed masses of paraformaldehyde and formalin were sublimated or evaporated, respectively, to generate formaldehyde vapor. Adsorbent cartridges were used to collect air samples from the test chamber at predetermined times. A validated method was used to extract the cartridges and analyze for formaldehyde via liquid chromatography. In addition, material demand for the formaldehyde was evaluated by inclusion of arrays of Plexiglas panels in the test chamber to determine the impact of varied surface areas within the test chamber. Temperature was controlled with a circulating water bath connected to a radiator and fan inside the chamber. Relative humidity was controlled with humidity fixed-point salt solutions and water vapor generated from evaporated water.

Results
Low temperature trials (approximately 10°C) resulted in decreased formaldehyde air concentrations throughout the 48-hour time-course when compared with formaldehyde concentrations in the ambient temperature trials (approximately 22°C). The addition of clear Plexiglas panels to increase the surface area of the test chamber interior resulted in appreciable decreases of formaldehyde air concentration when compared to an empty test chamber.

Conclusion
This work has shown that environmental variables and surface-to-volume ratios in the decontaminated space may affect the availability of formaldehyde in the air and, therefore, may affect decontamination effectiveness.

Choi|Young W|YW|
Sunderman|Michelle M|MM|
McCauley|Martha W|MW|
Richter|William R|WR|
Willenberg|Zachary J|ZJ|
Wood|Joseph|J|
Serre|Shannon|S|
Mickelsen|Leroy|L|
Willison|Stuart|S|
Rupert|Rich|R|
Muñiz Ortiz|Jorge G|JG|
Casey|Sara|S|
Calfee|M Worth|MW|0000-0001-6544-329X

formaldehyde
environmental
air sampling
paraformaldehyde
formalin
material demand


Control of breathing and ventilatory acclimatization to hypoxia in deer mice native to high altitudes.

Abstract:
AIM
We compared the control of breathing and heart rate by hypoxia between high- and low-altitude populations of Peromyscus mice, to help elucidate the physiological specializations that help high-altitude natives cope with O2 limitation.

METHODS
Deer mice (Peromyscus maniculatus) native to high altitude and congeneric mice native to low altitude (Peromyscus leucopus) were bred in captivity at sea level. The F1 progeny of each population were raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa, simulating hypoxia at ~4300 m) for 5 months. Responses to acute hypoxia were then measured during stepwise reductions in inspired O2 fraction.

RESULTS
Lowlanders exhibited ventilatory acclimatization to hypoxia (VAH), in which hypoxia acclimation enhanced the hypoxic ventilatory response, made breathing pattern more effective (higher tidal volumes and lower breathing frequencies at a given total ventilation), increased arterial O2 saturation and heart rate during acute hypoxia, augmented respiratory water loss and led to significant growth of the carotid body. In contrast, highlanders did not exhibit VAH - exhibiting a fixed increase in breathing that was similar to hypoxia-acclimated lowlanders - and they maintained even higher arterial O2 saturations in hypoxia. However, the carotid bodies of highlanders were not enlarged by hypoxia acclimation and were similar in size to those of normoxic lowlanders. Highlanders also maintained consistently higher heart rates than lowlanders during acute hypoxia.

CONCLUSIONS
Our results suggest that highland deer mice have evolved high rates of alveolar ventilation and respiratory O2 uptake without the significant enlargement of the carotid bodies that is typical of VAH in lowlanders, possibly to adjust the hypoxic chemoreflex for life in high-altitude hypoxia.

hypoxic ventilatory response
chemoreception
genetic assimilation
glomus cells
high-altitude adaptation


Barriers and Facilitators of Community-Based Health Insurance Membership in Rural Amhara Region, Northwest Ethiopia: A Qualitative Study.

Abstract:
Background
More than 150 million people encounter huge cost of health expenses every year, and most of these treatment seekers face poverty owing to out-of-pocket payments. Community-based health insurance (CBHI) won popularity as a makeshift health financing mechanism for out-of-pocket payments in poor communities. The aim of this study was therefore to explore the facilitators and impediments of enrollment to community-based health insurance in rural parts of the Amhara region, Ethiopia.

Methods
Focus Group Discussion (FGD) was the main data collection instrument supplemented by key informant interview (KII). The FGD participants were selected using a purposive sampling technique. The participants were therefore selected based on their membership status of CBHI (members or non-members). Six FGDs and four KIIs were conducted in November 2019 in three districts. Before analyzing the data, all FGDs and KIIs were transcribed and transferred into ATLAS.ti version 7.1 software. An inductive thematic analysis approach was done, that is, on the basis of major themes emerged from the data.

Results
Low level of awareness, perception of high amount of premium, poor perception of quality of services and lack of trust are the barriers to join community-based health insurance.

Conclusion
There has been low level of awareness and misconception about community-based health insurance. The major reason to decline to join CBHI was low capacity to pay the premium.

community-based health insurance
Ethiopia
enrolment


Relationships between facial temperature changes, end-exercise affect and during-exercise changes in affect: a preliminary study.

Abstract: The present study was performed as an evaluation of the relationships between changes in facial temperature and self-reported pleasure-displeasure during an acute aerobic exercise bout. Ninety-two students performed a 10-minute long session of cycle ergometry at 80-85% of age-predicted maximal heart rate. Using infrared thermography and a single-item measure of pleasure-displeasure (the Feeling Scale, FS), facial temperature and the FS score were sampled at the beginning (Min1:00) and at the end of the exercise session (Min9:00). Statistical analyses revealed that cheek (but not forehead) temperature was higher at the end of the exercise bout compared to Min1:00 (it increased by about 5%). Change in cheek temperature was negatively related to end-exercise affect (β = -0.28, P < 0.001) and to during-exercise affective changes (β = -0.35, P < 0.001). No significant relationship with forehead temperature was found. Some of the possible reasons for this differential effect as well as theoretical and practical implications of our findings are discussed.

Legrand|Fabien D|FD|
Bertucci|William M|WM|
Arfaoui|Ahlem|A|

Exercise
measurement
psychology
thermal infrared images


Deconvolution of the particle size distribution of ProRoot MTA and MTA Angelus.

Abstract: Objective Mineral trioxide aggregate (MTA) cements contain two types of particles, namely Portland cement (PC) (nominally 80% w/w) and bismuth oxide (BO) (20%). This study aims to determine the particle size distribution (PSD) of PC and BO found in MTA. Materials and methods The PSDs of ProRoot MTA (MTA-P) and MTA Angelus (MTA-A) powder were determined using laser diffraction, and compared to samples of PC (at three different particle sizes) and BO. The non-linear least squares method was used to deconvolute the PSDs into the constituents. MTA-P and MTA-A powders were also assessed with scanning electron microscopy. Results BO showed a near Gaussian distribution for particle size, with a mode distribution peak at 10.48 μm. PC samples milled to differing degrees of fineness had mode distribution peaks from 19.31 down to 4.88 μm. MTA-P had a complex PSD composed of both fine and large PC particles, with BO at an intermediate size, whereas MTA-A had only small BO particles and large PC particles. Conclusions The PSD of MTA cement products is bimodal or more complex, which has implications for understanding how particle size influences the overall properties of the material. Smaller particles may be reactive PC or unreactive radiopaque agent. Manufacturers should disclose particle size information for PC and radiopaque agents to prevent simplistic conclusions being drawn from statements of average particle size for MTA materials.

Ha|William Nguyen|WN|
Shakibaie|Fardad|F|
Kahler|Bill|B|
Walsh|Laurence James|LJ|

Deconvolution
particle size distribution
mineral trioxide aggregate


Effective Management Of Topical Nosocomial Aspergillus Spp. Infections In Three Severely Burned Patients.

Abstract: Nosocomial opportunistic fungal infections by Aspergillus spp. represent increasing morbidity and mortality factors for severely burned patients, who are fragile and immunocompromised. Voriconazole (VRC), a modern antifungal drug, is used as a first-line therapy against systemic mold and yeast infections. Little has been published about the place, relative importance and efficacy of voriconazole in the treatment protocols involving Aspergillus spp. in Burn Centers. The objective of the present work was to assess the place and importance of voriconazole for the treatment of burn patients presenting superficial Aspergillus spp. infections. We performed a retrospective evaluation of VRC treatment in three severely burned patients with superficial nosocomial Aspergillus spp. infections in our Burn Center. Results showed that VRC allowed for control and cure of topical nosocomial Aspergillus spp. infections. In two cases, treatment with VRC had to be discontinued because of hepatotoxicity. In two cases, following or during systemic treatment with VRC, a 1% terbinafine cream was applied to resolve the infection in order to continue standard wound management. Overall, VRC has been shown to be an effective antifungal agent and is an alternative to amphotericin B to fight Aspergillus spp. infections developing in the wounds of severely burned patients.

Pantet|O|O|
Laurent|A|A|
Abdel-Sayed|P|P|
Hirt-Burri|N|N|
Michetti|M|M|
Raffoul|W|W|
Monod|M|M|
Applegate|L A|LA|
de Buys Roessingh|A S|AS|

Aspergillus infection burns voriconazole antifungals


Identification, characterization, and functional prediction of circular RNAs in maize.

Abstract: Circular RNAs (circRNAs) are a new type of intracellular regulator that have been widely identified in animals and plants by high-throughput sequencing. However, there are still few functional studies on circRNAs in plants. To better understand maize circRNAs and their potential functions, we identified 1199 circRNAs in maize from RiboMinus RNA-Seq transcriptome data, and found distinct features of splicing site selection bias, longer flanking introns, and miniature inverted-repeat transposable element (MITE) insertions in flanking introns in maize circRNAs compared to other plant circRNAs. In total, 31 and 36 orthologous circRNAs were identified in rice and maize, respectively, but the orthologous parental genes could not produce orthologous circRNAs, mostly because of long-sequence insertions/deletions at flanking introns and approximately 24.3% of them contained MITE sequences. The majority of maize circRNAs showed high diversity of expression under different treatments and/or in different genetic backgrounds, implying that circRNAs could be involved in various regulatory networks. Twenty-six ecircRNAs were predicted to contain one or more target mimics, and 229 circRNAs had high coding potential, indicating that circRNAs could perform peptide-encoding functions in plants. These results will broaden understanding of the roles of circRNAs in plants and support further functional work on maize.

D018506:Gene Expression Regulation, Plant

circRNA
Orthologous
Expression regulation
Maize (Zea mays)
Target mimicry


Predicting homelessness among individuals diagnosed with substance use disorders using local treatment records.

Abstract: One in five homeless people in the United States has a substance use and/or a mental health disorder. Substance use disorders substantially impact the ability to obtain and retain appropriate housing. Professionals who provide substance use treatment are typically required to provide housing assistance by prioritizing clients according to their risk for becoming or remaining homeless; however, existing methods for prioritizing clients can be time-consuming and staff- and training-intensive. This study analyzed the potential use of variables from locally collected and readily available treatment admission records to prioritize clients needing housing assistance. This study analyzed county-level substance use treatment admission and discharge records of 1862 treatment episodes for 1642 clients in publicly funded treatment programs in Utah County, Utah. For at least one admission or discharge, 185 clients lived on the streets or in a homeless shelter. Approximately 55% of treatment episodes that ended in homelessness at discharge did not originally begin with clients being homeless, suggesting a gap in prioritizing individuals for housing assistance. Logistic regression showed statistically significant associations between eventually becoming homeless at the time of discharge and being originally homeless on admission; older age (45 years or older); methamphetamine as primary drug used; and a diagnosis of axis I/II psychiatric disorder besides substance use disorder. These findings suggest that local and routinely collected substance use treatment records may be predictive of homelessness and potentially useful in prioritizing clients for housing assistance.

Moxley|Victor B A|VBA|
Hoj|Taylor H|TH|
Novilla|M Lelinneth B|MLB|

D016320:Substance Abuse Treatment Centers

Homelessness
Substance use
Housing assistance
Case management
Treatment Episode Dataset (TEDS)


A poor appetite or ability to eat and its association with physical function amongst community-dwelling older adults: age, gene/environment susceptibility-Reykjavik study.

Abstract: A poor appetite or ability to eat and its association with physical function have not been explored considerably amongst community-dwelling older adults. The current study examined whether having an illness or physical condition affecting one's appetite or ability to eat is associated with body composition, muscle strength, or physical function amongst community-dwelling older adults. This is a secondary analysis of cross-sectional data from the age, gene/environment susceptibility-Reykjavik study (n = 5764). Illnesses or physical conditions affecting one's appetite or ability to eat, activities of daily living, current level of physical activity, and smoking habits were assessed with a questionnaire. Fat mass, fat-free mass, body mass index, knee extension strength, and grip strength were measured, and the 6-m walk test and timed up-and-go test were administered. Individuals who reported illnesses or physical conditions affecting their appetite or ability to eat were considered to have a poor appetite. The associations of appetite or the ability to eat with body composition and physical function were analysed with stepwise linear regression models. A total of 804 (14%) individuals reported having conditions affecting their appetite or ability to eat and had a significantly lower fat-free mass and body mass index, less grip strength, and poorer physical function than did those without any conditions affecting their appetite or ability to eat. Although the factors reported to affect one's appetite or ability to eat are seldom considered severe, their strong associations with physical function suggest that any condition affecting one's appetite or ability to eat requires attention.

Chang|Milan|M|0000-0002-3556-3810
Geirsdottir|Olof G|OG|
Launer|Lenore J|LJ|
Gudnasson|Vilmundur|V|
Visser|Marjolein|M|
Gunnarsdottir|Ingibjorg|I|

Appetite
Physical function
Ageing
Body composition
Muscle strength


Psychedelic medicine: The biology underlying the persisting psychedelic effects.

Abstract: Psychedelic substances have regained interest as therapeutic agents in the treatment of stress-related disorders. The effects seem to be of persisting nature even after a single dose. Also in lower than 'regular' recreational doses, so-called micro-doses, without the typical effects on consciousness, users report beneficial effects on cognitive processes and well-being. The exact neurobiological mechanism underlying these persisting effects is not clear. While previous research has mainly focused on the central nervous system including the immune system and the neuroendocrine system, I propose a central role for sleep and the microbiome in the effects of regular and low doses of psychedelics respectively. It will be explained why this is hypothesized and studies to test this idea proposed. It is concluded that while these studies are needed to understand the biology underlying psychedelic medicine, it is also important to approach it in a holistic way, including all the above mentioned biological processes psychedelics are known to affect, and explore the role of other substance-related factors like route of administration and form, and factors like diet and lifestyle which are part of the psychedelic experience.

Psychedelic medicine
Stress-related disorders
Gut-brain axis
Psilocybin
Sleep microbiome


Compensatory upregulation of aldo-keto reductase 1B10 to protect hepatocytes against oxidative stress during hepatocarcinogenesis.

Abstract: Aldo-keto reductase 1B10 (AKR1B10), a member of aldo-keto reductase superfamily, contributes to detoxification of xenobiotics and metabolization of physiological substrates. Although increased expression of AKR1B10 was found in hepatocellular carcinoma (HCC), the role of AKR1B10 in the development of HCC remains unclear. This study aims to illustrate the role of AKR1B10 in hepatocarcinogenesis based on its intrinsic oxidoreduction abilities. HCC cell lines with AKR1B10 overexpression or knockdown were treated with doxorubicin or hydrogen peroxide to determinate the influence of aberrant AKR1B10 expression on cells' response to oxidative stress. Using Akr1b8 (the ortholog of human AKR1B10) knockout mice, diethylnitrosamine (DEN) induced liver injury, chronic inflammation and hepatocarcinogenesis were explored. Clinically, the pattern of serum AKR1B10 relevant to disease progression was investigated in a patient cohort with chronic hepatitis B (n=30), liver cirrhosis (n=30) and HCC (n=40). AKR1B10 expression in HCC tissues was analyzed using both the TCGA database (n=371) and our collected HCC samples (n=67). AKR1B10 overexpression reduced hepatocyte injury while AKR1B10 knockdown augmented reactive oxygen species (ROS) accumulation and apoptotic cell death. Consistently, Akr1b8 deficiency in mice promoted DEN-induced hepatocyte damage and liver inflammation characterized by increased phospho-H2AX, serum alanine aminotransferase, interleukin-6 and tumor necrosis factor alpha level, myeloid cell infiltration and led to more severe hepatocarcinogenesis and metastasis compared with wild type mice due to significant alteration on detoxification and oxidoreduction. AKR1B10 was compensatory expressed and gradually upregulated in the process of liver disease progression in HCC and increased oxidative stress upregulated AKR1B10 through NRF2. Our results here suggested that through oxidoreduction and detoxification, AKR1B10 played an important role in protecting hepatocytes from damage induced by ROS. Deficiency of AKR1B10 might accelerate hepatotoxin and inflammation-associated hepatocarcinogenesis. AKR1B10 expression elevation in HCC could be a result of compensatory upregulation, rather than a driver of malignant transformation during the development of HCC.

Liu|Yongzhen|Y| Zhang|Jing|J| Liu|Hui|H| Guan|Guiwen|G| Zhang|Ting|T| Wang|Leijie|L| Qi|Xuewei|X| Zheng|Huiling|H| Chen|Chia-Chen|CC| Liu|Jia|J| Cao|Deliang|D| Lu|Fengmin|F| Chen|Xiangmei|X|

Hepatocarcinogenesis AKR1B10 oxidoreduction ROS


Projecting the impacts of rising seawater temperatures on the distribution of seaweeds around Japan under multiple climate change scenarios.

Abstract: Seaweed beds play a key role in providing essential habitats and energy to coastal areas, with enhancements in productivity and biodiversity and benefits to human societies. However, the spatial extent of seaweed beds around Japan has decreased due to coastal reclamation, water quality changes, rising water temperatures, and heavy grazing by herbivores. Using monthly mean sea surface temperature (SST) data from 1960 to 2099 and SST-based indices, we quantitatively evaluated the effects of warming seawater on the spatial extent of suitable versus unsuitable habitats for temperate seaweed Ecklonia cava, which is predominantly found in southern Japanese waters. SST data were generated using the most recent multiple climate projection models and emission scenarios (the Representative Concentration Pathways or RCPs) used in the Coupled Model Intercomparison Project phase 5 (CMIP5). In addition, grazing by Siganus fuscescens, an herbivorous fish, was evaluated under the four RCP simulations. Our results suggest that continued warming may drive a poleward shift in the distribution of E. cava, with large differences depending on the climate scenario. For the lowest emission scenario (RCP2.6), most existing E. cava populations would not be impacted by seawater warming directly but would be adversely affected by intensified year-round grazing. For the highest emission scenario (RCP8.5), previously suitable habitats throughout coastal Japan would become untenable for E. cava by the 2090s, due to both high-temperature stress and intensified grazing. Our projections highlight the importance of not only mitigating regional warming due to climate change, but also protecting E. cava from herbivores to conserve suitable habitats on the Japanese coast.

Takao|Shintaro|S|
Kumagai|Naoki H|NH|
Yamano|Hiroya|H|
Fujii|Masahiko|M|
Yamanaka|Yasuhiro|Y|

seaweed
climate change
herbivores
Barren ground
future projection
global warming


The prevalence of high school multi-sport participation in elite national football league athletes.

Abstract: Objectives: Early youth specialization is increasingly being researched and identified as a risk factor for overuse injuries and burnout. This study aimed to characterize high school sport specialization in top National Football League (NFL) athletes and determine whether associations exist between single-sport specialization and future injury risk, performance, and longevity.Methods: For NFL first-round draft picks from 2008-2017, data on the number of games played in the NFL, overuse injuries causing athletes to miss one or more regular season games, Pro Bowl selections, and current status in the NFL were collected using publicly available information.Results: A total of 318 athletes were analyzed. Multi-sport athletes were highly prevalent (88%, n = 280), while only 12% (n = 38) of athletes were classified as single-sport. No difference between multi-sport and single-sport athletes was found regarding games missed to upper (p = 0.93) or lower extremity injuries (p = 0.49), total games played (p = 0.57), or NFL longevity (p = 0.97). There was no significant difference in the proportions of athletes reaching at least 1 Pro Bowl.Conclusion: The majority of NFL first-round draft picks were multi-sport athletes in high school. Single-sport football participation in high school does not appear to aid athletes in reaching or succeeding in the NFL.

Sport specialization
performance
athletic injuries
youth sports


Circumscribed Storiform Collagenoma Associated with Rubinstein-Taybi Syndrome in a Young Adolescent.

Abstract: Rubinstein-Taybi syndrome is a rare congenital neurodevelopmental disorder characterized by dysmorphic features, skeletal abnormalities, growth deficiency, and mental retardation. Circumscribed storiform collagenoma is a distinct benign fibromatous tumor that presents either as solitary tumor or in association with other syndromes. In this report, we describe a 16-year-old male with Rubinstein-Taybi syndrome associated with circumscribed storiform collagenoma. To our knowledge, this association has not been previously described in the literature.

Zavras|Nick|N| Mennonna|Rosario|R| Maris|Spyros|S| Vaos|George|G|

Circumscribed storiform collagenoma
Adolescent
Rubinstein-Teybi syndrome


A voltage-dependent Ca2+ homeostat operates in the plant vacuolar membrane.

Abstract: Cytosolic calcium signals are evoked by a large variety of biotic and abiotic stimuli and play an important role in cellular and long distance signalling in plants. While the function of the plasma membrane in cytosolic Ca2+ signalling has been intensively studied, the role of the vacuolar membrane remains elusive. A newly developed vacuolar voltage clamp technique was used in combination with live-cell imaging, to study the role of the vacuolar membrane in Ca2+ and pH homeostasis of bulging root hair cells of Arabidopsis. Depolarisation of the vacuolar membrane caused a rapid increase in the Ca2+ concentration and alkalised the cytosol, while hyperpolarisation led to the opposite responses. The relationship between the vacuolar membrane potential, the cytosolic pH and Ca2+ concentration suggests that a vacuolar H+ /Ca2+ exchange mechanism plays a central role in cytosolic Ca2+ homeostasis. Mathematical modelling further suggests that the voltage-dependent vacuolar Ca2+ homeostat could contribute to calcium signalling when coupled to a recently discovered K+ channel-dependent module for electrical excitability of the vacuolar membrane.

vacuolar membrane
calcium signalling
voltage clamp
Arabidopsis thaliana
R-GECO1 cytosolic Ca2+ reporter
TPC1 channel
computational cell biology
cpYFP cytosolic pH reporter


CDK7 inhibition suppresses rheumatoid arthritis inflammation via blockage of NF-κB activation and IL-1β/IL-6 secretion.

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. Anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARDs) may improve RA process. However, in most patients the treatment effect is still not satisfactory. Cyclin-dependent kinase 7 (CDK7) plays a well-established role in the regulation of the eukaryotic cell division cycle, and recent studies indicated that it exerted anti-inflammatory effect. In our previous research, we found that inhibition of CDK7 by highly selective inhibitor BS-181 significantly impeded the development of collagen-induced arthritis (CIA) mice. However, the underlying mechanism of CDK7 in RA remains to be explored. We elucidated the molecular mechanism of CDK7 inhibition in RA inflammation by administration of CDK7 highly selective inhibitor BS-181 and siRNA-CDK7. We found that both IL-1β, IL-6, IL-8 and RANKL transcript levels and IL-1β/IL-6 secretion were effectively suppressed by BS-181 treatment as well as CDK7 knockdown. Furthermore, CDK7 inhibition prevented NF-κB signalling pathway activation and restrained p65 nuclear translocation. Moreover, CDK7 selective inhibitor BS-181 also blocked phosphorylation of p65 in MH7A cells. These results strongly indicate that CDK7 inhibition by BS-181 and siRNA-CDK7 significantly suppresses rheumatoid arthritis inflammation, which may be via blockage of NF-κB signalling pathway and IL-1β/IL-6 secretion.

Hong|Honghai|H|0000-0003-2138-9118 Zeng|Yingmin|Y| Jian|Wenxuan|W| Li|Lei|L| Lin|Liying|L| Mo|Yousheng|Y| Liu|Meiling|M| Fang|Shuhuan|S| Xia|Yong|Y|


The effect of testosterone therapy on personality traits of trans men: a controlled prospective study in Germany and Switzerland.

Abstract: Gender dysphoria in transgender men is generally treated with exogenous testosterone administration aiming to suppress secondary female sex characteristics and achieve masculinization. However, the effect of testosterone on the personality of transgender men remains largely unknown. Therefore, we conducted a controlled study with 23 trans men (M = 27.2 years, Range = 18-51 years), recruited from internet-groups, medical and psychiatric services in Switzerland and Germany versus 27 cisgender women matched by age as control group. Data were collected prior to hormone therapy (HT), three and six months after the first treatment. Non-pathological personality traits (Big Five) were measured with the revised NEO-Personality-Inventory (NEO-PI-R). The greatest changes in the Big Five and its subdimensions occurred within the first three months. Interaction effects showed a significant decrease in the dimension Neuroticism (p < 0.01) - with the most relevant decline in its facet Depression - conversely, Extraversion (p < 0.001) increased, in particular, within its facets of Assertiveness (p < 0.01) and Warmth (p < 0.01). Expectedly, personality traits were stable in the control group. An overall decrease in interpersonal stress-related traits and a substantial increase in enhanced social-interaction traits and personal well-being occurred. These results enable medical services to ensure that informed-consent prior to HT is evidence-based with respect to potential changes in personality and may reduce concerns of trans men and their significant others regarding increased aggressiveness.

Gender dysphoria
Transgender
Hormone therapy
Non-pathological personality traits
Big Five
Social-interaction
Gender incongruence


Post-translational modifications and chromatin dynamics.

Abstract: The dynamic structure of chromatin is linked to gene regulation and many other biological functions. Consequently, it is of importance to understand the factors that regulate chromatin dynamics. While the in vivo analysis of chromatin has verified that histone post-translational modifications play a role in modulating DNA accessibility, the complex nuclear environment and multiplicity of modifications prevents clear conclusions as to how individual modifications influence chromatin dynamics in the cell. For this reason, in vitro analyses of model reconstituted nucleosomal arrays has been pivotal in understanding the dynamic nature of chromatin compaction and the affects that specific post-translational modifications can have on the higher order chromatin structure. In this mini-review, we briefly describe the dynamic chromatin structures that have been observed in vitro and the environmental conditions that give rise to these various conformational states. Our focus then turns to a discussion of the specific histone post-translational modifications that have been shown to alter formation of these higher order chromatin structures in vitro and how this may relate to the biological state and accessibility of chromatin in vivo.

Tolsma|Thomas O|TO|
Hansen|Jeffrey C|JC|0000-0002-3348-9071

nucleosome
chromatin modification
higher order structure


Injection molding as a one-step process for the direct production of pharmaceutical dosage forms from primary powders.

Abstract: The objective of the present study was to develop a one-step process for the production of tablets directly from primary powder by means of injection molding (IM), to create solid-dispersion based tablets. Fenofibrate was used as the model API, a polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft co-polymer served as a matrix system. Formulations were injection-molded into tablets using state-of-the-art IM equipment. The resulting tablets were physico-chemically characterized and the drug release kinetics and mechanism were determined. Comparison tablets were produced, either directly from powder or from pre-processed pellets prepared via hot melt extrusion (HME). The content of the model drug in the formulations was 10% (w/w), 20% (w/w) and 30% (w/w), respectively. After 120min, both powder-based and pellet-based injection-molded tablets exhibited a drug release of 60% independent of the processing route. Content uniformity analysis demonstrated that the model drug was homogeneously distributed. Moreover, analysis of single dose uniformity also revealed geometric drug homogeneity between tablets of one shot.

Eggenreich|K|K|
Windhab|S|S|
Schrank|S|S|
Treffer|D|D|
Juster|H|H|
Steinbichler|G|G|
Laske|S|S|
Koscher|G|G|
Roblegg|E|E|
Khinast|J G|JG|

Injection molding
Fenofibrate
Graft co-polymer
Hot melt extrusion
Direct powder processing
Solid dispersion


Integrating physiological threshold experiments with climate modeling to project mangrove species' range expansion.

Abstract: Predictions of climate-related shifts in species ranges have largely been based on correlative models. Due to limitations of these models, there is a need for more integration of experimental approaches when studying impacts of climate change on species distributions. Here, we used controlled experiments to identify physiological thresholds that control poleward range limits of three species of mangroves found in North America. We found that all three species exhibited a threshold response to extreme cold, but freeze tolerance thresholds varied among species. From these experiments, we developed a climate metric, freeze degree days (FDD), which incorporates both the intensity and the frequency of freezes. When included in distribution models, FDD accurately predicted mangrove presence/absence. Using 28 years of satellite imagery, we linked FDD to observed changes in mangrove abundance in Florida, further exemplifying the importance of extreme cold. We then used downscaled climate projections of FDD to project that these range limits will move northward by 2.2-3.2 km yr(-1) over the next 50 years.

Cavanaugh|Kyle C|KC|
Parker|John D|JD|
Cook-Patton|Susan C|SC|
Feller|Ilka C|IC|
Williams|A Park|AP|
Kellner|James R|JR|

range expansion
climate change
freeze tolerance
Avicennia germinans
Laguncularia racemosa
Rhizophora mangle
ecological thresholds
species distribution modeling


The selective 5-HT1A receptor agonist, NLX-112, exerts anti-dyskinetic effects in MPTP-treated macaques.

Abstract:
BACKGROUND
Long-term treatment of Parkinson's disease (PD) with l-DOPA typically leads to development of l-DOPA induced dyskinesia (LID). Amantadine, an NMDA antagonist, attenuates LID, but with limited efficacy and considerable side-effects. NLX-112 (also known as befiradol or F13640), a highly selective and efficacious 5-HT1A receptor agonist, reduced LID when tested in rodent and marmoset models of PD.

METHODS
The effects of NLX-112 (0.03, 0.1 and 0.3 mg/kg PO) on established LID evoked by acute challenge with l-DOPA (27.5 ± 3.8 mg/kg PO) were assessed in MPTP-treated cynomolgus macaques. Amantadine (10 mg/kg PO) was tested as a positive control. Plasma exposure of NLX-112 (0.1 mg/kg PO) was determined.

RESULTS
NLX-112 significantly and dose-dependently reduced median LID levels by up to 96% during the first hour post-administration (0.3 mg/kg). Moreover, NLX-112 reduced the duration of 'bad on-time' associated with disabling LID by up to 48% (0.3 mg/kg). In contrast, NLX-112 had negligible impact on the anti-parkinsonian benefit of l-DOPA. NLX-112 exposure peaked at ~50 ng/ml at 30 min post-administration but decreased to ~15 ng/ml at 2h. Amantadine reduced by 42% 'bad on-time' associated with l-DOPA, thereby validating the model.

CONCLUSION
These data show that, in MPTP-lesioned cynomolgus macaques, NLX-112 exerts robust anti-dyskinetic effects, without reducing the anti-parkinsonian benefit of l-DOPA. These observations complement previous findings and suggest that selective and high efficacy activation of 5-HT1A receptors by NLX-112 may constitute a promising approach to combat LID in PD, providing an alternative for patients in whom amantadine is poorly tolerated or without useful effect.

Depoortere|R|R|
Johnston|T H|TH|
Fox|S H|SH|
Brotchie|J M|JM|
Newman-Tancredi|A|A|

D058825:Serotonin 5-HT1 Receptor Agonists

NLX-112
Macaques
Parkinson's disease
Amantadine
Befiradol
MPTP
Serotonin 5-HT(1A) receptors
l-DOPA-induced dyskinesia


Pretreatment texture analysis of routine MR images and shape analysis of the diffusion tensor for prediction of volumetric response after radiosurgery for meningioma.

Abstract: OBJECTIVEThe goal of this study was to identify parameters from routine T1- and T2-weighted MR sequences and diffusion tensor imaging (DTI) that best predict the volumetric changes in a meningioma after treatment with Gamma Knife radiosurgery (GKRS).METHODSIn 32 patients with meningioma, routine MRI and DTI data were measured before GKRS. A total of 78 parameters derived from first-level texture analysis of the pretreatment MR images, including calculation of the mean, SD, 2.5th and 97.5th percentiles, and kurtosis and skewness of data in histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow-up period of 3 years (range 19.5-63.3 months).RESULTSSeveral DTI-derived parameters correlated significantly with a meningioma volume change. The parameter that best predicted the results of GKRS was the 2.5th percentile value of the smallest eigenvalue (L3) of the diffusion tensor (correlation coefficient 0.739, p ≤ 0.001), whereas among the non-DTI parameters, only the SD of T2-weighted images correlated significantly with a tumor volume change (correlation coefficient 0.505, p ≤ 0.05, after correction for family-wise errors using false-detection-rate correction).CONCLUSIONSDTI-derived data had a higher correlation to shrinkage of meningioma volume after GKRS than data from T1- and T2-weighted image sequences. However, if only routine MR images are available, the SD of T2-weighted images can be used to predict control or possible progression of a meningioma after GKRS.

Speckter|Herwin|H| Bido|Jose|J| Hernandez|Giancarlo|G| Rivera|Diones|D| Suazo|Luis|L| Valenzuela|Santiago|S| Miches|Isidro|I| Oviedo|Jairo|J| Gonzalez|Cesar|C| Stoeter|Peter|P|

texture analysis
meningioma
diffusion tensor imaging
Gamma Knife
CC = correlation coefficient
CE = contrast enhanced
Cl = longitudinal index
Cp = planar index
Cs = spherical index
DTI = diffusion tensor imaging
FA = fractional anisotropy
GKRS = Gamma Knife radiosurgery
SK = skewness of tensor shape
SRS = stereotactic radiosurgery
oncology
stereotactic radiosurgery


Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy.

Abstract: Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m2 with an excess body weight loss of 54.9%. The AUC24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.

obesity
clinical research/practice
complication: medical/metabolic
kidney transplantation/nephrology
pharmacokinetics/pharmacodynamics
pharmacology
recipient selection


Support Vector Machine Classifiers Show High Generalizability in Automatic Fall Detection in Older Adults.

Abstract: Falls are a major cause of morbidity and mortality in neurological disorders. Technical means of detecting falls are of high interest as they enable rapid notification of caregivers and emergency services. Such approaches must reliably differentiate between normal daily activities and fall events. A promising technique might be based on the classification of movements based on accelerometer signals by machine-learning algorithms, but the generalizability of classifiers trained on laboratory data to real-world datasets is a common issue. Here, three machine-learning algorithms including Support Vector Machine (SVM), k-Nearest Neighbors (kNN), and Random Forest (RF) were trained to detect fall events. We used a dataset containing intentional falls (SisFall) to train the classifier and validated the approach on a different dataset which included real-world accidental fall events of elderly people (FARSEEING). The results suggested that the linear SVM was the most suitable classifier in this cross-dataset validation approach and reliably distinguished a fall event from normal everyday activity at an accuracy of 93% and similarly high sensitivity and specificity. Thus, classifiers based on linear SVM might be useful for automatic fall detection in real-world applications.

Alizadeh|Jalal|J| Bogdan|Martin|M| Classen|Joseph|J|0000-0001-7182-6967 Fricke|Christopher|C|

fall detection
older adults
SVM
kNN
random forest
cross-dataset validation
machine learning


Smokers' behavioral intentions in response to a low-nicotine cigarette policy.

Abstract:
INTRODUCTION
Evidence suggests that reducing the nicotine concentration in cigarettes to sub-addictive levels would reduce use. Until a low-nicotine cigarette policy is enacted, population-level effects are unknown. This study examines the behavioral intentions of current U.S. cigarette smokers if a low-nicotine policy were implemented.

METHODS
Data were drawn from a nationally representative probability-based panel and opt-in panel. Weighted logistic regressions examined likelihood to (1) smoke lower nicotine cigarettes, (2) quit using tobacco, (3) use e-cigarettes, (4) illegally buy high-nicotine cigarettes, and (5) smoke cigars, cigarillos, or little cigars (CLCCs) among smokers, controlling for demographics, tobacco products used, dependence, and intentions to quit cigarettes. Latent class analyses (LCA) characterized patterns of behavioral intentions.

RESULTS
If a low-nicotine policy were implemented, most participants indicated a likelihood to smoke low-nicotine cigarettes (78.4%) or quit tobacco (61.9%), followed by use e-cigarettes (46.5%). Individuals with greater dependence had greater odds of intending to smoke low-nicotine cigarettes, use e-cigarettes, and illegally buy high-nicotine cigarettes. Current e-cigarette or CLCCs users had higher odds of intending to use these products. LCA revealed that individuals would 1) use low-nicotine cigarettes with low intentions to use other tobacco products or 2) use multiple tobacco products, including low-nicotine cigarettes.

CONCLUSIONS
A reduced nicotine standard for all combustible tobacco products is needed given that many tobacco users would likely intend to continue to use tobacco products. Differences in intentions by tobacco use and demographic characteristics indicate a need for additional cessation support and education around the harms of continued use of combustible tobacco.

Patel|Minal|M|
Cuccia|Alison F|AF|
Czaplicki|Lauren|L|
Donovan|Emily M|EM|
Simard|Bethany|B|
Pitzer|Lindsay|L|
Hair|Elizabeth C|EC|
Schillo|Barbara A|BA|
Vallone|Donna M|DM|

D066300:Electronic Nicotine Delivery Systems

Behavioral intentions
Low-nicotine cigarettes
Policy
Tobacco use


Complete mitochondrial genome of the Chinese lizard gudgeon, Saurogobio dabryi (Teleostei: Cypriniformes: Cyprinidae).

Abstract: The Chinese lizard gudgeon, Saurogobio dabryi Bleeker, belongs to the subfamily Gobioninea, which is an economic fish widely distributed in East Asia. In this study, we sequenced the complete mitochondrial genome of the S. dabryi. The complete mitogenome was 16,601 bp in size, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and 1 control region. It has the typical circular molecule structure of vertebrate's mitochondrial genome. The whole base composition was estimated to be 29.64%A, 26.47%T, 27.06%C and 16.83%G with AT bias of 56.11%. This study is a first report the complete mitogenome of S. dabryi and provides the basis for preservation of genetic resources and phylogenetic analyses on this species.

Xu|Hao|H| Xue|Yang|Y| Li|Xin-yue|XY| Luo|Xi|X| Li|Yang|Y| Li|Yun|Y|

D000818:Animals
D001483:Base Sequence
D003530:Cyprinidae
D020459:Genes, rRNA
D054629:Genome, Mitochondrial
D008969:Molecular Sequence Data
D016366:Open Reading Frames
D012343:RNA, Transfer
D017422:Sequence Analysis, DNA

mitochondrial genome
Saurogobio dabryi
Cyprinidae
Gobioninae


Increased distractibility in schizotypy: Independent of individual differences in working memory capacity?

Abstract: Individuals with schizophrenia typically show increased levels of distractibility. This has been attributed to impaired working memory capacity (WMC), since lower WMC is typically associated with higher distractibility, and schizophrenia is typically associated with impoverished WMC. Here, participants performed verbal and spatial serial recall tasks that were accompanied by to-be-ignored speech tokens. For the few trials wherein one speech token was replaced with a different token, impairment was produced to task scores (a deviation effect). Participants subsequently completed a schizotypy questionnaire and a WMC measure. Higher schizotypy scores were associated with lower WMC (as measured with operation span, OSPAN), but WMC and schizotypy scores explained unique variance in relation to the mean magnitude of the deviation effect. These results suggest that schizotypy is associated with heightened domain-general distractibility, but that this is independent of its relationship with WMC.

Marsh|John E|JE|
Vachon|François|F|
Sörqvist|Patrik|P|

D011569:Psychiatric Status Rating Scales

Distraction
Schizotypy
Working memory capacity
Schizophrenia
Domain-specificity
Verbal working memory
Visuo-spatial working memory


Customer Care in Pediatric Cardiac Transplant Pathology: Basic Concepts and Critical Analysis in the Setting of Precision Medicine.

Abstract: Customer care relies on Quality Control and the following script is a critical analysis of Pediatric Heart Transplantation Programs seen through the eyes of a pediatrician and pathologist. This narrative (non-systematic) script entails protocols that may be considered transferable to other transplantation services. A blueprint for the evaluation of processes following the obtainment of cardiac tissue biopsies is crucial to identify the pitfalls in the healthcare process involving organ transplantation. The current workflow in Pediatric Heart Transplant Pathology at our institution, along with concepts of quality assurance, quality control, and quality improvement is presented.

pathology
quality
Heart transplant
healthcare
children
economics
policy


Neurovascular anatomic relationships to arthroscopic posterior and transseptal portals in different knee positions.

Abstract:
BACKGROUND
No study exists that directly measures the distances between posterior portals and the popliteal artery under arthroscopic conditions.

PURPOSE
To define the anatomic relationship between the neural structures and standard posterior arthroscopic portals and between the popliteal artery and posterior as well as transseptal portals in different knee positions.

STUDY DESIGN
Descriptive laboratory study.

METHODS
Seventeen fresh-frozen cadaveric knees were used. The posterolateral, posteromedial, and transseptal portals were established at 90° of knee flexion. The popliteal artery was revealed using a shaver placed through the posteromedial portal. The distance from those portals to the popliteal artery was measured using a precision caliper. After the measurements were made, each specimen was dissected. The distance from a needle, blade, and cannula in each portal site to the adjacent neural structures was successively measured at 30°, 90°, and 120° of knee flexion.

RESULTS
The mean distance (in millimeters) from the posterolateral, posteromedial, and transseptal portals to the popliteal artery was significantly smaller at 30° (32.1 ± 4.6, 36.5 ± 4.9, and 9.0 ± 3.9, respectively) than at 90° (40.7 ± 5.1, 41.0 ± 3.8, and 18.0 ± 3.8, respectively) and 120° (38.4 ± 4.8, 38.7 ± 6.0, and 21.0 ± 4.0, respectively) of knee flexion. The mean distance from the posterolateral portal to the common peroneal nerve at 90° of flexion (needle, 26.6 ± 9.5; blade, 24.7 ± 6.9; cannula, 22.1 ± 6.9) was significantly greater than the distance at 30° (needle, 23.4 ± 6.5; blade, 21.4 ± 6.4; cannula, 18.4 ± 6.3) and 120° (needle, 21.8 ± 6.6; blade, 19.1 ± 6.3; cannula, 17.4 ± 6.7) of knee flexion. The mean distance between the posteromedial portal and the inferior infrapatellar branch of the saphenous nerve at 30° (needle, 18.6 ± 4.3; blade, 15.5 ± 3.3; cannula, 13.7 ± 5.8) of flexion was smaller than at 90° (needle, 20.1 ± 6.1; blade, 16.5 ± 5.3; cannula, 14.3 ± 4.4) and 120° (needle, 21.1 ± 3.6; blade, 17.7 ± 4.9; cannula, 15.1 ± 5.9) of flexion, but there was no statistical significance. The mean distance from the posteromedial portal to the sartorial branch of the saphenous nerve at 30° (needle, 22.8 ± 6.1; blade, 19.8 ± 5.3; cannula, 17.7 ± 6.2) of flexion was significantly smaller than that at 90° (needle, 29.7 ± 3.6; blade, 26.3 ± 6.3; cannula, 23.1 ± 4.7) and 120° (needle, 31.5 ± 3.9; blade, 28.9 ± 4.1; cannula, 25.4 ± 5.1) of flexion. Conclusion/

CLINICAL RELEVANCE
The position of 90° of knee flexion is safe to establish posterior and transseptal arthroscopic portals. The position of 120° of knee flexion is practically safe to establish posteromedial and transseptal portals, but it is unsafe to create a posterolateral portal because the risk of damaging the common peroneal nerve is high. The position of 30° of knee flexion is not recommended to establish posterior arthroscopic portals.

Makridis|Konstantinos G|KG|
Wajsfisz|Anthony|A|
Agrawal|Nikhil|N|
Basdekis|Georgios|G|
Djian|Patrick|P|

anatomic relationships
popliteal artery
neural structures
posterior arthroscopic portals
cadaveric study


Inhibition of the formation of amyloid-like fibrils with spices, especially cloves.

Abstract: During the study of inhibition of amyloid fibril formation, α-chymotrypsin protein was developed in 55% ethanol at pH 7.0. We investigated the inhibitory effect of different spices on amyloid fibril formation using turbidity measurements and Congo red binding assays. We found that all spices except the black pepper and caraway seed prevented fibril formation. The highest inhibition was measured with the clove, which reduced the amount of aggregates by 90%. We studied the inhibitory effect of the cloves at different concentrations on aggregation, it was found that the inhibitory activity of clove is dependent on concentration. We have measured the total phenolic content of the spice extracts too. Based on all these findings we have come to the following conclusion: Our results indicate that spices can contain other compounds too - not only phenolic compounds - which influence the formation of amyloid fibrils, and the effectiveness of various phenolic compounds are different.

Kotormán|Márta|M|
Varga|Alexandra|A|
Kasi|Phanindra Babu|PB|
Nemcsók|János|J|

spice
clove
amyloid fibrils
α-chymotrypsin
polyphenols


Increased Central Arterial Stiffness after Spinal Cord Injury: Contributing Factors, Implications, and Possible Interventions.

Abstract: Individuals with spinal cord injury (SCI) experience life-threatening cardiovascular events and various autonomic consequences in addition to the well-appreciated motor and neurological impairments. As a result, cardiovascular disease is a major cause of death after SCI, corresponding to a two-to-fourfold increased risk of cardiovascular events. A combination of neuroanatomical changes, unstable blood pressure, and rapid deconditioning as a result of decreased physical activity likely contributes to accelerated cardiovascular disease progression after SCI. Aortic pulse wave velocity (aPWV) is considered the gold-standard technique for evaluating central arterial stiffness, which itself is a correlate for greater cardiovascular disease risk in healthy individuals and a plethora of clinical conditions. In this review, we discuss central arterial stiffness after SCI, and demonstrate that it is consistently elevated in this population 2-3 m/sec, which corresponds to a 30-45% increased risk of cardiovascular mortality and an approximate 40-year acceleration of age-related cardiovascular decline. The potential factors contributing to increased central arterial stiffness are also reviewed in light of the available literature, including autonomic disruptions, blood pressure instability, metabolic changes, and physical inactivity. Further, measurement techniques, risk factors, cardiac dysfunction, and differences in arterial stiffness from able-bodied populations are discussed. Finally, potential therapeutic interventions for preventing or improving central arterial stiffening are also explored, including dietary, physical activity, and pharmacological strategies.

Lee|Amanda H X|AH|
Phillips|Aaron A|AA|
Krassioukov|Andrei V|AV|

D001018:Aortic Diseases
D006801:Humans
D013119:Spinal Cord Injuries
D059289:Vascular Stiffness

clinical management of central nervous system (CNS) injury


3D Printing of Layered Gradient Pore Structure of Brain-like Tissue.

Abstract: The pathological research and drug development of brain diseases require appropriate brain models. Given the complex, layered structure of the cerebral cortex, as well as the constraints on the medical ethics and the inaccuracy of animal models, it is necessary to construct a brain-like model in vitro. In this study, we designed and built integrated three-dimensional (3D) printing equipment for cell printing/culture, which can guarantee cell viability in the printing process and provide the equipment foundation for manufacturing the layered structures with gradient distribution of pore size. Based on this printing equipment, to achieve the purpose of printing the layered structures with multiple materials, we conducted research on the performance of bio-inks with different compositions and optimized the printing process. By extruding and stacking materials, we can print the layered structure with the uniform distribution of cells and the gradient distribution of pore sizes. Finally, we can accurately print a structure with 30 layers. The line width (resolution) of the printed monolayer structure was about 478 mm, the forming accuracy can reach 97.24%, and the viability of cells in the printed structure is as high as 94.5%.

Pei|Na|N| Hao|Zhiyan|Z| Wang|Sen|S| Pan|Binglei|B| Fang|Ao|A| Kang|Jianfeng|J| Li|Dichen|D| He|Jiankang|J| Wang|Ling|L|

Integrated cell printing/culture equipment


Inter-limb coordination and control in boys with and without DCD in ball catching.

Abstract: The purpose of the study was to examine the nature of inter-limb coordination and control, exhibited by ten boys with (M=10.5 years, SD=1.0) and without Developmental Coordination Disorder (DCD), in a ball catching task across different ball speeds. In line with the predictions of coordinated structure theory boys who were typically developing preserved strong and effective temporal relations when catching balls in baseline and fast conditions. Boys with DCD exhibited temporal symmetry in baseline but not in fast attempts, where the decoupling was uniformed across the group, coinciding with failures on ≥ 50% of the attempts. In terms of stability, no differences in intra-individual variability were observed between the groups. The analysis of spatial and temporal adaptations showed that boys who were typically developing, in essence, covered the same "ground" by decreasing their movement time. The opposite was true for boys with DCD who contacted the ball closer to the body, while failing to adapt the velocity of their hands. Taken together, both groups exhibited strong and stable coordinative relations, in a steady-state but not in a fast condition, where all boys with DCD failed to preserve the desired symmetry. This decoupling also coincided with different and less effective spatio-temporal adaptations at the effector level. Thus, it appears that movement control, hence flexibility of their synergistic relations, represents a movement limiter for boys with DCD who exhibit specific balls skills issues, at inter-limb level of organization. It should be noted, however, that large intra-group variance observed across some variables warrants caution when interpreting the aggregate data.

Przysucha|Eryk P|EP|
Maraj|Brian K V|BK|

DCD
Coordination/control
Degrees of freedom problem
Inter-coupling


p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells.

Abstract: Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients. p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE(-/-) mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n = 20) and PCS-treated group (n = 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 μmol/L PCS for in vitro evaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.

Han|Hui|H| Chen|Yanjia|Y| Zhu|Zhengbin|Z| Su|Xiuxiu|X| Ni|Jingwei|J| Du|Run|R| Zhang|Ruiyan|R| Jin|Wei|W|

p-cresyl sulfate
vascular smooth muscle cell
atherosclerosis
plaque stability


Design, implementation, and evaluation of a pediatric and adolescent type 2 diabetes management program at a tertiary pediatric center.

Abstract: Global rates of type 2 diabetes in children and adolescents have increased significantly over the past three decades. Type 2 diabetes is a relatively new disease in this age group, and there is a dearth of information about how to structure treatment programs to manage its comorbidities and complications. In this paper, we describe the design and implementation of a personalized multidisciplinary, family-centered, pediatric and adolescent type 2 diabetes program at a tertiary pediatric center in Hamilton, Ontario, Canada. We report the process of designing and implementing such a program, and show that this multidisciplinary program led to improvement in glycated hemoglobin (n=17, 8% at baseline versus 6.4% at 1 year, 95% confidence interval (0.1-0.28), P-value <0.0001) and stabilized body mass index, with lowered C-peptide and no change in fitness or metabolic biomarkers of lipid metabolism and liver function. As type 2 diabetes becomes more prevalent in youth, the need for programs that successfully address the complex nature of this disease is central to its management and to mitigate its long-term adverse outcomes.

Samaan|M Constantine|MC|
Valencia|Marlie|M|
Cheung|Connie|C|
Wilk|Boguslaw|B|
Lau|Keith|K|
Thabane|Lehana|L|

pediatric
adolescents
type 2 diabetes
multidisciplinary
program design


A Case of Persistent Left Superior Vena Cava and Left Pulmonary Venous Drainage to the Coronary Sinus.

Abstract: We report a case of a persistent left superior vena cava draining to the right atrium via the coronary sinus in conjunction with partial anomalous pulmonary venous return of the left pulmonary veins to the coronary sinus. Although a persistent left superior vena cava is typically of little clinical consequence, in this case, it complicated surgical repair of the congenital heart disease. Successful repair of this unusual combination of systemic and pulmonary venous anomalies required a combination of two well-described surgical techniques.

Rabinowitz|Edon J|EJ|
Misra|Nilanjana|N|
Meyer|David B|DB|

D000083402:Persistent Left Superior Vena Cava


The antiproliferative and proapoptotic effects of cladosporols A and B are related to their different binding mode as PPARγ ligands.

Abstract: Cladosporols are secondary metabolites from Cladosporium tenuissimum characterized for their ability to control cell proliferation. We previously showed that cladosporol A inhibits proliferation of human colon cancer cells through a PPARγ-mediated modulation of gene expression. In this work, we investigated cladosporol B, an oxidate form of cladosporol A, and demonstrate that it is more efficient in inhibiting HT-29 cell proliferation due to a robust G0/G1-phase arrest and p21(waf1/cip1) overexpression. Cladosporol B acts as a PPARγ partial agonist with lower affinity and reduced transactivation potential in transient transfections as compared to the full agonists cladosporol A and rosiglitazone. Site-specific PPARγ mutants and surface plasmon resonance (SPR) experiments confirm these conclusions. Cladosporol B in addition displays a sustained proapoptotic activity also validated by p21(waf1/cip1) expression analysis in the presence of the selective PPARγ inhibitor GW9662. In the DMSO/H2O system, cladosporols A and B are unstable and convert to the ring-opened compounds 2A and 2B. Finally, docking experiments provide the structural basis for full and partial PPARγ agonism of 2A and 2B, respectively. In summary, we report here, for the first time, the structural characteristics of the binding of cladosporols, two natural molecules, to PPARγ. The binding of compound 2B is endowed with a lower transactivation potential, higher antiproliferative and proapoptotic activity than the two full agonists as compound 2A and rosiglitazone (RGZ).

Zurlo|Diana|D|
Ziccardi|Pamela|P|
Votino|Carolina|C|
Colangelo|Tommaso|T|
Cerchia|Carmen|C|
Dal Piaz|Fabrizio|F|
Dallavalle|Sabrina|S|
Moricca|Salvatore|S|
Novellino|Ettore|E|
Lavecchia|Antonio|A|
Colantuoni|Vittorio|V|
Lupo|Angelo|A|

D050759:Cyclin-Dependent Kinase Inhibitor p21

Cladosporols
Docking
Apoptosis
Colorectal cancer cells
Full and partial PPARγ agonists


Can India's primary care facilities deliver? A cross-sectional assessment of the Indian public health system's capacity for basic delivery and newborn services.

Abstract:
OBJECTIVES
To assess input and process capacity for basic delivery and newborn (intrapartum care hereafter) care in the Indian public health system and to describe differences in facility capacity between rural and urban areas and across states.

DESIGN
Cross-sectional study.

SETTING
Data from the nationally representative 2012-2014 District Level Household and Facility Survey, which includes a census of community health centres (CHC) and sample of primary health centres (PHC) across 30 states and union territories in India.

PARTICIPANTS
8536 PHCs and 4810 CHCs.

OUTCOME MEASURES
We developed a summative index of 33 structural and process capacity items matching the Indian Public Health Standards for PHCs as a metric of minimum facility capacity for intrapartum care. We assessed differences in performance on this index across facility type and location.

RESULTS
About 30% of PHCs and 5% of CHCs reported not offering any intrapartum care. Among those offering services, volumes were low: median monthly delivery volume was 8 (IQR=13) in PHCs and 41 (IQR=73) in CHCs. Both PHCs and CHCs failed to meet the national standards for basic intrapartum care capacity. Mean facility capacity was low in PHCs in both urban (0.64) and rural (0.63) areas, while in CHCs, capacity was slightly higher in urban areas (0.77vs0.74). Gaps were most striking in availability of skilled human resources and emergency obstetric services. Poor capacity facilities were more concentrated in the more impoverished states, with 37% of districts from these states receiving scores in the lowest third of the facility capacity index (<0.70), compared with 21% of districts otherwise.

CONCLUSIONS
Basic intrapartum care capacity in Indian public primary care facilities is weak in both rural and urban areas, especially lacking in the poorest states with worst health outcomes. Improving maternal and newborn health outcomes will require focused attention to quality measurement, accountability mechanisms and quality improvement. Policies to address deficits in skilled providers and emergency service availability are urgently required.

Sharma|Jigyasa|J|0000-0001-8860-0710
Leslie|Hannah H|HH|
Regan|Mathilda|M|
Nambiar|Devaki|D|
Kruk|Margaret E|ME|

health systems
newborn health
health policy
maternal health
quality in healthcare


In silico analysis of the chemotactic system of Agrobacterium tumefaciens.

Abstract: Agrobacterium tumefaciens is an efficient tool for creating transgenic host plants. The first step in the genetic transformation process involves A. tumefaciens chemotaxis, which is crucial to the survival of A. tumefaciens in changeable, harsh and even contaminated soil environments. However, a systematic study of its chemotactic signalling pathway is still lacking. In this study, the distribution and classification of chemotactic genes in the model A. tumefaciens C58 and 21 other strains were annotated. Local blast was used for comparative genomics, and hmmer was used for predicting protein domains. Chemotactic phenotypes for knockout mutants of ternary signalling complexes in A. tumefaciens C58 were evaluated using a swim agar plate. A major cluster, in which chemotaxis genes were consistently organized as MCP (methyl-accepting chemotaxis protein), CheS, CheY1, CheA, CheR, CheB, CheY2 and CheD, was found in A. tumefaciens, but two coupling CheW proteins were located outside the 'che' cluster. In the ternary signalling complexes, the absence of MCP atu0514 significantly impaired A. tumefaciens chemotaxis, and the absence of CheA (atu0517) or the deletion of both CheWs abolished chemotaxis. A total of 465 MCPs were found in the 22 strains, and the cytoplasmic domains of these MCPs were composed of 38 heptad repeats. A high homology was observed between the chemotactic systems of the 22 A. tumefaciens strains with individual differences in the gene and receptor protein distributions, possibly related to their ecological niches. This preliminary study demonstrates the chemotactic system of A. tumefaciens, and provides some reference for A. tumefaciens sensing and chemotaxis to exogenous signals.

Xu|Nan|N| Wang|Mingqi|M| Yang|Xiaojing|X| Xu|Yujuan|Y| Guo|Minliang|M|

Agrobacterium tumefaciens
chemotaxis
methyl-accepting chemotaxis protein
Che cluster


Quality of life in patients with progressive supranuclear palsy: one-year follow-up.

Abstract: The aim of this prospective cohort study that included 46 patients with progressive supranuclear palsy (PSP) was to estimate which demographic and clinical factors were the main contributors to the health-related quality of life (HRQoL) and how did the HRQoL change over a follow-up period of 1 year in these patients. The hierarchical regression analyses showed that the final models demonstrated that gender, included clinical variables and psychiatric/neuropsychological scales, accounted for 68% of the variance in the Physical Composite Score and 73% of the variance of the Mental Composite Score of the 36-item Short Form Health Survey (SF-36). Among variables in both final models, only the score of the Apathy Evaluation Scale showed statistically significant negative predictive value (p < 0.05). Changes in the HRQoL scores were assessed in 28 PSP patients who completed 1-year follow-up period after the baseline examination. Statistically significant decline in the HRQoL was detected for the following scales of the SF-36: physical functioning, vitality, social functioning, and role emotional, as well as in both composite scores (Physical Composite Score and Mental Composite Score). The analyses of magnitude of changes in the HRQoL during 1-year follow-up period showed large effect size (≥0.80) for total scores, as well as for the physical functioning, vitality, and social functioning. In conclusion, despite certain limitations, our study provided some new insights into potential predictors of the HRQoL and its longitudinal changes in patients with PSP.

Pekmezović|Tatjana|T|
Ječmenica-Lukić|Milica|M|
Petrović|Igor|I|
Špica|Vladana|V|
Tomić|Aleksandra|A|
Kostić|Vladimir S|VS|

D000368:Aged
D000369:Aged, 80 and over
D057565:Apathy
D004185:Disability Evaluation
D005260:Female
D005500:Follow-Up Studies
D006304:Health Status
D006801:Humans
D008297:Male
D008875:Middle Aged
D008962:Models, Theoretical
D011446:Prospective Studies
D011788:Quality of Life
D013494:Supranuclear Palsy, Progressive
D011795:Surveys and Questionnaires

Quality of life
Progressive supranuclear palsy
Follow-up
Predictors


Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.

Abstract: An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with compound 1 established the importance of the C3 and C4 substituent to antiviral potency against viruses with different aa124/aa125 variants of IN. The importance of the C7 position on the serum shifted potency was established. Introduction of a quinoline substituent at the C4 position provided a balance of potency and metabolic stability. Combination of these findings ultimately led to the discovery of compound 26 (BI 224436), the first NCINI to advance into a phase Ia clinical trial.

Fader|Lee D|LD|
Malenfant|Eric|E|
Parisien|Mathieu|M|
Carson|Rebekah|R|
Bilodeau|François|F|
Landry|Serge|S|
Pesant|Marc|M|
Brochu|Christian|C|
Morin|Sébastien|S|
Chabot|Catherine|C|
Halmos|Ted|T|
Bousquet|Yves|Y|
Bailey|Murray D|MD|
Kawai|Stephen H|SH|
Coulombe|René|R|
LaPlante|Steven|S|
Jakalian|Araz|A|
Bhardwaj|Punit K|PK|
Wernic|Dominik|D|
Schroeder|Patricia|P|
Amad|Ma'an|M|
Edwards|Paul|P|
Garneau|Michel|M|
Duan|Jianmin|J|
Cordingley|Michael|M|
Bethell|Richard|R|
Mason|Stephen W|SW|
Bös|Michael|M|
Bonneau|Pierre|P|
Poupart|Marc-André|MA|
Faucher|Anne-Marie|AM|
Simoneau|Bruno|B|
Fenwick|Craig|C|
Yoakim|Christiane|C|
Tsantrizos|Youla|Y|

NCINI
HIV Integrase
LTR DNA 3′-processing
allosteric inhibitor


High-Resolution Imaging of Interaction Between Thrombus and Stent-Retriever in Patients With Acute Ischemic Stroke.

Abstract:
BACKGROUND
Currently, acute ischemic stroke is still a leading cause of mortality and morbidity. Approximately 2 years ago, mechanical thrombectomy was proven beneficial as a revolutionary new therapy for stroke in the MR-CLEAN trial (A Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). However, the mechanisms by which the thrombectomy device, or stent-retriever, interacts with the thrombus are largely unknown. A better understanding could lead to improved efficacy of mechanical thrombectomy devices.

METHODS AND RESULTS
Seven stent-retrievers with thrombi still entrapped were collected directly after thrombectomy. The stent-retrievers were studied using micro computed tomography, followed by scanning electron microscopy and light microscopy. Two independent observers rated interaction type and thrombus surface structure (porous filamentous or dense) at the interaction sites.A total of 79 interaction sites between thrombus and stent-retriever were categorized. Thrombus-stent-retriever interaction was found to be adhesive (n=44; 56%) or mechanical (n=35; 44%). Adhesive interaction was most frequently observed at interaction sites with a dense surface, compared with interaction sites with a porous filamentous fibrin surface (38/58; 66% versus 6/21; 29%, P=0.011).

CONCLUSIONS
The interaction between thrombus and stent-retriever was predominantly adhesive, not mechanical. Adhesive interaction was strongly associated with the presence of a dense thrombus surface without a porous filamentous fibrin network.

Autar|Anouchska S A|ASA|
Hund|Hajo M|HM|
Ramlal|Sharad A|SA|
Hansen|Daniël|D|
Lycklama À Nijeholt|Geert J|GJ|
Emmer|Bart J|BJ|
de Maat|Moniek P M|MPM|
Dippel|Diederik W J|DWJ|
van der Lugt|Aad|A|
van Es|Adriaan C G M|ACGM|
van Beusekom|Heleen M M|HMM|
|||

thrombus
ischemic stroke
mechanical thrombectomy
scanning electron microscopy
stent‐retriever


Integrated treatment using intraperitoneal radioimmunotherapy and positron emission tomography-guided surgery with 64Cu-labeled cetuximab to treat early- and late-phase peritoneal dissemination in human gastrointestinal cancer xenografts.

Abstract: Peritoneal dissemination is a common cause of death from gastrointestinal cancers and is difficult to treat using current therapeutic options, particularly late-phase disease. Here, we investigated the feasibility of integrated therapy using 64Cu-intraperitoneal radioimmunotherapy (ipRIT), alone or in combination with positron emission tomography (PET)-guided surgery using a theranostic agent (64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab) to treat early- and late-phase peritoneal dissemination in mouse models. In this study, we utilized the OpenPET system, which has open space for conducting surgery while monitoring objects at high resolution in real time, as a novel approach to make PET-guided surgery feasible. 64Cu-ipRIT with cetuximab inhibited tumor growth and prolonged survival with little toxicity in mice with early-phase peritoneal dissemination of small lesions. For late-phase peritoneal dissemination, a combination of 64Cu-ipRIT for down-staging and subsequent OpenPET-guided surgery for resecting large tumor masses effectively prolonged survival. OpenPET clearly detected tumors (≥3 mm in size) behind other organs in the peritoneal cavity and was useful for confirming the presence or absence of residual tumors during an operation. These findings suggest that integrated 64Cu therapy can serve as a novel treatment strategy for peritoneal dissemination.

Yoshii|Yukie|Y|
Yoshimoto|Mitsuyoshi|M|
Matsumoto|Hiroki|H|
Tashima|Hideaki|H|
Iwao|Yuma|Y|
Takuwa|Hiroyuki|H|
Yoshida|Eiji|E|
Wakizaka|Hidekatsu|H|
Yamaya|Taiga|T|
Zhang|Ming-Rong|MR|
Sugyo|Aya|A|
Hanadate|Sayaka|S|
Tsuji|Atsushi B|AB|
Higashi|Tatsuya|T|

64Cu-labeled cetuximab
64Cu-intraperitoneal radioimmunotherapy
OpenPET
PET-guided surgery
integrated 64Cu therapy