Social monogamy vs. polyandry: ecological factors associated with sex roles in two closely related birds within the same habitat.

Abstract: Why mainly males compete and females take a larger share in parental care remains an exciting question in evolutionary biology. Role-reversed species are of particular interest, because such 'exceptions' help to test the rule. Using mating systems theory as a framework, we compared the reproductive ecology of the two most contrasting coucals with regard to sexual dimorphism and parental care: the black coucal with male-only care and the biparental white-browed coucal. Both species occur in the same lush habitat and face similar ecological conditions, but drastically differ in mating system and sexual dimorphism. Black coucals were migratory and occurred at high breeding densities. With females being obligatory polyandrous and almost twice as heavy as males, black coucals belong to the most extreme vertebrates with reversed sexual dimorphism. Higher variance in reproductive success in fiercely competing females suggests that sexual selection is stronger in females than in males. In contrast, resident white-browed coucals bred at low densities and invariably in pairs. They were almost monomorphic and the variance in reproductive success was similar between the sexes. Black coucals were more likely to lose nests than white-browed coucals, probably facilitating female emancipation of parental care in black coucals. We propose that a combination of high food abundance, high population density, high degree of nest loss and male bias in the adult sex ratio represent ecological conditions that facilitate role reversal and polyandry in coucals and terrestrial vertebrates in general.

Goymann|W|W| Makomba|M|M| Urasa|F|F| Schwabl|I|I|

parental care
mating system
coucal
variance in reproductive success
sexual selection
sex ratio
migration
predation
sex-role reversal


Circadian Phase and Phase Angle Disorders in Primary Insomnia.

Abstract:
Objectives
We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia.

Methods
We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days. Circadian phase was assessed from salivary dim light melatonin onset (DLMO) time during a 12-hour laboratory visit.

Results
Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46 females, 35.5 ± 12.3 years [M ± SD]) and 21 controls (14 females, 34.4 ± 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 hours vs. 24:13 ± 1:30 hours, respectively; p = .84) but had a later average DLMO times (20:56 ± 1:55 hours, 18:17-01:21 vs. 22:02 ± 2:02 hours, 17:11-04:52, respectively; p = .04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 hours (± 1:43) vs. 3:10 hours (± 1:08), respectively; p = .008), of whom 10% tried to sleep at or before DLMO (compared to 0 controls), and 22% tried to sleep before or within 1 hour after DLMO (compared to 6% of controls).

Conclusions
A substantial proportion (10%-22%) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.

Flynn-Evans|Erin E|EE|
Shekleton|Julia A|JA|
Miller|Belinda|B|
Epstein|Lawrence J|LJ|
Kirsch|Douglas|D|
Brogna|Lauren A|LA|
Burke|Liza M|LM|
Bremer|Erin|E|
Murray|Jade M|JM|
Gehrman|Philip|P|
Rajaratnam|Shantha M W|SMW|
Lockley|Steven W|SW|

D020178:Sleep Disorders, Circadian Rhythm

D007319:Sleep Initiation and Maintenance Disorders

circadian
phase angle
insomnia
melatonin
DLMO
6-sulfatoxymelatonin
circadian rhythms


MicroCT imaging as a tool to study vessel endings in situ.

Abstract:
PREMISE OF THE STUDY
Despite the strong influence of the frequency and distribution of vessel endings on both hydraulic safety and efficiency, detailed anatomical descriptions or measurements of these structures are generally lacking.

METHODS
Here we used high-resolution x-ray microcomputed tomography (microCT) to identify and describe xylem vessel endings within Acer rubrum root segments (1.0-2.1 mm diameter, ∼2 mm long). We then compared vessel-lumen diameter, pit density, vessel element length, and perforation plate angle between non-ending vessels (those that traverse an entire segment) and those that end within a segment using three-dimensional image analysis.

KEY RESULTS
We found 214 vessel endings, 37 complete vessels, and 385 non-ending vessels within four A. rubrum root segments. Vessels that ended within the segments tended to have more acute perforation plate angles and had a smaller diameter than those that did not end within the segments. Most vessel diameters tapered within the last few vessel elements, but the perforation plate angle apparently changed over longer distances. Intervessel pit density and vessel element length did not differ between ending and non-ending vessels.

CONCLUSIONS
Vessel endings were surprisingly frequent in A. rubrum roots despite the common perception that root vessels are longer than vessels in other tissues. MicroCT proved to be a useful tool for studying the three-dimensional arrangement of vessel endings within xylem networks, and these data will be helpful in developing a better understanding of vessel ending microstructure and function.

Wason|Jay W|JW|
Huggett|Brett A|BA|
Brodersen|Craig R|CR|

xylem
Acer rubrum
taper
intervessel pitting
Aceraceae
anatomy
end wall
termination
vessel network


Arthroscopic management of unexplained pain following total knee arthroplasty.

Abstract:
INTRODUCTION
Arthrofibrosis develops in 3-10% of knees after total knee arthroplasty (TKA), which may result in pain and restricted range-of-motion. Treatment options include manipulation under anaesthesia, arthroscopic debridement, and quadricepsplasty, but there is little consensus on their efficacy for treatment of unexplained pain after TKA. The purpose of this study was to report the prevalence and characteristics of unexplained pain after TKA as revealed by arthroscopic exploration, and assess the efficacy of arthroscopic procedures to relieve pain.

MATERIALS AND METHODS
From a consecutive series of 684 TKAs, 11 patients (1.6%) had unexplained pain at 7-48 months after TKA. Causes of pain remained unidentified after systematic and differential assessment, but arthroscopic exploration revealed fibrotic tissues, which were debrided during the same procedure. Patients were assessed first at 6-61 months and last at 90-148 months, with pain on a visual analog scale (pVAS) and range-of-motion recorded during both assessments, but Oxford Knee Score (OKS) and Forgotten Joint Score (FJS) only during the last assessment. Residual pain was classified as little or no pain (pVAS, 0-1), moderate pain (pVAS, 2-4), and severe pain (pVAS, 5-10).

RESULTS
At first follow-up (n = 11) pVAS improved by 4.1 ± 1.1 (p < 0.001), and range-of-motion improved by 5.0° ± 7.1° (p = 0.041). Seven patients (64%) had little or no residual pain, while four (36%) had moderate residual pain. At final follow-up (n = 9) pVAS improved by 3.2 ± 2.9 (p < 0.001), and range-of-motion improved by 4.4° ± 8.5° (p = 0.154). Six patients (67%) had little or no residual pain, while one (11%) had moderate and two (22%) had severe residual pain.

CONCLUSION
Arthroscopic exploration revealed that all 11 knees with unexplained pain had fibrotic tissues, the removal of which alleviated pain in only 67%, while moderate to severe pain persisted in 33% which merits further scrutiny.

Unexplained pain
Total knee arthroplasty
Arthroscopy
Fibrosis
Patient reported outcomes
Total knee replacement


Salami-Tactics: when is it time for a major cut after multiple minor amputations?

Abstract:
INTRODUCTION
Repetitive minor amputations carry the concomitant risks of multiple surgical procedures, major amputations have physical and economical major drawbacks. The aim of this study was to evaluate whether there is a distinct number of minor amputations predicting a major amputation in the same leg and to determine risk factors for major amputation in multiple minor amputations.

MATERIALS AND METHODS
A retrospective chart review including 429 patients with 534 index minor amputations between 07/1984 and 06/2019 was conducted. Patient demographics and clinical data including number and level of re-amputations were extracted from medical records and statistically analyzed.

RESULTS
290 legs (54.3%) had one or multiple re-amputations after index minor amputation. 89 (16.7%) legs needed major amputation during follow up. Major amputation was performed at a mean of 32.5 (range 0 - 275.2) months after index minor amputation. No particular re-amputation demonstrated statistically significant elevated odds ratio (a.) to be a major amputation compared to the preceding amputation and (b.) to lead to a major amputation at any point during follow up. Stepwise multivariate Cox regression analysis revealed minor re-amputation within 90 days (HR 3.8, 95% CI 2.0-7.3, p <0.001) as the only risk factor for major amputation if at least one re-amputation had to be performed.

CONCLUSIONS
There is no distinct number of prior minor amputations in one leg that would justify a major amputation on its own. If a re-amputation has to be done, the timepoint needs to be considered as re-amputations within 90 days carry a fourfold risk for major amputation.

LEVEL OF EVIDENCE
Retrospective comparative study (Level III).

Minor Amputation
Major Amputation
Diabetes
Osteomyelitis
PAD
Ulcer


CircRNA-100338 Is Associated With mTOR Signaling Pathway and Poor Prognosis in Hepatocellular Carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. Despite advances in the diagnosis and treatment of HCC, incidence, and mortality continue to rise. For accurate diagnosis and treatment of HCC, there is an urgent need to precisely understand the molecular mechanisms underlying HCC tumorigenesis and progression. Accumulating evidence showed that circRNAs, which are normally produced by scrambling of exons at the splicing process, are recognized as a novel class of endogenous noncoding RNA, which have microRNA sponging properties. In this study, we aim to investigate the circRNA-100338 mediated downstream pathway, and evaluate its association with clinicopathological parameters. Integrated analysis of circRNA-100338, miR-141-3p, and target genes revealed that RHEB, a key regulator in mTOR signaling pathway, was the target of miR-141-3p in hepatitis B-related HCC. CircRNA-100338 regulates the activity of mTOR signaling pathway in vitro. IHC analysis revealed that mTOR signaling pathway was more active in HCC tissues with elevated circRNA-100338 expression. These results indicated that circRNA-100338 could regulate mTOR signaling pathway through circRNA-100338/miR-141-3p/RHEB axis. Finally, correlation analysis of RHEB and EIF5 expression with clinicopathological parameters of HCC patients revealed that the circRNA-100338, RHEB, and EIF5 were indicators of poor prognosis in hepatitis B-related HCC. In conclusion, elevated circRNA-100338 activates mTOR signaling pathway in HCC via circRNA-100338/miR-141-3p/RHEB axis and associates with poor prognosis of hepatitis B-related HCC patients.

Huang|Xiu-Yan|XY| Huang|Zi-Li|ZL| Zhang|Ping-Bao|PB| Huang|Xin-Yu|XY| Huang|Jin|J| Wang|Hong-Cheng|HC| Xu|Bin|B| Zhou|Jian|J| Tang|Zhao-You|ZY|


Inferring mobility measures from GPS traces with missing data.

Abstract: With increasing availability of smartphones with Global Positioning System (GPS) capabilities, large-scale studies relating individual-level mobility patterns to a wide variety of patient-centered outcomes, from mood disorders to surgical recovery, are becoming a reality. Similar past studies have been small in scale and have provided wearable GPS devices to subjects. These devices typically collect mobility traces continuously without significant gaps in the data, and consequently the problem of data missingness has been safely ignored. Leveraging subjects' own smartphones makes it possible to scale up and extend the duration of these types of studies, but at the same time introduces a substantial challenge: to preserve a smartphone's battery, GPS can be active only for a small portion of the time, frequently less than $10\%$, leading to a tremendous missing data problem. We introduce a principled statistical approach, based on weighted resampling of the observed data, to impute the missing mobility traces, which we then summarize using different mobility measures. We compare the strengths of our approach to linear interpolation (LI), a popular approach for dealing with missing data, both analytically and through simulation of missingness for empirical data. We conclude that our imputation approach better mirrors human mobility both theoretically and over a sample of GPS mobility traces from 182 individuals in the Geolife data set, where, relative to LI, imputation resulted in a 10-fold reduction in the error averaged across all mobility features.

D056808:Biostatistics
D004812:Epidemiologic Methods
D040362:Geographic Information Systems
D062305:Geographic Mapping
D006801:Humans
D062206:Spatial Analysis

Mobility
GPS
Missing data
Imputation
Precision medicine
mHealth


Deep learning-based evaluation of the relationship between mandibular third molar and mandibular canal on CBCT.

Abstract:
OBJECTIVES
The objective of our study was to develop and validate a deep learning approach based on convolutional neural networks (CNNs) for automatic detection of the mandibular third molar (M3) and the mandibular canal (MC) and evaluation of the relationship between them on CBCT.

MATERIALS AND METHODS
A dataset of 254 CBCT scans with annotations by radiologists was used for the training, the validation, and the test. The proposed approach consisted of two modules: (1) detection and pixel-wise segmentation of M3 and MC based on U-Nets; (2) M3-MC relation classification based on ResNet-34. The performances were evaluated with the test set. The classification performance of our approach was compared with two residents in oral and maxillofacial radiology.

RESULTS
For segmentation performance, the M3 had a mean Dice similarity coefficient (mDSC) of 0.9730 and a mean intersection over union (mIoU) of 0.9606; the MC had a mDSC of 0.9248 and a mIoU of 0.9003. The classification models achieved a mean sensitivity of 90.2%, a mean specificity of 95.0%, and a mean accuracy of 93.3%, which was on par with the residents.

CONCLUSIONS
Our approach based on CNNs demonstrated an encouraging performance for the automatic detection and evaluation of the M3 and MC on CBCT. Clinical relevance An automated approach based on CNNs for detection and evaluation of M3 and MC on CBCT has been established, which can be utilized to improve diagnostic efficiency and facilitate the precision diagnosis and treatment of M3.

Mandibular third molar
Mandibular canal
CBCT
Deep learning
Convolutional neural networks


Reversible Strategy of Water Monitoring Aimed at Amphiphilic Pollutants.

Abstract: For monitoring diverse pollutants in a complicated water environment, the design and development of various detection strategies are necessary. Here, we introduce a general strategy of water monitoring aimed at amphiphilic pollutants using carbon nanotube based film. The pollutants with amphiphilic characteristics can tune the wetting behavior between carbon nanotubes and water molecules, leading to the change in the interface resistance of the carbon nanotube based film. The experimental results demonstrate that the change ratio of the film resistance is related to the concentration of pollutants in solution. This monitoring strategy is general for the detection of amphiphilic materials in mixed solution, such as surfactants and some organic solvent. The ability to achieve a sensitive and repeatable change in film resistance has potential applications in high-sensitivity, real-time, long-lasting, and multiple water monitoring.

Zhang|Quan|Q| Meng|Peng|P| Wu|Yulong|Y| Zheng|Ruiting|R| Wu|Xiaoling|X| Cheng|Guoan|G|

water monitoring
wetting behavior
interface resistance
amphiphilic property
conductivity


Gross anatomy and ultrastructure of Moorish Gecko, Tarentola mauritanica skin.

Abstract: The epidermis of Tarentola mauritanica in the skin regions of back, flank and belly has been described using light and electron microscopy. This animal model was useful to give an insight of the functional pattern involved in pigmentation, cryptism and photosensitivity. Skin from back and flanks, in electron microscopy, shows a high concentration of chromatophores, among those melanophores, xanthophores and iridophores have been reported. Interestingly, in the flank-back transition region electron microscopy reveals the presence of nerve endings. Our contribution adds new knowledge about the skin of this species, and it could be useful to study in deep the mechanism of cryptic colour change in reptiles.

Avallone|Bice|B| Tizzano|Monica|M| Cerciello|Raimondo|R| Buglione|Maria|M| Fulgione|Domenico|D|


Molecular genetics of citrullinemia types I and II.

Abstract: Over the past decade, the ASS1 and SLC25A13 genes, which are responsible for citrullinemia types I and II, have been identified, and numerous mutations in these genes have been reported. The clinical manifestations of citrullinemia are quite heterogeneous, and most studies have reported mutations in a small number of patients from a few families. Comprehensive integration of previous knowledge is important to understand the mutation spectrum and effect of the mutations on clinical manifestations. Therefore, we reviewed the English literature on mutations in the ASS and SLC25A13 genes, and their genotype-phenotype correlations to provide valuable insights into the molecular genetic background of citrullinemia types I and II.

Woo|Hye In|HI|
Park|Hyung-Doo|HD|
Lee|Yong-Wha|YW|

D033681:Mitochondrial Membrane Transport Proteins


Comprehensive cardiac magnetic resonance imaging and spectroscopy reveal a high burden of myocardial disease in HIV patients.

Abstract:
BACKGROUND
HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy.

METHODS AND RESULTS
Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels (P <0.003) and 74% higher median plasma triglyceride levels (both P<0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects (P<0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders.

CONCLUSIONS
Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.

Holloway|Cameron J|CJ|
Ntusi|Ntobeko|N|
Suttie|Joseph|J|
Mahmod|Masliza|M|
Wainwright|Emma|E|
Clutton|Genevieve|G|
Hancock|Gemma|G|
Beak|Philip|P|
Tajar|Abdelouahid|A|
Piechnik|Stefan K|SK|
Schneider|Jurgen E|JE|
Angus|Brian|B|
Clarke|Kieran|K|
Dorrell|Lucy|L|
Neubauer|Stefan|S|

myocardial fibrosis
fibrosis
HIV-1
heart function tests
imaging, diagnostic


Emulating human microcapillaries in a multi-organ-chip platform.

Abstract: Current microfluidic chip-based tissue culture systems lack a capillary endothelial vessel system, which would enable perfusion with blood. We utilise spatial cell cultures to populate a perfused multi-organ-chip platform-a microfluidic device recently introduced for substance testing. Complete biological vascularization of such culture systems is vital to properly emulate physiological tissue behaviour. In this study, we incorporated a fibrin scaffold into the two-organ-chip design. Herein, adipose-derived stromal cells (ASCs) directed human umbilical vein endothelial cells (HUVECs) to organise into tube-like structures. The ASCs induced tube formation of HUVECs in static and dynamic conditions. The replacement of full medium enriched with growth factors and foetal calf serum with basal medium resulted in viable cells with similar gene expression profiles. We regard this as a prerequisite for studies with organ constructs that have a need for a different medium formulation. Furthermore, we here address stability issues of the fibrin gel and fibrin composition for optimal microvessel formation.

Hasenberg|Tobias|T| Mühleder|Severin|S| Dotzler|Andrea|A| Bauer|Sophie|S| Labuda|Krystyna|K| Holnthoner|Wolfgang|W| Redl|Heinz|H| Lauster|Roland|R| Marx|Uwe|U|

D061307:Human Umbilical Vein Endothelial Cells

Multi-organ-chip
Fibrin scaffold
Co-culture models
Tissue engineering
Vasculature
Vasculogenesis


H2S induces Th1/Th2 imbalance with triggered NF-κB pathway to exacerbate LPS-induce chicken pneumonia response.

Abstract: H2S is one of the air pollutants, which can cause multiple organ damage to the body. H2S exposure will directly damage respiratory system and cause inflammatory reaction. In this experiment, the effect of H2S on LPS-induce chicken pneumonia is explored from the Th1/Th2 balance and the NF-κB pathway. 42-day-old broilers was selected as research object, exposed to exogenous H2S, received an intraperitoneal injection of LPS to establish inflammatory model on forty-second days. We carry out qRT-PCR and Western blot to detect the expression of cytokines secreted by Th1/Th2, PPAR-γ/HO-1 genes, NF-κB pathway genes and the downstream genes COX-2 and iNOS. We found the expression of IL-4, IL-6, TNF-α and IL-1β increased and that of IFN-γ decreased, which indicating the immune imbalance of Th1/Th2 was occurred and the level of PPAR-γ/HO-1 was significantly suppressed. In addition, the activation of I-κB-β and NF-κB genes with the degradation of I-κB-α indicated that NF-κB pathway has been activated, which accompanied with COX-2, PGE and iNOS increasing. These results suggested that H2S exposure can lead to Th1/Th2 immune imbalance, repress the anti-inflammatory effect of PPAR-γ/HO-1, and then activate NF-κB pathway-related genes and the downstream genes to aggravate pneumonia induced by LPS.

Wang|Wei|W| Chen|Menghao|M| Jin|Xi|X| Li|Xiaojing|X| Yang|Zijiang|Z| Lin|Hongjin|H| Xu|Shiwen|S|

Chicken lungs
H(2)S
Inflammation
NF-κB-pathway


Social stigmatization in Turkish patients with chronic hepatitis B and C.

Abstract:
BACKGROUND AND AIM
Viral hepatitis is the most important cause of chronic hepatitis worldwide. Stigmatization is defined as a feeling of rejection and isolation of patients by society due to illness. There are no studies on chronic viral hepatitis in the literature in English, which has its own religious and socio-cultural structure. In our study, we aimed to investigate the presence of social stigmatism and psychosocial effects on patients with different stages of chronic viral hepatitis B and C.

METHODS
Forty-five patients with chronic hepatitis C and 114 patients with chronic hepatitis B were enrolled in the study. Berger's scale was used for stigmatization, composed of 40 four-point Likert items that have four subscales: personalized stigma, disclosure, negative self-image, and public attitude. Stigma score ranges between one and four. Stigma is accepted as present if the overall score is above two.

RESULTS
Overall the mean stigma scores were 1.97±0.58 and 2.14±0.57 for chronic hepatitis B and C, respectively. There was stigma in 47.4% of the patients with chronic hepatitis B, and 60% of the patients with chronic hepatitis C. Being male was the risk factor on overall stigma, disclosure and public attitude in chronic hepatitis C. Living in an urban setting was the risk factor on negative self-image in chronic hepatitis C and on personalized stigma and disclosure in chronic hepatitis B.

CONCLUSIONS
To the best of our knowledge, this is the first study that provides qualitative information about chronic hepatitis-related stigma. Stigmatization is a major problem in Turkey and worldwide. We believe that increasing the knowledge of the patients and society by teaching about the transmission routes of the disease and focusing on vaccination studies will prevent stigmatization.

Yozgat|Ahmet|A| Can|Guray|G| Can|Hatice|H| Ekmen|Nergiz|N| Akyol|Taner|T| Kasapoglu|Benan|B| Kekilli|Murat|M|

Stigmatization
Chronic hepatitis B
Chronic hepatitis C
Estigmatización
Hepatitis B crónica
Hepatitis C crónica


Fecal incontinence after total mesorectal excision for rectal cancer-impact of potential risk factors and pelvic intraoperative neuromonitoring.

Abstract:
BACKGROUND
Fecal incontinence frequently occurs after total mesorectal excision for rectal cancer. This prospective study analyzed predictive factors and the impact of pelvic intraoperative neuromonitoring at different follow-up intervals.

METHODS
Fifty-two patients were included undergoing total mesorectal excision for rectal cancer, and 29 under control of pelvic intraoperative neuromonitoring. Fecal incontinence was assessed using the Wexner Score at 3 and 6 months after stoma closure (follow-ups 1 and 2) as well as 1 and 2 years after surgery (follow-ups 3 and 4). Risk factors were identified by means of logistic regression.

RESULTS
New onset of fecal incontinence was significantly lower in the neuromonitoring group at each follow-up (follow-up 1: 2 of 29 patients (7%) vs. 8 of 23 (35%), (p = 0.014); follow-up 2: 3 of 29 (10%) vs. 9 of 23 (39%), (p = 0.017); follow-up 3: 5 of 29 (17%) vs. 11 of 23 (48%), p = 0.019; follow-up 4: 6 of 28 (21%) vs. 11 of 22 (50%), p = 0.035). Non-performance of neuromonitoring was found to be an independent predictor for fecal incontinence throughout the survey. Neoadjuvant chemoradiotherapy was an independent predictor in the further course 1 and 2 years after surgery.

CONCLUSIONS
Performance of pelvic intraoperative neuromonitoring is associated with significantly lower rates of fecal incontinence. Neoadjuvant chemoradiotherapy was found to have negative late effects. This became evident 1 year after surgery.

Fecal incontinence
Rectal cancer
Autonomic nervous system
Intraoperative monitoring
Neoadjuvant therapy


Leptin Potentiates BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling.

Abstract: Mesenchymal stem cells (MSCs) are multipotent progenitors that have the ability to differentiate into multiple lineages, including bone, cartilage, and fat. We previously demonstrated that the least known bone morphogenetic protein (BMP)9 (also known as growth differentiation factor 2) is one of the potent osteogenic factors that can induce both osteogenic and adipogenic differentiation of MSCs. Nonetheless, the molecular mechanism underlying BMP9 action remains to be fully understood. Leptin is an adipocyte-derived hormone in direct proportion to the amount of body fat, and exerts pleiotropic functions, such as regulating energy metabolism, bone mass, and mineral density. In this study, we investigate the potential effect of leptin signaling on BMP9-induced osteogenic differentiation of MSCs. We found that exogenous leptin potentiated BMP9-induced osteogenic differentiation of MSCs both in vitro and in vivo, while inhibiting BMP9-induced adipogenic differentiation. BMP9 was shown to induce the expression of leptin and leptin receptor in MSCs, while exogenous leptin upregulated BMP9 expression in less differentiated MSCs. Mechanistically, we demonstrated that a blockade of JAK signaling effectively blunted leptin-potentiated osteogenic differentiation induced by BMP9. Taken together, our results strongly suggest that leptin may potentiate BMP9-induced osteogenesis by cross-regulating BMP9 signaling through the JAK/STAT signaling pathway in MSCs. Thus, it is conceivable that a combined use of BMP9 and leptin may be explored as a novel approach to enhancing efficacious bone regeneration and fracture healing.

Zhang|Bo|B|
Yang|Lijuan|L|
Zeng|Zongyue|Z|
Feng|Yixiao|Y|
Wang|Xi|X|
Wu|Xiaoxing|X|
Luo|Huaxiu|H|
Zhang|Jing|J|
Zhang|Meng|M|
Pakvasa|Mikhail|M|
Wagstaff|William|W|
He|Fang|F|
Mao|Yukun|Y|
Qin|Kevin|K|
Ding|Huimin|H|
Zhang|Yongtao|Y|
Niu|Changchun|C|
Wu|Meng|M|
Zhao|Xia|X|
Wang|Hao|H|
Huang|Linjuan|L|
Shi|Dayao|D|
Liu|Qing|Q|
Ni|Na|N|
Fu|Kai|K|
Athiviraham|Aravind|A|
Moriatis Wolf|Jennifer|J|
Lee|Michael J|MJ|
Hynes|Kelly|K|
Strelzow|Jason|J|
El Dafrawy|Mostafa|M|
Xia|Yayi|Y|
He|Tong-Chuan|TC|

leptin
osteogenic differentiation
mesenchymal stem cells
BMP9
bone mass
osteogenesis
adipogenesis


Delirium-A Framework to Improve Acute Care for Older Persons.

Abstract: This article is based on the M. Powell Lawton Award Lecture that I delivered at the 2016 Gerontological Society of America Annual Meeting. I provide an overview of my journey in geriatric medicine and delirium research. I created new measures, including the Confusion Assessment Method, for identification of delirium; conceptualized a multifactorial risk model; and developed and tested intervention strategies for delirium prevention. The Hospital Elder Life Program arose from this work. In addition, like Dr. Lawton, I am working to apply my work to the policy arena. As the population ages, we face an unprecedented opportunity to realize the full benefit of aging in our society, an untapped resource. The field of aging is facing innumerable challenges in terms of continued stigma and funding shortfalls for clinical care and research. I issue a call to action to clinicians, researchers, and leaders in aging to seize this opportunity to use our know-how and expertise to transform the experience of aging for all.

D000368:Aged
D000369:Aged, 80 and over
D002983:Clinical Competence
D003693:Delirium
D015577:Geriatric Assessment
D005851:Geriatric Nursing
D006299:Health Services for the Aged
D006801:Humans
D018802:Patient-Centered Care

Delirium
Confusion Assessment Method
Hospital Elder Life Program
Acute care for elders


Uplink Sparse Channel Estimation for Hybrid Millimeter Wave Massive MIMO Systems by UTAMP-SBL.

Abstract: The compressive sensing (CS)-based sparse channel estimator is recognized as the most effective solution to the excessive pilot overhead in massive MIMO systems. However, due to the complex signal processing in the wireless communication systems, the measurement matrix in the CS-based channel estimation is sometimes "unfriendly" to the channel recovery. To overcome this problem, in this paper, the state-of-the-art sparse Bayesian learning using approximate message passing with unitary transformation (UTAMP-SBL), which is robust to various measurement matrices, is leveraged to address the multi-user uplink channel estimation for hybrid architecture millimeter wave massive MIMO systems. Specifically, the sparsity of channels in the angular domain is exploited to reduce the pilot overhead. Simulation results demonstrate that the UTAMP-SBL is able to achieve effective performance improvement than other competitors with low pilot overhead.

channel estimation
compressive sensing
sparse Bayesian learning
millimeter-wave massive MIMO


Towards Biohydrogen Separation Using Poly(Ionic Liquid)/Ionic Liquid Composite Membranes.

Abstract: Considering the high potential of hydrogen (H₂) as a clean energy carrier, the implementation of high performance and cost-effective biohydrogen (bioH₂) purification techniques is of vital importance, particularly in fuel cell applications. As membrane technology is a potentially energy-saving solution to obtain high-quality biohydrogen, the most promising poly(ionic liquid) (PIL)⁻ionic liquid (IL) composite membranes that had previously been studied by our group for CO₂/N₂ separation, containing pyrrolidinium-based PILs with fluorinated or cyano-functionalized anions, were chosen as the starting point to explore the potential of PIL⁻IL membranes for CO₂/H₂ separation. The CO₂ and H₂ permeation properties at the typical conditions of biohydrogen production (T = 308 K and 100 kPa of feed pressure) were measured and discussed. PIL⁻IL composites prepared with the [C(CN)₃]- anion showed higher CO₂/H₂ selectivity than those containing the [NTf₂]- anion. All the membranes revealed CO₂/H₂ separation performances above the upper bound for this specific separation, highlighting the composite incorporating 60 wt% of [C₂mim][C(CN)₃] IL.

Gouveia|Andreia S L|ASL|
Ventaja|Lucas|L|
Tomé|Liliana C|LC|
Marrucho|Isabel M|IM|

CO2/H2 separation
PIL–IL composite membranes
biohydrogen purification
gas permeation properties


Liver transplantation using hepatitis B core positive grafts with antiviral monotherapy prophylaxis.

Abstract:
BACKGROUND & AIMS
The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients.

METHODS
This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors.

RESULTS
A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT.

CONCLUSIONS
De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant.

LAY SUMMARY
The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.

Wong|Tiffany Cho-Lam|TC|
Fung|James Yan-Yue|JY|
Cui|Tracy Yu-Shi|TY|
Lam|Allan Hoi-Kin|AH|
Dai|Jeff Wing-Chiu|JW|
Chan|Albert Chi-Yan|AC|
Cheung|Tan-To|TT|
Chok|Kenneth Siu-Ho|KS|
Ng|Kelvin Kwok-Chai|KK|
Lo|Chung-Mau|CM|

Entecavir
De novo HBV
De novo hepatocellular carcinoma
Extended criteria organ
Long-term survival


Augmented ustekinumab dosing is needed to achieve clinical response in patients with anti-TNF refractory pediatric Crohn's disease: a retrospective chart review.

Abstract: Background: Ustekinumab is a monoclonal antibody that inhibits interleukins 12 and 23. It is approved for treatment of Crohn's disease (CD) in adults; however, there is a paucity of data regarding its use in pediatric CD. We describe our experience using ustekinumab in anti-TNF refractory CD pediatric patients. Methods: We performed a retrospective chart review on pediatric patients with CD who were started on ustekinumab from January 2016 to November 2018. We collected patient's clinical history, previous treatment history, surgeries related to CD, disease severity, as measured by abbrPCDAI, and endoscopic severity as recorded by SES-CD before and after ustekinumab. Results: We identified 10 patients with CD who were started on ustekinumab due to non-response to currently approved agents. Seven patients needed augmented maintenance dosing every 4-6 weeks to achieve clinical response or remission. Six of these seven patients had therapeutic drug monitoring during the course of treatment, with five patients showing subtherapeutic drug levels of <4.5 μg/mL while on standard maintenance dosing every 8 weeks, and four patients showing therapeutic drug levels of >4.5 μg/mL on augmented dosing interval. The remaining three patients were on standard maintenance dosing for the duration of treatment. Conclusion: In this retrospective chart review, 7 out of 10 patients with anti-TNF refractory pediatric-onset CD required augmented maintenance doses of ustekinumab to achieve clinical response or remission. A prospective study is needed to define appropriate ustekinumab dosing and interval in management of pediatric CD.

Do|Phinga|P|0000-0003-2255-9991 Andersen|John|J| Patel|Ashish|A| Semrin|Gaith|G| Sifuentes-Dominguez|Luis|L| Luu|Phuong|P| Gurram|Bhaskar|B|0000-0003-3169-2225

D000079424:Tumor Necrosis Factor Inhibitors

Ustekinumab
Clinical response
Pediatric Crohn's disease
Therapeutic drug monitoring
Inflammatory bowel disease
anti-TNF-refractory Crohn's disease


Malignant lymphoma mimics miliary tuberculosis by diffuse micronodular radiographic findings.

Abstract: This case reports rare findings on computed tomography of a manifestation of malignant lymphoma, in which diffuse lung shadows appeared as miliary nodules distributed throughout the lungs bilaterally. The patient had a history of surgical treatment of rectal cancer and had received chemotherapy for suspicious liver metastasis. At her current presentation for evaluation suspected miliary tuberculosis on chest radiography, subsequent liver biopsy revealed a mass infiltration of atypical lymphocytes, which was diagnosed as follicular lymphoma. The miliary tuberculosis was suspected more than neoplastic lesions, such as metastatic rectal cancer or malignant lymphoma. Despite repeated bacteriologic tests of various samples, including sputum, urine, bronchial secretion, peripheral blood, bone marrow aspiration, and gastric lavage, all results were negative for mycobacterium tuberculosis. Finally, multiple, small, mass lesions of lymphocytes were demonstrated in the lung obtained from video-assisted thoracic surgery, and a diagnosis of follicular lymphoma was given. The final interpretations of liver mass and military lung lesions were tumor involvement by the follicular lymphoma. This radiologic findings of multiple miliary opacities throughout the whole lungs confused definite diagnosis because these images were remarkably similar with miliary tuberculous. This case reminds us to consider a wide variety of differential diagnoses even we assumed to be familiar with radiographic imaging at first glance.

Yagyu|Kyoko|K| Kobayashi|Masaaki|M| Ueda|Takahiro|T| Uenishi|Riki|R| Nakatsuji|Yuko|Y| Matsushita|Haruhiko|H|

Follicular lymphoma
Miliary opacity
Diagnostic imaging
Pulmonary secondary lymphoma


Optimizing the Profile of [99mTc]Tc-NT(7-13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors.

Abstract:
BACKGROUND
The overexpression of neurotensin subtype 1 receptors (NTS1Rs) in human tumors may be elegantly exploited for directing neurotensin (NT)-based radionuclide carriers specifically to cancer sites for theranostic purposes. We have recently shown that [99mTc]Tc-DT1 ([99mTc]Tc-[N4-Gly7]NT(7-13)) and [99mTc]Tc-DT5 ([99mTc]Tc-[N4-βAla7,Dab9]NT(7-13)) show notably improved uptake in human colon adenocarcinoma WiDr xenografts in mice treated with neprilysin (NEP) inhibitors and/or angiotensin-converting enzyme (ACE) inhibitors compared with untreated controls. Aiming toward translation of this promising approach in NTS1R-positive pancreatic ductal adenocarcinoma (PDAC) patients, we now report on the impact of registered NEP/ACE inhibitors on the performance of [99mTc]Tc-DT1 and [99mTc]Tc-DT5 in pancreatic cancer models.

METHODS
The cellular uptake of [99mTc]Tc-DT1 and [99mTc]Tc-DT5 was tested in a panel of pancreatic cell lines, and their stability was assessed in mice treated or not treated with Entresto, lisinopril, or their combinations. Biodistribution was conducted in severe combined immunodeficiency (SCID) mice bearing pancreatic AsPC-1 xenografts.

RESULTS
The Entresto + lisinopril combination maximized the metabolic stability of the fast-internalizing [99mTc]Tc-DT1 in mice, resulting in notably enhanced tumor uptake (7.05 ± 0.80% injected activity (IA)/g vs. 1.25 ± 0.80% IA/g in non-treated controls at 4 h post-injection; p < 0.0001).

CONCLUSIONS
This study has shown the feasibility of optimizing the uptake of [99mTc]Tc-DT1 in pancreatic cancer models with the aid of clinically established NEP/ACE inhibitors, in favor of clinical translation prospects.

Kanellopoulos|Panagiotis|P|
Nock|Berthold A|BA|0000-0002-6028-9112
Krenning|Eric P|EP|
Maina|Theodosia|T|0000-0002-1123-2486

pancreatic cancer
neurotensin
neurotensin subtype 1 receptor
theranostics
neprilysin
Entresto
lisinopril
clinical translation
[99mTc]Tc radiotracer
angiotensin_converting enzyme


Nutrient Challenge Testing Is Not Equivalent to Scintigraphy-Lactulose Hydrogen Breath Testing in Diagnosing Small Intestinal Bacterial Overgrowth.

Abstract:
Background/Aims
Small intestinal bacterial overgrowth (SIBO) is a common condition in disorders of gut-brain interaction (DGBI). Recently, a combined scintigraphy-lactulose hydrogen breath test (ScLHBT) was described as an accurate tool diagnosing SIBO. We aim to analyze whether a lactulose nutrient challenge test (NCT), previously shown to separate DGBI from healthy volunteers, is equivalent to ScLHBT in diagnosing SIBO.

Methods
We studied data of 81 DGBI patients undergoing ScLHBT with 30 g lactulose and 300 mL water as well as NCT with 30 g lactulose and a 400 mL liquid test meal. Differences in proportion of positive SIBO diagnoses according to specified cecal load and time criteria for NCT and ScLHBT, respectively, were tested in an equivalence trial. An odds ratio (OR) range of 0.80-1.25 was considered equivalent.

Results
Diagnosis of SIBO during NCT was not equivalent to SIBO diagnosis in ScLHBT, considering a hydrogen increase before cecal load of 5.0%, 7.5%, or 10.0%, respectively ([OR, 3.76; 90% CI, 1.99-7.09], [OR, 1.87; 90% CI, 1.06-3.27], and [OR, 1.11; 90% CI, 0.65- 1.89]). Considering only time to hydrogen increase as criterion, the odds of a positive SIBO diagnosis in the NCT (0.65) was lower than in ScLHBT (1.70) (OR, 0.38; 90% CI, 0.23-0.65).

Conclusions
This study could not show an equivalence of NCT and ScLHBT in diagnosing SIBO. A possible explanation might be the different transit times owing to unequal testing substances. The effect of this deviation in relation to consecutive therapy regimens should be tested in further prospective studies.

Schindler|Valeria|V|
Huellner|Martin|M|
Murray|Fritz|F|
Schnurre|Larissa|L|
Becker|Anton S|AS|
Bordier|Valentine|V|
Pohl|Daniel|D|

Nutrients
Hydrogen
Breath test
Lactulose
Radionuclide imaging


Risk of female-specific cancers according to obesity and menopausal status in 2•7 million Korean women: Similar trends between Korean and Western women.

Abstract:
Background
Studies examining the relationship between obesity and female-specific cancers have been mainly conducted in Western populations. We aimed to investigate the risk of female-specific cancers according to obesity and menopausal status using a nationwide cohort in Korea.

Methods
We identified 2,708,938 women from the National Health Insurance Service cohort, and obtained baseline body mass index (BMI), waist circumference (WC), and other healthcare data, measured and collected during a health examinations and cancer-screening survey. By setting a normal weight/WC group (BMI, 18•5-22•9 kg/m2 or WC, 80•0-84•9 cm) as the reference, we conducted multivariate analyses using the Cox proportional hazard model to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for each cancer.

Findings
The total follow-up duration was 22389854•63 person-years. In post-menopausal women, the risk of breast, endometrial, and ovarian cancers significantly increased as the BMI classification level increased from normal to class II obesity (aHRs [95% CIs], 1•49 [1•38-1.61], 2•11 [1•81-2•46], and 1•38 [1•20-1•58], respectively). The risk of breast and endometrial cancers also increased as the WC classification increased from < 75•0 to ≥ 95•0 cm. With a WC of 80•0-84•9 cm as the reference, the lowest risk of breast and endometrial cancers was observed in WC < 75•0 cm (aHRs [95% CIs], 0•85 [0•81-0•89] and 0•75 [0•67-0•84], respectively) while the highest risk was observed in WC ≥ 95•0 cm (aHRs [95% CIs], 1•19 [1•10-1•29] and 1•56 [1•33-1•82], respectively). In pre-menopausal women, the risk of breast cancer significantly decreased in those with class I and II obesity compared to those with normal BMI (aHRs [95% CIs], 0•96 [0•92-0•999] and 0•89 [0•81-0•97], respectively), whereas the trends of endometrial and ovarian cancer incidence in pre-menopausal women were similar to those observed in post-menopausal women. For cervical cancer, only class II obesity was significantly associated with increased risks in both post-menopausal and pre-menopausal women (aHRs [95% CIs], 1•18 [1•01-1•39] and 1•27 [1•02-1•57], respectively).

Interpretation
In this large population-based cohort study in Korean women, we observed that the impact of obesity on the development of female-specific cancers differs according to the malignancy type and menopausal status. Similar trends were observed between Korean and Western women.

Funding
The Korea Health Industry Development Institute (no. HI16C2037).

Park|In Sil|IS|
Kim|Se Ik|SI|
Han|Youngjin|Y|
Yoo|Juhwan|J|
Seol|Aeran|A|
Jo|HyunA|H|
Lee|Juwon|J|
Wang|Wenyu|W|
Han|Kyungdo|K|
Song|Yong Sang|YS|

Obesity
Menopause
Body mass index
Waist circumference
Ovarian cancer
Endometrial cancer
Breast cancer
Incidence
Cervical cancer


Migraine, Celiac Disease and Intestinal Microbiota.

Abstract: Investigators from four European tertiary care hospitals (in Paris, France; Milan, Udine and Perugia, Italy) performed a case-control study of children and adolescents aged 6 to 17 years diagnosed with primary headaches in the emergency department by a pediatric neurologist using the validated ICHD-3 criteria.

Celiac Disease
Headache
Gastrointestinal Microbiota


It's time to move on from the bell curve.

Abstract: The bell curve was first described in the 18th century by de Moivre and Gauss to depict the distribution of binomial events, such as coin tossing, or repeated measures of physical objects. In the 19th and 20th centuries, the bell curve was appropriated, or perhaps misappropriated, to apply to biologic and social measures across people. For many years we used it to derive reference values for our electrophysiologic studies. There is, however, no reason to believe that electrophysiologic measures should approximate a bell-curve distribution, and empiric evidence suggests they do not. The concept of using mean ± 2 standard deviations should be abandoned. Reference values are best derived by using non-parametric analyses, such as percentile values. This proposal aligns with the recommendation of the recent normative data task force of the American Association of Neuromuscular & Electrodiagnostic Medicine and follows sound statistical principles. Muscle Nerve 56: 859-860, 2017.

reference values
statistics
nerve conduction
normal values


The optimal number of embryo cells for effective pregnancy and decrease of multiple pregnancy rate in frozen-thawed embryo transfer.

Abstract: To investigate the effect of the number of embryo cells on the clinical outcome of frozen-thawed embryo transfer and explore the optimal policy for decreases of multiple pregnancy rate, patients who experienced day 3 vitrified double frozen-thawed embryo transfer were retrospectively analyzed. According to the number of embryonic cells in each pre-frozen embryo, the patients were divided into six groups: 8C2 (two 8-cell embryos), 8C1- < 8C1 (one 8-cell embryo and one under-8-cell embryo), 8C1- > 8C1 (one 8-cell embryo and one over-8-cell embryo), < 8C2 (two under-8-cell embryos), < 8C1- > 8C1 (one under-8-cell embryo and one over-8-cell embryo), and > 8C2 (two over-8-cell embryos). The clinical data were analyzed. The classification decision tree was used to analyze the optimal transfer strategy. A total of 2184 cycles of day 3 vitrified double frozen-thawed embryo transfer were enrolled. In day 3 double frozen-thawed embryo cycles, the 8C2 group and 8C1- > 8C1 group had significantly (P < 0.05) higher pregnancy and multiple pregnancy rates than the other groups. No significant (P > 0.05) difference existed in the pregnancy rate and live birth rate between the 8C1- < 8C1 group, 8C2 group and 8C1- > 8C1 group, but the implantation rate and multiple pregnancy rate in the 8C1- < 8C1 group were significantly (P < 0.05) lower than in the other two groups. Compared with the multiple pregnancy rate of all cycles, the cycles in two branches showed significantly (P < 0.05) higher multiple pregnancy rates (≤ 29 years old: 8C2 / 8C1- > 8C1; 29 < age ≤ 36 years for the first transfer: 8C2 / 8C1- < 8C1 / 8C1- > 8C1, one branch showed similar rate (≤ 29 years old: 8C2 / 8C1- > 8C1) for the first transfer, and the remaining four branches demonstrated significantly (P < 0.05) lower rates. The clinical pregnancy rates before and after optimization were 51.0% vs 50.5%, and the multiple pregnancy rates were 38.5% vs 16.9%. In conclusion, the number of pre-frozen embryonic cells is an important factor affecting the clinical outcome of frozen-thawed embryo transfer in day 3 double good embryos frozen-thawed cycles. The age of patient, number of embryo cells, and the first time of transfer are the most valuable parameters for prediction. For women ≤ 29 years old, the single embryo transfer (SET) strategy was to choose an embryo ≥ 8 cells, and for women with < 29 age ≤ 36 years old, the SET strategy in the first transfer was to choose an embryo ≥ 8 cells.

D000328:Adult
D000367:Age Factors
D002452:Cell Count
D015925:Cryopreservation
D046149:Embryo Culture Techniques
D010064:Embryo Implantation
D004624:Embryo Transfer
D004622:Embryo, Mammalian
D005260:Female
D005307:Fertilization in Vitro
D006801:Humans
D011247:Pregnancy
D018873:Pregnancy Rate
D011272:Pregnancy, Multiple
D012189:Retrospective Studies
D014021:Tissue Preservation
D055815:Young Adult

Multiple pregnancy rate
Frozen-thawed embryo transfer
Birth rate
Embryonic cell numbers
Morphological score


Genetic Diversity of Porcine Epidemic Diarrhea Virus With a Naturally Occurring Truncated ORF3 Gene Found in Guangxi, China.

Abstract: Porcine epidemic diarrhea virus (PEDV) is one of the major enteric pathogens, causing severe enteric disease, resulting in enormous economic losses. The ORF3 gene encodes an accessory protein which is related to the infectivity and virulence of PEDV. In this study, 33 PEDV positive field samples were collected from Guangxi, from 2017 to 2019, and the genetic diversity of ORF3 was investigated. Thirty-eight strains of ORF3 were obtained, and these were composed of five strains of ORF3 named Guangxi naturally truncated strains that were 293 bp in length, with continuous deletions from 172 to 554 bp. The Guangxi naturally truncated strains encoded a truncated protein of 89 amino acids, which had clustered into a new group referred to as Group 3, and these might be involved in the variations of virulence. Three genotypes (G1-1 subgroup, G1-3 subgroup, and Group 3) existed simultaneously in Guangxi based on the genetic and evolutionary analysis of the ORF3 gene. The sequence information in the current study will hopefully facilitate the establishment of a diagnostic method that can differentiate the PEDV field stains. Continued surveillance will be useful for monitoring PEDV transmission. Differentiation of the ORF3 genes in PEDV field strains can help us to choose an appropriate PEDV vaccine candidate in the future and prevent outbreaks of PED more effectively.

Lu|Ying|Y| Su|Xueli|X| Du|Chen|C| Mo|Liyuan|L| Ke|Purui|P| Wang|Ruomu|R| Zhong|Lian|L| Yang|Cui|C| Chen|Ying|Y| Wei|Zuzhang|Z| Huang|Weijian|W| Liao|Yuying|Y| Ouyang|Kang|K|

genetic diversity
ORF3
PEDV
naturally truncated gene
pigs


Assessing the Quality of the Systems of Care for Children with Congenital Zika Virus Infection and Other Neurodevelopmental Disabilities in the United States Pacific Island Territories.

Abstract: Congenital Zika virus (ZIKV) infection can cause lifelong medical and developmental conditions and management needs. There is limited information on the strengths and weaknesses of the systems of care for addressing ZIKV and other neurodevelopmental disabilities (NRD) in the United States (US) Affiliated Pacific Island Territories. Therefore, the purpose of the study was to assess the quality of the chronic illness systems of care for children with congenital ZIKV and other NRD in the US Pacific Island Territories. A cross-sectional study was conducted among health professionals from American Samoa, Guam, and Commonwealth of the Northern Mariana Islands. Participants completed an adapted version of the Assessment of Chronic Illness Care 3.5 (ACIC), which is based on the Chronic Care Model. The median Total Program Score was calculated, which ranged from limited support (0-2), basic support (3-5), reasonably good support (6-8), to fully developed support for care (9-11). Among the 17 health professionals who completed the survey, 47% were Guamanian/Chamorro, 24% were Samoan, 12% were Filipino, and 6% were Other Pacific Islanders. The median (25th percentile, 75th percentile [interquartile range]) Total Program Score was 5 (3, 6 [3]), indicating basic support for ZIKV and other NRD care for children. As more is learned about the full spectrum of clinical findings related to ZIKV, it is critical to continue to build an interdisciplinary maternal and child health workforce with the capacity and preparation to adequately address the special needs of children with ZIKV and other NRD.

Zai|Tiffany|T|
Yasuda|Patrice M|PM|
Rao|Sheela|S|
Iizumi|Staci|S|
Vanderbilt|Douglas L|DL|
Deavenport-Saman|Alexis|A|

D044468:Native Hawaiian or Other Pacific Islander

congenital Zika virus infection
neurodevelopmental disabilities
US Pacific Island Territories
chronic care model
interdisciplinary


Successful treatment of Ureaplasma-induced hyperammonemia syndrome post-lung transplant.

Abstract: Hyperammonemia, in the absence of significant liver dysfunction, is an uncommon but often fatal occurrence following orthotopic lung transplant. Prior reports have provided evidence to support Ureaplasma species as an etiology for this syndrome. This case report describes an individual post-lung transplant, treated emperically with doxycycline along with other measures to lower ammonia levels, at the time hyperammonemia with encephalopathy was recognized. The patient clinically improved. Ureaplasma species were subsequently identified using 16S ribosomal RNA gene PCR/sequencing of pleural fluid, and by culture of bronchoalveolar (BAL) fluid. This case provides further support for empiric treatment of Ureaplasma species upon recognition of hyperammonemia syndrome post-lung transplant.

D029424:Pulmonary Disease, Chronic Obstructive

Hyperammonemia
lung transplantation
Ureaplasma


Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer.

Abstract: Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (O2MB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to O2MBs (O2MB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the O2MB-Gem and a Rose Bengal loaded O2MB (O2MB-RB) as a targeted treatment for pancreatic cancer. Specifically, UTMD using the O2MB-Gem and O2MB-RB conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299 pancreatic cancer cells by >60% (p < 0.001) and provided significant tumour growth delay (>80%, p < 0.001) compared to untreated animals when human xenograft MIA PaCa-2 tumours were treated in SCID mice. The toxicity of the O2MB-Gem conjugate was also determined in healthy non-tumour bearing MF1 mice and revealed no evidence of renal or hepatic damage. Therefore, the results presented in this manuscript suggest that chemo-sonodynamic therapy using the O2MB-Gem and O2MB-RB conjugates, is potentially an effective targeted and safe treatment modality for pancreatic cancer.

Nesbitt|Heather|H|
Sheng|Yingjie|Y|
Kamila|Sukanta|S|
Logan|Keiran|K|
Thomas|Keith|K|
Callan|Bridgeen|B|
Taylor|Mark A|MA|
Love|Mark|M|
O'Rourke|Declan|D|
Kelly|Paul|P|
Beguin|Estelle|E|
Stride|Eleanor|E|
McHale|Anthony P|AP|
Callan|John F|JF|

D023041:Xenograft Model Antitumor Assays

Gemcitabine
Microbubbles
Pancreatic cancer
Antimetabolite therapy
Sonodynamic therapy
Ultrasound


The multifaceted role of cell cycle regulators in the coordination of growth and metabolism.

Abstract: Adapting to changes in nutrient availability and environmental conditions is a fundamental property of cells. This adaptation requires a multi-directional coordination between metabolism, growth, and the cell cycle regulators (consisting of the family of cyclin-dependent kinases (CDKs), their regulatory subunits known as cyclins, CDK inhibitors, the retinoblastoma family members, and the E2F transcription factors). Deciphering the mechanisms accountable for this coordination is crucial for understanding various patho-physiological processes. While it is well established that metabolism and growth affect cell division, this review will focus on recent observations that demonstrate how cell cycle regulators coordinate metabolism, cell cycle progression, and growth. We will discuss how the cell cycle regulators directly regulate metabolic enzymes and pathways and summarize their involvement in the endolysosomal pathway and in the functions and dynamics of mitochondria.

D050756:Cyclin-Dependent Kinase Inhibitor Proteins

cell cycle regulators
metabolism
endolysosomes
mitochondria
cell growth


Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results.

Abstract:
BACKGROUND
Biliary tract cancer (BTC) has a poor prognosis and lacks a standardized second-line therapy. Vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR) 4, and platelet-derived growth factor receptor (PDGFR) are highly expressed in BTC. Therefore, lenvatinib (a known inhibitor of VEGF receptors 1-3, FGFRs 1-4, and PDGFR-α) was evaluated for second-line treatment of BTC.

METHODS
In this single-arm, multicenter, open-label, phase 2 study, patients with BTC received lenvatinib 24 mg orally once daily in 28-day cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), PFS rate at 12 weeks, disease control rate, clinical benefit rate, safety and pharmacokinetic profiles.

RESULTS
Twenty-six Japanese patients were enrolled and treated; 3 had a confirmed partial response per investigator assessment and per independent imaging review (IIR); ORR was 11.5% (90% confidence interval [CI]: 3.2-27.2). Median PFS was 3.19 months (95% CI: 2.79-7.23) per investigator assessment and 1.64 months (95% CI: 1.41-3.19) per IIR. Median OS was 7.35 months (95% CI: 4.50-11.27). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 21 patients (80.8%) and included hypertension (n = 10 [38.5%]), proteinuria (n = 3 [11.5%]), palmar-plantar erythrodysesthesia (n = 3 [11.5%]), decreased appetite (n = 3 [11.5%]), and anemia (n = 3 [11.5%]). Two deaths occurred due to TEAEs between treatment initiation and 30 days after last dose, but neither were considered treatment related.

CONCLUSIONS
Lenvatinib demonstrated antitumor activity in BTC, with a tolerable safety profile, and should be further evaluated as potential second-line therapy for this difficult to treat population.

TRIAL REGISTRATION
ClinicalTrials.gov NCT02579616 . Date of registration: October 19, 2015.

Lenvatinib
Biliary tract cancer
Ampulla of Vater
Cholangiocarcinoma
Gallbladder cancer


Effects of a blend of green tea and curcuma extract supplementation on lipopolysaccharide-induced inflammation in horses and ponies.

Abstract:
Background
In horses and ponies numerous medical conditions are known to be linked with inflammation in different tissues, especially in the liver. Besides affecting other metabolic pathways such as the expression of certain interleukins (IL), inflammation is associated with stress of the endoplasmic reticulum (ER). In particular, ER stress leads to adaptive stress response and can be measured by several markers of inflammatory and stress signalling pathways, like nuclear factor κB (NF-kB).

Objectives
To investigate lipopolysaccharide (LPS)-induced inflammatory reactions and their modulation in horses and ponies by feeding a polyphenol-rich supplement consisting of green tea and curcuma.

Methods
In a cross-over study, 11 animals were allocated to either a placebo or a supplement group and supplemented with 10 g of a blend of green tea and curcuma extract (GCE) or a placebo (calcium carbonate) once daily. After 21 days of supplementation, all animals underwent a LPS challenge to induce moderate systemic inflammation. Blood samples and liver biopsies were taken at standardized time points: 24 hours before and 12 hours after LPS challenge. Inflammatory blood parameters such as serum amyloid A (SAA), haptoglobin and retinol binding protein 4 (RBP4) were measured in serum. Hepatic mRNA levels of selected markers of inflammation such as haptoglobin, tumor necrosis factor  were quantified by RT-qPCR. In addition, liver biopsies were examined histologically for inflammatory alterations.

Results
Blood markers of acute inflammatory response increased after LPS challenge. In the liver, the proinflammatory cytokine IL-1β showed significantly lower mRNA levels after LPS challenge in the supplemented group (P = 0.04) compared to the placebo group. Levels of the hepatic CD68 mRNA increased significantly in the placebo group (P = 0.04). There were no significant differences between supplemented and placebo groups concerning other markers of inflammation and markers of ER stress within the liver. The number of hepatic macrophages were not different after LPS challenge in both feeding groups.

Conclusion
LPS was able to induce inflammation but seemed less suitable to induce ER stress in the horses and ponies. The polyphenol-rich supplement showed some potential to reduce inflammatory responses. Nevertheless, the supplementation did not exert an overall anti-inflammatory effect in horses and ponies.

Starzonek|Janine|J| Roscher|Katja|K| Blüher|Matthias|M| Blaue|Dominique|D| Schedlbauer|Carola|C| Hirz|Manuela|M| Raila|Jens|J| Vervuert|Ingrid|I|

Catechin Curcumin ER-stress Equines Polyphenols


Epigenetic control of group V phospholipase A2 expression in human malignant cells.

Abstract: Secreted phospholipases A2 (sPLA2) are suggested to play an important role in inflammation and tumorigenesis. Different mechanisms of epigenetic regulation are involved in the control of group IIA, III and X sPLA2s expression in cancer cells, but group V sPLA2 (GV-PLA2) in this respect has not been studied. Here, we demonstrate the role of epigenetic mechanisms in regulation of GV-PLA2 expression in different cell lines originating from leukaemia and solid cancers. In blood leukocytes from leukaemic patients, levels of GV-PLA2 transcripts were significantly lower in comparison to those from healthy individuals. Similarly, in DU-145 and PC-3 prostate and CAL-51 and MCF-7 mammary cancer cell lines, levels of GV-PLA2 transcripts were significantly lower in relation to those found in normal epithelial cells of prostate or mammary. By sequencing and methylation-specific high-resolution melting (MS-HRM) analyses of bisulphite-modified DNA, distinct CpG sites in the GV-PLA2 promoter region were identified that were differentially methylated in cancer cells in comparison to normal epithelial and endothelial cells. Spearman rank order analysis revealed a significant negative correlation between the methylation degree and the cellular expression of GV-PLA2 (r = -0.697; p = 0.01). The effects of demethylating agent (5-aza-2'-deoxycytidine) and histone deacetylase inhibitor (trichostatin A) on GV-PLA2 transcription in the analysed cells confirmed the importance of DNA methylation and histone modification in the regulation of the GV-PLA2 gene expression in leukaemic, prostate and mammary cancer cell lines. The exposure of tumour cells to human recombinant GV-PLA2 resulted in a reduced colony forming activity of MCF-7, HepG2 and PC-3 cells, but not of DU-145 cells suggesting a cell-type-dependent effect of GV-PLA2 on cell growth. In conclusion, our results suggest that epigenetic mechanisms such as DNA methylation and histone modification play an important role in downregulation of GV-PLA2 expression in cancer cells.

Menschikowski|Mario|M|
Hagelgans|Albert|A|
Nacke|Brit|B|
Jandeck|Carsten|C|
Mareninova|Olga A|OA|
Asatryan|Liana|L|
Siegert|Gabriele|G|

D015972:Gene Expression Regulation, Neoplastic

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction

Group V sPLA2
Leukaemia
DNA methylation
Solid cancer cells


The effect of organizational justice as perceived by occupational drivers on traffic accidents: Mediating effects of job satisfaction.

Abstract:
INTRODUCTION
Considerable research supports a positive association between the safety climate (which is a direct organizational factor) and safety performance (such as safe driving). However, indirect organizational variables that influence safe driving have gone largely unexplored. This study contributes to safety research by examining the relationship between organizational justice, which is a distal organizational factor, and traffic accidents and the mediating role of job satisfaction.

METHOD
233 occupational drivers employed by taxi and bus companies in South Korea participated in the study. Regression analysis was conducted using police records on participants' on-the-job traffic accidents.

RESULTS
The analysis shows that the mediation model is statistically significant. That is, drivers with a lower level of perceived organizational justice showed a higher frequency of traffic accidents, and the mediating effect of job satisfaction was also significant. Based on the results, implications and limitations are discussed. Practical applications: The findings demonstrate that in order to decrease traffic accidents, transportation companies would benefit by examining distal factors such as organizational justice. This approach suggests that the conventional framework for safety management should be broadened to include aspects of the entire organization.

D000062:Accidents, Occupational
D000063:Accidents, Traffic
D000328:Adult
D001334:Automobile Driving
D003430:Cross-Sectional Studies
D006801:Humans
D007588:Job Satisfaction
D008297:Male
D008875:Middle Aged
D017146:Models, Organizational
D015279:Organizational Culture
D056910:Republic of Korea
D017751:Safety Management
D012933:Social Identification
D011795:Surveys and Questionnaires
D017132:Workplace

Organizational justice
Occupational drivers
Traffic accidents
Job satisfaction


Effects of Heart Rate Variability Biofeedback in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

Abstract:
BACKGROUND
Autonomic dysfunction, cognitive impairment, and psychological distress are associated with poorer prognosis in patients with acute ischemic stroke (AIS). Heart rate variability (HRV) biofeedback (BF) improves autonomic dysfunction, cognitive impairment, and psychological distress in other patient populations, but its effect in patients with AIS is still unclear.

OBJECTIVE
This study investigated the effects of an HRVBF intervention on autonomic function, cognitive impairment, and psychological distress in patients with AIS.

METHOD
In this randomized, controlled, single-blind trial, patients with AIS were randomly assigned to the experimental or control group. The experimental group received four HRVBF training sessions. The control group received usual care. Repeated measures of HRV, mini-mental status examination (MMSE), and Hospital Anxiety and Depression Scales (HADS) were collected prior to and at 1 and 3 months postintervention.

RESULTS
A total of 35 patients completed the study (19 experimental, 16 control). HRV and HADS significantly improved in the experimental group (p < .001) but not in the control group. Likewise, only the experimental group showed significant improvements in HRV, MMSE, and HADS over time (p < .05).

CONCLUSION
HRVBF is a promising intervention for improving autonomic function, cognitive impairment, and psychological distress in patients with AIS. More studies of HRVBF interventions are needed to further optimize the effects of HRVBF on autonomic, cognitive, and psychological function in patients with AIS.

Chang|Wan-Ling|WL|
Lee|Jiunn-Tay|JT|
Li|Chi-Rong|CR|
Davis|Amy H T|AHT|
Yang|Chia-Chen|CC|
Chen|Yu-Ju|YJ|0000-0002-5454-2695

biofeedback
acute ischemic stroke
autonomic dysfunction
cognitive impairment
psychological distress


Exposure to constant light impairs cognition with FTO inhibition and m6A-dependent TrκB repression in mouse hippocampus.

Abstract: N6-methyladenosine (m6A) mRNA methylation plays a role in various brain functions. Exposure to chronic constant light (CCL) has been reported to impair cognition, yet whether the underlying mechanism involves m6A remains unknown. In this study, mice exposed to CCL for 3 weeks show impaired cognitive behavior, which was associated with increased m6A level in hippocampus. Accordingly, the m6A demethylase FTO was inhibited while the methyltransferases METTL3, METTL14 and WTAP, as well as the reader protein YTHDF2, were elevated in the hippocampus of CCL-exposed mice. CCL exposure significantly activated hippocampal expression of circadian regulator cryptochrome 1 and 2 (CRY1 and 2). Meanwhile, hippocampal neurogenesis was impaired with suppression of BDNF/TrκB/ERK pathway. To further delineate the signaling pathway and the role of m6A, we altered the expression of CRY1/2 in hippocampus neuron cells. CRY1/2 overexpression inhibited FTO and increased m6A levels, while CRY1/2 knockdown led to opposite results. Luciferase reporter analysis further confirmed CRY1/2-induced FTO suppression. Furthermore, FTO knockdown increased m6A on 3'UTR of TrκB mRNA, and decreased TrκB mRNA stability and TrκB protein expression, in a YTHDF2-dependent manner. These results indicate that CCL-activated CRY1/2 causes transcriptional inhibition of FTO, which suppresses TrκB expression in hippocampus via m6A-dependent post-transcriptional regulation and contributes to impaired cognitive behavior in mice exposed to constant light.

Yang|Yang|Y| Feng|Yue|Y| Hu|Yun|Y| Liu|Jie|J| Shi|Hailing|H| Zhao|Ruqian|R|

FTO
Chronic constant light
Cryptochromes
Hippocampal neurogenesis
BDNF/TrκB/ERK


Homeobox B9 is overexpressed in hepatocellular carcinomas and promotes tumor cell proliferation both in vitro and in vivo.

Abstract: HomeoboxB9 (HOXB9), a nontransforming transcription factor that is overexpressed in multiple tumor types, alters tumor cell fate and promotes tumor progression. However, the role of HOXB9 in hepatocellular carcinoma (HCC) development has not been well studied. In this paper, we found that HOXB9 is overexpressed in human HCC samples. We investigated HOXB9 expression and its prognostic value for HCC. HCC surgical tissue samples were taken from 89 HCC patients. HOXB9 overexpression was observed in 65.2% of the cases, and the survival analysis showed that the HOXB9 overexpression group had significantly shorter overall survival time than the HOXB9 downexpression group. The ectopic expression of HOXB9 stimulated the proliferation of HCC cells; whereas the knockdown of HOXB9 produced an opposite effect. HOXB9 also modulated the tumorigenicity of HCC cells in vivo. Moreover, we found that the activation of TGF-β1 contributes to HOXB9-induced proliferation activities. The results provide the first evidence that HOXB9 is a critical regulator of tumor growth factor in HCC.

Li|Fangyi|F| Dong|Lei|L| Xing|Rong|R| Wang|Li|L| Luan|Fengming|F| Yao|Chenhui|C| Ji|Xuening|X| Bai|Lizhi|L|

D053773:Transforming Growth Factor beta1


Longitudinal study of bovine rotavirus group A in newborn calves from vaccinated and unvaccinated dairy herds.

Abstract: Reports of rotavirus excretion in calves usually result from cross-sectional studies, and in face of the conflicting results regarding protection of calves born to vaccinated dams against diarrhea, the aim of the present study was to evaluate rotavirus excretion in dairy calves born to vaccinated or unvaccinated dams, to identify the genotypes of bovine rotavirus group A (RVA) strains isolated from these animals as well as to investigate characteristics of the disease in naturally occurring circumstances throughout the first month of life. Five hundred fifty-two fecal samples were taken from 56 calves, 28 from each farm and, in the vaccinated herd, 11/281 samples (3.91%) taken from six different calves tested positive for RVA while in the unvaccinated herd, 3/271 samples (1.11%) taken from 3 different calves tested positive. The genotyping of the VP7 genes showed 91.2% nucleotide sequence identity to G6 genotype (NCDV strain), and for the VP4 gene, strains from the vaccinated herd were 96.6% related to B223 strain, while strains from the unvaccinated herd were 88% related to P[5] genotype (UK strain). Genotypes found in this study were G6P[11] in the vaccinated herd and G6P[5] in the unvaccinated herd. All calves infected with rotavirus presented an episode of diarrhea in the first month of life, and the discrepancy between the genotypes found in the commercial vaccine (G6P[1] and G10P[11]) and the rotavirus strains circulating in both vaccinated and unvaccinated herds show the importance of keeping constant surveillance in order to avoid potential causes of vaccination failure.

Rocha|Thaís Gomes|TG|
Silva|Fernanda Dornelas Florentino|FD|
Gregori|Fábio|F|
Alfieri|Amauri Alcindo|AA|
Buzinaro|Maria da Glória|MD|
Fagliari|José Jurandir|JJ|

Dairy calves
RVA
VP7 gene
Sequencing
VP4 gene
Calf diarrhea


Population insight of the relationship between lifestyle and cancer: A population-based survey.

Abstract:
Background
There is a substantial rise in the incidence of cancer in Saudi Arabia. Life style models and lack of awareness are the prime suspect in this substantial increase. Therefore, the objective of the present study was to assess the relationship between lifestyle and cancer in a population-based Survey in Northern Saudi Arabia.

Methodology
This cross-sectional study was conducted in North Saudi Arabia (Hail Region). Data was collected as a part of a community based cancer's awareness movement that covered an area inhibited with approximately 500,000 individuals.

Results
In this study, about 2558/3227 (79.3%) and 641/794 (80.7%) believed that tobacco smoking and smokeless are not a risk of cancer development. In this study large section (87.2%) of the study population believe that exposure to diverse occupational or non-occupational chemicals has no role in cancer development. Furthermore, around 59% of the study subjects in the current study believed that repeated exposure to insecticidal chemicals doesn't influence the risk of cancer.

Conclusion
The present study point to the urgent need for awareness educational programs and preventive measures towards may lifestyle factors that can increase or decrease the overall risk of cancer among Saudi population.

Alshammari|Fawaz Dabea|FD|
Ahmed|Hussain Gadelkarim|HG|
Alshammari|Dena|D|
Alharbi|Ahmed Mulfy|AM|
Alsaedi|Atif Saud|AS|
Elasbaly|Abdulbaset|A|

lifestyle
cancer
Saudi Arabia
cancer awareness
risk factors


Effect of switching to teneligliptin from other dipeptidyl peptidase-4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease.

Abstract:
AIMS/INTRODUCTION
The objective of the present study was to elucidate the effect of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors on glucose control and renoprotection in type 2 diabetes mellitus patients with diabetic kidney disease.

MATERIALS AND METHODS
The present study was a single-arm, open-label, observational study. A total of 23 patients, who had urinary albumin/creatinine ratios (UACR) ≥30 mg/gCr in their first urine in the early morning, and received other DPP-4 inhibitors and renin-angiotensin system inhibitors, switched to teneligliptin 20 mg/day. After switching to teneligliptin for 24 weeks, we evaluated changes in glycated hemoglobin (HbA1c), fasting plasma glucose levels, plasma DPP-4 activity and UACR.

RESULTS
HbA1c, fasting plasma glucose and UACR values showed no significant change after 24 weeks compared with baseline. However, plasma DPP-4 activity was significantly reduced after 24 weeks (0.57 ± 0.26 nmol/min/mL, P = 0.012, vs baseline), compared with baseline (1.49 ± 1.73 nmol/min/mL), and there was a positive relationship between the change rate of plasma DPP-4 activity (Δ%DPP-4) for 24 weeks and the levels of plasma DPP-4 activity (r = -0.5997, P = 0.0025) and fasting plasma glucose (r = -0.4235, P = 0.0440) at baseline. Additionally, the Δ%DPP-4 for 24 weeks was significantly correlated to the change rate of UACR (r = 0.556, P = 0.0059). However, there was no relationship between Δ%DPP-4 and ΔHbA1c (amount of HbA1c change).

CONCLUSIONS
Switching to teneligliptin from other DPP-4 inhibitors for 24 weeks reduces plasma DPP-4 activity, which is associated with a reduction in albuminuria, independent of the change in glucose levels, in type 2 diabetes mellitus patients with diabetic kidney disease.

Teneligliptin
Diabetic kidney disease
Plasma DPP-4 activity


Determinants of participation in family and recreational activities of young children with cerebral palsy.

Abstract:
PURPOSE
To test a model of child, family and service determinants of participation in family and recreational activities for young children with cerebral palsy (CP).

METHODS
Participants were a convenience sample of 429 children (242 males) with CP, aged 18 to 60 months, representing all levels of the Gross Motor Function Classification System (GMFCS). Children were divided into two groups by GMFCS levels, levels I to II and levels III to V. Data on impairments and gross motor function were collected by therapists; parents provided information about children's health conditions and adaptive behaviour. Seven months later, parents reported on family life and services received. One year after the beginning of the study, parents reported their children's participation. Data from the two groups of children were analysed separately using structural equation modelling.

RESULTS
The model explained 35% and 40% of the variance of frequency of participation in family and recreation and 28% and 38% of enjoyment in participation, for the two groups of children, respectively. Children's adaptive behaviour, family ecology, and number of community recreational programs were associated with the frequency of participation for both groups. Gross motor function was only associated with the frequency of participation for children in levels III-V. Adaptive behaviour was associated with enjoyment for both groups. The extent services met children's needs was associated with enjoyment for children in levels I to II and family ecology was a determinant of enjoyment for children in levels III to V.

CONCLUSION
Supporting children's adaptive behaviour, family ecology, and access to community recreational programmes may foster participation in family and recreational activities for young children with CP. Implications for Rehabilitation Participation in family and recreational activities for young children with CP is complex and influenced by child, family and environmental factors. Practitioners are encouraged to support children's adaptive behaviour and access to community programs and family relationships, involvement in community activities and expectations of their children. Optimizing gross motor function for children who have limitations in self-mobility may enhance their participation in family and recreational activities. For children with a good prognosis for walking, providing services perceived by parents to meet their children's needs may enhance children's enjoyment of participation.

Chiarello|Lisa A|LA|
Bartlett|Doreen J|DJ|
Palisano|Robert J|RJ|
McCoy|Sarah Westcott|SW|
Fiss|Alyssa LaForme|AL|
Jeffries|Lynn|L|
Wilk|Piotr|P|

D000223:Adaptation, Psychological
D000328:Adult
D002170:Canada
D002547:Cerebral Palsy
D002675:Child, Preschool
D015331:Cohort Studies
D062309:Community Integration
D004185:Disability Evaluation
D005192:Family Health
D005195:Family Relations
D006297:Health Services Accessibility
D006801:Humans
D007223:Infant
D009048:Motor Skills
D010290:Parents
D010358:Patient Participation
D011446:Prospective Studies
D011998:Recreation
D014481:United States

participation
recreational activities
young children
Cerebral palsy
enjoyment and adaptive behaviour


Inclusion, Diversity, Access, and Equity (IDA&E) Roadmap: Infectious Diseases Society of America's Commitment to the Future.

Abstract: This article identifies the major elements of the strategic road map for the Infectious Diseases Society of America's (IDSA) Inclusion, Diversity, Access, and Equity (IDA&E) initiative and discusses the long-term goals and the proposed steps needed to achieve these goals.

Desruisseaux|Mahalia S|MS|
Tan|Tina Q|TQ|


External validation and clinical utility of prognostic prediction models for gestational diabetes mellitus: A prospective cohort study.

Abstract:
INTRODUCTION
We performed an independent validation study of all published first trimester prediction models, containing non-invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated.

MATERIAL AND METHODS
Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies.

RESULTS
The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models.

CONCLUSIONS
The best performing prediction models showed acceptable performance measures and may enable more personalized medicine-based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies.

external validation
prediction
gestational diabetes mellitus
decision curve analysis
risk assessment


The prebiotic effect of CPP-ACP sugar-free chewing gum.

Abstract:
OBJECTIVES
To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance of Streptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study.

MATERIALS AND METHODS
Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks. The study also involved no gum chewing (no gum) for the same two week period. Participants were randomly assigned to one of the test gums or no gum for each intervention period. Participants abstained from oral hygiene and had washout periods of two weeks between intervention periods. After each intervention period, supragingival plaque was collected and analysed for bacterial composition by sequencing the V4 variable region of the 16S rRNA gene. Data were analysed using a linear mixed model.

RESULTS
The CPP-ACP gum intervention produced a significant (p < 0.01) increase in the proportions of S. sanguinis (112%), as well as the commensal species Rothia dentocariosa (127%), Corynebacterium durum (80%) and Streptococcus mitis (55%) when compared with the no gum intervention. All the species that were promoted by the CPP-ACP gum are known to possess one or both of the alkali-producing enzymes arginine deiminase and nitrate reductase.

CONCLUSION
This clinical study demonstrated that chewing a sugar-free gum containing CPP-ACP promoted prebiosis by significantly increasing the proportion of S. sanguinis and other health-associated bacterial species in supragingival plaque.

CLINICAL SIGNIFICANCE
Regular chewing of CPP-ACP sugar-free gum increases the proportions of health-associated commensal species in supragingival plaque to promote prebiosis and oral homeostasis.

Fernando|James R|JR|
Butler|Catherine A|CA|
Adams|Geoffrey G|GG|
Mitchell|Helen L|HL|
Dashper|Stuart G|SG|
Escobar|Karen|K|
Hoffmann|Brigitte|B|
Shen|Peiyan|P|
Walker|Glenn D|GD|
Yuan|Yi|Y|
Reynolds|Coralie|C|
Reynolds|Eric C|EC|

CPP-ACP
Sugar-free chewing gum
Prebiosis
Supragingival dental plaque microbiome


A New Case Manager for Diabetic Patients: A Pilot Observational Study of the Role of Community Pharmacists and Pharmacy Services in the Case Management of Diabetic Patients.

Abstract: The adherence of type 2 diabetes mellitus (DM2) patients with an individual care plan (ICP) is often not satisfactory, nor does it allow for a significant improvement in outcome, because of poor accessibility to services, poor integration of pathway articulations, poor reconciliation with the patient's life, or the lack of a constant reference person. The purpose of this study was to evaluate the contribution of community pharmacists and pharmacy services in improving adherence with periodic controls in DM2. The study was conducted at a rural pharmacy. A sample of 40 patients was calculated with respect to a historical cohort and subsequently enrolled. Clinical and personal data were collected in an electronic case report form. Pharmacists acting as a case manager followed patients carrying out their ICP developed by an attending physician. Some of the activities foreseen by the ICP, such as electrocardiogram, fundus examination, and self-analysis of blood and urine, were carried out directly in the pharmacy by the pharmacist through the use of telemedicine services and point of care units. Activities that could not be performed in the pharmacy were booked by the pharmacist at the accredited units. Examination results were electronically reported by the pharmacist to the attending physician. The primary endpoint was the variation in patient adherence with the ICP compared to a historical cohort. Secondary endpoints were variation in waiting time for the examinations, mean percentage change in glycated hemoglobin (HbA1c) and low-density lipoprotein (LDL) cholesterol levels and blood pressure, impact on healthcare-related costs, and perceived quality of care. Adherence to the ICP significantly increased. Waiting times were reduced and clinical outcomes improved with conceivable effects on costs. Patients appreciated the easier access to services. Community pharmacists and pharmacy services represent ideal actors and context that, integrated in the care network, can really favor ICP adherence and obtain daily morbidity reduction and cost savings through proper disease control and an early diagnosis of complications.

case management
diabetes
pharmacist
pharmacy services
telemedicine
clinical pathway
community pharmacy
health-system transformation
interprofessional care
interprofessional cooperation


Biphasic regulation of InsP3 receptor gating by dual Ca2+ release channel BH3-like domains mediates Bcl-xL control of cell viability.

Abstract: Antiapoptotic Bcl-2 family members interact with inositol trisphosphate receptor (InsP3R) Ca(2+)release channels in the endoplasmic reticulum to modulate Ca(2+)signals that affect cell viability. However, the molecular details and consequences of their interactions are unclear. Here, we found that Bcl-xL activates single InsP3R channels with a biphasic concentration dependence. The Bcl-xLBcl-2 homology 3 (BH3) domain-binding pocket mediates both high-affinity channel activation and low-affinity inhibition. Bcl-xL activates channel gating by binding to two BH3 domain-like helices in the channel carboxyl terminus, whereas inhibition requires binding to one of them and to a previously identified Bcl-2 interaction site in the channel-coupling domain. Disruption of these interactions diminishes cell viability and sensitizes cells to apoptotic stimuli. Our results identify BH3-like domains in an ion channel and they provide a unifying model of the effects of antiapoptotic Bcl-2 proteins on the InsP3R that play critical roles in Ca(2+) signaling and cell viability.

Yang|Jun|J|
Vais|Horia|H|
Gu|Wenen|W|
Foskett|J Kevin|JK|

Bcl-2
ion channel
apoptosis
calcium
mitochondria


Combining quantitative 2D and 3D image analysis in the serial block face SEM: application to secretory organelles of pancreatic islet cells.

Abstract: A combination of two-dimensional (2D) and three-dimensional (3D) analyses of tissue volume ultrastructure acquired by serial block face scanning electron microscopy can greatly shorten the time required to obtain quantitative information from big data sets that contain many billions of voxels. Thus, to analyse the number of organelles of a specific type, or the total volume enclosed by a population of organelles within a cell, it is possible to estimate the number density or volume fraction of that organelle using a stereological approach to analyse randomly selected 2D block face views through the cells, and to combine such estimates with precise measurement of 3D cell volumes by delineating the plasma membrane in successive block face images. The validity of such an approach can be easily tested since the entire 3D tissue volume is available in the serial block face scanning electron microscopy data set. We have applied this hybrid 3D/2D technique to determine the number of secretory granules in the endocrine α and β cells of mouse pancreatic islets of Langerhans, and have been able to estimate the total insulin content of a β cell.

Shomorony|A|A|
Pfeifer|C R|CR|
Aronova|M A|MA|
Zhang|G|G|
Cai|T|T|
Xu|H|H|
Notkins|A L|AL|
Leapman|R D|RD|

serial block face SEM
pancreatic islets
stereology
secretory granules
β cells
α cells


Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels.

Abstract: Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.

Popovici|Violeta|V|0000-0001-9696-5728
Matei|Elena|E|
Cozaru|Georgeta Camelia|GC|
Aschie|Mariana|M|
Bucur|Laura|L|
Rambu|Dan|D|
Costache|Teodor|T|0000-0003-2116-4672
Cucolea|Iulia Elena|IE|
Vochita|Gabriela|G|
Gherghel|Daniela|D|
Caraiane|Aureliana|A|
Badea|Victoria|V|

usnic acid
Usnea barbata
apoptosis
DNA damage
blood cells
cytotoxic effect
oxidative stress
secondary metabolites


Hepatocyte growth factor promotes proliferation, invasion, and metastasis of myeloid leukemia cells through PI3K-AKT and MAPK/ERK signaling pathway.

Abstract: This study aims to investigate effects of HGF expression on biological behaviors of Kasumi-1 and HL60. Expression of HGF and c-Met gene were detected using qRT-PCR. Short hairpin RNA (shRNA) was used to reduce HGF expression. Silencing effect of shRNA was verified by qRT-PCR and western blot. Cell reproductive capacity, cell clonality and cell cycle (apoptosis) were detected by CCK-8, clone formation, flow cytometry (FCM), respectively. Cell adhesion, cell invasion ability and cell proliferation were also examined. Changes of PI3K-AKT, MAPK/ERK signaling factors were detected by western blot. HGF and c-Met expression in first-vist AML group was significantly higher than in AML-relief and normal control group. HGF shRNA can inhibit cell proliferation, inhibit cloning ability. Compared with control group, apoptosis ratios of Kasumi-1 and HL60 cell in interference groups were significantly higher. After shRNA interference, the number of adherent cells and transmembrane cells were significantly decreased compared with control group. Meanwhile, shRNA also down-regulated Bad, Bcl-XL, Bcl-2, CDK1, Cyclin B, MMP2, MMP9, and up-regulated cleaved caspase9, cleaved caspase3, cleaved PARP, Bax, and P21. Moreover, phosphorylated c-Met, AKT, Erk, and mTOR were also reduced. In conclusion, HGF and c-Met gene highly expressed among first-visit AML patients, but decreased after relief treatment. HGF may promote proliferation, invasion, and metastasis of AML cells through PI3K-AKT and MAPK/ERK signaling pathway. Therefore, proliferation and invasion ability of AML cell can be inhibited by down-regulating HGF gene to retardate cell in G2/M stage.

Guo|Jiang-Rui|JR| Li|Wei|W| Wu|Yong|Y| Wu|Lin-Qing|LQ| Li|Xin|X| Guo|Ya-Fei|YF| Zheng|Xiao-Hui|XH| Lian|Xiao-Lan|XL| Huang|Hui-Fang|HF| Chen|Yuan-Zhong|YZ|