Acute gastroesophageal intussusception in a patient with pneumomediastinum, pneumoperitoneum, and extensive subcutaneous emphysema resulting from iatrogenic colonic perforation.

Abstract: Acute gastroesophageal intussusception is a rare condition in which the stomach invaginates into the adjacent esophagus. We report a case of acute gastroesophageal intussusception with massive pneumomediastinum, pneumoperitoneum, and subcutaneous emphysema, effectively treated with conservative management.

Hwang|Geum Hee|GH|
Kim|Jun Ho|JH|
Lee|Kyung Hee|KH|
Kim|Ga Ram|GR|
Ku|Yu Jin|YJ|
Jeon|Yong Sun|YS|
Cho|Soon Gu|SG|

Intussusception
stomach
esophagus
computed tomography (CT)


Spectrophotometric simultaneous determination of Tenofovir disoproxil fumarate and Emtricitabine in combined tablet dosage form by ratio derivative, first order derivative and absorbance corrected methods and its application to dissolution study.

Abstract: Three simple, economical, precise, and accurate methods are described for the simultaneous determination of Tenofovir disoproxil fumarate (TE) and Emtricitabine (EM) in combined tablet dosage form. The first method is ratio derivative spectra, second is first-order derivative spectrophotometry and third is absorption corrected method. The amplitudes at 271.07 and 302.17 nm in the ratio derivative method, 224.38 and 306.88 nm in the first order derivative method were selected to determine Tenofovir disoproxil fumarate (TE) and Emtricitabine (EM), respectively, in combined formulation. Beer's law is obeyed in the concentration range of 3-21 μg/ml for TE and 2-14 μg/ml for EM for first two methods and range for third method was 6-30 μg/ml of TE and 4-20 μg/ml of EM. The percent assay for commercial formulation was found to be in the range 98.91%-101.72% for both the analytes by the proposed three methods. Absorption corrected method was successfully applied to carry out dissolution study of commercial tablet formulation by using USP II dissolution test apparatus. The methods were validated with respect to linearity, precision, and accuracy. Recoveries by proposed methods were found in the range of 99.06 %-101.34 % for both the analytes.

Choudhari|Vishnu P|VP|
Ingale|Snehal|S|
Gite|Sacchidanand R|SR|
Tajane|Dipali D|DD|
Modak|Vikram G|VG|
Ambekar|Archana|A|

Tenofovir disoproxil fumarate
Emtricitabine
tablet dosage form
Absorbance corrected
derivative spectrophotometry
ratio derivative spectrophotometry


The Asia-Pacific Society of Cardiology (APSC) Expert Committee Consensus Recommendations for Assessment of Suspected Acute Coronary Syndrome Using High-Sensitivity Cardiac Troponin T in the Emergency Department.

Abstract: The Asia-Pacific Society of Cardiology (APSC) high-sensitivity troponin T (hs-TnT) consensus recommendations and rapid algorithm were developed to provide guidance for healthcare professionals in the Asia-Pacific region on assessing patients with suspected acute coronary syndrome (ACS) using a hs-TnT assay. Experts from Asia-Pacific convened in 2 meetings to develop evidence-based consensus recommendations and an algorithm for appropriate use of the hs-TnT assay. The Expert Committee defined a cardiac troponin assay as a high-sensitivity assay if the total imprecision is ≤10% at the 99th percentile of the upper reference limit and measurable concentrations below the 99th percentile are attainable with an assay at a concentration value above the assay's limit of detection for at least 50% of healthy individuals. Recommendations for single-measurement rule-out/rule-in cutoff values, as well as for serial measurements, were also developed. The Expert Committee also adopted similar hs-TnT cutoff values for men and women, recommended serial hs-TnT measurements for special populations, and provided guidance on the use of point-of-care troponin T devices in individuals suspected of ACS. These recommendations should be used in conjunction with all available clinical evidence when making the diagnosis of ACS.

Tan|Wei Chieh Jack|WCJ|
Inoue|Kenji|K|
AbdelWareth|Laila|L|
Giannitsis|Evangelos|E|
Kasim|Sazzli|S|
Shiozaki|Masayuki|M|
Aw|Tar Choon|TC|
Cheng|Federick|F|
Dung|Ho Thuong|HT|
Li|Yi-Heng|YH|
Lim|Swee Han|SH|
Lukito|Antonia Anna|AA|
Than|Martin|M|
Chu|Fang-Yeh|FY|
Devasia|Tom|T|
Lee|Chien-Chang|CC|
Phrommintikul|Arintaya|A|
Youn|Jong-Chan|JC|
Chew|Derek P|DP|

Asia-Pacific
Consensus recommendations
Acute coronary syndrome
High-sensitivity troponin T


Maps, trends, and temperature sensitivities-phenological information from and for decreasing numbers of volunteer observers.

Abstract: Phenology serves as a major indicator of ongoing climate change. Long-term phenological observations are critically important for tracking and communicating these changes. The phenological observation network across Germany is operated by the National Meteorological Service with a major contribution from volunteering activities. However, the number of observers has strongly decreased for the last decades, possibly resulting in increasing uncertainties when extracting reliable phenological information from map interpolation. We studied uncertainties in interpolated maps from decreasing phenological records, by comparing long-term trends based on grid-based interpolated and station-wise observed time series, as well as their correlations with temperature. Interpolated maps in spring were characterized by the largest spatial variabilities across Bavaria, Germany, with respective lowest interpolated uncertainties. Long-term phenological trends for both interpolations and observations exhibited mean advances of -0.2 to -0.3 days year-1 for spring and summer, while late autumn and winter showed a delay of around 0.1 days year-1. Throughout the year, temperature sensitivities were consistently stronger for interpolated time series than observations. Such a better representation of regional phenology by interpolation was equally supported by satellite-derived phenological indices. Nevertheless, simulation of observer numbers indicated that a decline to less than 40% leads to a strong decrease in interpolation accuracy. To better understand the risk of declining phenological observations and to motivate volunteer observers, a Shiny app is proposed to visualize spatial and temporal phenological patterns across Bavaria and their links to climate change-induced temperature changes.

Map interpolation
Citizen science
Inverse distance weighting
Leave-one-out cross validation
Multiple linear regression
Phenological season


Association between the application of ISO 9001:2008 alone or in combination with health-specific standards and quality-related activities in Hungarian hospitals.

Abstract:
Objective
To investigate how International Organization for Standardization (ISO) 9001 and the Hungarian Health Care Standards (HHCS) certifications are associated with quality management, patient safety, patient rights and human resource management activities.

Design
A cross-sectional study was implemented using the 2009 Hungarian hospital survey's database.

Setting
Hungary.

Participants
Fifty-three general hospitals were included in the statistical analysis.

Intervention
No intervention was carried out in the study.

Main Outcome Measures
The outcomes included the percentage of compliance in the dimensions of quality management, patient safety, patient rights, human resource management and the overall score for each hospital, and they were grouped according to the hospitals' certifications.

Results
Sixteen hospitals did not have either ISO 9001 or HHCS certifications, 19 had ISO 9001 certification only and 18 had both. Hospitals with ISO 9001 alone or in combination with the HHCS significantly outperformed hospitals with no certifications in terms of quality management and human resource management activities but not in terms of patient safety or patient rights activities. Combined, the two models provided the highest median levels in all cases. Nevertheless, no significant differences were observed when the hospitals with both certifications were compared with hospitals with ISO 9001 only.

Conclusions
Although the combination of ISO 9001 and the HHCS showed the best results, the benefits were not decisive. Furthermore, although the HHCS include standards addressing patient safety, no direct association was found with regard to compliance. Thus, further investigation is required to understand this enigma.

Dombrádi|Viktor|V|
Csenteri|Orsolya Karola|OK|
Sándor|János|J|
Godény|Sándor|S|

standards
certification
quality management
patient safety
Hungary
hospital care


Continuous Kidney Replacement Therapy of the Future: Innovations in Information Technology, Data Analytics, and Quality Assurance Systems.

Abstract: Continuous kidney replacement therapy is commonly used in the critically ill population. Despite the recent development in continuous kidney replacement therapy technology and clinical informatics, many aspects of continuous kidney replacement therapy delivery are still not fully standardized, and quality assurance programs for the provision of continuous kidney replacement therapy are not fully developed. This is in part explained by practice variations, suboptimal integration between machine and clinical data, and the lack of validated continuous kidney replacement therapy quality indicators that are feasible for measurement and monitoring. The further development and sustainable implementation of quality assurance systems that support continuous kidney replacement therapy delivery rely on the collaborative work of the critical care nephrology community and the continuous evolution of clinical informatics. In this article, we describe the present status of information technology and quality assurance systems for continuous kidney replacement therapy delivery and provide a framework for technology development and implementation which is in the pipeline of enhanced continuous kidney replacement therapy delivery.

Neyra|Javier A|JA|
Nadkarni|Girish N|GN|

D058186:Acute Kidney Injury
D016638:Critical Illness
D000077488:Data Science
D006801:Humans
D000073256:Information Technology
D017582:Renal Replacement Therapy

Continuous kidney replacement therapy
Information technology
Quality assurance
CKRT
Quality improvement


Effects of salubrinal on ER stress in an experimental model of polycystic ovary syndrome.

Abstract: This study aimed to investigate the role of endoplasmic reticulum (ER) stress in polycystic ovary syndrome (PCOS) and the effect of salubrinal (SAL) on this role. Animals were divided into four groups as control, PCOS, PCOS+SAL and SAL. Weights and serum testosterone levels were increased in the PCOS group while serum LH and ATF4 expressions were decreased. Morphometrically, number of follicles with a diameter between 150 and 300 µm were declined and number of follicles larger than 300 µm as well as the percentage of cystic follicles (CFs) were increased. Immunoreactivities of GRP78 and p-eIF2α were decreased, whereas oxidative stress (OS) dependent PAR expression was increased. Ultrastructurally, the PCOS group had no ER enlargement which was observed in the control group, while there were mitochondrial damage in granulosa cells (GCs). Elevated OS levels did not induce but rather decreased ER stress in GCs, and SAL injection in the PCOS model was ineffective on searched parameters. Since ER stress plays roles in certain physiological processes, we suggest that inhibitors of ER stress may not be always useful for reproductive tissues.

D000091342:Endoplasmic Reticulum Chaperone BiP

salubrinal
ER stress
PCOS
oxidative stress
electron microscopy


Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease.

Abstract: The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Miguelez|Cristina|C|
Morera-Herreras|Teresa|T|
Torrecilla|Maria|M|
Ruiz-Ortega|Jose A|JA|
Ugedo|Luisa|L|

5-HT
basal ganglia
Parkinson's disease
L-DOPA induced dyskinesia
electrophysiology


High-resolution three-dimensional T1-weighted hepatobiliary MR cholangiography using Gd-EOB-DTPA for assessment of biliary tree anatomy: Parallel imaging versus compressed sensing.

Abstract:
PURPOSE
To compare the quality of images obtained by T1-weighted hepatobiliary MR cholangiography using Gd-EOB-DTPA with 1-mm isovoxel acquisition and compressed sensing (T1-MRCCS) or parallel imaging (T1-MRCPI) for assessment of biliary tree anatomy.

METHOD
We prospectively reviewed T1-MRCCS, T1-MRCPI, and respiratory-triggered 3D T2-weighted MR cholangiography (T2-MRC) images in 58 patients. Two radiologists independently assessed the three sets of images and scored the biliary tree visualization and overall image quality in all cases using a 5-point Likert scale. The resulting scores were compared among T1-MRCCS, T1-MRCPI, and T2-MRC images using a Friedman test followed by a Scheffe test. The inter-reader agreement in scoring was assessed using κ statistics.

RESULTS
The image quality scores for the gallbladder on both T1-MRCCS and T1-MRCPI were significantly lower than those on T2-MRC (p < 0.01) for both readers. Meanwhile, the image quality scores for the right and left hepatic ducts and the anterior and posterior branches of the right hepatic duct on both T1-MRCCS and T1-MRCPI were significantly higher than those on T2-MRC (p < 0.05) for both readers. For Reader 2, the overall image quality scores on T1-MRCCS and T1-MRCPI were both significantly higher than those on T2-MRC (p < 0.05). There were no significant differences between the image quality scores on T1-MRCCS and T1-MRCPI for visualization of each bile duct (p < 0.05).

CONCLUSIONS
There may be no significant difference in quality between T1-MRCCS images and T1-MRCPI images for assessment of biliary tree anatomy, and both types of images may be better than T2-MRC images, although clinical indication is limited compared with T2-MRC.

Suzuki|Takeshi|T|
Aonuma|Takanori|T|
Oyama|Kazuki|K|
Yamada|Akira|A|
Kitoh|Yoshihiro|Y|
Adachi|Yasuo|Y|
Hayashihara|Hayato|H|
Nickel|Marcel D|MD|
Maruyama|Katsuya|K|
Fujinaga|Yasunari|Y|

MR cholangiography
Gd-EOB-DTPA
Parallel imaging
Compressed sensing


Impact of freezing on the emergence of Culicoides chiopterus and Culicoides dewulfi from bovine dung.

Abstract: The emergence of Culicoides chiopterus (Meigen), 1830 and C. dewulfi Goetghebuer, 1936 (Diptera: Ceratopogonidae) from cowpats in northwestern Germany was investigated. In order to investigate the survival of both species at low temperatures, cowpat subsamples were frozen for 48h at -18 and -21°C. Emergence from frozen and non-frozen samples was compared. The number of emerging adults of C. chiopterus from samples frozen at -18°C was greatly reduced and no emergence was observed from samples frozen at -21°C. No adult C. dewulfi emerged from frozen samples, suggesting this species is less resistant to these temperatures, compared to C. chiopterus.

Freezing Emergence Development Larvae Overwintering


In vitro profiling of toxic effects of environmental polycyclic aromatic hydrocarbons on nuclear receptor signaling, disruption of endogenous metabolism and induction of cellular stress.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) may interact with multiple intracellular receptors and related signaling pathways. We comprehensively evaluated the toxicity profiles of six environmentally relevant PAHs differing in structure, genotoxicity and their ability to activate the aryl hydrocarbon receptor (AhR). We focused particularly on their impact on intracellular hormone-, xenobiotic- and lipid-sensing receptors, as well as on cellular stress markers, combining a battery of human reporter gene assays and qRT-PCR evaluation of endogenous gene expression in human hepatocyte-like HepaRG cells, with LC/MS-MS analysis of cellular sphingolipids. The effects of PAHs included: activation of estrogen receptor α (in case of fluoranthene (Fla), pyrene (Pyr), benz[a]anthracene (BaA), benzo[a]pyrene (BaP)), suppression of androgen receptor activity (Fla, BaA, BaP and benzo[k]fluoranthene (BkF)), enhancement of dexamethasone-induced glucocorticoid receptor activity (chrysene (Chry), BaA, and BaP), and potentiation of triiodothyronine-induced thyroid receptor α activity (all tested PAHs). PAHs also induced transcription of endogenous gene targets of constitutive androstane receptor (Fla, Pyr), or repression of target genes of pregnane X receptor and peroxisome proliferator-activated receptor α (in case of the AhR-activating PAHs - Chry, BaA, BaP, and BkF) in HepaRG cells. In the same cell model, the AhR agonists reduced the expression of glucose metabolism genes (PCK1, G6PC and PDK4), and they up-regulated levels of glucosylceramides, together with a concomitant induction of expression of UGCG, glucosylceramide synthesis enzyme. Finally, both BaP and BkF were found to induce expression of early stress and genotoxicity markers: ATF3, EGR1, GDF15, CDKN1A/p21, and GADD45A mRNAs, while BaP alone increased levels of IL-6 mRNA. Overall, whereas low-molecular-weight PAHs exerted significant effects on nuclear receptors (with CYP2B6 induction observed already at nanomolar concentrations), the AhR activation by 4-ring and 5-ring PAHs appeared to be a key mechanism underlying their impact on nuclear receptor signaling, endogenous metabolism and induction of early stress and genotoxicity markers.

Šimečková|Pavlína|P| Pěnčíková|Kateřina|K| Kováč|Ondrej|O| Slavík|Josef|J| Pařenicová|Martina|M| Vondráček|Jan|J| Machala|Miroslav|M|

Polycyclic aromatic hydrocarbons
Nuclear receptors
Sphingolipids
Cellular stress response
Energy metabolism


Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I).

Abstract: Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.

Sebastian|Shaji|S|
Hernández|Vincent|V|
Myrelid|Pär|P|
Kariv|Revital|R|
Tsianos|Epameinondas|E|
Toruner|Murat|M|
Marti-Gallostra|Marc|M|
Spinelli|Antonino|A|
van der Meulen-de Jong|Andrea E|AE|
Yuksel|Elif Sarıtas|ES|
Gasche|Christoph|C|
Ardizzone|Sandro|S|
Danese|Silvio|S|

Colorectal cancer
Inflammatory bowel disease
Pathogenesis
Epidemiology
IBD
Chemoprevention
Outcomes
CRC
5-ASA
5-amino salicylic acid
AOM
Azoxymethane
CAC
CD
CIN
Chromosomal instability
Colitis-associated cancer
Crohn's disease
DSS
Dextran sodium sulphate
IC
IL
Indeterminate colitis
Interleukins
MRR
MSI
Microsatellite instability
Mortality rate ratio
NF-κB
Nuclear factor-κB
OR
Odds ratio
PSC
Primary sclerosing cholangitis
RR
Relative risk
SIR
Standardised incidence ratio
TGFβ
TLR
TNFα
Toll-like receptor
Transforming growth factor-β
Tumour necrosis factor-α
UC
Ulcerative colitis

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


A Temporal Network Approach to Paranoia: A Pilot Study.

Abstract: Paranoid beliefs have been conceptualized as a central psychological process linked to schizophrenia and many mental disorders. Research on paranoia has indicated that it is pivotal to consider not only levels but also dynamic aspects of incriminated related mechanisms over time. In the present study, we conceptualized paranoia as a system of interacting elements. To do so, we used temporal network analysis to unfold the temporal dynamics between core psychological paranoia-related mechanisms, such as self-esteem, sadness, feeling close to others, and experiential avoidance. Time-series data of 23 participants with high scores in paranoia and/or interpersonal sensitivity were collected via experience sampling methodology (ESM). We applied a multilevel vector autoregressive (mlVAR) model approach and computed three distinct and complementary network models (i.e., contemporaneous, temporal, and between-subject) to disentangle associations between paranoia-related mechanisms in three different time frames. The contemporaneous model indicated that paranoia and sadness co-occurred within the same time frame, while sadness was associated with both low self-esteem and lack of closeness to others. The temporal model highlighted the importance of feeling close to others in predicting low paranoia levels in the next time frame. Finally, the between-subject model largely replicated an association found in both contemporaneous and temporal models. The current study reveals that the network approach offers a viable data-driven methodology for elucidating how paranoia-related mechanisms fluctuate over time and may determine its severity. Moreover, this novel perspective may open up new directions toward identifying potential targets for prevention and treatment of paranoia-related problems.

Contreras|Alba|A| Valiente|Carmen|C| Heeren|Alexandre|A| Bentall|Richard|R|

paranoia
temporal network analysis
self-esteem
sadness
experience sampling methodology
intensive time-series


Carbon Quantum Dots: Synthesis, Characterization and Biomedical Applications.

Abstract: CQD are small carbon nanoparticles smallerl than 10 nm comprising distinctive properties, which have become an obligatory tool for traceable targeted delivery, biomedical research, and different therapy applications. The objective of the present work was to consolidate the current literature on the synthesis, characterization techniques, and biomedical applications of CQD. Two types of synthetic methods viz. top-down approach and bottom-up approach were used for the synthesis of CQD. The top-down approach includes the arc-discharge method, laser ablation method, and electrochemical method. The bottom-up approach includes the thermal method, microwave-assisted method, hydrothermal and aqueous method, and the template method. In this review, we explain the recent progress of CQD in the biomedical field, focusing on their synthetic methods and characterization, followed by different applications. Carbon dots have extensive adequacy for in vivo and in vitro bioimaging and drug delivery studies. Although more cytotoxicity studies of carbon dots are needed, the data above suggest a bright future for carbon dots in drug delivery and bioimaging studies.

Carbon quantum dots
nanoparticles
carbon dots
nanocomposites
photoluminescence
quantum yield


Identification of tele-ICU system requirements using a content validity assessment.

Abstract:
OBJECTIVES
Telemedicine in intensive care (tele-ICU) involves the use of information technologies to deliver care instructions from a command center to remote hospitals. To ensure acceptance and usability, clinicians should participate early in the design. This study surveyed clinical professionals to identify and rank important functions for a tele-ICU system.

METHODS
This cross-sectional, prospective, structured, two-round survey included European intensive-care professionals that were not familiar with tele-ICU systems. In the first round, statements of system function specifications were evaluated for validity; in the second round, unclear items were rephrased and new items were added. Item-level content validity indexes (I-CVI) were calculated, and values above a 0.75 threshold were considered relevant. Weighted ranking points (WRP) was calculated from the ranking data.

RESULTS
A total of 26 responses were received from professionals for four European countries; the majority were intensive-care specialists (77%). A total set of 50 items were selected for the survey. Thirty-six functional specifications were identified with I-CVIs above 0.75, including online access to all patient data (13 items), related risks and alarms (8 items), audio-visual contact for consultations and for monitoring patient beds (5 items), information security (5 items), and resource allocation (5 items). The highest ranking system functions were real time monitoring, alarms, audio-visual connections, and data security.

CONCLUSIONS
Professionals not familiar with tele-ICUs regarded full patient data access, alarms, data security, and audio-visual connections the most important functions in pre-implementation phase.

Larinkari|Simo|S|
Liisanantti|Janne H|JH|
Ala-Lääkkölä|Timo|T|
Meriläinen|Merja|M|
Kyngäs|Helvi|H|
Ala-Kokko|Tero|T|

Tele-ICU
Content validity assessment
Telemedicine


Discovery of trisubstituted pyrazolines as a novel scaffold for the development of selective phosphodiesterase 5 inhibitors.

Abstract: Celecoxib, is a selective cyclooxygenase-2 (COX2) inhibitor with a 1,5-diaryl pyrazole scaffold. Celecoxib has a better safety profile compared to other COX2 inhibitors having side effects of systemic hypertension and thromboembolic complications. This may be partly attributed to an off-target activity involving phosphodiesterase 5 (PDE5) inhibition and the potentiation of NO/cGMP signalling allowing coronary vasodilation and aortic relaxation. Inspired by the structure of celecoxib, we synthesized a chemically diverse series of compounds containing a 1,3,5-trisubstituted pyrazoline scaffold to improve PDE5 inhibitory potency, while eliminating COX2 inhibitory activity. SAR studies for PDE5 inhibition revealed an essential role for a carboxylic acid functionality at the 1-phenyl and the importance of the non-planar pyrazoline core over the planar pyrazole with the 5-phenyl moiety tolerating a range of substituents. These modifications led to new PDE5 inhibitors with approximately 20-fold improved potency to inhibit PDE5 and no COX-2 inhibitory activity compared with celecoxib. PDE isozyme profiling of compound 11 revealed a favorable selectivity profile. These results suggest that trisubstituted pyrazolines provide a promising scaffold for further chemical optimization to identify novel PDE5 inhibitors with potential for less side effects compared with available PDE5 inhibitors used for the treatment of penile erectile dysfunction and pulmonary hypertension.

Abdel-Halim|Mohammad|M|
Tinsley|Heather|H|
Keeton|Adam B|AB|
Weam|Mohammed|M|
Atta|Noha H|NH|
Hammam|Mennatallah A|MA|
Hefnawy|Amr|A|
Hartmann|Rolf W|RW|
Engel|Matthias|M|
Piazza|Gary A|GA|
Abadi|Ashraf H|AH|

D054706:Cyclic Nucleotide Phosphodiesterases, Type 5

Pyrazoline
Celecoxib
PDE5
PDE5 inhibitors
cGMP elevation


Seasonal H3N2 influenza A virus fails to enhance Staphylococcus aureus co-infection in a non-human primate respiratory tract infection model.

Abstract: Staphylococcus aureus community-acquired pneumonia is often associated with influenza or an influenza-like syndrome. Morbidity and mortality due to methicillin-resistant S. aureus (MRSA) or influenza and pneumonia, which includes bacterial co-infection, are among the top causes of death by infectious diseases in the United States. We developed a non-lethal influenza A virus (IAV) (H3N2)/S. aureus co-infection model in cynomolgus macaques (Macaca fascicularis) to test the hypothesis that seasonal IAV infection predisposes non-human primates to severe S. aureus pneumonia. Infection and disease progression were monitored by clinical assessment of animal health; analysis of blood chemistry, nasal swabs, and X-rays; and gross pathology and histopathology of lungs from infected animals. Seasonal IAV infection in healthy cynomolgus macaques caused mild pneumonia, but unexpectedly, did not predispose these animals to subsequent severe infection with the community-associated MRSA clone USA300. We conclude that in our co-infection model, seasonal IAV infection alone is not sufficient to promote severe S. aureus pneumonia in otherwise healthy non-human primates. The implication of these findings is that comorbidity factors in addition to IAV infection are required to predispose individuals to secondary S. aureus pneumonia.

Kobayashi|Scott D|SD|
Olsen|Randall J|RJ|
LaCasse|Rachel A|RA|
Safronetz|David|D|
Ashraf|Madiha|M|
Porter|Adeline R|AR|
Braughton|Kevin R|KR|
Feldmann|Friederike|F|
Clifton|Dawn R|DR|
Kash|John C|JC|
Bailey|John R|JR|
Gardner|Donald J|DJ|
Otto|Michael|M|
Brining|Douglas L|DL|
Kreiswirth|Barry N|BN|
Taubenberger|Jeffrey K|JK|
Parnell|Michael J|MJ|
Feldmann|Heinz|H|
Musser|James M|JM|
DeLeo|Frank R|FR|

influenza a virus
Staphylococcus aureus
pneumonia
MRSA
USA300
coinfection


Caregiver Burden, Spirituality, and Psychological Well-Being of Parents Having Children with Thalassemia.

Abstract: The research determined the relationship of caregiving burden, spirituality and psychological well-being of parents of Pakistani thalassemic patients in a crosssectional research design. The sociodemographic form, Montgomery-Borgatta burden measure (Montgomery et al. in Who should care for the elderly? An east-west value divide. World Scientific, River Edge, pp 27-54, 2000), Multidimensional Measure of Islamic Spirituality (Dasti and Sitwat in J Muslim Ment Health 8(2):47-67, 2014. doi: 10.3998/jmmh.10381607.0008.204 ) and Ryff Scale of Psychological Well-being (Ryff in J Pers Soc Psychol 57(6):1069-1081, 1989. doi: 10.1037/0022-3514.57.6.1069 ) were administered on a sample of 80 parents (32 fathers and 48 mothers) recruited from different Thalassemic Centers of Lahore city, Pakistan. Data were analyzed through correlation and mediational analyses. Results indicated that the caregiver burden was negatively correlated with the psychological well-being and the domains of spirituality, while the psychological well-being and spirituality were positively correlated. We identified that the caregiver burden has direct effect on the psychological well-being of the parents and it influences the psychological well-being through the pathway of the two domains of spirituality, i.e., self-discipline and meanness-generosity. These results highlighted the role of spirituality upon the psychological well-being of caregivers, which could be utilized to prevent pathological influences (such as hard feelings, hopelessness, depressed mood, anxiety, and relationship problems) of caregiver burden and enhance psychological well-being through spiritual counseling. Caregivers can work on their well-being and burden by disciplining their lives and forgoing hard feelings toward others.

Caregiver burden
Spirituality
Psychological well-being
Thalassemia


Improved Hydrogenation Kinetics of TiMn1.52 Alloy Coated with Palladium through Electroless Deposition.

Abstract: The deterioration of hydrogen charging performances resulting from the surface chemical action of electrophilic gases such as CO2 is one of the prevailing drawbacks of TiMn1.52 materials. In this study, we report the effect of autocatalytic Pd deposition on the morphology, structure, and hydrogenation kinetics of TiMn1.52 alloy. Both the uncoated and Pd-coated materials were characterized using scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS) and X-ray diffraction (XRD). XRD analyses indicated that TiMn1.52 alloy contains C14-type Laves phase without any second phase, while the SEM images, together with a particle size distribution histogram, showed a smooth non-porous surface with irregular-shaped particles ranging in size from 1 to 8 µm. The XRD pattern of Pd-coated alloy revealed that C14-type Laves phase was still maintained upon Pd deposition. This was further supported by calculated crystallite size of 29 nm for both materials. Furthermore, a Sieverts-type apparatus was used to study the kinetics of the alloys after pre-exposure to air and upon vacuum heating at 300 °C. The Pd-coated AB2 alloy exhibited good coating quality as confirmed by EDS with enhanced hydrogen absorption kinetics, even without activation. This is attributed to improved surface tolerance and a hydrogen spillover mechanism, facilitated by Pd nanoparticles. Vacuum heating at 300 °C resulted in removal of surface barriers and showed improved hydrogen absorption performances for both coated and uncoated alloys.

TiMn1.52 alloy
AB2 alloys
hydrogen storage materials
palladium deposition


Deep Count: Fruit Counting Based on Deep Simulated Learning.

Abstract: Recent years have witnessed significant advancement in computer vision research based on deep learning. Success of these tasks largely depends on the availability of a large amount of training samples. Labeling the training samples is an expensive process. In this paper, we present a simulated deep convolutional neural network for yield estimation. Knowing the exact number of fruits, flowers, and trees helps farmers to make better decisions on cultivation practices, plant disease prevention, and the size of harvest labor force. The current practice of yield estimation based on the manual counting of fruits or flowers by workers is a very time consuming and expensive process and it is not practical for big fields. Automatic yield estimation based on robotic agriculture provides a viable solution in this regard. Our network is trained entirely on synthetic data and tested on real data. To capture features on multiple scales, we used a modified version of the Inception-ResNet architecture. Our algorithm counts efficiently even if fruits are under shadow, occluded by foliage, branches, or if there is some degree of overlap amongst fruits. Experimental results show a 91% average test accuracy on real images and 93% on synthetic images.

D000465:Algorithms
D000069550:Machine Learning
D016571:Neural Networks, Computer

simulated learning
deep learning
yield estimation
agricultural sensors


Surgical errors and complications following cesarean delivery in the United States.

Abstract:
BACKGROUND
Cesarean delivery is the most common inpatient surgery performed internationally. Although cesarean delivery is typically performed to prevent adverse maternal and fetal outcomes, there is still a risk of surgical errors and complications. This study examined maternal and hospital risk factors associated with errors and complications following cesarean delivery in the United States.

OBJECTIVE
To determine the prevalence of, and associated individual- and hospital-level risk factors for, surgical errors and complications following cesarean delivery in the United States.

MATERIALS AND METHODS
Data were obtained from the 2012-2014 National Inpatient Sample. Surgical errors (eg,. foreign body retained during surgery, anesthetic error) can be the result of human error, whereas complications (eg, mortality, postpartum hemorrhage) can be due to external factors such as pre-existing comorbidities. The overall prevalence of surgical errors and complications in cesarean delivery was calculated. Multilevel logistic regression models were used to examine the association between individual and hospital characteristics and surgical errors/complications.

RESULTS
Among 648,584 cesarean delivery hospitalizations, 1.98% (95% confidence interval, 1.95-2.01%) and 8.43% (95% confidence interval, 8.40-8.46%) of women had an error or complication, respectively. The most common errors were anesthetic errors, errors involving blood vessels, and errors involving the bladder. The most common complications were postpartum hemorrhage, infection, and hysterectomy. Both individual- and hospital-level factors were associated with errors and complications. Women with Medicaid insurance had increased odds of errors (odds ratio, 1.40; 95% confidence interval, 1.37-1.43) but lower odds of complications (odds ratio, 0.89; 95% confidence interval, 0.88-0.90) compared to women with private insurance. Compared to non-Hispanic white women, women of all races had lower odds of error, and only non-Hispanic black women had greater odds of complications (odds ratio, 1.14; 95% confidence interval, 1.13-1.16). Similarly, rural hospitals had lower odds of surgical errors (odds ratio, 0.59; 95% confidence interval, 0.56-0.62) and complications (odds ratio, 0.61; 95% confidence interval, 0.59-0.62), whereas hospitals with a large bed number had greater odds of errors and complications than medium-bed size hospitals, at 1.13 (95% confidence interval, 1.09-1.17), and 1.13 (95% confidence interval, 1.11-1.15), respectively.

CONCLUSION
This study identified specific risk factors for errors and complications that can be further examined through quality improvement frameworks to reduce the prevalence of adverse maternal events during cesarean delivery.

Sheikh|Manal S|MS|
Nelson|Gregg|G|
Wood|Stephen L|SL|
Metcalfe|Amy|A|


Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy.

Abstract: Hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (mean arterial pressure [MAP]) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared with control pregnant rats. To examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy, we examined the role of endogenous ANGII in AT1-AA-infused pregnant rats, and that of endothelin-1 and oxidative stress in AT1-AA+ANGII-treated rats. Chronic ANGII increased MAP from 95±2 in normal pregnant rats to 115±2 mm Hg; chronic AT1-AA increased MAP to 118±1 mm Hg in normal pregnant rats, which further increased to 123±2 mm Hg with AT1-AA+ANGII. Increasing ANGII from 10(-11) to 10(-8) decreased afferent arteriole diameter from 15% to 20% but sharply decreased afferent arteriole diameter to 60% in AT1-AA-pretreated vessels. Renal artery resistance index increased from 0.67 in normal pregnant rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA+ANGII-infused rats. AT1-AA-induced hypertension decreased with enalapril but was not attenuated. Both tissue endothelin-1 and reactive oxygen species increased with AT1-AA+ANGII compared with AT1-AA alone, and blockade of either of these pathways had significant effects on MAP or renal artery resistance index. These data support the hypothesis that AT1-AA, via activation of endothelin-1 and oxidative stress and interaction with endogenous ANGII, is an important mechanism whereby MAP and renal vascular responses are enhanced during preeclampsia.

Brewer|Justin|J|
Liu|Ruisheng|R|
Lu|Yan|Y|
Scott|Jeremy|J|
Wallace|Kedra|K|
Wallukat|Gerd|G|
Moseley|Janae|J|
Herse|Florian|F|
Dechend|Ralf|R|
Martin|James N|JN|
Lamarca|Babbette|B|


Editing Myosin VB Gene to Create Porcine Model of Microvillus Inclusion Disease, With Microvillus-Lined Inclusions and Alterations in Sodium Transporters.

Abstract:
BACKGROUND & AIMS
Microvillus inclusion disease (MVID) is caused by inactivating mutations in the myosin VB gene (MYO5B). MVID is a complex disorder characterized by chronic, watery, life-threatening diarrhea that usually begins in the first hours to days of life. We developed a large animal model of MVID to better understand its pathophysiology.

METHODS
Pigs were cloned by transfer of chromatin from swine primary fetal fibroblasts, which were edited with TALENs and single-strand oligonucleotide to introduce a P663-L663 substitution in the endogenous swine MYO5B (corresponding to the P660L mutation in human MYO5B, associated with MVID) to fertilized oocytes. We analyzed duodenal tissues from patients with MVID (with the MYO5B P660L mutation) and without (controls), and from pigs using immunohistochemistry. Enteroids were generated from pigs with MYO5B(P663L) and without the substitution (control pigs).

RESULTS
Duodenal tissues from patients with MVID lacked MYO5B at the base of the apical membrane of intestinal cells; instead MYO5B was intracellular. Intestinal tissues and derived enteroids from MYO5B(P663L) piglets had reduced apical levels and diffuse subapical levels of sodium hydrogen exchanger 3 and SGLT1, which regulate transport of sodium, glucose, and water, compared with tissues from control piglets. However, intestinal tissues and derived enteroids from MYO5B(P663L) piglets maintained CFTR on apical membranes, like tissues from control pigs. Liver tissues from MYO5B(P663L) piglets had alterations in bile salt export pump, a transporter that facilitates bile flow, which is normally expressed in the bile canaliculi in the liver.

CONCLUSIONS
We developed a large animal model of MVID that has many features of the human disease. Studies of this model could provide information about the functions of MYO5B and MVID pathogenesis, and might lead to new treatments.

Engevik|Amy C|AC|
Coutts|Alexander W|AW|
Kaji|Izumi|I|
Rodriguez|Paula|P|
Ongaratto|Felipe|F|
Saqui-Salces|Milena|M|
Medida|Ramya Lekha|RL|
Meyer|Anne R|AR|
Kolobova|Elena|E|
Engevik|Melinda A|MA|
Williams|Janice A|JA|
Shub|Mitchell D|MD|
Carlson|Daniel F|DF|
Melkamu|Tamene|T|
Goldenring|James R|JR|

D019005:Cystic Fibrosis Transmembrane Conductance Regulator

D020022:Genetic Predisposition to Disease

Malabsorption
Missense Mutation
Motor Protein
Plasma Membrane


Towards high-accuracy primary spectral radiometry from 400 K to 1300 K.

Abstract: We describe the design, construction, calibration and use of a near-infrared thermodynamic radiation thermometer to measure blackbodies from 400 K to 1300 K. The motivation for this work is the pending redefinition of the kelvin and the need for direct, thermodynamic temperature measurements of the fixed-point blackbodies presently used in the realization of the temperature scale. The challenges of accurately measuring Planck radiances which vary greatly in radiance level and spectral shape are discussed. Methods to characterize the components used in the radiation thermometer design are described. The use of this radiation thermometer as a relative primary thermometer and the resulting residuals are shown. We describe radiometric calibration procedures for using the radiation thermometer as an absolute primary thermometer. Preliminary data showing the initial radiometric calibration steps are discussed.

radiometry
thermodynamic temperature
temperature scale
radiation thermometry


Remote cognitive and behavioral assessment: Report of the Alzheimer Society of Canada Task Force on dementia care best practices for COVID-19.

Abstract:
Introduction
Despite the urgent need for remote neurobehavioral assessment of individuals with cognitive impairment, guidance is lacking. Our goal is to provide a multi-dimensional framework for remotely assessing cognitive, functional, behavioral, and physical aspects of people with cognitive impairment, along with ethical and technical considerations.

Methods
Literature review on remote cognitive assessment and multidisciplinary expert opinion from behavioral neurologists, neuropsychiatrists, neuropsychologists, and geriatricians was integrated under the auspices of the Alzheimer Society of Canada Task Force on Dementia Care Best Practices for COVID-19. Telephone and video approaches to assessments were considered.

Results
Remote assessment is shown to be acceptable to patients and caregivers. Informed consent, informant history, and attention to privacy and autonomy are paramount. A range of screening and domain-specific instruments are available for telephone or video assessment of cognition, function, and behavior. Some neuropsychological tests administered by videoconferencing show good agreement with in-person assessment but still lack validation and norms. Aspects of the remote dementia-focused neurological examination can be performed reliably.

Discussion
Despite challenges, current literature and practice support implementation of telemedicine assessments for patients with cognitive impairment. Convergence of data across the clinical interview, reliable and brief remote cognitive tests, and remote neurological exam increase confidence in clinical interpretation and diagnosis.

Geddes|Maiya R|MR|
O'Connell|Megan E|ME|
Fisk|John D|JD|
Gauthier|Serge|S|
Camicioli|Richard|R|
Ismail|Zahinoor|Z|
|||

assessment
dementia
cognitive impairment
telemedicine
Alzheimer's disease
telehealth


Repetitive Transcranial Magnetic Stimulation in Youth With Treatment Resistant Major Depression.

Abstract: Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD. Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13-21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a >50% reduction in Ham-D scores. Safety and tolerability were also examined. Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p < 0.00001). We observed 18 (56%) responders (≥ 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ≤ 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%. Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01731678.

MacMaster|Frank P|FP|
Croarkin|Paul E|PE|
Wilkes|T Christopher|TC|
McLellan|Quinn|Q|
Langevin|Lisa Marie|LM|
Jaworska|Natalia|N|
Swansburg|Rose M|RM|
Jasaui|Yamile|Y|
Zewdie|Ephrem|E|
Ciechanski|Patrick|P|
Kirton|Adam|A|

transcrancial magnetic stimulation (TMS)


The vitamin D receptor in the proximal renal tubule is a key regulator of serum 1α,25-dihydroxyvitamin D₃.

Abstract: It is well established that the mitochondria of proximal convoluted tubule cells of the kidney are the site of production of circulating 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The production of 1,25(OH)2D3 at this site is tightly regulated. Parathyroid hormone markedly stimulates 1,25(OH)2D3 production, whereas 1,25(OH)2D3 itself suppresses production. The mechanism of suppression by 1,25(OH)2D3 has not yet been elucidated. We have now found that in the absence of vitamin D (vitamin D deficiency), the vitamin D receptor (VDR) is found in the interior of the apical brush border of the proximal tubule cells. This is unique for the proximal tubule cells, since this has not been observed in the distal tubule cells or in other epithelial cells, such as intestinal mucosa. Administration of 1,25(OH)2D3 to vitamin D-deficient rats results in the movement of VDR from the brush border to the cytoplasm and nucleus presumably bound to reabsorbed 1,25(OH)2D3. The VDR bound to 1,25(OH)2D3 suppresses expression of 25-hydroxyvitamin D3 1α-hydroxylase and stimulates the 25-hydroxyvitamin D3 24-hydroxylase. Thus, VDR in the apical brush border of the proximal convoluted tubule cells serves to "sense" the level of circulating 1,25(OH)2D3 and modulates the activity of the 1α-hydroxylase and the 24-hydroxylase accordingly.

Wang|Yongji|Y|
Zhu|Jinge|J|
DeLuca|Hector F|HF|

vitamin D receptor
proximal renal tubule
1α-hydroxylase
24-hydroxylase
1,25-dihydroxyvitamin D
calcium


Nutrition Status and Health-Related Quality of Life Among Outpatients With Advanced Head and Neck Cancer.

Abstract: This pilot study evaluated nutrition status and health-related quality of life (HRQOL) outcomes among outpatients with head and neck cancer (HNC). Data were collected from 19 patients (18 males, 1 female) during 3 time points: once before chemoradiotherapy (CRT) initiation and 1 and 3 months after CRT. Nutrition status was evaluated using the Scored Patient-Generated Subjective Global Assessment (PG-SGA). Malnutrition was defined as PG-SGA stage B (moderate/suspected malnutrition) or stage C (severely malnourished). HRQOL was assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its HNC-specific module (QLQ-H&N35). We found that well-nourished patients reported having fewer issues with pain, fatigue, appetite loss, chewing, sticky saliva, coughing, and social eating than those categorized as malnourished (P < .05). The association between the global quality-of-life score and PG-SGA score was statistically significant but weak in strength (r = -0.37, P = .012). Although PG-SGA identified 70% as either moderately or severely malnourished before treatment initiation, the mean body mass index was in the overweight category (29 ± 5 kg/m2 ). Compared with pretreatment, patients reported more severe problems with chewing, swallowing, sticky saliva, dry mouth, speech, social eating, and taste and smell sensations at 1-month follow-up, although issues with dry mouth persisted 3 months post treatment (P = .003). In conclusion, malnourished patients reported having worse HRQOL symptoms compared with well-nourished patients. Routine nutrition and psychosocial assessment through PG-SGA and EORTC tools might help identify patients in need of nutrition and psychosocial care.

quality of life
head and neck cancer
PG-SGA
malnutrition
nutrition station


The Structural Imaging Characteristics and Its Clinical Relevance in Patients with Cerebral Venous Thrombosis-A Retrospective Analysis from One Single Center in China.

Abstract:
Background
Few studies have investigated structural imaging findings of cerebral venous thrombosis (CVT) in China. The structural imaging [head computed tomography (CT) and routine brain magnetic resonance imaging (MRI)] can assess any parenchymal lesion secondary to the venous thrombosis and reveal direct signs of intraluminal thrombus. In recent years, many patients can be diagnosed with CVT more rapidly and directly by structural imaging. The aim of the present study is to determine the performance of structural imaging in the diagnosis and outcome of CVT in a large cohort single center of Chinese patients.

Methods
We evaluated consecutive patients admitted to our hospital with CVT receiving structural imaging from 1991 to 2015. A neuroradiologist, blinded to clinical data, independently reviewed the structural imaging, including head CT and routine MRI for parenchymal lesions and signs of dural venous sinus thrombosis, as well as the MRV/DSA findings. The Clinical and laboratory data were reviewed and recorded for further analysis.

Results
117 patients were included in this study, 68 (58.1%) were females. Parenchymal lesions were identified in 56.4% (66/117) of the patients on structural imaging, including focal edema in 30.8%, hemorrhage in 19.7%, and brain swelling in 4.3% of the patients. Patients with parenchymal lesions presented with more often seizures (P < 0.001) and less often headache (P = 0.049). Intraluminal thrombus within the sinuses or veins on structural imaging was found in 28.2% (33/117) of the patients. Patients with both intraluminal thrombus and parenchymal lesions on structural imaging had more acute onset (P = 0.01) and present more consciousness disturbance (P = 0.007).

Conclusion
Intracranial lesions on structural imaging are frequently found in patients with CVT. Patients with parenchymal lesions on structural imaging, especially with intraluminal thrombus simultaneously, tend to have a severe clinical picture and might lead to a devastating or fatal outcome. Structural imaging may help on early diagnosis and predict the poor outcome of CVT.

Zhou|Li-Xin|LX| Yao|Ming|M| Cui|Li-Ying|LY| Li|Ming-Li|ML| Zhu|Yi-Cheng|YC| Ni|Jun|J| Peng|Bin|B|

imaging
cerebral venous thrombosis
magnetic resonance imaging
parenchymal lesion
intraluminal thrombosis


Necroptosis: Modules and molecular switches with therapeutic implications.

Abstract: Among the various programmed cell death (PCD) pathways, "Necroptosis" has gained much importance as a novel paradigm of cell death. This pathway has emerged as a backup mechanism when physiologically conserved PCD (apoptosis) is non-functional either genetically or pathogenically. The expanding spectrum of necroptosis from physiological development to diverse patho-physiological disorders, including xenobiotics-mediated toxicity has now grabbed the attention worldwide. The efficient role of necroptosis regulators in disease development and management are under constant examination. In fact, few regulators (e.g. MLKL) have already paved their way towards clinical trials and others are in queue. In this review, emphasis has been paid to the various contributing factors and molecular switches that can regulate necroptosis. Here we linked the overview of current knowledge of this enigmatic signaling with magnitude of therapeutics that may underpin the opportunities for novel therapeutic approaches to suppress the pathogenesis of necroptosis-driven disorders.

Arora|Deepika|D|
Sharma|Pradeep Kumar|PK|
Siddiqui|Mohammed Haris|MH|
Shukla|Yogeshwer|Y|

Necroptosis
Therapeutics
Programmed cell death
Inflammation


Hard tissue dimensional changes following implant removal due to peri-implantitis: A retrospective study.

Abstract:
BACKGROUND
The current evidence regarding the alterations experienced by the alveolar ridge (hard tissue changes) after implant removal due to peri-implantitis is limited.

PURPOSE
To assess the hard tissue dimensional changes following implant removal due to peri-implantitis.

MATERIAL AND METHODS
Clinical records were examined to identify patients with implants that had to be removed due to a hopeless prognosis secondary to peri-implantitis due to expendability of peri-implantitis implants for functional reasons. Patients with preoperative and postoperative cone-beam computed tomography (CBCT) scans were included. Patient-related, implant-related, and surgery-related factors were assessed based on the clinical records. Linear measurements were made to evaluate the influence of bone plate thickness (BPT), ridge width (RW), and ridge height (RH) at various levels upon the outcome of implant removal. A descriptive statistical analysis of the quantitative and qualitative variables was performed. Correlations of the variables with the primary outcome (dimensional changes) were tested using univariate and multivariate analyses (multinomial random intercept mixed model linear regressions).

RESULTS
A total of 26 patients (nimplants = 79) met the eligibility criteria. The mean decrease in RW at 1 and 3 mm below the crest was 11.3% and 4.4%, respectively (P < 0.001). Buccal and lingual RH was significantly reduced by 2.2% and 6.3%, respectively (P < 0.001). Few patient-related, implant-related, and surgery-related factors appeared to have an impact upon the hard tissue dimensional changes. Bone regeneration simultaneous to implant removal minimized the dimensional changes of the ridge both vertically (5% lesser buccal RH reduction) and horizontally (12% lesser RW reduction) when compared with spontaneous healing. The use of a reverse-torque removal kit seemed to be critical in limiting the dimensional changes of the ridge.

CONCLUSIONS
Minimal hard tissue changes can be expected following implant removal due to peri-implantitis. Simultaneous bone regeneration procedures and the use of a removal kit may considerably reduce the impact upon the dimensional changes (NCT04534361).

D016301:Alveolar Bone Loss
D000539:Alveolar Process
D001861:Bone Regeneration
D015921:Dental Implants
D006801:Humans
D057873:Peri-Implantitis
D012189:Retrospective Studies

peri-implantitis
alveolar bone
dental implants
peri-implant disease


Vascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury.

Abstract:
AIMS
Neural stem cells (NSCs) in the adult mammalian spinal cord are activated in response to spinal cord injury (SCI); however, mechanisms modulating this process are not clear. Here, we noticed SCI elevated expression of vascular endothelial growth factor (VEGF) and we aimed to validate the roles of VEGF in NSCs activation after SCI and investigated the related signals during the process.

METHODS
In vitro we detected whether VEGF promoted spinal cord NSCs proliferation and investigated the involved signals; In vivo, we injected VEGF into rat spinal cord to check the NSCs activation.

RESULTS
In vitro, VEGF triggered spinal cord NSCs proliferation and maintained self-renewal. Further investigations demonstrated VEGF transactivated epidermal growth factor receptor (EGFR) through VEGF receptor 2 (VEGFR2) to promote spinal cord NSCs proliferation. In vivo, we injected VEGF into spinal cord by laminectomy to confirm the roles of VEGF-VEGFR2-EGFR signals in NSCs activation. VEGF significantly elevated the number of activated NSCs and increased EGFR phosphorylation. In contrast, intraspinal injection of specific inhibitors targeting EGFR and VEGFR2 decreased NSCs activation after SCI. Our results demonstrate that VEGF-VEGFR2-EGFR axis is important for NSCs activation after SCI, providing new insights into the mechanisms of spinal cord NSCs activation postinjury.

Liu|Su-Mei|SM| Xiao|Zhi-Feng|ZF| Li|Xing|X| Zhao|Yan-Nan|YN| Wu|Xian-Ming|XM| Han|Jin|J| Chen|Bing|B| Li|Jia-Yin|JY| Fan|Cai-Xia|CX| Xu|Bai|B| Xue|Xiao-Yu|XY| Xue|Wei-Wei|WW| Yang|Ying|Y| Dai|Jian-Wu|JW|0000-0002-3379-9053

D042461:Vascular Endothelial Growth Factor A

D040301:Vascular Endothelial Growth Factor Receptor-2

vascular endothelial growth factor
epidermal growth factor receptor
spinal cord injury
VEGF receptor 2
neural stem cells activation


Impulsivity-related traits, college alcohol beliefs, and alcohol outcomes: Examination of a prospective multiple mediation model among college students in Spain, Argentina, and USA.

Abstract:
OBJECTIVES
The present study examined (both cross-sectionally and prospectively) the mediational role of college alcohol beliefs in the relationship between impulsivity-related traits and alcohol outcomes (i.e., alcohol use and negative consequences) among college student drinkers from the United States (U.S.), Spain, and Argentina.

METHOD
A sample of 1429 (U.S. = 733, Spain = 292, Argentina = 404) drinkers (at least one drinking episode within the previous month) completed the baseline survey, and 242 drinkers completed the follow-up. To test study aims, a cross-sectional model was first employed to examine whether the proposed double-mediated paths (i.e., each dimension of impulsivity → college alcohol beliefs → alcohol use → negative alcohol-related consequences) extends across samples with different cultural backgrounds (i.e., structural invariance testing). A longitudinal model was then conducted to assess if college alcohol beliefs prospectively mediate the associations between trait impulsivity and alcohol outcomes.

RESULTS
College alcohol beliefs were concurrently and prospectively associated with both greater alcohol use and increased number of negative alcohol-related consequences. These internalized beliefs about college student drinking culture significantly mediated the effects of several distinct impulsivity-related traits on alcohol-related outcomes including urgency (positive and negative), sensation seeking, and perseverance. These findings were invariant across gender and across three countries (Argentina, Spain, and the U.S.).

CONCLUSIONS
Our findings highlight the modulatory role of cognitive factors on problematic alcohol use among college students with different cultural backgrounds. Our results suggest that, despite the cultural differences exhibited by these three countries, the unique and mediational effects of college alcohol beliefs appear relatively universal.

Bravo|Adrian J|AJ|
Pearson|Matthew R|MR|
Pilatti|Angelina|A|
Read|Jennifer P|JP|
Mezquita|Laura|L|
Ibáñez|Manuel I|MI|
Ortet|Generós|G|

College alcohol beliefs
Alcohol
College students
Impulsivity
Cross-cultural


Prevalence of pathological flatfoot in school-age children.

Abstract:
BACKGROUND
Prevalence of pathological flatfoot has not been well defined in the literature. The objective of this study was to establish the prevalence of pathological flatfoot in school-age children and investigate the factors associated with this deformity.

METHODS
A total of 667 children (327 girls and 340 boys) were recruited for this cross-sectional study with multi-stage clustered random sampling. The diagnosis of flatfoot was based on clinical observations and measurements using a suggested systematic protocol. Pathological flatfoot in this study did not merely screen for structural flatfoot, it included symptomatic conditions as well as musculoskeletal risk factors predisposing a progressive flatfoot in children.

RESULTS
Prevalence of pathological flatfoot was 10.3% in children aged 7-14 years, but this prevalence decreased with age. There was no difference in prevalence of pathological flatfoot between the genders. Children with high BMI were more likely to have pathological flatfoot. Heel valgus (r=0.1; p=0.01) and dorsiflexion range (r=0.14; p<0.001) were both significantly associated with the presence of pathological flatfoot in children; but with only small correlations.

CONCLUSIONS
Pathological flatfoot was a prevalent condition in school-age children in Iran. Forty six percent of the flatfeet observed in school-age children were classified as pathological.

Sadeghi-Demneh|Ebrahim|E|
Melvin|Jonathan M A|JMA|
Mickle|Karen|K|

Pathological Flatfoot Children Symptomatic


Assessment of urinary volatile compounds and proteins in the female goat Capra hircus: A pilot study to reveal potential indicators of oestrus.

Abstract: Urine samples of female goats in pro-oestrus, oestrus and post-oestrus phases were analysed for finding oestrus-specific volatile compounds using gas chromatograph-mass spectrometry (GC-MS), and proteins using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Fourteen urinary volatile were identified covering all three phases among which four compounds, 1-Tetradecanol, n-Pentadecanol, 3-Methylene tridecane and 2-Ethyl-1-dodecene, were unique to oestrus. Also, oestrus urine contained a 25 kDa protein, which was totally absent in pro-oestrus urine, and less-expressed in post-oestrus urine. This protein revealed to be complement C3 fragment. This pilot study, for the first time, reveals the difference in urinary volatile compounds and proteins in the female goat during the different phases of oestrous cycle. The four unique volatile compounds and a 25 kDa protein that appeared as oestrus-specific in this study warrant further investigation to consider them as urinary biomarkers of oestrus in goats.

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

volatiles
urine
biomarkers
oestrus detection


Evaluation of cerebral arteriovenous shunts: a comparison of parallel imaging time-of-flight magnetic resonance angiography (TOF-MRA) and compressed sensing TOF-MRA to digital subtraction angiography.

Abstract:
PURPOSE
Time-of-flight (TOF)-MR angiography (MRA) is an important imaging sequence for the surveillance and analysis of cerebral arteriovenous shunt (AVS), including arteriovenous malformation (AVM) and arteriovenous fistula (AVF). However, this technique has the disadvantage of a relatively long scan time. The aim of this study was to compare diagnostic accuracy between compressed sensing (CS)-TOF and conventional parallel imaging (PI)-TOF-MRA for detecting and characterizing AVS.

METHODS
This study was approved by the institutional review board for human studies. Participants comprised 56 patients who underwent both CS-TOF-MRA and PI-TOF-MRA on a 3-T MR unit with or without cerebral AVS between June 2016 and September 2018. Imaging parameters for both sequences were almost identical, except the acceleration factor of 3× for PI-TOF-MRA and 6.5× for CS-TOF-MRA, and the scan time of 5 min 19 s for PI-TOF-MRA and 2 min 26 s for CS-TOF-MRA. Two neuroradiologists assessed the accuracy of AVS detection on each sequence and analyzed AVS angioarchitecture. Concordance between CS-TOF, PI-TOF, and digital subtraction angiography was calculated using unweighted and weighted kappa statistics.

RESULTS
Both CS-TOF-MRA and PI-TOF-MRA yielded excellent sensitivity and specificity for detecting intracranial AVS (reviewer 1, 97.3%, 94.7%; reviewer 2, 100%, 100%, respectively). Interrater agreement on the angioarchitectural features of intracranial AVS on CS-MRA and PI-MRA was moderate to good.

CONCLUSION
The diagnostic performance of CS-TOF-MRA is comparable to that of PI-TOF-MRA in detecting and classifying AVS with a reduced scan time under 2.5 min.

Parallel imaging
Compressed sensing
Arteriovenous malformation
Arterial venous fistula
MR angiography


Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation.

Abstract: Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cell types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 Mb downstream from Myc that are occupied by SWI/SNF as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in ∼3% of acute myeloid leukemias. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs.

Shi|Junwei|J|
Whyte|Warren A|WA|
Zepeda-Mendoza|Cinthya J|CJ|
Milazzo|Joseph P|JP|
Shen|Chen|C|
Roe|Jae-Seok|JS|
Minder|Jessica L|JL|
Mercan|Fatih|F|
Wang|Eric|E|
Eckersley-Maslin|Melanie A|MA|
Campbell|Amy E|AE|
Kawaoka|Shinpei|S|
Shareef|Sarah|S|
Zhu|Zhu|Z|
Kendall|Jude|J|
Muhar|Matthias|M|
Haslinger|Christian|C|
Yu|Ming|M|
Roeder|Robert G|RG|
Wigler|Michael H|MH|
Blobel|Gerd A|GA|
Zuber|Johannes|J|
Spector|David L|DL|
Young|Richard A|RA|
Vakoc|Christopher R|CR|

D015972:Gene Expression Regulation, Neoplastic


Adolescents, alcohol, and marijuana: Context characteristics and problems associated with simultaneous use.

Abstract: We investigated contexts of simultaneous use of alcohol and marijuana and the impact of simultaneous use on problems among adolescents. Ecological momentary assessment data were obtained over two weekends from 150 adolescents in California (47% female, M age=16.36years), using smartphone surveys administered early and late in the evening and again the following morning. We assessed whether, in what context, and with whom adolescents drank alcohol and used other substances over 3 evening hours. We assessed problems they experienced each evening on the following morning. Results showed that greater adult supervision in every context was associated with a 55% lower risk of simultaneous use (RRR=0.45, p≤.05). Contexts with no other underage drinkers were associated with 99% lower risk of simultaneous use (RRR=0.01, p≤.005). Each occasion of simultaneous use was related to 110% increase in the number of problems (IRR=2.10, p≤.005), with 83%, 221% and 311% greater odds of violence (OR=1.83, p≤.05), driving under the influence or riding with a drunk driver (OR=3.21, p≤.05), or being drunk (OR=4.11, p≤.005). Additional analyses showed that these problems may be attributed largely to the alcohol consumed in each context. Results demonstrate that it is essential to consider situational and social characteristics of substance use contexts to better understand adolescent simultaneous use of alcohol and drugs and problems.

Lipperman-Kreda|Sharon|S|
Gruenewald|Paul J|PJ|
Grube|Joel W|JW|
Bersamin|Melina|M|

Adolescents
Alcohol
Marijuana
Simultaneous use
Substance use contexts


Fortune of temporary ileostomies in patients treated with laparoscopic low anterior resection for rectal cancer.

Abstract:
PURPOSE
The current study aims to analyze the risk factors for the failure of ileostomy reversal after laparoscopic low anterior resection for rectal cancer.

METHODS
All patients who underwent a laparoscopic low anterior resection for rectal cancer with a diverting ileostomy between 2007 and 2014 were abstracted. The patients who underwent and did not undergo a diverting ileostomy procedure were compared regarding patient, tumor, treatment related parameters, and survival.

RESULTS
Among 160 (103 males [64.4%], mean [± standard deviation] age was 58.1 ± 11.9 years) patients, stoma reversal was achieved in 136 cases (85%). Anastomotic stricture (n = 13, 52.4%) was the most common reason for stoma reversal. These were the risk factors for the failure of stoma reversal: Male sex (P = 0.035), having complications (P = 0.01), particularly an anastomotic leak (P < 0.001), or surgical site infection (P = 0.019) especially evisceration (P = 0.011), requirement for reoperation (P = 0.003) and longer hospital stay (P = 0.004). Multivariate analysis revealed that male sex (odds ratio [OR], 7.82; P = 0.022) and additional organ resection (OR, 6.71; P = 0.027) were the risk factors. Five-year survival rates were similar (P = 0.143).

CONCLUSION
Fifteen percent of patients cannot receive a stoma reversal after laparoscopic low anterior resection for rectal cancer. Anastomotic stricture is the most common reason for the failure of stoma takedown. Having complications, particularly an anastomotic leak and the necessity of reoperation, limits the stoma closure rate. Male sex and additional organ resection are the risk factors for the failure in multivariate analyses. These patients require a longer hospitalization period, but have similar survival rates as those who receive stoma closure procedure.

Haksal|Mustafa|M|
Okkabaz|Nuri|N|
Atici|Ali Emre|AE|
Civil|Osman|O|
Ozdenkaya|Yasar|Y|
Erdemir|Ayhan|A|
Aksakal|Nihat|N|
Oncel|Mustafa|M|


Gender-partitioned patient medians of serum albumin requested by general practitioners for the assessment of analytical stability.

Abstract:
BACKGROUND
Recently, the use of separate gender-partitioned patient medians of serum sodium has revealed potential for monitoring analytical stability within the optimum analytical performance specifications for laboratory medicine. The serum albumin concentration depends on whether a patient is sitting or recumbent during phlebotomy. We therefore investigated only examinations requested by general practitioners (GPs) to provide data from sitting patients.

METHODS
Weekly and monthly patient medians of serum albumin requested by GP for both male and female patients were calculated from the raw data obtained from three analysers in the hospital laboratory on examination of samples from those >18 years. The half-range of medians were applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated (females/males).

RESULTS
The medians for male and female patients were closely related despite considerable variation due to the current analytical variation. This relationship was confirmed by the calculated half-range for the monthly ratio between the genders of 0.44%, which surpasses the optimum analytical performance specification for bias of serum albumin (0.72%). The weekly ratio had a half-range of 1.83%, which surpasses the minimum analytical performance specifications of 2.15%.

CONCLUSIONS
Monthly gender-partitioned patient medians of serum albumin are useful for monitoring of long-term analytical stability, where the gender medians are two independent estimates of changes in (delta) bias: only results requested by GP are of value in this application to ensure that all patients are sitting during phlebotomy.

Hansen|Steen Ingemann|SI|
Petersen|Per Hyltoft|PH|
Lund|Flemming|F|
Fraser|Callum G|CG|
Sölétormos|György|G|

medians of serum albumin
requests by general practitioners
analytical stability
partitioning by gender
ratio between gender medians
raw data for serum albumin


Individualized perturbation of the human connectome reveals reproducible biomarkers of network dynamics relevant to cognition.

Abstract: Large-scale brain networks are often described using resting-state functional magnetic resonance imaging (fMRI). However, the blood oxygenation level-dependent (BOLD) signal provides an indirect measure of neuronal firing and reflects slow-evolving hemodynamic activity that fails to capture the faster timescale of normal physiological function. Here we used fMRI-guided transcranial magnetic stimulation (TMS) and simultaneous electroencephalography (EEG) to characterize individual brain dynamics within discrete brain networks at high temporal resolution. TMS was used to induce controlled perturbations to individually defined nodes of the default mode network (DMN) and the dorsal attention network (DAN). Source-level EEG propagation patterns were network-specific and highly reproducible across sessions 1 month apart. Additionally, individual differences in high-order cognitive abilities were significantly correlated with the specificity of TMS propagation patterns across DAN and DMN, but not with resting-state EEG dynamics. Findings illustrate the potential of TMS-EEG perturbation-based biomarkers to characterize network-level individual brain dynamics at high temporal resolution, and potentially provide further insight on their behavioral significance.

cognition
fMRI
TMS-EEG
resting-state networks


Comparative Genomics Analyses Reveal the Differences between B. longum subsp. infantis and B. longum subsp. longum in Carbohydrate Utilisation, CRISPR-Cas Systems and Bacteriocin Operons.

Abstract: Bifidobacterium longum is one of the most widely distributed and abundant Bifidobacterium in the human intestine, and has been proven to have a variety of physiological functions. In this study, 80 strains of B. longum isolated from human subjects were classified into subspecies by ANI and phylogenetic analyses, and the functional genes were compared. The results showed that there were significant differences in carbohydrate metabolism between the two subspecies, which determined their preference for human milk oligosaccharides or plant-derived carbohydrates. The predicted exopolysaccharide (EPS) gene clusters had large variability within species but without difference at the subspecies level. Four subtype CRISPR-Cas systems presented in B. longum, while the subtypes I-U and II-C only existed in B. longum subsp. longum. The bacteriocin operons in B. longum subsp. infantis were more widely distributed compared with B. longum subsp. longum. In conclusion, this study revealed the similarities and differences between B. longum subsp. infantis and B. longum subsp. longum, which could provide a theoretical basis for further exploring the probiotic characteristics of B. longum.

Li|Mingjie|M|
Zhou|Xingya|X|
Stanton|Catherine|C|0000-0002-6724-7011
Ross|R Paul|RP|0000-0003-4876-8839
Zhao|Jianxin|J|
Zhang|Hao|H|
Yang|Bo|B|0000-0002-1347-3718
Chen|Wei|W|

comparative genomics
B. longum subsp. infantis
B. longum subsp. longum
CRISPR-Cas systems
bacteriocin
carbohydrate metabolism


Hormonal manipulations in the 5-day timed artificial insemination protocol to optimize estrous cycle synchrony and fertility in dairy heifers.

Abstract: Objectives were to determine the effects of GnRH at the initiation of the 5-d timed artificial insemination (AI) program combined with 2 injections of PGF2α on ovarian responses and pregnancy per AI (P/AI) in dairy heifers, and the role of progesterone concentrations on LH release and ovulation in response to GnRH. In study 1, heifers received a controlled internal drug release (CIDR) insert containing 1.38 g of progesterone on d 0, an injection of 25 mg of PGF2α and CIDR removal on d 5, and an injection of 100 μg GnRH concurrently with AI on d 8. Heifers were assigned to receive no additional treatment (control; n=559) or an injection of GnRH on d 0 and a second injection of PGF2α on d 6 (G2P; n=547). In study 2, all heifers were treated as described for the control in study 1, and were allocated to receive no additional treatment (control; n=723), an injection of PGF2α on d 6 (NG2P; n=703), or an injection of GnRH on d 0 and an injection of PGF2α on d 6 (G2P; n=718). In study 3, heifers received a CIDR on d 7 after ovulation and were assigned randomly to a low-progesterone (LP; n=6) treatment in which 2 injections of 25 mg of PGF2α each were administered 12h apart, on d 7 and 7.5 after ovulation, or to a high-progesterone (HP; n=12) treatment in which no PGF2α was administered. On d 8, heifers received 100 μg of GnRH and blood was sampled at every 15 min from -30 to 180 min relative to the GnRH for assessment of LH concentrations. Additionally, 94 heifers were assigned to LP or HP and ovulation in response to GnRH was evaluated. In study 1, P/AI was greater for G2P than for the control on d 32 (59.4 vs. 53.5%) and 60 after AI (56.6 vs. 51.3%). In study 2, administration of GnRH on d 0 increased the proportion of heifers with a new corpus luteum on d 5 (control=21.9 vs. NG2P=20.1 vs. G2P=34.4%). Administration of a second PGF2α increased the proportion of heifers with progesterone <0.5 ng/mL at AI (control=83.1 vs. NG2P=93.0 and G2P=87.2%). Pregnancy per AI was greater for G2P than for control and NG2P on d 32 (control=52.9 vs. NG2P=55.0 vs. G2P=61.7%) and 60 (control=49.0 vs. NG2P=51.6 vs. G2P=59.1%). In study 3, HP attenuated LH release and reduced ovulation (19.0 vs. 48.4%) in response to GnRH compared with LP. Combining GnRH and 2 doses of PGF2α in the 5-d timed AI protocol improved follicle turnover, luteolysis, and P/AI in heifers. Elevated concentrations of progesterone suppressed LH release and are linked with the low ovulatory response to the initial GnRH treatment of the protocol.

Lima|F S|FS|
Ribeiro|E S|ES|
Bisinotto|R S|RS|
Greco|L F|LF|
Martinez|N|N|
Amstalden|M|M|
Thatcher|W W|WW|
Santos|J E P|JEP|

dairy heifer
5-d timed artificial insemination
ovulation
luteolysis


Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes.

Abstract: Obesity is associated with insulin resistance and is known to be a risk factor for type-2 diabetes. In obese individuals, pancreatic beta-cells try to compensate for the increased insulin demand in order to maintain euglycemia. Most studies have reported that this adaptation is due to morphological changes. However, the involvement of beta-cell functional adaptations in this process needs to be clarified. For this purpose, we evaluated different key steps in the glucose-stimulated insulin secretion (GSIS) in intact islets from female ob/ob obese mice and lean controls. Obese mice showed increased body weight, insulin resistance, hyperinsulinemia, glucose intolerance and fed hyperglycemia. Islets from ob/ob mice exhibited increased glucose-induced mitochondrial activity, reflected by enhanced NAD(P)H production and mitochondrial membrane potential hyperpolarization. Perforated patch-clamp examination of beta-cells within intact islets revealed several alterations in the electrical activity such as increased firing frequency and higher sensitivity to low glucose concentrations. A higher intracellular Ca(2+) mobilization in response to glucose was also found in ob/ob islets. Additionally, they displayed a change in the oscillatory pattern and Ca(2+) signals at low glucose levels. Capacitance experiments in intact islets revealed increased exocytosis in individual ob/ob beta-cells. All these up-regulated processes led to increased GSIS. In contrast, we found a lack of beta-cell Ca(2+) signal coupling, which could be a manifestation of early defects that lead to beta-cell malfunction in the progression to diabetes. These findings indicate that beta-cell functional adaptations are an important process in the compensatory response to obesity.

Irles|Esperanza|E|
Ñeco|Patricia|P|
Lluesma|Mónica|M|
Villar-Pazos|Sabrina|S|
Santos-Silva|Junia Carolina|JC|
Vettorazzi|Jean F|JF|
Alonso-Magdalena|Paloma|P|
Carneiro|Everardo M|EM|
Boschero|Antonio C|AC|
Nadal|Ángel|Á|
Quesada|Ivan|I|

Pancreatic beta-cell
Obesity
Diabetes
Insulin secretion
Electrical activity
Calcium signals


Communication skills training and the conceptual structure of empathy among medical students.

Abstract:
INTRODUCTION
Medical and healthcare professionals' empathy for patients is crucially important for patient care. Some studies have suggested that a significant decline in empathy occurs during clinical training years in medical school as documented by self-assessed empathy scales. Moreover, a recent study provided qualitative evidence that communication skills training in an examination context, such as in an objective structured clinical examination, might stimulate perspective taking but inhibit the development of compassionate care. Therefore, the current study examined how perspective taking and compassionate care relate to medical students' willingness to show empathic behaviour and how these relations may change with communication skills training.

METHODS
A total of 295 fourth-year Japanese medical students from three universities completed the Jefferson Empathy Scale and a newly developed set of items on willingness to show empathic behaviour twice after communication skills training, pertaining to post-training and retrospectively for pre-training.

RESULTS
The findings indicate that students' willingness to show empathic behaviour is much more correlated with perspective taking than with compassionate care. Qualitative descriptive analysis of open-ended question responses revealed a difficulty of feeling compassion despite showing empathic behaviour.

DISCUSSION
These findings shed light on the conceptual structure of empathy among medical students and generate a number of hypotheses for future intervention and longitudinal studies on the relation between communication skills training and empathy.

Son|Daisuke|D| Shimizu|Ikuo|I| Ishikawa|Hirono|H| Aomatsu|Muneyoshi|M| Leppink|Jimmie|J|

Objective structured clinical examination


Emergency surgery for tubo-ovarian abscess identified extended-spectrum beta-lactamase-producing Escherichia coli: the first case presentation revealing causative bacteria.

Abstract: We report herein a 41-year-old female with a tubo-ovarian abscess (TOA), which microbial cultures showed to contain extended-spectrum beta-lactamase (ESBL)-producing E. coli, a causative agent of community-acquired infection. The patient initially presented with acute abdominal pain and back pain. Pelvic computed tomography and transvaginal ultrasonography revealed multiple cystic lesions in the bilateral ovaries that suggested TOA. An emergency laparotomy was therefore performed due to the potential for life-threatening septic shock from the TOA-associated pelvic inflammatory disease. Microbial cultures of postoperative fluid discharge from the placed intra-abdominal catheter, vaginal secretions, urine, blood, and feces detected ESBL-producing E.coli. In summary, we successfully performed emergency surgery for life-threatening septic TOA caused by ESBL-producing E. coli infection.

Tokumaru|Teppei|T| Shima|Yasuo|Y| Okabayashi|Takehiro|T| Hayashi|Kazutoshi|K| Yamamoto|Yorito|Y| Ozaki|Kazuhide|K| Iwata|Jun|J|

Emergency surgery
Surgery
Tubo-ovarian abscess
Extended-spectrum beta-lactamase


Gastro-caval fistula after distal esophageal resection: a case report and review of the literature.

Abstract: Peptic ulceration with fistula formation into the inferior vena cava is rare, difficult to diagnose, and associated with high mortality. The nonspecific signs and symptoms make diagnosis challenging, delaying optimal treatment. Although there have been reports on duodeno-caval fistulas, gastric communication with the inferior vena cava is very rare. We report the second case of a fatal gastro-caval fistula and performed a review of the literature on entero-caval fistulas to emphasize the importance of early suspicion and to understand the most common presentation, as well as the best diagnostic and treatment modalities of this rare pathology.

Gastro-caval
Fistula
Peptic ulcer
Duodeno-caval
Entero-caval


Intracranial Hemorrhage Secondary to a Delayed Cerebral Pseudoaneurysm Rupture 18 Years after Cranial Trauma.

Abstract: We report the case of a 38-year-old male with a previous history of severe cranial trauma and subsequent large subdural and subarachnoid hemorrhage on whom an emergent hematoma evacuation was performed with a good outcome and follow-up. Despite a good clinical evolution, the patient experienced a further intracranial hematoma 18 years after the trauma, with severe aphasia and mild right hemiparesis. After complete etiological study, two cranial pseudoaneurysms were observed in the cerebral angiography. Endovascular treatment was successfully completed, achieving full embolization without complications. No rebleeding was detected during follow-up. The patient had a good clinical outcome at 3 months and achieved complete recovery. Cranial pseudoaneurysm rupture is a rare cause of intracerebral hemorrhage, especially if the trauma occurs years before the bleeding.

Terceño|Mikel|M| Remollo|Sebastià|S| Silva|Yolanda|Y| Bashir|Saima|S| Castaño|Carlos|C| Serena|Joaquín|J|

Intracranial hemorrhage
Cranial pseudoaneurysm
Endovascular treatment


Polymorphic chiral squaraine crystallites in textured thin films.

Abstract: An enantiomerically pure (R)-2-methylpyrrolidine-based anilino squaraine crystallizes in two chiral polymorphs adopting a monoclinic C2 and an orthorhombic P21 21 21 structure, respectively. By various thin-film preparation techniques, a control of the polymorph formation is targeted. The local texture of the resulting textured thin films is connected to the corresponding optical properties. Special attention is paid to an unusual Davydov splitting, the anisotropic chiroptical response arising from preferred out-of-plane orientation of the crystallites, and the impact of the polymorph specific excitonic coupling.

Davydov splitting
X-ray diffraction
circular dichroism
imaging Mueller matrix polarimetry
polarized spectro-microscopy


The impact of cytochrome 450 and Paraoxonase polymorphisms on clopidogrel resistance and major adverse cardiac events in coronary heart disease patients after percutaneous coronary intervention.

Abstract:
BACKGROUND
Clopidogrel is an inactive prodrug, it catalyzed into its active form by Cytochrome 450 and Paraoxonase-1(PON-1). polymorphisms of genes encoding these enzymes will affect the efficacy of Clopidogrel. The main objective of our study was to investigate the association of CYP2C19*2, CYP2C19*3 and PON-1Q192R polymorphisms with Clopidogrel resistance and major adverse cardiac events in Jin Hua district in the middle of Zhe Jiang Province in China.

METHODS
One hundred sixty coronary heart disease patients with percutaneous coronary intervention, who were followed-up for 1 year, were enrolled in our study. These patients were co-administered aspirin 100 mg/d and clopidogrel 75 mg/d following a loading dose of 300 mg. The ADP-induced platelet aggregation rate was measured by Platelet aggregator. Genotypes of CYP2C19*2, CYP2C19*3, PON-1Q192R were determined using Sanger sequencing in all patients. Various clinical data were collected.

RESULTS
The frequencies of CYP2C19*2, CYP2C19*3 and PON-1Q192R homozygous mutant genotypes were significantly lower in non-responders than those in responders. After for all variables, CYP2C19*2, CYP2C19*3 and PON-1Q192R independently increased the risk of clopidogrel resistance with adjusted ORs 46.65(95% CI,1.77-25.04; p = 0.005); 22.74(95% CI, 3.11-166.27; p = 0.002); 5.69 (95% CI,1.06-30.47; p = 0.042). Over a follow-up of 12 months, the incidence of major adverse cardiac events (MACE) in CYP2C19*1/*2, *1/*3, *2/*2, *2/*3 was significantly higher than no mutant genotype (18/40vs.2/63,3/9vs.2/63, 11/6vs.2/63, 7/1vs2/63, respectively). There was no significant correlation between PON-1Q192R mutant allele and MACE.

CONCLUSION
Our study was first time to report on CYP2C19 and PON-1 polymorphisms in Jin Hua population in the middle of Zhe Jiang province in China. The carriage of CYP2C19*2 or *3 mutant allele significantly reduced the platelet response to clopidogrel and increase the MACE. The carriage of PON-1 mutant allele also significantly reduced the platelet response to clopidogrel, but would not increase the major adverse cardiac events after 1 year follow-up.

TRIAL REGISTRATION
ChiCTR, ChiCTR1800018316. Registered 11 September 2018 - prospective registered, http://www.chictr.org.cn/edit.aspx?pid=30927&htm=4.

Zhang|Zhaowei|Z|0000-0003-0997-5253 Chen|Mingxiao|M| Zhang|Long|L| Zhao|Qiang|Q|

Cytochrome 450
Polymorphism
Clopidogrel resistance
Major adverse cardiac events
Paraoxonase-1


Response to neoadjuvant chemotherapy based on pathologic complete response in very young patients with ER-positive breast cancer: a large, multicenter, observational study.

Abstract:
BACKGROUND
In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible.

METHODS
We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged < 50 years who had been treated with neoadjuvant chemotherapy were included for analysis. We compared pCR rate between patients aged < 35 years with ER-positive tumors and the other groups.

RESULTS
The proportion of patients aged < 35 years was 14.0% of patients with ER-positive BC in this cohort of under 50 years old, and 16.8% of patients with ER-negative BC in this cohort of under 50 years old. Although most characteristics of tumors according to age were comparable, tumors with high Ki-67 expression were more common in patients aged < 35 years than in patients aged 35-49 years in both ER-positive and -negative group (P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged < 35 years in ER-negative group (P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (< 35 years) was correlated with poor overall survival (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group.

CONCLUSIONS
Chemotherapy response based on pCR was not better in young patients (< 35 years) with ER-positive BC than in older premenopausal patients with non-metastatic ER-positive BC. Young age cannot be a predictive factor of response to neoadjuvant chemotherapy in ER-positive BC. Different biological characteristics such as high proliferative index should be considered.

TRIAL REGISTRATION
Retrospectively registered.

D000971:Antineoplastic Combined Chemotherapy Protocols

Neoadjuvant chemotherapy
Pathologic complete response
Young patients
ER-positive
Breast cancer


Unusual manifestations of Kawasaki disease with retropharyngeal edema and shock syndrome in a Taiwanese child.

Abstract: We report a 3-year-old girl with Kawasaki disease who presented with retropharyngeal edema and shock syndrome. This is the first reported case in Taiwan. The patient initially presented with fever, cough, and pyuria followed by rapidly progressive enlarged bilateral cervical lymphadenopathy. On the third day of the fever, computed tomography for airway compression sign found widening of the retropharyngeal space mimicking a retropharyngeal abscess. Later, an endotracheal tube was inserted for respiratory distress. A skin rash over her trunk was also noted. On the fifth day of the fever, the clinical course progressed to hypotension and shock syndrome. Because of more swelling of bilateral neck lymph nodes, computed tomography was arranged again and revealed partial resolution of the edematous changes in the retropharyngeal space. Edema of the hands and feet, bilateral bulbar conjunctivitis, and fissured lips were subsequently found. The diagnosis of Kawasaki disease was confirmed on the eighth day of fever. There was no evidence of bacterial infection. She was administered intravenous immunoglobulin (2 mg/kg) and high dose aspirin (100 mg/kg/day). One day later, the fever subsided, and her blood pressure gradually became stable. Heart echocardiography on the Day 13 revealed dilated left coronary artery and mitral regurgitation. Follow-up echocardiography six months later showed normal coronary arteries. To date, the patient has not experienced any complications. This case illustrates that retropharyngeal edema and shock syndrome can be present in the same clinical course of Kawasaki disease. Clinicians and those who work in intensive care units should be aware of unusual presentations of Kawasaki disease to decrease rates of cardiovascular complications.

Fang|Li-Ching|LC| Shyur|Shyh-Dar|SD| Peng|Chun-Chih|CC| Jim|Wai-Tim|WT| Chu|Szu-Hung|SH| Kao|Yu-Hsuan|YH| Chen|Chen-Kuan|CK| Liu|Ling-Chun|LC|

D009080:Mucocutaneous Lymph Node Syndrome

Kawasaki disease
Retropharyngeal edema
Shock


Cancer caregivers' experiences of prognosis in Australia: a qualitative interview study.

Abstract:
OBJECTIVES
Forecasting survival in cancer is a particularly challenging facet of oncological work and can involve complex interactions with patients and their families. While there is considerable research on patient experiences of being provided with, or becoming aware of, their prognosis, there has been much less emphasis placed on the experiences of caregivers. The aim of this paper was to examine caregivers' experiences of prognosis.

DESIGN
This study used semistructured interviews; transcripts were analysed thematically using the framework approach. These data are part of a larger research project focused on experiences of cancer survivorship.

SETTING
Recruitment was from two metropolitan hospitals in Queensland, Australia.

PARTICIPANTS
50 caregivers of patients living with cancer and receiving treatment at two metropolitan hospitals (32% male, 68% female) participated in this study.

RESULTS
Four main themes were identified: (1) caregivers' uncertainty around the meaning and implications of prognosis, (2) caregivers' sense of exclusion in prognostic conversations, (3) the practice of situating prognosis within a context of hope and (4) the precarious balance between realism, optimism and strategic 'ignorance'.

CONCLUSIONS
Caregivers are in many respects the unseen third party of prognostic communication. Developing a better understanding of caregivers' perceptions of prognosis, including how this may be challenged, accepted or otherwise, is important in engaging caregivers in the process of communicating prognostic information. Facilitating greater participation by caregivers in prognostic conversations could potentially address evident complexities and even improve the experiences of all stakeholders in cancer care settings.

cancer
prognosis
clinical forecasting
informal care
qualitative research