Engineering Promoter Architecture in Oleaginous Yeast Yarrowia lipolytica.

Abstract: Eukaryotic promoters have a complex architecture to control both the strength and timing of gene transcription spanning up to thousands of bases from the initiation site. This complexity makes rational fine-tuning of promoters in fungi difficult to predict; however, this very same complexity enables multiple possible strategies for engineering promoter strength. Here, we studied promoter architecture in the oleaginous yeast, Yarrowia lipolytica. While recent studies have focused on upstream activating sequences, we systematically examined various components common in fungal promoters. Here, we examine several promoter components including upstream activating sequences, proximal promoter sequences, core promoters, and the TATA box in autonomously replicating expression plasmids and integrated into the genome. Our findings show that promoter strength can be fine-tuned through the engineering of the TATA box sequence, core promoter, and upstream activating sequences. Additionally, we identified a previously unreported oleic acid responsive transcription enhancement in the XPR2 upstream activating sequences, which illustrates the complexity of fungal promoters. The promoters engineered here provide new genetic tools for metabolic engineering in Y. lipolytica and provide promoter engineering strategies that may be useful in engineering other non-model fungal systems.

Shabbir Hussain|Murtaza|M|
Gambill|Lauren|L|
Smith|Spencer|S|
Blenner|Mark A|MA|

D060888:Real-Time Polymerase Chain Reaction

promoter
Yarrowia lipolytica
enhancers
POX2
UAS
oleate response elements


Comparing eSRT and eCAP measurements in pediatric MED-EL cochlear implant users.

Abstract:
INTRODUCTION
Electrically evoked compound action potentials (eCAP) and electrically evoked stapedius reflexes are the most frequently used objective measurements for programming a cochlear implant (CI) audio processor. Objective methods are particularly beneficial for children and CI users that encounter difficulties in providing feedback. In this study, we compared the threshold and the slope of the eCAP amplitude growth function with the electrically evoked stapedius reflex threshold (eSRT) in pediatric CI users. Furthermore, the duration times required to perform eCAP and eSRT recordings were compared.

METHODS
During a regular fitting session, 52 pediatric CI users with recordable eSRTs having MED-EL devices (MED-EL GmbH, Innsbruck, Austria) were programmed using the eSRT fitting method. The eCAP thresholds and the slopes of the amplitude growth function were measured across one apical, one medial, and one basal electrode contact.

RESULTS
There was a weak to medium correlation between eCAP thresholds and eSRTs. The eCAP threshold profile did not correlate with the eSRT profile. Typically ECAP thresholds were at a lower stimulation charge than eSRTs with only 4/152 being higher. An eCAP threshold was found on 152/156 electrode contacts with eSRTs. On average, the eCAP measurements took 4.2 times longer to record per electrode than eSRT measurements (median durations 35 s vs. 120 s).

CONCLUSION
eSRTs were significantly higher than eCAP thresholds and eSRT and eCAP profiles were generally different from each other reducing the clinical relevance of eCAP testing for setting MCLs across the array. Additionally, the eSRT measurements were faster to record than the eCAP threshold and slope determination measurements.

Kosaner|Julie|J|
Spitzer|Philipp|P|
Bayguzina|Svetlana|S|
Gultekin|Muammer|M|
Behar|Laurie Arum|LA|

eSRT
eCAP
Pediatric
MED-EL
Cochlear implant
Threshold
Slope
ART


Estrogen metabolism by cytochrome P450 1B1 modulates the hypertensive effect of angiotensin II in female mice.

Abstract: To determine the role of cytochrome P450 (CYP) 1B1 in the sex difference in response to angiotensin II (Ang II)-induced hypertension, female Cyp1b1(+/+) and Cyp1b1(-/-) mice were infused with Ang II (700 ng/kg per minute) or vehicle with or without ovariectomy. In addition, mice were treated with the CYP1B1 inhibitor, 2,3',4,5'-tetramethoxystilbene (TMS; 300 μg/kg IP, every third day), and 17-β estradiol metabolites, 2-hydroxyestradiol (2-OHE), 4-OHE, or 2-methoxyestradiol (1.5 mg/kg per day IP, for 2 weeks) and systolic blood pressure (SBP) measured. Ang II increased SBP more in Cyp1b1(-/-) than in Cyp1b1(+/+) mice (119±3-171±11 versus 120±4-149±4 mm Hg; P<0.05). Ang II caused cardiovascular remodeling and endothelial dysfunction and increased vascular reactivity and oxidative stress in Cyp1b1(-/-) but not in Cyp1b1(+/+)mice. The Ang II-induced increase in SBP was enhanced by ovariectomy and TMS in Cyp1b1(+/+) but not in Cyp1b1(-/-) mice. 2-OHE did not alter Ang II-induced increase in SBP in Cyp1b1(+/+) mice but minimized it in Cyp1b1(-/-) mice, whereas 4-OHE enhanced Ang II-induced increase in SBP in Cyp1b1(+/+) mice but did not alter the increased SBP in Cyp1b1(-/-) mice. 2-OHE-derived catechol-O-methyltransferase metabolite, 2-methoxyestradiol, inhibited Ang II-induced increase in SBP in Cyp1b1(-/-) mice. Ang II increased plasma levels of 2-methoxyestradiol in Cyp1b1(+/+) but not in Cyp1b1(-/-) mice and increased activity of cardiac extracellular signal-regulated kinase 1/2, p38 mitogen-activated kinase, c-Src, and Akt in Cyp1b1(-/-) but not in Cyp1b1(+/+) mice. These data suggest that CYP1B1 protects against Ang II-induced hypertension and associated cardiovascular changes in female mice, most likely mediated by 2-methoxyestradiol-inhibiting oxidative stress and the activity of these signaling molecules.

Jennings|Brett L|BL|
George|L Watson|LW|
Pingili|Ajeeth K|AK|
Khan|Nayaab S|NS|
Estes|Anne M|AM|
Fang|Xiao R|XR|
Gonzalez|Frank J|FJ|
Malik|Kafait U|KU|

cytochrome P450 1B1
hypertension
ovariectomy
2-methoxyestradiol
oxidative stress


Limiting glioma development by photodynamic therapy-generated macrophage vaccine and allo-stimulation: an in vivo histological study in rats.

Abstract: Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage (MaF98) vaccines can be increased by: (1) photodynamic therapy (PDT) of the priming tumor cells and (2) intracranial injection of allogeneic glioma cells directly into the tumor site. Experiments were conducted in an in vivo brain tumor development model using Fischer rats and F98 (syngeneic) and BT4C (allogeneic) glioma cells. The results showed that immunization with Ma (acting as antigen-presenting cells), primed with PDT-treated tumor cells (MaF98), significantly slowed but did not prevent the growth of F98-induced tumors in the brain. Complete suppression of tumor development was obtained via MaF98 inoculation combined with direct intracranial injection of allogeneic glioma cells. No deleterious effects were noted in any of the animals during the 14-day observation period.

Madsen|Steen J|SJ|
Christie|Catherine|C|
Huynh|Khoi|K|
Peng|Qian|Q|
Uzal|Francisco A|FA|
Krasieva|Tatiana B|TB|
Hirschberg|Henry|H|

glioma
macrophages
photodynamic therapy
allogeneic cells
immunogenic apoptotic cells
photodynamic therapy-macrophage vaccine


The phenotype of bilateral hippocampal sclerosis and its management in "real life" clinical settings.

Abstract:
OBJECTIVE
There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics.

METHODS
Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers.

RESULTS
In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80 years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P = .002; Fisher's exact test).

SIGNIFICANCE
The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition.

Sen|Arjune|A|0000-0002-8948-4763
Dugan|Patricia|P|0000-0001-6199-1870
Perucca|Piero|P|0000-0002-7855-7066
Costello|Daniel|D|
Choi|Hyunmi|H|
Bazil|Carl|C|
Radtke|Rod|R|
Andrade|Danielle|D|
Depondt|Chantal|C|
Heavin|Sinead|S|
Adcock|Jane|J|0000-0001-5181-0925
Pickrell|W Owen|WO|0000-0003-4396-5657
McGinty|Ronan N|RN|0000-0002-4606-7783
Nascimento|Fábio|F|0000-0002-7161-6385
Smith|Philip|P|
Rees|Mark I|MI|
Kwan|Patrick|P|0000-0001-7310-276X
O'Brien|Terence J|TJ|
Goldstein|David|D|
Delanty|Norman|N|

phenotype
bilateral hippocampal sclerosis
EPIGEN
epilepsy surgery
seizure semiology


Arrhythmogenic Antitussive: A Case of Pediatric Benzonatate Overdose With Torsades de Pointes, Cardiac Arrest, and Complete Recovery Without Neurologic Deficits.

Abstract: Benzonatate is a commonly prescribed antitussive with rapid and deadly effects in overdose. We report a 14-year-old female who ingested 14 capsules containing 200 mg benzonatate. Her case represents the only reported benzonatate overdose with torsades de pointes, as well as the only reported pediatric benzonatate ingestion complicated by cardiac arrest with full recovery.

pediatric
benzonatate
torsades de pointes
cardiac arrest
Tessalon


Diagnostic value of cerebro-spinal fluid biomarkers in dementia with lewy bodies.

Abstract: Dementia with Lewy Bodies (DLB) is the second most common form of dementia after Alzheimer's disease (AD), accounting for 15% to 20% of neuropathologically defined cases. Two-thirds of the patients affected are not or misdiagnosed because of the clinical similarity of these two pathologies. In this review, we evaluate the discriminatory power of cerebrospinal fluid (CSF) biomarkers by focusing more specifically on differential diagnosis between DLB and AD. We focus on the AD biological biomarkers used in clinical routine as well as the biomarkers under study and more particularly the alpha-synuclein assay. Thus, among the AD biomarkers (t-Tau, phospho-Tau181, Aβ42 and Aβ40) used routinely, t-Tau and phospho-Tau181 have shown excellent discrimination whatever the clinical stages severity. Aβ42 level is pathological in DLB patients at the demented stage, but is almost not impacted at the prodromal stage. Alpha-synuclein assay in the CSF has also an interest in the discrimination between DLB and AD but not in segregation between DLB and healthy elderly subjects. Thus, globally the biological diagnosis on CSF basis makes it possible, to separate the DLBs from the ADs. In addition, the development of biomarkers such as phospho-alpha-synuclein and oligomeric alpha-synuclein should help to reinforce this discrimination power.

Cerebro-spinal fluid
Biomarkers
Dementia with Lewy bodies
Alzheimer's disease
Differential diagnosis
Prodromal stage


Diverse strategies targeting α7 homomeric and α6β2* heteromeric nicotinic acetylcholine receptors for smoking cessation.

Abstract: Preclinical studies suggest that a diversity of nicotinic acetylcholine receptors (nAChRs) with different sensitivities to nicotine may contribute to tobacco addiction. Using rodent intravenous nicotine self-administration as a preclinical model with good predictive validity for therapeutic efficacy for tobacco cessation, investigators have identified heteromeric α6β2* and homomeric α7 nAChRs as promising novel therapeutic targets to promote smoking abstinence (*denotes possible assembly with other subunits). The data suggest that diverse strategies that target these subclasses of nAChRs, namely inhibition of α6β2* nAChRs and stimulation of α7 nAChRs, will support tobacco cessation. α6β2* nAChRs, members of the high-affinity family of β2* nAChRs, function similarly to α4β2* nAChRs, the primary target of the FDA-approved drug varenicline, but have a much more selective neuroanatomical pattern of expression in catecholaminergic nuclei. Although activation of β2* nAChRs facilitates nicotine self-administration, stimulation of α7 nAChRs appears to negatively modulate both nicotine reinforcement and β2* nAChR function in the mesolimbic dopamine system. Although challenges and caveats must be considered in the development of therapeutics that target these nAChR subpopulations, an accumulation of data suggests that α7 nAChR agonists, partial agonists, or positive allosteric modulators and α6β2* nAChR antagonists, partial agonists, or negative allosteric modulators may prove to be effective therapeutics for tobacco cessation.

Brunzell|Darlene H|DH|
McIntosh|J Michael|JM|
Papke|Roger L|RL|

D064569:alpha7 Nicotinic Acetylcholine Receptor

α7
nicotinic
smoking cessation
drug development
nicotine dependence
α6


A case of 18p deletion syndrome after blepharoplasty.

Abstract:
OBJECTIVE
The deletion of the short arm of chromosome 18 is thought to be one of the rare chromosomal aberrations. Here, we report a case to review this disease.

CASE REPORT
The proband is a five-and-a-half-year-old girl who has had phenotypes manifested mainly by ptosis, broad face, broad neck with low posterior hairline, mental retardation, short stature, and other malformations. Chromosomal analysis for her mother showed a normal karyotype. Her father and younger brother were phenotypically normal.

RESULT
Phenotypical features were quite similar throughout other cases and in accordance with the usual phenotype of del(18p) suggested within the same cases and among the del(18p) cases described. She underwent blepharoplasty, which improved her appearance.

CONCLUSION
18p deletion syndrome is diagnosed by gene analysis. Plastic surgeries for improving the appearance might be an option for these patients.

Xu|Li-Juan|LJ| Wu|Lv-Xian|LX| Yuan|Qing|Q| Lv|Zhi-Gang|ZG| Jiang|Xue-Yan|XY|


Standardized Transfer Process for a Neurointensive Care Unit and Assessment of Patient Bounceback.

Abstract:
BACKGROUND
Patients who require readmission to an intensive care unit (ICU) after transfer to a lower level of care ("bounceback") suffer from increased mortality and longer hospital stays. We aimed to create a multifaceted standardized transfer process for patients moving from the neurointensive care unit (neuro-ICU) to a lower level of care. We hypothesized that this process would lead to improvement in provider-rated safety and a decreased rate of bouncebacks to the neuro-ICU after transfer.

METHODS
The study took place at the Hospital of the University of Pennsylvania from October 2018 to October 2020. A standardized five-step transfer process was created and implemented for transferring patients from the neuro-ICU to a lower level of care. Patient care providers completed a survey before and after implementation of the protocol to assess a variety of components related to safety concerns when transferring patients. The rate of bouncebacks pre and post intervention was calculated by using a two-sample Wilcoxon rank-sum test, and disposition at discharge was calculated by using Fisher's exact test.

RESULTS
Of the 1176 total patient transfers out of the neuro-ICU, 29 patients bounced back within 48 h. The average age of patients who bounced back was 63.3 years old, with a similar distribution among men and women. The most common reason for bounceback was respiratory distress, followed by cardiac arrhythmia, stroke, and sepsis. Implementation of the standardized process led to a decrease in provider-rated concern of overall safety (5 to 3, p = 0.008). There was improvement in transfer delays due to bed availability (3 to 4.5, p = 0.020), identification of high-risk patients (5 to 6, p = 0.021), patient assignment to the appropriate level of care (5 to 6, p = 0.019), and use of the electronic medical record handoff indicator (5 to 6, p = 0.003). There was no statistically significant difference in terms of patient bounceback rate after implementation of the process (2.4% vs. 2.5%, p = 1.00) or patient disposition at discharge (p = 0.553).

CONCLUSIONS
Patients who bounceback to the neuro-ICU within 48 h had an increased length of hospital stay, had an increased length of ICU stay, and were more likely to be intubated for more than 96 h. Implementation of a standardized five-step transfer process from the neuro-ICU to a lower level of care resulted in improvement in multiple provider-rated safety outcomes and identification of high-risk patients but led to no difference in the patient bounceback rate or patient disposition at discharge.

Readmission
Patient transfer
Neurocritical care
Patient handoff
Quality improvement


Anti-inflammatory and antioxidant activities of naringin isolated from Carissa carandas L.: In vitro and in vivo evidence.

Abstract:
BACKGROUND
Carissa carandas L. is known in folk medicine for its anti-inflammatory and hepatoprotective activities. Meanwhile it is an evergreen shrub that constitutes a continuous source of leaves throughout the year.

HYPOTHESIS/PURPOSE
The leaves of Carissa carandas L. may be rich in compounds that can be used as safe anti-inflammatory and antioxidant remedies. The combined antioxidant and anti-inflammatory activities provoked the study of the hepatoprotective effects.

STUDY DESIGN
To isolate major constituents from the leaves of Carissa carandas L. and test their anti-inflammatory and antioxidant activities in-vivo and in-vitro.

METHODS
The leaves of Carissa carandas L. were extracted with 80% MeOH and then defatted with CHCl3 to yield Carissa carandas defatted extract (CCDE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, then subjected to different chromatographic separation steps and naringin (NG) was isolated in a high yield. The anti-inflammatory activity of NG was investigated in-vivo by carrageenan induced hind rat paw edema model at two dose levels (50 and 25 mg/kg). The anti-inflammatory activity was also evaluated in-vitro by measuring its inhibitory effect on LPS induced release of NO from RAW 264.7 macrophages. The antioxidant activity was evaluated by superoxide and DPPH radical scavenging ability. The safety of NG was tested against primary rat hepatocytes. The hepatoprotective effect of CCDE was evaluated by detecting its effects on serum liver function markers and liver cell oxidative stress markers.

RESULTS
NG exhibited potent inhibition of inflammation as compared to indomethacin (20 mg/kg). NG inhibited LPS induced release of NO from macrophages (IC50, 6.4 μM). NG showed significant antioxidant activity as it scavenged the superoxide radical (EC90, 10.95 μM) and DPPH radical (EC50, 11.2 μM). CCDE inhibited the elevation of the serum liver marker enzymes and increased GSH and decreased MDA contents in the liver homogenate. Liver histopathology supported the biochemical findings.

CONCLUSION
C. carandas has potent anti-inflammatory, antioxidant and hepatoprotective activities.

El-Desoky|Ahmed H|AH|
Abdel-Rahman|Rehab F|RF|
Ahmed|Osama K|OK|
El-Beltagi|Hossam S|HS|
Hattori|Masao|M|

Anti-inflammatory
Antioxidant
Naringin
Carissa carandas
Hepatoprotective
Raw264.7 macrophage


Digital conversations about suicide among teenagers and adults with epilepsy: A big-data, machine learning analysis.

Abstract:
OBJECTIVE
Digital media conversations can provide important insight into the concerns and struggles of people with epilepsy (PWE) outside of formal clinical settings and help generate useful information for treatment planning. Our study aimed to explore the big data from open-source digital conversations among PWE with regard to suicidality, specifically comparing teenagers and adults, using machine learning technology.

METHODS
Advanced machine-learning empowered methodology was used to mine and structure open-source digital conversations of self-identifying teenagers and adults who endorsed suffering from epilepsy and engaged in conversation about suicide. The search was limited to 12 months and included only conversations originating from US internet protocol (IP) addresses. Natural language processing and text analytics were employed to develop a thematic analysis.

RESULTS
A total of 222 000 unique conversations about epilepsy, including 9000 (4%) related to suicide, were posted during the study period. The suicide-related conversations were posted by 7.8% of teenagers and 3.2% of adults in the study. Several critical differences were noted between teenagers and adults. A higher percentage of teenagers are: fearful of "the unknown" due to seizures (63% vs 12% adults), concerned about social consequences of seizures (30% vs 21%), and seek emotional support (29% vs 19%). In contrast, a significantly higher percentage of adults show a defeatist ("given up") attitude compared to teenagers (42% vs 4%). There were important differences in the author's determined sentiments behind the conversations among teenagers and adults.

SIGNIFICANCE
In this first of its kind big data analysis of nearly a quarter-million digital conversations about epilepsy using machine learning, we found that teenagers engage in an online conversation about suicide more often than adults. There are some key differences in the attitudes and concerns, which may have implications for the treatment of younger patients with epilepsy.

suicide
teenagers
epilepsy
machine learning
big data
social media


Highly enantioselective hydrogenation of 1-alkylvinyl benzoates: a simple, nonenzymatic access to chiral 2-alkanols.

Abstract: Going chiral! Highly enantioselective catalytic hydrogenations of enol esters 1 by using a Rh catalyst bearing a P-OP ligand are described (see scheme; NBD=norbornadiene). The catalytic system has a broad scope and allows the preparation of a wide range of chiral esters 2 bearing diverse alkyls or a benzyl group with high enantioselectivities. These esters can easily be converted in highly enantioenriched 2-alkanols.

Kleman|Patryk|P|
González-Liste|Pedro J|PJ|
García-Garrido|Sergio E|SE|
Cadierno|Victorio|V|
Pizzano|Antonio|A|

enantioselectivity
esters
alcohols
asymmetric hydrogenation
rhodium


Reduced ELABELA expression attenuates trophoblast invasion through the PI3K/AKT/mTOR pathway in early onset preeclampsia.

Abstract:
INTRODUCTION
Early onset preeclampsia is linked to abnormal trophoblast invasion, leading to insufficient recasting of uterine spiral arteries and shallow placental implantation. This study investigated ELABELA (ELA) expression and its involvement in the pathogenesis of early onset preeclampsia.

METHODS
We used immunohistochemistry, quantitative PCR and Western blot to calculate ELA levels in the placentas. Transwell assays were utilize to assess the invasion and migration of trophoblastic Cells. Western blot was used to identify the concentrations of vital kinases in PI3K/AKT/mTOR pathways and invasion-related proteins in trophoblast cells.

RESULTS
ELA was expressed in villous cytotrophoblasts and syncytiotrophoblasts in placental tissue. Compared with the normal pregnancies, ELA mRNA and protein expression was significantly reduced in early onset preeclampsia placentas. In the HTR-8/SVneo cells, when ELA was knocked down, the invasion and migration capability of cells decreased significantly, with MMP2 and MMP9 expression downregulated and the expression of important kinases in the PI3K/AKT/mTOR pathways being significantly decreased compared to the control group. Overexpression of ELA was on the contrary. Besides, while PI3K was blocked, the invasion and migration capability of HTR-8/SVneo cells and the expression of key kinases in PI3K/AKT/mTOR pathways were decreased significantly.

DISCUSSION
ELA stimulates the invasion and migration of trophoblastic cells through activation of downstream PI3K/AKT/mTOR pathway and is complicit in early onset preeclampsia pathogenesis. Our research offers a potential novel treatment for PE.

Wang|Lijing|L| Zhang|Yan|Y| Qu|Hongmei|H| Xu|Fengsen|F| Hu|Haiyan|H| Zhang|Qian|Q| Ye|Yuanhua|Y|


Diffusion MR Imaging with T2-based Water Suppression (T2wsup-dMRI).

Abstract:
PURPOSE
This study proposes and assesses a new diffusion MRI (dMRI) technique to solve problems related to the quantification of parameter maps (apparent diffusion coefficient [ADC] or mean diffusivity [MD], fractional anisotropy [FA]) and misdrawing of fiber tractography (FT) due to cerebrospinal fluid (CSF)-partial volume effects (PVEs) for brain tissues by combining with the T2-based water suppression (T2wsup) technique.

METHODS
T2wsup-diffusion-weighted imaging (DWI) images were obtained by subtracting those images from the acquired multi-b value (b) DWI images after correcting the signal intensities of multiecho time (TE) images using long TE water signal-dominant images. Quantitative parameter maps and FT were obtained from minimum data points and were compared with those using the standard (without wsup) DWI method, and partly compared with those obtained using other alternative DWI methods of applying fluid attenuation inversion recovery (FLAIR), non-b-zero (NBZ) by theoretical or noise-added simulation and MR images.

RESULTS
In the T2wsup-dMRI method, the hyperintense artifacts due to CSF-PVEs in MRI data were dramatically suppressed even at lower b (≲ 500 s/mm2) while keeping the tissue SNR. The quantitative parameter map values became precisely close to the pure tissue values precisely even in water (CSF) PVE voxels in healthy brain tissues (T2 ≲ 100 ms). Furthermore, the fiber tracts were correctly connected, particularly at the fornix in closest contact to the CSF.

CONCLUSION
Solving the problem of CSF-PVE in the current dMRI technique using our proposed T2wsup-dMRI technique is easy, with higher SNR than those obtained with FLAIR or NBZ methods when applying to healthy brain tissues. The proposed T2wsup-dMRI could be useful in clinical settings, although further optimization of the pulse sequence and processing techniques and clinical assessments are required, particularly for long T2 lesions.

water suppression
cerebrospinal fluid
diffusion tensor imaging
diffusion-weighted imaging
partial volume effects


Free-Range Feeding Alters Fatty Acid Composition at the sn-2 Position of Triglycerides and Subcutaneous Fat Physicochemical Properties in Heavy Pigs.

Abstract: The nutritional value of fat consumption depends on both the fatty acid composition and the positional distribution of fatty acids within the triglyceride molecule. This research studies the effect of feeding with three different diets (4% lard-enriched; 11.5% high-oleic sunflower-enriched; and extensive feeding mainly with acorns) on the composition of fatty acids in the sn-2 position (and sn-1,3) of triglycerides and the textural properties of subcutaneous fat in heavy Iberian pigs (n = 210 castrated males). A moderate dietary enrichment with oleic acid in mixed diets did not alter the regulation of the sn-2 position of triglyceride (69.9% and 13.9% of palmitic and oleic acids, respectively), but the extremely high intake of oleic acid in pigs fed mainly on acorns changed the proportions of palmitic and oleic acids at the sn-2 position in the subcutaneous fat of pigs (55.0% and 27.2%, respectively). Hardness, adhesiveness, cohesiveness, gumminess, and chewiness showed the least values in EXT pigs, and the greatest values in LARD-fed barrows. SUN cohesiveness and gumminess did not differ from those fed LARD. In addition, Iberian pigs raised in free-range conditions had a more favorable nutritional lipid profile for human health compared to pigs fed conventional diets.

fatty acid
positional distribution
adipose tissue
swine
triacylglyceride structure


Impact on process results of clinical decision support systems (CDSSs) applied to medication use: overview of systematic reviews.

Abstract:
Objective
The purpose of this overview (systematic review of systematic reviews) is to evaluate the impact of clinical decision support systems (CDSS) applied to medication use in the care process.

Methods
A search for systematic reviews that address CDSS was performed on Medline following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane recommendations. Terms related to CDSS and systematic reviews were used in combination with Boolean operators and search field tags to build the electronic search strategy. There was no limitation of date or language for inclusion. We included revisions that investigated, as a main or secondary objective, changes in process outcomes. The Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) score was used to evaluate the quality of the studies.

Results
The search retrieved 954 articles. Five articles were added through manual search, totaling an initial sample of 959 articles. After screening and reading in full, 44 systematic reviews met the inclusion criteria. In the medication-use processes where CDSS was used, the most common stages were prescribing (n=38 (86.36%) and administering (n=12 (27.27%)). Most of the systematic reviews demonstrated improvement in the health care process (30/44 - 68.2%). The main positive results were related to improvement of the quality of prescription by the physicians (14/30 - 46.6%) and reduction of errors in prescribing (5/30 - 16.6%). However, the quality of the studies was poor, according to the score used.

Conclusion
CDSSs represent a promising technology to optimize the medication-use process, especially related to improvement in the quality of prescriptions and reduction of prescribing errors, although higher quality studies are needed to establish the predictors of success in these systems.

Decision Support Systems, Clinical
Drug Information Services
Medical Informatics
Medication Errors
Medication Systems
Review Literature as Topic


Nanoelectronic impedance detection of target cells.

Abstract: Detection of cells is typically performed using optical fluorescence based techniques such as flow cytometry. Here we present the impedance detection of target cells using a nanoelectronic probe we have developed, which we refer to as the nanoneedle biosensor. The nanoneedle consists of a thin film conducting electrode layer at the bottom, an insulative oxide layer above, another conductive electrode layer above, and a protective oxide above. The electrical impedance is measured between the two electrode layers. Cells captured on the surface of the nanoneedle tip results in a decrease in the impedance across the sensing electrodes. The basic mechanisms behind the electrical response of cells in solution under an applied alternating electrical field stems from modulation of the relative permittivity at the interface. In this paper we discuss, the circuit model, the nanofabrication, and the testing and characterization of the sensor. We demonstrate proof of concept for detection of yeast cells with specificity. We envision the sensor presented in this paper to be combined with microfluidic pre-concentration technologies to develop low cost point-of-care diagnostic assays for the clinical setting.

Esfandyarpour|Rahim|R|
Javanmard|Mehdi|M|
Koochak|Zahra|Z|
Harris|James S|JS|
Davis|Ronald W|RW|

impedance detection
biosensing
cell detection
nanobiotechnology
nanotechnology


Abstract: Excess energy intake causes obesity, which leads to insulin resistance and various other complications of metabolic syndrome, including diabetes, atherosclerosis, dyslipidemia, and nonalcoholic fatty liver disease. Although recent studies have depicted altered lipid metabolism as an underlying feature, the detailed mechanisms are still unclear. Here we describe a possible role in high-fat diet (HFD)-induced obesity for monoacylglycerol lipase (MGL), an enzyme that is also known to hydrolyze the endocannabinoid 2-arachidonoylglycerol in brain. MGL-deficient [MGL-knockout (KO)] mice fed a HFD gained less body weight than wild-type mice and were protected from insulin resistance and hepatic steatosis. Food intake and energy expenditure were not altered in MGL-KO mice, but blood triglyceride levels after oral olive oil gavage were suppressed, indicating a role for MGL in intestinal fat absorption. Experiments with cannabinoid receptor type 1 (CB1)/MGL double-KO mice revealed that these phenotypes may include mechanisms that are independent of CB1-receptor-mediated endocannabinoid functions. We also noted that MGL-KO mice had less preference for HFD over normal chow diet. Oral but not intraperitoneal lipid administration strongly suppressed the appetites of MGL-KO and CB1/MGL double-KO mice, but not of wild-type and CB1-KO mice. Appetite suppression was reversed by vagotomy, suggesting involvement of MGL in the gut-brain axis regulation of appetite. Our results provide mechanistic insights of MGL's role in diet-induced obesity, lipid metabolic disorder, and regulation of appetite.-Yoshida, K., Kita, Y., Tokuoka, S. M., Hamano, F., Yamazaki, M., Sakimura, K., Kano, M., Shimizu, T. Monoacylglycerol lipase deficiency affects diet-induced obesity, fat absorption, and feeding behavior in CB1 cannabinoid receptor-deficient mice.

Yoshida|Kenji|K|
Kita|Yoshihiro|Y|
Tokuoka|Suzumi M|SM|
Hamano|Fumie|F|
Yamazaki|Maya|M|
Sakimura|Kenji|K|
Kano|Masanobu|M|
Shimizu|Takao|T|

D000818:Animals
D001212:Asialoglycoproteins
D001835:Body Weight
D059305:Diet, High-Fat
D004435:Eating
D004734:Energy Metabolism
D005234:Fatty Liver
D005247:Feeding Behavior
D007333:Insulin Resistance
D007408:Intestinal Absorption
D037181:Lectins, C-Type
D008297:Male
D008565:Membrane Proteins
D051379:Mice
D008810:Mice, Inbred C57BL
D018345:Mice, Knockout
D009765:Obesity
D043884:Receptor, Cannabinoid, CB1

metabolic syndrome
liver
intestine
adipose tissue
satiety


Neurobiological correlates of social anxiety disorder: an update.

Abstract: Social anxiety disorder (SAD) is a condition characterized by pervasiveness and impairment in social functioning, with a prevalence in the general population between 1.9% and 12.1%. The most consistent findings on its neurobiological underpinnings involve a wide range of neurotransmitters (serotonin, norepinephrine, glutamate, and GABA) and neuropeptides (oxytocin), but no comprehensive hypothesis is yet available. In particular, oxytocin is becoming increasingly established as a "prosocial neuropeptide" and, as such, is a major focus of current research, with a great range of therapeutic applications including SAD treatment. Specifically, the amygdala plays a pivotal role in conditioning and processing of fear, and exaggerated amygdala responses in SAD patients have been observed during various social-emotional stimuli. In addition to the amygdala, other brain areas of interest in SAD-related circuitry are represented by the medial prefrontal cortex, dorsal raphe, striatum, locus coeruleus, prefrontal cortex, insular cortex, and anterior cingulate cortex. The aim of this review is to provide an update on neurobiological correlates of SAD, with a special focus on neurotransmitters and brain areas possibly involved, and suggestions for future research that could lead to more specific therapeutic interventions.

Marazziti|Donatella|D|
Abelli|Marianna|M|
Baroni|Stefano|S|
Carpita|Barbara|B|
Ramacciotti|Carla E|CE|
Dell'Osso|Liliana|L|


Sleepless nights and sleepy days: a qualitative study exploring the experiences of patients with chronic heart failure and newly verified sleep-disordered breathing.

Abstract:
BACKGROUND
Sleep-disordered breathing, including obstructive sleep apnoea and central sleep apnoea, is a common disorder among patients with chronic heart failure. Obstructive sleep apnoea is often treated with continuous positive airway pressure, but central sleep apnoea lacks a clear treatment option. Knowledge of how sleep-disordered breathing is experienced (e.g. difficulties and care needs) and handled (e.g. self-care actions) by the patients is limited, but needed, to provide patient-centred care.

AIM
To explore how newly verified sleep-disordered breathing is experienced by patients with chronic heart failure.

METHODS
Data were collected through semi-structured interviews and analysed with qualitative content analysis. Seventeen participants (14 men, three women), mean age 60 years (range 41-80) diagnosed with chronic heart failure and objectively verified sleep-disordered breathing (nine obstructive, seven central and one mixed) were strategically selected from heart failure outpatient clinics at two Norwegian university hospitals.

RESULTS
Patients with chronic heart failure and newly verified sleep-disordered breathing (SDB) described experiences of poor sleep that had consequences for their daily life and their partners. Different self-care strategies were revealed, but they were based on 'common sense' and were not evidence-based. The awareness of having SDB was varied; for some, it gave an explanation to their trouble while others were surprised by the finding.

CONCLUSION
Patients with chronic heart failure and sleep-disordered breathing experienced reduced sleep quality, influencing their daily life. Possible underlying causes of disrupted sleep, such as sleep-disordered breathing, should be identified to establish proper patient-centred treatment strategies. There is a need for new strategies to approach patients with chronic heart failure (i.e. those with central sleep apnoea) who are not subject to continuous positive airway pressure treatment for their sleep-disordered breathing.

chronic heart failure
sleep-disordered breathing
sleep apnoea
qualitative content analysis
patient experience


Two-photon fluorescence lifetime for label-free microfluidic droplet sorting.

Abstract: Microfluidic droplet sorting systems facilitate automated selective micromanipulation of compartmentalized micro- and nano-entities in a fluidic stream. Current state-of-the-art droplet sorting systems mainly rely on fluorescence detection in the visible range with the drawback that pre-labeling steps are required. This limits the application range significantly, and there is a high demand for alternative, label-free methods. Therefore, we introduce time-resolved two-photon excitation (TPE) fluorescence detection with excitation at 532 nm as a detection technique in droplet microfluidics. This enables label-free in-droplet detection of small aromatic compounds that only absorb in a deep-UV spectral region. Applying time-correlated single-photon counting, compounds with similar emission spectra can be distinguished due to their fluorescence lifetimes. This information is then used to trigger downstream dielectrophoretic droplet sorting. In this proof-of-concept study, we developed a polydimethylsiloxane-fused silica (FS) hybrid chip that simultaneously provides a very high optical transparency in the deep-UV range and suitable surface properties for droplet microfluidics. The herein developed system incorporating a 532-nm picosecond laser, time-correlated single-photon counting (TCSPC), and a chip-integrated dielectrophoretic pulsed actuator was exemplarily applied to sort droplets containing serotonin or propranolol. Furthermore, yeast cells were screened using the presented platform to show its applicability to study cells based on their protein autofluorescence via TPE fluorescence lifetime at 532 nm.

Fluorescence lifetime
Droplet sorting
Two-photon excitation
Cell sorting
Label-free fluorescence detection
Microfluidics/microfabrication


Sexual and reproductive health needs of HIV-positive people in Tehran, Iran: a mixed-method descriptive study.

Abstract:
BACKGROUND
People Living with HIV (PLHIV) are highly stigmatized and consequently hard-to-access by researchers and importantly, public health outreach in Iran, possibly due to the existing socio-cultural situation in this country. The present study aimed to evaluate the sexual and reproductive health needs of PLHIV in Tehran, the capital of Iran.

METHODS
As a mixed-method descriptive study, this project was conducted in 2012 in Tehran, Iran. In this study, we evaluated and discussed socio-demographic characteristics, family and social support, sexual behaviors, fertility desires and needs, PMTCT services, contraceptive methods, unintended pregnancy and safe abortion, and Pap smear tests among 400 participants referring to the behavioral disorders consulting centers.

RESULTS
Of the sample 240 (60%) were male and 160 (40%) were female. About 50% of women and 40% of men were 25-34 years old. More than 60% of men and 96% of women were married, while more than 50% of the participants had HIV-positive spouses at the time of study. According to the results, fertility desire was observed among more than 30% of female and 40% of male participants. Results of the in-depth interviews indicate that the participants are not satisfied with most of the existing services offered to address their sexual and reproductive health needs.

CONCLUSION
Despite the availability of services, most of sexual and reproductive health needs of the PLHIV are overlooked by the health system in Iran. Paying attention to sexual and reproductive health needs of PLHIV in Iran not only protects their right to live long and healthy lives, but also may prevent the transmission of HIV from the patients to others within the community.

Nedjat|Saharnaz|S|
Moazen|Babak|B|
Rezaei|Farimah|F|
Hajizadeh|Shayesteh|S|
Majdzadeh|Reza|R|
Setayesh|Hamid Reza|HR|
Mohraz|Minoo|M|
Gooya|Mohammad Mehdi|MM|

D007722:Health Knowledge, Attitudes, Practice

D006301:Health Services Needs and Demand

Reproductive Health
Iran
HIV
Sexual Behavior
Multimethodology


Recurrent laryngeal nerve lymph node dissection in minimally invasive esophagectomy.

Abstract: Minimally invasive esophagectomy (MIE) has become increasingly important in the treatment for resectable esophageal cancer. However, it's still controversial about the effects of recurrent laryngeal nerve (RLN) lymph node dissection in MIE. Patient was placed in the lateral prone position. RLN lymph node dissection was performed in MIE. MIE can get comparable results of RLN lymph node dissection as open surgery. The number of dissected lymph nodes is 9.8±4.3 pieces and the time of lymphadenectomy is about 24 mins. RLN lymph node dissection is feasible and safe in MIE. The helpful surgical techniques include clear exposure of RLN, good collaboration with assistant, esophageal suspension, and so on.

Lin|Miao|M| Shen|Yaxing|Y| Wang|Hao|H| Feng|Mingxiang|M| Tan|Lijie|L|

Lymph node dissection
minimally invasive esophagectomy (MIE)
esophageal cancer
recurrent laryngeal nerve (RLN)


Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine.

Abstract:
BACKGROUND
Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by WHO found no convincing evidence that DTP increases mortality in females.

METHODS
We used previous DTP reviews as well as the recent WHO review for assessing the hypotheses. As pre-specified we excluded studies with survival or frailty bias; if children had received BCG and DTP simultaneously; and if the children had received neonatal vitamin A.

RESULTS
In seven studies of BCG-vaccinated children, DTP vaccination was associated with a 2.54 (95% CI 1.68-3.86) increase in mortality in girls (with no increase in boys [ratio 0.96, 0.55-1.68]). In 10 studies of BCG-vaccinated children, the female-to-male mortality ratio was 2.45 (1.48-4.06) times higher after DTP than before DTP. In 15 studies of children who had received DTP after previous BCG vaccination, mortality was 1.53 (1.21-1.93) times higher in girls than boys. The findings were similar in studies conducted before and after formulation of the hypotheses.

CONCLUSIONS
The two hypotheses were confirmed in the studies that fulfilled pre-specified criteria.

Aaby|Peter|P|
Ravn|Henrik|H|
Fisker|Ane B|AB|
Rodrigues|Amabelia|A|
Benn|Christine S|CS|

D016032:Randomized Controlled Trials as Topic

Strategic Advisory Group of Experts on Immunization (SAGE)


Joule Heating-Induced Metal-Insulator Transition in Epitaxial VO2/TiO2 Devices.

Abstract: DC and pulse voltage-induced metal-insulator transition (MIT) in epitaxial VO2 two terminal devices were measured at various stage temperatures. The power needed to switch the device to the ON-state decrease linearly with increasing stage temperature, which can be explained by the Joule heating effect. During transient voltage induced MIT measurement, the incubation time varied across 6 orders of magnitude. Both DC I-V characteristic and incubation times calculated from the electrothermal simulations show good agreement with measured values, indicating Joule heating effect is the cause of MIT with no evidence of electronic effects. The width of the metallic filament in the ON-state of the device was extracted and simulated within the thermal model.

Li|Dasheng|D|
Sharma|Abhishek A|AA|
Gala|Darshil K|DK|
Shukla|Nikhil|N|
Paik|Hanjong|H|
Datta|Suman|S|
Schlom|Darrell G|DG|
Bain|James A|JA|
Skowronski|Marek|M|

Joule heating
epitaxial thin film
metal−insulator transition
threshold switching
vanadium dioxide


Evolution of Rheological Behaviors of Styrene-Butadiene-Styrene/Crumb Rubber Composite Modified Bitumen after Different Long-Term Aging Processes.

Abstract: In this study, a new type of composite modified bitumen was developed by blending styrene-butadiene-styrene (SBS) and crumb rubber (CR) with a chemical method to satisfy the durability requirements of waterproofing material in the waterproofing layer of high-speed railway subgrade. A pressure-aging-vessel test for 20, 40 and 80 h were conducted to obtain bitumen samples in different long-term aging conditions. Multiple stress creep recovery (MSCR) tests, linear amplitude scanning tests and bending beam rheometer tests were conducted on three kinds of asphalt binders (SBS modified asphalt, CR modified asphalt and SBS/CR composite modified asphalt) after different long-term aging processes, including high temperature permanent deformation performance, resistance to low temperature thermal and fatigue crack. Meanwhile, aging sensitivities were compared by different rheological indices. Results showed that SBS/CR composite modified asphalt possessed the best properties before and after aging. The elastic property of CR in SBS/CR composite modified asphalt improved the ability to resist low temperature thermal and fatigue cracks at a range of low and middle temperatures. Simultaneously, the copolymer network of SBS and CR significantly improved the elastic response of the asphalt SBS/CR modified asphalt at a range of high temperatures. Furthermore, all test results indicated that the SBS/CR modified asphalt possesses the outstanding ability to anti-aging. SBS/CR is an ideal kind of asphalt to satisfy the demand of 60 years of service life in the subgrade of high speed railway.

Ye|Yangsheng|Y| Xu|Gang|G| Lou|Liangwei|L| Chen|Xianhua|X|0000-0001-8395-5002 Cai|Degou|D| Shi|Yuefeng|Y|

long-term aging
SBS/CR modified asphalt
anti-aging
high speed railway


Response factors associated with electrocautery treatment of intra-anal high-grade squamous intraepithelial lesions in a population of HIV-positive men who have sex with men.

Abstract:
BACKGROUND
Ablative treatment of anal high-grade squamous intraepithelial lesions (HSIL) reduces the risk of progression to anal squamous cell carcinoma.

OBJECTIVES
To identify factors that influence the response to treatment of anal HSIL by electrocautery ablation (ECA) in a population of HIV-positive men who have sex with men (MSM).

DESIGN
Retrospective study of ECA treatment response in a prospectively followed anal dysplasia cohort. HIV-positive MSM diagnosed with anal HSIL were included. Demographic and HIV data were recorded. Response to treatment was assessed by biopsy after at least 18 months of follow-up.

RESULTS
One hundred and twenty-eight HSILs in 91 men were included in this study. The overall response rate at 18 months was 70.3%. The number of electrocautery sessions required (2 ECA sessions vs 1: adjusted odds ratio [aOR] = 0.36 (95%CI 0.13-1.01); >=3 sessions vs 1: aOR = 0.10 (95%CI 0.04-0.29); p < 0.001]) and the history of previous HPV-related anal pathology (previous anal lesions vs no previous lesions AOR = 2.83 (95%CI 1.14-7.02), p = 0.024) were independently associated with response at 18 months. No serious adverse events were reported.

CONCLUSIONS
Consideration should be given to alternative therapies in patients with unresolved HSIL after 1 ECA treatment.

Fuertes|Irene|I|0000-0002-9314-1843
Cranston|Ross|R|
de Lazzari|Elisa|E|
Rodriguez-Carunchio|Leonardo|L|
Blanco|José L|JL|

Anal high-grade squamous intraepithelial lesions


METTL3 plays multiple functions in biological processes.

Abstract: N6-methyladenosine (m6A) is the most common internal modification of mRNAs in higher eukaryotic. This process is performed by methyltransferase. Methyltransferase-like 3 (METTL3) is the best known m6A methyltransferase that functions in the reversible epi-transcriptome modulation of m6A modification. Besides acting as a m6A methyltransferase, METTL3 also regulates mRNA translation and other biological processes. In recent years, studies have identified numerous roles and molecular mechanisms associated with METTL3 in multiple biological processes. However, these findings have not been summarized. In this review, we have systematically summarized the most recent important roles of METTL3 in various biological processes, including cell cycle progression, cell proliferation, cell apoptosis, cell migration and invasion, cell differentiation and inflammatory response. In addition, we discuss the prospect of using a METTL3 as a new diagnostic biomarker and therapeutic target for human cancers.

Liu|Shuiping|S| Zhuo|Lvjia|L| Wang|Jianjun|J| Zhang|Qin|Q| Li|Qiujie|Q| Li|Guohua|G| Yan|Lili|L| Jin|Ting|T| Pan|Ting|T| Sui|Xinbing|X| Lv|Qun|Q| Xie|Tian|T|

METTL3
biological process
m6A modification
diagnostic biomarker
cancer therapy


Nursing students' perspectives of the cause of medication errors.

Abstract:
BACKGROUND
Medication errors complicate up to half of inpatient stays and some have very serious consequences. To our knowledge, this is the first qualitative study of Iranian nursing students' perspectives of medication errors.

OBJECTIVES
To describe nursing students' perspectives of the causes of medication errors.

DESIGN
Four focus groups were held with 24 nursing students from 4 different academic semesters in the nursing school in Tehran, between November 2011 and November 2012. Using a qualitative descriptive design, themes and subthemes were identified by content analysis.

RESULTS
Two main themes emerged from the data: "under-developed caring skills in medication management" and "unfinished learning of safe medication management", which was subdivided into "drifting between being worried and being careful", and "contextualising pharmacology education". All respondents felt that their education programmes were leaving them vulnerable to "drug errors" and cited incidents where patient safety had been jeopardised.

CONCLUSION
Nursing curricula need to increase investment in medicines management. If nursing students are to become competent, skilful and safe practitioners, their learning will require extensive support from their academic institutions and clinical mentors.

Vaismoradi|Mojtaba|M| Jordan|Sue|S| Turunen|Hannele|H| Bondas|Terese|T|

D001291:Attitude of Health Personnel
D017144:Focus Groups
D006801:Humans
D007492:Iran
D007858:Learning
D008508:Medication Errors
D061214:Patient Safety
D036301:Qualitative Research
D013338:Students, Nursing

Nursing
Students
Medication errors
Patient safety
Qualitative research


Proteomic analysis reveals the effects of melatonin on soybean root tips under flooding stress.

Abstract: Flooding constrains soybean growth, while melatonin enhances the ability of plants to tolerate abiotic stresses. To interpret the melatonin-mediated flooding response in soybeans, proteomic analysis was performed in root tips. Retarded growth and severe cell death were observed in flooded soybeans, but these phenotypes were ameliorated by melatonin treatment. A total of 634, 1401, and 1205 proteins were identified under control, flood, and flood plus melatonin conditions, respectively; and these proteins were predominantly associated with metabolism of protein, RNA, and the cell wall. Among these melatonin-induced proteins, eukaryotic aspartyl protease family protein was increased after flood compared with melatonin treatment group, in accordance with its upregulated transcript levels during stress. Eukaryotic translation initiation factor 5A was decreased after flood compared with melatonin. When stress was prolonged, its transcript levels were upregulated by flood, while they were not changed by melatonin. Furthermore, 13-hydroxylupanine O-tigloyltransferase was decreased by flood compared with melatonin; however, its transcription was upregulated by melatonin. In addition, reduced lignification in root tips of flooded soybeans was restored by melatonin. These results suggest that factors related to protein degradation and functional states of RNA play critical roles in promoting the effects of melatonin on soybean plants under flooding. SIGNIFICANCE: Flooding stress threatens soybean growth, while melatonin treatment enhances plant tolerance to stress stimuli. To examine the effects of melatonin on flooded soybeans, morphological analysis was performed. Melatonin promoted soybean growth as judged from greater fresh weight of plant, longer seedling length, and less evident cell death in flooding-stressed soybeans treated with melatonin than those plants exposed to flood alone. Proteomic analysis was conducted to explore the promoting effects of melatonin on soybeans under flooding stress. As a result, metabolism of protein metabolism, RNA regulation, and cell wall was enriched by proteins identified under control, flood, and flood plus melatonin conditions. Among these melatonin-induced proteins, abundance of eukaryotic aspartyl protease family protein, eukaryotic translation initiation factor 5A, and 13-hydroxylupanine O-tigloyltransferase displayed similar change patterns between the control and melatonin compared with flood; and transcript levels of genes encoding these proteins responded to flooding stress and melatonin treatment. In addition, activated cell degradation, expanded intercellular spaces, and reduced lignification in root tips of flooded soybeans were ameliorated by melatonin treatment.

Wang|Xin|X| Li|Fang|F| Chen|Zhenyuan|Z| Yang|Bingxian|B| Komatsu|Setsuko|S| Zhou|Shunli|S|

D018506:Gene Expression Regulation, Plant

Proteomics
Melatonin
Soybean
Root tip
Flooding


Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities.

Abstract: Superparamagnetic iron oxide nanoparticles (SPION) have received immense interest for biomedical applications, with the first clinical application as negative contrast agent in magnetic resonance imaging (MRI). However, the first generation MRI contrast agents with dextran-enwrapped, polydisperse iron oxide nanoparticle clusters are limited to imaging of the liver and spleen; this is related to their poor colloidal stability in biological media and inability to evade clearance by the reticuloendothelial system. We investigate the qualitatively different performance of a new generation of individually PEG-grafted core-shell SPION in terms of relaxivity and cell uptake and compare them to benchmark iron oxide contrast agents. These PEG-grafted SPION uniquely enable relaxivity measurements in aqueous suspension without aggregation even at 9.4 T magnetic fields due to their extraordinary colloidal stability. This allows for determination of the size-dependent scaling of relaxivity, which is shown to follow a d2 dependence for identical core-shell structures. The here introduced core-shell SPION with ∼15 nm core diameter yield a higher R2 relaxivity than previous clinically used contrast agents as well as previous generations of individually stabilized SPION. The colloidal stability extends to control over evasion of macrophage clearance and stimulated uptake by SPION functionalized with protein ligands, which is a key requirement for targeted MRI.

D003287:Contrast Media
D003911:Dextrans
D005290:Ferric Compounds
D008279:Magnetic Resonance Imaging
D058185:Magnetite Nanoparticles

superparamagnetic iron oxide nanoparticles


Clinical features of patients treated by peritoneal dialysis for over a decade.

Abstract:
BACKGROUND
Peritoneal dialysis (PD) is well-established as renal replacement therapy in end stage renal disease and has survival rates similar or better than hemodialysis (HD) for the initial years on dialysis therapy. However retention rate is lower due to higher technique failure rates than in HD and few patients stay on PD for more than 10 years (PD>10 yrs). Here we investigated clinical features characterizing PD>10 yrs patients.

PATIENTS AND METHODS
In a single center study of 450 prevalent PD patients, 35 PD>10 yrs patients (n=35) were compared with patients (n=415) who had been on PD for shorter periods of time in terms of clinical characteristics. Peritoneal transport, blood pressure, solute clearance, nutrition status, and blood calcium, phosphate and parathyroid hormone levels were measured dialysis start and, in PD>10 yrs patients, also after 5 and 10 years of PD.

RESULTS
The PD>10 yrs patients differed from the other PD patients in that (1) the proportion of women was higher; (2) body mass index (BMI) was lower; (3) there was no patient with diabetic nephropathy as primary diagnosis; (4) the incidence of peritonitis was lower; (5) glomerular filtration rate was higher; and (6) parathyroid hormone (PTH) levels were lower in those with decade-long PD treatment. In PD>10 yrs patients, serum albumin was maintained at a high level throughout the 10 year follow up; hemoglobin levels after 5 and 10 years of PD were higher than at the beginning of the treatment; blood calcium and phosphate concentrations were maintained at acceptable levels; while the dialysate/plasma ratio of creatinine, D/P-value, increased during the decade-long PD treatment.

CONCLUSIONS
Patients receiving PD>10 years had lower incidence of peritonitis, lower BMI, adequate control of blood calcium and phosphate levels and solute clearance, and were more often women than PD patients treated for shorter periods of time.

Tong|Mengli|M| Wang|Yuhui|Y| Ni|Jun|J| Weng|Ning|N| Chen|Chuanxia|C| Chen|Hongyu|H| Bengt|Lindholm|L|

peritoneal dialysis
End stage renal disease
technique failure
long term patient survival


Comparative genomics of Lactobacillus sakei supports the development of starter strain combinations.

Abstract: Strains of Lactobacillus sakei can be isolated from a variety of sources including meat, fermented sausages, sake, sourdough, sauerkraut or kimchi. Selected strains are widely used as starter cultures for sausage fermentation. Recently we have demonstrated that control about the lactic microbiota in fermenting sausages is achieved rather by pairs or strain sets than by single strains. In this work we characterized the pan genome of L. sakei to enable exploitation of the genomic diversity of L. sakei for the establishment of assertive starter strain sets. We have established the full genome sequences of nine L. sakei strains from different sources of isolation and included in the analysis the genome of L. sakei 23K. Comparative genomics revealed an accessory genome comprising about 50% of the pan genome and different lineages of strains with no relation to their source of isolation. Group and strain specific differences could be found, which namely referred to agmatine and citrate metabolism. The presence of genes encoding metabolic pathways for fructose, sucrose and trehalose as well as gluconate in all strains suggests a general adaptation to plant/sugary environments and a life in communities with other genera. Analysis of the plasmidome did not reveal any specific mechanisms of adaptation to a habitat. The predicted differences of metabolic settings enable prediction of partner strains, which can occupy the meat environment to a large extent and establish competitive exclusion of autochthonous microbiota. This may assist the development of a new generation of meat starter cultures containing L. sakei strains.

Eisenbach|Lara|L|
Geissler|Andreas J|AJ|
Ehrmann|Matthias A|MA|
Vogel|Rudi F|RF|

Comparative genomics
Lactobacillus sakei
Assertiveness
Accessory-
Competiveness
Core-genome
Lactic acid bacteria
Pan-
Raw fermented sausages


Incidental finding of a giant asymptomatic right atrial tumor.

Abstract: Primary cardiac tumors are very rare, atrial myxoma being the most common benign tumor of the heart. They may present with a great variety of incidental asymptomatic masses to severe life-threatening cardiovascular complications necessitating emergency surgery. Here we report the diagnostic evaluation and successful surgical resection of such a giant cardiac tumor which was found on a routine medical check-up in a 62-year-old patient. Histology confirmed diagnosis of unusually huge myxoma. This article demonstrates it's necessary to include cardiac tumors in the differential diagnosis of subtle and non-specific cardiothoracic symptoms.

Strecker|Thomas|T|
Agaimy|Abbas|A|
Zelzer|Peter|P|
Weyand|Michael|M|
Wachter|David Lukas|DL|

Cardiac tumors
myxoma
surgery
echocardiography
pathology


Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate.

Abstract: Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. Graphical Abstract .

Oyler|Benjamin L|BL|
Khan|Mohd M|MM|
Smith|Donald F|DF|
Harberts|Erin M|EM|
Kilgour|David P A|DPA|
Ernst|Robert K|RK|
Cross|Alan S|AS|
Goodlett|David R|DR|

D002460:Cell Line
D004926:Escherichia coli
D004927:Escherichia coli Infections
D022361:Escherichia coli Vaccines
D006801:Humans
D008070:Lipopolysaccharides
D053719:Tandem Mass Spectrometry

Top down
Lipopolysaccharide
Vaccine
Collision induced dissociation
FT-ICR
Lipid A
Oligosaccharide


Error rate control for classification rules in multiclass mixture models.

Abstract: In the context of finite mixture models one considers the problem of classifying as many observations as possible in the classes of interest while controlling the classification error rate in these same classes. Similar to what is done in the framework of statistical test theory, different type I and type II-like classification error rates can be defined, along with their associated optimal rules, where optimality is defined as minimizing type II error rate while controlling type I error rate at some nominal level. It is first shown that finding an optimal classification rule boils down to searching an optimal region in the observation space where to apply the classical Maximum A Posteriori (MAP) rule. Depending on the misclassification rate to be controlled, the shape of the optimal region is provided, along with a heuristic to compute the optimal classification rule in practice. In particular, a multiclass FDR-like optimal rule is defined and compared to the thresholded MAP rules that is used in most applications. It is shown on both simulated and real datasets that the FDR-like optimal rule may be significantly less conservative than the thresholded MAP rule.

Mary-Huard|Tristan|T| Perduca|Vittorio|V| Martin-Magniette|Marie-Laure|ML| Blanchard|Gilles|G|

error rate control
classification rule
mixture models


The effects of elevated temperature and dissolved ρCO2 on a marine foundation species.

Abstract: Understanding how climate change and other environmental stressors will affect species is a fundamental concern of modern ecology. Indeed, numerous studies have documented how climate stressors affect species distributions and population persistence. However, relatively few studies have investigated how multiple climate stressors might affect species. In this study, we investigate the impacts of how two climate change factors affect an important foundation species. Specifically, we tested how ocean acidification from dissolution of CO 2 and increased sea surface temperatures affect multiple characteristics of juvenile eastern oysters (Crassostrea virginica). We found strong impacts of each stressor, but no interaction between the two. Simulated warming to mimic heat stressed summers reduced oyster growth, survival, and filtration rates. Additionally, we found that CO 2-induced acidification reduced strength of oyster shells, which could potentially facilitate crab predation. As past studies have detected few impacts of these stressors on adult oysters, these results indicate that early life stages of calcareous marine organisms may be more susceptible to effects of ocean acidification and global warming. Overall, these data show that predicted changes in temperature and CO 2 can differentially influence direct effects on individual species, which could have important implications for the nature of their trophic interactions.

Speights|Cori J|CJ|0000-0003-4790-5061
Silliman|Brian R|BR|
McCoy|Michael W|MW|

climate change
acidification
oyster
warming
multiple stressors


Subclinical mastitis in dairy cows in major milk-producing areas of Sri Lanka: Prevalence, associated risk factors, and effects on reproduction.

Abstract: Compared with clinical mastitis, the subclinical form of mastitis (SCM) is more common and thought to cause more economic losses to the dairy industry. The current study aimed to investigate the prevalence, risk factors of SCM, and effects on reproduction of dairy cows in major milk-producing areas of Sri Lanka. A total of 1,357 cows of selected farms in 3 regions were examined in the study. California Mastitis Test was conducted for individual cows, and a score of 2 or more for any quarter without any clinical symptoms and abnormalities in milk was considered as positive for SCM. Samples from infected animals were collected and subjected to bacteriological analysis. A pretested questionnaire was used to collect data on individual cows and herds. Risk factors associated with SCM were analyzed using binary logistic regression in generalized linear mixed models. The effect of SCM on calving to conception interval and days from calving to artificial insemination were analyzed by survival analysis using Cox's proportional hazards regression and Kaplan-Meier survival function estimates, respectively. A Poisson regression model was run to determine the effect of SCM on number of artificial inseminations per conception. The prevalence of SCM was 57.5, 11.8, and 45.5% in the regions A, B, and C, respectively. The most common pathogen was Staphylococcus aureus, with 87.1, 56.5, and 92.3% in the regions A, B, and C, respectively. Logistic regression analysis showed that parity, farming system, milking area, region, and herd significantly affect the prevalence of SCM. Subclinical mastitis during the pre-breeding period was associated with 14% increase in the chance of having a greater number of artificial inseminations per conception. Likewise, median days from calving to artificial insemination was longer in cows with SCM compared with normal cows (79 and 64 d, respectively). Therefore, SCM affected the inseminated proportion of studied cows. However, SCM was not associated with the calving to conception interval. The results revealed that the cow factors and milk hygiene play a significant role in the prevalence of SCM.

Ranasinghe|R M S B K|RMSBK|
Deshapriya|R M C|RMC|
Abeygunawardana|D I|DI|
Rahularaj|R|R|
Dematawewa|C M B|CMB|

subclinical mastitis
dairy cow
risk factor
reproductive parameter


Point-of-care ultrasound diagnosis of a pyogenic liver abscess in the emergency department.

Abstract: Pyogenic liver abscess (PLA) is a rarely encountered condition in the emergency department (ED) that necessitates a timely diagnosis by the emergency physician. An early ED diagnosis is challenging as the presenting symptoms of PLA are often variable and nonspecific. The rapid bedside diagnosis of PLA with point-of-care ultrasound (POCUS) performed by emergency physicians has not been investigated thoroughly. This case report describes the expeditious identification and ED management of PLA by implementing emergency physician-performed POCUS as the initial diagnostic modality.

McClure|Matthew B|MB|
Patel|Kishan|K|
Cabrera|Gabriel|G|
Kalivoda|Eric J|EJ|

pyogenic liver abscess
emergency department
emergency ultrasound
hepatic abscess
point‐of‐care ultrasound
ultrasonography


The triad of current asthma, rhinitis and eczema is uncommon among adults: Prevalence, sensitization profiles, and risk factors.

Abstract:
BACKGROUND
Coexistence of asthma, rhinitis, and eczema has been studied in children, but data are lacking in adults. As new treatments emerge, epidemiological data on the coexistence are needed.

AIMS
To study the prevalence of concomitant asthma, rhinitis and eczema in the general adult population and among those sensitized to aeroallergens, and to study associations between background characteristics and risks of phenotypes of asthma, rhinitis, and eczema.

METHODS
In the West Sweden Asthma Study, phenotypes and sensitization profiles of 1103 randomly selected adults (16-75 years) were assessed. The methods included measures of serum-IgE and structured interviews on asthma, rhinitis, eczema, their associated symptoms, and relevant risk factors.

RESULTS
Among all participants and in those sensitized, 2% and 6% had concomitant asthma, rhinitis, and eczema, respectively, and the condition did not differ by age or sex. Corresponding figures for asthma and rhinitis, but not eczema, was 8% and 19%, respectively. Determinants of coexistence of the three conditions were family history of asthma/allergy, body mass index, and occupational exposure to gas, dust and fumes. Allergic sensitization in those with asthma, rhinitis and eczema was found in 78%, in those with asthma and rhinitis but not eczema in 65%, in those with asthma and eczema but not rhinitis in 40%, while only 5% were sensitized among those having asthma only.

CONCLUSIONS
In the general adult population about 2% have concomitant asthma, rhinitis, and eczema. Of sensitized adults, about 6% has coexistence of the three conditions.

Pullerits|Teet|T|
Rönmark|Erik P|EP|
Ekerljung|Linda|L|
Palmqvist|Mona Andersson|MA|
Arvidsson|Monica|M|
Mincheva|Roxana|R|
Backman|Helena|H|
Kankaanranta|Hannu|H|
Ilmarinen|Pinja|P|
Rådinger|Madeleine|M|
Lundbäck|Bo|B|
Nwaru|Bright I|BI|

Prevalence
Risk factors
Allergic sensitization
Combined asthma-rhinitis-eczema
Population study


Cross-cultural adaptation of the professional version of the Readiness for Interprofessional Learning Scale (RIPLS) in Japanese.

Abstract: Interprofessional education (IPE) for healthcare professionals is important in Japan because of its rapidly aging population and increasingly complex healthcare needs. However, no tools have been validated in the Japanese context to evaluate healthcare professionals' attitudes towards, or readiness for, IPE. The professional version of the Readiness for Interprofessional Learning Scale (RIPLS) with 23 items was selected for cross-cultural adaptation because it has been widely used internationally and a Japanese edition of the student version has already been developed. We followed a guideline for cross-cultural adaptation and subsequently conducted factor analysis with 368 responses from over 16 professions. Face and content validity was confirmed through the translation process. We obtained four factors with good internal consistency (Cronbach's alpha > 0.7). These results were similar to those of the original UK study, apart from one factor being divided into two different factors in this study. Studies are required to further confirm the rigor and generalisability of the results; however, the Japanese RIPLS can be used to evaluate healthcare professionals' attitudes towards IPE, which can eventually lead to a better IPE development for healthcare professionals in Japan.

Oishi|Ai|A| Haruta|Junji|J| Yoshimi|Kenji|K| Goto|Michiko|M| Yoshida|Kazue|K| Yoshimoto|Hisashi|H|

D001291:Attitude of Health Personnel
D054521:Cultural Competency
D006801:Humans
D007400:Interprofessional Relations
D007564:Japan
D011594:Psychometrics
D015203:Reproducibility of Results
D013336:Students, Health Occupations
D011795:Surveys and Questionnaires

Interprofessional learning
Japan
post-qualifying/post-licensure
professional identity
psychometric analysis
surveys


The effects of different gait speeds and lower arm weight on the activities of the latissimus dorsi, gluteus medius, and gluteus maximus muscles.

Abstract: [Purpose] This study researched the effects of different gait speeds and lower arm weight on the activities of the latissimus dorsi, gluteus medius, and gluteus maximus muscles. [Subjects] Fourteen healthy adult men participated in this study. [Methods] All the participants carried out walking on a treadmill at speeds of 3.5 km/h and 5.5 km/h for half a minute. During treadmill gait, electromyographic activity muscle was measured of the latissimus dorsi, gluteus medius and gluteus maximus. [Result] There were significant differences in the muscle activities due to changes in gait speed and lower arm load in the latissimus dorsi and gluteus maximus, but there were no significant differences in the muscle activities of the gluteus medius. [Conclusion] According to our results, arm swing is related to increasing gait speed, and lower arm load is influences the muscle activity of the lower extremities through the posterior oblique sling system.

Kim|Tae-Young|TY| Yoo|Won-Gyu|WG| An|Duk-Hyun|DH| Oh|Jae-Seop|JS| Shin|Seung-Je|SJ|

Arm weight
Arm swing
Posterior oblique sling system


Lung ultrasonography decreases radiation exposure in newborns with respiratory distress: a retrospective cohort study.

Abstract: Chest X-ray (CXR) is commonly used as a first-line imaging method to determine the cause of respiratory distress in NICUs. The aim of the study was to retrospectively assess the decrease in the number of CXRs performed due to the use of lung ultrasonography on the first day of life for newborns with respiratory distress. Infants who were admitted to the NICU on the first day of life due to respiratory distress were enrolled in this study (ClinicalTrials.gov identifier NCT04722016) and divided into two groups: the study group (n = 104) included patients born between January 2019 and June 2020, and the historical control group (n = 73) included patients born between June 2017 and December 2018. As a first-line technique for lung imaging, only CXR had been used in the historical control group, whereas ultrasound had been preferred in the study group. The radiation dose to the newborns and the number of CXRs performed in the first day of life were compared between the two groups. Significant reductions in the number of CXRs performed and radiation exposure were observed in the study group. The radiation dose decreased from 5.54 to 4.47 µGy per baby when LUS was routinely used. The proportion of patients who underwent CXR decreased from 100 to 71.2%.Conclusion: We observed that using lung ultrasonography as a first-line evaluation method in neonates with respiratory distress decreased both the number of CXRs performed and radiation exposure. What is Known: • Chest X-ray is commonly used as a first line imaging method to diagnose the reason of respiratory distress in NICUs. • Lung ultrasound is a new diagnostic tool for lung imaging. What is New: • With the use of lung ultrasonography, radiation exposure of both newborns and healthcare workers can be reduced. • This retrospective study revealed that most of the babies with respiratory distress were treated without CXR.

Lung ultrasonography
Radiation exposure
Newborn
Respiratory distress
Premature


Association of Exposure to particular matter and Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis.

Abstract:
BACKGROUND
Long time exposure to particular matter has been linked to myocardial infarction, stroke and blood pressure, but its association with atherosclerosis is not clear. This meta-analysis was aimed at assessing whether PM₂.₅ and PM₁₀ have an effect on subclinical atherosclerosis measured by carotid intima-media thickness (CIMT).

METHODS
Pubmed, Ovid Medline, Embase and NICK between 1948 and 31 March 2015 were searched by combining the keywords about exposure to the outcome related words. The random-effects model was applied in computing the change of CIMT and their corresponding 95% confidence interval (95% CI). The effect of potential confounding factors was assessed by stratified analysis and the impact of traffic proximity was also estimated.

RESULTS
Among 56 identified studies, 11 articles satisfied the inclusion criteria. In overall analysis increments of 10 μg/m³ in PM₂.₅ and PM₁₀ were associated with an increase of CIMT (16.79 μm; 95% CI, 4.95-28.63 μm and 4.13 μm; 95% CI, -5.79-14.04 μm, respectively). RESULTS shown in subgroup analysis had reference value for comparing with those of the overall analysis. The impact of traffic proximity on CIMT was uncertain.

CONCLUSIONS
Exposure to PM₂.₅ had a significant association with CIMT and for women the effect may be more obvious.

Liu|Xiaole|X| Lian|Hui|H| Ruan|Yanping|Y| Liang|Ruijuan|R| Zhao|Xiaoyi|X| Routledge|Michael|M| Fan|Zhongjie|Z|

D000393:Air Pollutants
D050197:Atherosclerosis
D059168:Carotid Intima-Media Thickness
D004781:Environmental Exposure
D006801:Humans
D052638:Particulate Matter

carotid intima-media thickness
meta-analysis
subclinical atherosclerosis
PM10
PM2.5
air pollution


Axial-Plane Biomechanical Evaluation of 2 Suspensory Cortical Button Fixation Constructs for Acromioclavicular Joint Reconstruction.

Abstract:
BACKGROUND
Although numerous suture-button fixation techniques for acromioclavicular (AC) joint reconstruction have been validated with biomechanical testing in the superior direction, clinical reports continue to demonstrate high rates of construct slippage and breakage.

PURPOSE
To compare the stability of a novel closed-loop double Endobutton construct with a commercially available cortical button system in both the axial and superior directions.

STUDY DESIGN
Controlled laboratory study.

METHODS
Six matched pairs of fresh-frozen cadaveric upper extremities were anatomically dissected and prepared to simulate a complete AC joint dislocation. One side of each pair was reconstructed with the double Endobutton (DE) construct and other side with the dog bone button (DB) construct. The specimens were then tested using a materials testing machine, determining initial superior and axial displacements with a preload, and then cyclically loaded in the axial direction with 70 N for 5000 cycles. Displacement was again measured with the same preloads at fixed cycle intervals. The specimens were then loaded superiorly to failure.

RESULTS
At 5000 cycles, the mean axial displacement was 1.7 mm for the DB group and 1.2 mm for the DE group (P = .19), and the mean superior displacement was 1.1 mm for the DB group and 0.7 mm for the DE group (P = .32). Load at failure was similar (558 N for DE, 552 N for DB; P = .96). There was no statistically significant difference in the modes of failure.

CONCLUSION
Biomechanical testing of both constructs showed similar fixation stability after cyclical axial loading and similar loads to failure.

CLINICAL RELEVANCE
The strength of both constructs after cyclical loading in the axial plane and load-to-failure testing in the superior plane validate their continued clinical use for achieving stability in AC joint reconstruction procedures.

Struhl|Steven|S|
Wolfson|Theodore S|TS|
Kummer|Frederick|F|

biomechanics
acromioclavicular joint
Endobutton
anatomic reconstruction
coracoclavicular ligament


ω-6 and ω-9 polyunsaturated fatty acids with double bonds near the carboxyl head have the highest affinity and largest effects on the cardiac IK s potassium channel.

Abstract:
AIM
The IK s channel is important for termination of the cardiac action potential. Hundreds of loss-of-function mutations in the IK s channel reduce the K+ current and, thereby, delay the repolarization of the action potential, causing Long QT Syndrome. Long QT predisposes individuals to Torsades de Pointes which can lead to ventricular fibrillation and sudden death. Polyunsaturated fatty acids (PUFAs) are potential therapeutics for Long QT Syndrome, as they affect IK s channels. However, it is unclear which properties of PUFAs are essential for their effects on IK s channels.

METHODS
To understand how PUFAs influence IK s channel activity, we measured effects on IK s current by two-electrode voltage clamp while changing different properties of the hydrocarbon tail.

RESULTS
There was no, or weak, correlation between the tail length or number of double bonds in the tail and the effects on or apparent binding affinity for IK s channels. However, we found a strong correlation between the positions of the double bonds relative to the head group and effects on IK s channels.

CONCLUSION
Polyunsaturated fatty acids with double bonds closer to the head group had higher apparent affinity for IK s channels and increased IK s current more; shifting the bonds further away from the head group reduced apparent binding affinity for and effects on the IK s current. Interestingly, we found that ω-6 and ω-9 PUFAs, with the first double bond closer to the head group, left-shifted the voltage dependence of activation the most. These results allow for informed design of new therapeutics targeting IK s channels in Long QT Syndrome.


Quantitation of the anaesthetic xylazine in ovine plasma by LC-MS/MS.

Abstract: Removal of the wool-bearing skin around a young lamb's rump (mulesing) provides long term health benefits for the animal, and the use of a sedative and analgesic agent such as xylazine may assist with pain relief to reduce discomfort and stress. Sensitive analytical methods are essential for monitoring pharmaceuticals and their metabolites in animals destined for human consumption. The following work reports a method that is 200 times more sensitive for xylazine detection than previously published methods, with lower limits of quantitation for xylazine and its primary metabolite in animals of 0.5pg and 2pg on-column, respectively. The use of a square wave solvent gradient immediately prior to analyte elution resulted in larger MS/MS peaks and a reduction in baseline noise, allowing reliable detection of lower analyte concentrations. The method uses as little as 1mL of plasma which allows replication within a sample if required, and requires simple sample preparation, minimising the introduction of matrix components into the MS/MS.

D002851:Chromatography, High Pressure Liquid

Xylazine Ovine 2,6-dimethylaniline Chromatography LC–MS/MS Sheep


Nuclear Theranostics in Indonesia: Past, Present, and Future.

Abstract: Nuclear medicine in Indonesia has a quite long history since the late 1960s. There are some problems and obstacles that have to be solved and overcome in order to develop nuclear medicine services, spread the services to reach every target area, and implement new novel therapeutic nuclear medicine as well. The right strategy and strong effort should be performed for a successful result. Theranostics nuclear medicine will play a more prominent role in the management of cancer patients.

Theranostics
Indonesia
Nuclear medicine
Cancer


The effect of unemployment on the smoking behavior of couples.

Abstract: Although unemployment likely entails various externalities, research examining its spillover effects on spouses is scarce. This is the first paper to estimate effects of unemployment on the smoking behavior of both spouses. Using German Socio-Economic Panel data, we combine matching and difference-in-differences estimation, employing the post-double-selection method for control variable selection via Lasso regressions. One spouse's unemployment increases both spouses' smoking probability and intensity. Smoking relapses and decreased smoking cessation drive the effects. Effects are stronger if the partner already smokes and if the male partner becomes unemployed. Of several mechanisms discussed, we identify smoking to cope with stress as relevant.

unemployment
smoking
spillover effects
post-double-selection method
job loss
risky health behaviors


Does corticosteroid treatment cause prolonged recovery and increased total bilirubin level in severe ADAMTS-13-deficient TTP patient?

Abstract: A 41-year-old female patient complaining of fatigue, headache, mild confusion, and rush on her lower extremities was admitted to our emergency department. Laboratory tests revealed that he had anemia, thrombocytopenia, and increased levels of indirect bilirubin and lactic dehydrogenase (LDH) in blood tests. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). The best supportive care was provided. Therapeutic plasma exchange (TPE) and 1 mg/kg methylprednisolone treatments were administered. On the 10th day of treatment, LDH level and fragmented red blood cells in peripheral blood smear were decreased, but his direct and indirect bilirubin levels increased despite the fact that he was treated with 1 mg/kg methylprednisolone and TPE. The patient had severe ADAMTS-13 deficiency. After discontinued steroids treatment, his bilirubin level normalized within 4 days. On the 4th day after bilirubin level normalized, vincristine treatment was administered. TPE was also continued. There was no consensus about the optimal schedule for discontinuing plasmapheresis therapy, and also we observed total bilirubin level improvement with discontinued corticosteroid treatment. In this case, corticosteroid treatment was linked with the increase of total bilirubin level in severe ADAMTS-13-deficient TTP patient.

Sayiner|Zeynel Abidin|ZA|
Acik|Didar Yanardag|DY|
Yilmaz|Mehmet|M|
Subari|Salih|S|
Mete|Ayse Ozlem|AO|
Dai|M Sinan|MS|

Corticosteroid treatment
TTP
TPE
Severe ADAMTS-13 deficiency
Hemolysis


Bioengineered three-dimensional co-culture of cancer cells and endothelial cells: A model system for dual analysis of tumor growth and angiogenesis.

Abstract: Angiogenesis marks the transformation of a benign local tumor into a life-threatening disease. Many in vitro assays are available on two-dimensional (2D) platforms, however, limited research has been conducted to investigate the behavior of tumors and endothelial cells (ECs) grown on three-dimensional (3D) platforms. This study provides a 3D co-culture spheroid of tumor cells with ECs to study the interplay between ECs and tumor cells. In a 3D co-culture with HepG2 hepatocellular carcinoma (HCC) cells, ECs differentiate to form tubule networks when in co-culture. Addition of angiogenic factors or angiogenesis inhibitors to the model system enhanced or inhibited endothelial differentiation in the 3D model, enabling investigations of the cellular signaling pathways utilized in HCC development. The 3D model demonstrated similar protein expression levels as a HCC xenograft, as well as exhibited upregulation of essential signaling proteins such as Akt/mTor in the 3D model, which is not reflected in the 2D model. The effects of several anti-angiogenic agents, such as sorafenib, sunitinib, and axitinib were analyzed in the 3D co-culture model by utilizing fluorescent proteins and a fluorescence resonance energy transfer (FRET)-based caspase-3 sensor in the ECs, which can detect apoptosis in real time. The apoptotic capability of a drug to inhibit angiogenesis in the 3D model can be easily distinguished via the FRET sensor, and dual screening of anti-angiogenesis and anti-tumor drugs can be achieved in a single step via the 3D co-culture model. In summary, a 3D co-culture model is constructed, where a HCC tumor microenvironment with a hypoxic core and true gradient penetration of drugs is achieved for drug screening purposes and in vitro studies utilizing a small HCC tumor. Biotechnol. Bioeng. 2017;114: 1865-1877. © 2017 Wiley Periodicals, Inc.

D002454:Cell Differentiation
D049109:Cell Proliferation
D018920:Coculture Techniques
D042783:Endothelial Cells
D056945:Hep G2 Cells
D006801:Humans
D009374:Neoplasms, Experimental
D009389:Neovascularization, Pathologic
D018874:Spheroids, Cellular
D023822:Tissue Engineering
D014407:Tumor Cells, Cultured

endothelial cells
tumor growth
angiogenesis
3D co-culture
FRET
liver cancer


A Backwards-step for Gillick: Trans Children's Inability to Consent to Treatment for Gender Dysphoria-Quincy Bell & Mrs A v The Tavistock and Portman NHS Foundation Trust and Ors [2020] EWHC 3274 (Admin).

Abstract: The case of Quincy Bell & Mrs A v The Tavistock and Portman NHS Foundation Trust and Ors is a judicial review into the treatment practices of the Gender Identity Development Service (GIDS) run by Tavistock and Portman NHS Foundation Trust (Tavistock). The Divisional Court considered whether children and young people with Gender Dysphoria (GD) can ever be Gillick competent to consent to treatment with Puberty Blockers (PBs), and if so whether GIDS provided sufficient information to support an informed consent. This commentary examines the six key areas of the judgment: the nature of GD and its treatment with PBs; the categorisation of PBs as experimental treatment; the high bar set to achieve Gillick competence; the convergence of information provision and competence; the role of parental consent; and finally the protective jurisdiction of the court. The conclusion of the court that transgender children aged under 16 years will find 'enormous difficulties' in reaching the Gillick threshold to be able to consent to PBs, and that even 16- to 17-year olds would benefit from a 'best interests determination' from the court, signals judicial thinking which is markedly protectionist. Considering the broad contemporary stance in healthcare of facilitating competence, valuing patient participation, and respecting rights, I argue that this judgment is out of step. It has implications not only for transgender children, but it may also be a worrying signal of a greater general retreat from Gillick and a corresponding advance in emphasis on judicially determined best interests.

Children
Gender Dysphoria
Gillick Competence
Experimental Treatment
Transgender
Decision-Making


Fabry disease with cardiovascular manifestation in a patient with end-stage renal disease.

Abstract: Fabry disease is a rare X-linked hereditary storage disease caused by a mutation of the gene encoding alpha-galactosidase A. The clinical manifestation of the classical disease form is variable depending on the degree of individual organs involvement, including especially kidney, myocardium, central nervous system (CNS) and skin. We report a case of a 51-year-old man whose diagnostic manifestation was cardiac involvement leading to endomyocardial biopsy, which significantly contributed to the diagnosis. Although at that time he was already 9 years dependent on dialysis with terminal renal failure.

Skopcová|Hana|H| Dostálová|Gabriela|G| Paleček|Tomáš|T| Linhart|Aleš|A| Honsová|Eva|E|

Fabry disease
renal failure
histopathology
hypertrophic cardiomyopathy
kidney failure


Pharmacology of Parsabiv® (etelcalcetide, ONO-5163/AMG 416), a novel allosteric modulator of the calcium-sensing receptor, for secondary hyperparathyroidism in hemodialysis patients.

Abstract: Etelcalcetide hydrochloride (Parsabiv®, ONO-5163/AMG 416) is an allosteric modulator of the calcium (Ca)-sensing receptor that was originally produced by KAI Pharmaceuticals Inc. (now Amgen Inc.). It has recently been approved as the first intravenous calcimimetic agent for secondary hyperparathyroidism (SHPT) in many countries. Etelcalcetide is an intravenous injectable drug that can be administered and eliminated through the dialysis circuit in chronic kidney disease patients. In the present study, we evaluated the in vitro pharmacological profile and in vivo parathyroid hormone (PTH)- and Ca-lowering activities of etelcalcetide in a rat 5/6 nephrectomy model of chronic renal insufficiency with SHPT. Etelcalcetide increased the intracellular Ca concentration in HEK-293T cells expressing human Ca-sensing receptor with an EC50 value (95% confidence interval) of 0.53 μM (0.28-1.0 μM) and suppressed PTH secretion from rat parathyroid gland cells with 0.36 μM (0.24-0.54 μM) by activating Ca-sensing receptor. The specificity of etelcalcetide was evaluated by examining its ability to stimulate or inhibit radioligand binding to a panel of 34 off-target proteins. There were no significant changes in the presence of 10 μM etelcalcetide. Furthermore, in a rat 5/6 nephrectomy model of chronic renal insufficiency with SHPT, single intravenous administration of etelcalcetide at 0.3, 1.0, and 3.0 mg/kg decreased plasma PTH and serum Ca levels. Taken together, the present findings identify etelcalcetide as a calcimimetic with potent PTH- and Ca-lowering effects via Ca-sensing receptor agonist activity.

Harada|Kazutsune|K| Fujioka|Aiko|A| Konno|Masakazu|M| Inoue|Atsuto|A| Yamada|Hiroyuki|H| Hirota|Yasushi|Y|

ONO-5163/AMG 416
Calcium-sensing receptor
Secondary hyperparathyroidism
Calcimimetic


Cell-type-specific binocular vision guides predation in mice.

Abstract: Predators use vision to hunt, and hunting success is one of evolution's main selection pressures. However, how viewing strategies and visual systems are adapted to predation is unclear. Tracking predator-prey interactions of mice and crickets in 3D, we find that mice trace crickets with their binocular visual fields and that monocular mice are poor hunters. Mammalian binocular vision requires ipsi- and contralateral projections of retinal ganglion cells (RGCs) to the brain. Large-scale single-cell recordings and morphological reconstructions reveal that only a small subset (9 of 40+) of RGC types in the ventrotemporal mouse retina innervate ipsilateral brain areas (ipsi-RGCs). Selective ablation of ipsi-RGCs (<2% of RGCs) in the adult retina drastically reduces the hunting success of mice. Stimuli based on ethological observations indicate that five ipsi-RGC types reliably signal prey. Thus, viewing strategies align with a spatially restricted and cell-type-specific set of ipsi-RGCs that supports binocular vision to guide predation.

Johnson|Keith P|KP|
Fitzpatrick|Michael J|MJ|
Zhao|Lei|L|
Wang|Bing|B|
McCracken|Sean|S|
Williams|Philip R|PR|
Kerschensteiner|Daniel|D|

D000818:Animals
D003867:Depth Perception
D007839:Functional Laterality
D051379:Mice
D011235:Predatory Behavior
D012165:Retinal Ganglion Cells
D015348:Vision, Binocular
D014795:Visual Pathways

hunting
ganglion cell
retina
depth perception
ipsilateral projection
prey capture
stereopsis