State-trait influences of Vipassana meditation practice on P3 EEG dynamics.

Abstract: Several studies have demonstrated that meditation naïve subjects can, in just a few weeks, become proficient enough in meditation to show cognitive improvements accompanied with functional and structural changes in the brain. Would long-term exposure to qualitatively different levels of meditative training bring about differences in cognitive processing? Would meditation prior to task performance help separate out these differences? Could the nature of the task influence the findings related to cognitive enhancements? To address these questions, we evaluated cognitive functions in three groups of experienced Vipassana practitioners (Novices: n=22, Mean±SD meditation experience=989±595h; Senior practitioners: 21, 10,510±5313; Teachers: 16, 14,648±9623) who differed in terms of duration and quality of meditative practice. Specifically, we employed "ANGEL" a gamified multilevel oddball paradigm, to assess P3 event-related potentials (ERPs) and associated EEG dynamics-power spectra, event related spectral perturbations (ERSP) and inter-trial coherence (ITC). In order to elicit the state-trait influences of meditation, the cognitive task was performed after the participants had undergone an hour long traditional meditation session. All participants could perform the task well and the gross ERP waveforms were similar for the three groups. As hypothesized, we found distinct state-trait influences of meditation leading to graded differences in P3 EEG dynamics. Specifically, we found reduced theta synchrony, enhanced alpha de-synchrony and lesser theta-alpha coherence in the more proficient meditators. Post hoc analyses revealed several differences between the novice and teacher groups but not as many between novice and seniors suggesting that the senior meditators formed an intermediate group. Our study demonstrates that both quantity and quality of meditation influence EEG dynamics during cognitive processing and that meditation prior to a task can provide additional state-trait effects involved in meeting the specific cognitive demands.

Kakumanu|Ratna Jyothi|RJ|
Nair|Ajay Kumar|AK|
Sasidharan|Arun|A|
John|John P|JP|
Mehrotra|Seema|S|
Panth|Ravindra|R|
Kutty|Bindu M|BM|

Vipassana
Proficiency
Cognition
Event-related potentials
Attention
Neural plasticity


Anesthesia Learning in the Digital Age: Are Program Directors and Residents on the Same Page?

Abstract:
Background
In our current digital age, textbooks have been supplemented or supplanted by multiple online modalities for knowledge acquisition. Trainees, often from a younger generation than their program directors (PDs), prefer asynchronous options such as podcasts, videos, and question banks. We sought to identify whether an educational gap exists between PDs and trainees regarding what is assigned and what is used.

Methods
A national cross-sectional survey was conducted in the United States in 2018-2019 to characterize anesthesiology resident and PD perceptions of academic knowledge acquisition.

Results
Of the 149 PDs, 85 completed the survey (57%). Of the 85 PDs, 36 forwarded the survey to residents. Of the 1414 residents who received the survey, 503 residents responded to the survey (36%). The PDs thought residents used didactics, assigned reading, and scheduled simulations more than residents reported (P < .001). Residents reported using self-directed learning more (P = .004). Most residents (74.1%) reported using textbooks or online reading materials. Those residents reporting >70th percentile on the In-Training Exam used textbooks or online materials more than those who reported low scores (<30th percentile; P = .001).

Conclusions
There is a discrepancy between PD and resident views on where and how knowledge acquisition occurs. Asynchronous forms of education (especially podcasts) are popular, but they are rarely assigned by programs. Although residents have a wide variety of learning preferences, textbook and online reading may be associated with higher In-Training Exam scores (a common way that knowledge acquisition is measured). The PDs should consider providing multiple options for optimizing knowledge acquisition, including textbook reading, to meet resident preferences and maximize testing success.

Wolpaw|Jed T|JT|
Uhlig|Elizabeth|E|
Isaac|Gillian R|GR|
Dwivedi|Priyanka|P|
Lekowski|Robert W|RW|
Toy|Serkan|S|

Medical education
residency curriculum
residency education
teaching and learning


Novel association between the nonsynonymous A803G polymorphism of the N-acetyltransferase 2 gene and impaired glucose homeostasis in obese children and adolescents.

Abstract:
BACKGROUND
The N-acetyltransferase 2 ( NAT2 ) A803G polymorphism has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin-resistance-related traits.

OBJECTIVE
Evaluate the association of this polymorphism with anthropometric and metabolic parameters in obese children and adolescents.

SUBJECTS
A total of 748 obese children and adolescents were enrolled.

METHODS
Anthropometric and laboratory data were collected. During oral glucose tolerance test, the presence of a possible exaggerated plasma glucose excursion at 1 h (1HPG) or impaired glucose tolerance (IGT) was considered. Homeostasis model assessment, oral disposition index (oDI) and insulinogenic index (IDI) were calculated. Patients were genotyped for the NAT2 A803G polymorphism.

RESULTS
The prevalence of both IGT and elevated-1HPG was higher in children carrying the A803 allele (P = .02 and P = .03). Moreover, this allele was associated with both oDI and IGI reduction (P = .01). No differences among the NAT2 A803G genotypes for the other parameters were shown. Children homozygous for the A allele presented an odds ratio (OR), to show IGT of 4.9 (P = .01). Children both homozygous and heterozygous for the A allele had higher risk to show elevated-1HPG (OR of 2.7, P = .005; and OR = 2.3, P = .005) compared with patients homozygous for the NAT2 803G allele.

CONCLUSIONS
NAT2 A803 allele seems to play a role in worsening the destiny of obese children carrying it, predisposing them to elevated-1HPG and IGT and then to a possible future type 2 diabetes mellitus throughout an impairment of pancreatic β-cellular insulin secretion as suggested by oDI and IGI reduction.

Marzuillo|Pierluigi|P|
Di Sessa|Anna|A|
Umano|Giuseppina Rosaria|GR|
Nunziata|Luigia|L|
Cirillo|Grazia|G|
Perrone|Laura|L|
Miraglia Del Giudice|Emanuele|E|
Grandone|Anna|A|


Structural analysis of a glucoglucuronan derived from laminarin and the mechanisms of its anti-lung cancer activity.

Abstract: Laminarin (LA), a storage glucan, was purified from the brown alga Sargassum thunbergii. After specific oxidation using the stable nitroxyl radical, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), together with NaBr and NaClO, glucoglucuronan (LAO) was obtained. Compositional analysis of LAO showed a molar ratio of glucuronic acid (GlcA) to glucose (Glc) of 12.7: 1. Nuclear magnetic resonance (NMR) and mass spectroscopy (MS) showed LAO to have a backbone of (1 → 3)-linked β-D-GlcpA interspersed with (1 → 3, 1 → 6)-linked β-D-Glcp, that was terminated with β-D-GlcpA. LAO inhibited human lung cancer A549 cell proliferation in vitro. IC50 values at 12 h and 24 h were 2.70 mg/mL and 2.85 mg/mL, respectively. Western blotting showed that TSC2 was up-regulated at an LAO concentration of 3.80 mg/mL. FAK, PI3K, P-AKT and mTOR were down-regulated, indicating LAO inhibited cancer cell proliferation through the FAK/PI3K/AKT/mTOR pathway. Surface plasmon resonance (SPR) studies revealed that LAO showed an IC50 of 0.07 mg/mL inhibiting the binding of heparin to fibroblast growth factor 1 (FGF1) LAO inhibition of heparin binding to FGF2 fluctuated between 15% and 28%, suggesting that LAO inhibits A549 cell proliferation by selectively interacting with FGF1.

Jin|Weihua|W|
He|Xinyue|X|
Wu|Wanli|W|
Bao|Yizhong|Y|
Wang|Sanying|S|
Cai|Min|M|
Zhang|Wenjing|W|
Wang|Chunyu|C|
Zhang|Fuming|F|
Linhardt|Robert J|RJ|
Mao|Genxiang|G|
Zhong|Weihong|W|

D002851:Chromatography, High Pressure Liquid

Glucoglucuronan
Laminarin
Anti-lung cancer activity


Outcomes of IVF cycles coupled with PGS by aCGH of embryos from donor and autologous oocytes, transferred after vitrification to women of advanced maternal age.

Abstract: It is well documented that aneuploidy rate in preimplantation embryos increases with the mother's age, and at the same time the number of oocytes diminishes. Consequently, for patients of advanced maternal age two options are available to overcome these limitations: use of oocytes from young donors, or use of own oocytes coupled with preimplantation genetic screening (PGS) for 24 chromosomes. However, it is not clear which strategy might be more effective. The aim of this retrospective study was to evaluate outcomes of IVF cycles coupled with transfer of vitrified embryos from donor or autologous oocytes, both with or without PGS. Our results demonstrate that while after PGS clinical pregnancy, twin pregnancy and spontaneous abortion rates are similar for embryos from donor and autologous oocytes, these rates are dramatically worse in all cycles without PGS. Therefore, PGS can be recommended as a screening method to all patients of advanced maternal age even when donor oocytes are used.

Fedorova|Elena M|EM|
Shlykova|Svetlana A|SA|
Shunkina|Ksenia V|KV|
Zaitceva|Olga G|OG|
Lapina|Elena N|EN|
Yanchuk|Taras V|TV|
Kalugina|Alla S|AS|

IVF
PGS
aCGH
advanced maternal age
aneuploidy
Preimplantation genetic screening
donor oocytes
clinical pregnancy rate


Hemichorea Associated with CASPR2 Antibody.

Abstract: This letter was written in response to: Ramdhani RA, Frucht SJ. Isolated chorea associated with LGI1 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8MG7MFC.

Vynogradova|Iryna|I|
Savitski|Vitali|V|
Heckmann|Josef G|JG|

hemichorea
CASPR2 antibody
chorea
Choreatic syndrome
paraneoplastic syndrome


Implementation of patient-reported outcome measures and patient-reported experience measures in melanoma clinical quality registries: a systematic review.

Abstract:
OBJECTIVES
To identify patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) in clinical quality registries, for people with cutaneous melanoma, to inform a new Australian Melanoma Clinical Outcomes Registry; and describe opportunities and challenges of routine PROM/PREM collection, especially in primary care.

DESIGN
Systematic review.

PRIMARY AND SECONDARY OUTCOME MEASURES
Which PROMs and PREMs are used in clinical quality registries for people with cutaneous melanoma, how they are collected, frequency of collection, participant recruitment methods and funding models for each registry.

RESULTS
1134 studies were identified from MEDLINE, PreMEDLINE, Embase, PsychInfo, Cochrane Database of Abstracts of Reviews of Effects databases and TUFTS Cost-Effectiveness Analysis Registry, alongside grey literature, from database inception to 5th February 2020. Following screening, 14 studies were included, identifying four relevant registries: Dutch Melanoma Registry, Adelphi Real-World Disease-Specific Programme (Melanoma), Patient-Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship Registry, and Cancer Experience Registry. These used seven PROMs: EuroQol-5 Dimensions, Functional Assessment of Cancer-General (FACT-G) and FACT-Melanoma (FACT-M), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer 30 (EORTC QLQ-C30), Fatigue Assessment Scale Hospital Anxiety and Depression Scale, Patient-Reported Outcome Measures Information System-29 and one PREM; EORTC QLQ-Information Module 26. PROMs/PREMs in registries were reported to improve transparency of care; facilitate clinical auditing for quality assessment; enable cost-effectiveness analyses and create large-scale research platforms. Challenges included resource burden for data entry and potential collection bias toward younger, more affluent respondents. Feedback from patients with melanoma highlighted the relevance of PROMs/PREMs in assessing patient outcomes and patient experiences.

CONCLUSIONS
Clinical registries indicate PROMs/PREMs for melanoma care can be incorporated and address important gaps, however cost and collection bias may limit generalisability.

PROSPERO REGISTRATION NUMBER
CRD42018086737.

Blood|Zachary|Z|
Tran|Anh|A|
Caleo|Lauren|L|
Saw|Robyn|R|
Dieng|Mbathio|M|
Shackleton|Mark|M|0000-0002-7673-4655
Soyer|H Peter|HP|
Arnold|Chris|C|
Mann|Graham J|GJ|
Morton|Rachael L|RL|0000-0001-7834-0572

D000071066:Patient Reported Outcome Measures

clinical audit
dermatological tumours
public health


BCHisto-Net: Breast histopathological image classification by global and local feature aggregation.

Abstract: Breast cancer among women is the second most common cancer worldwide. Non-invasive techniques such as mammograms and ultrasound imaging are used to detect the tumor. However, breast histopathological image analysis is inevitable for the detection of malignancy of the tumor. Manual analysis of breast histopathological images is subjective, tedious, laborious and is prone to human errors. Recent developments in computational power and memory have made automation a popular choice for the analysis of these images. One of the key challenges of breast histopathological image classification at 100× magnification is to extract the features of the potential regions of interest to decide on the malignancy of the tumor. The current state-of-the-art CNN based methods for breast histopathological image classification extract features from the entire image (global features) and thus may overlook the features of the potential regions of interest. This can lead to inaccurate diagnosis of breast histopathological images. This research gap has motivated us to propose BCHisto-Net to classify breast histopathological images at 100× magnification. The proposed BCHisto-Net extracts both global and local features required for the accurate classification of breast histopathological images. The global features extract abstract image features while local features focus on potential regions of interest. Furthermore, a feature aggregation branch is proposed to combine these features for the classification of 100× images. The proposed method is quantitatively evaluated on red a private dataset and publicly available BreakHis dataset. An extensive evaluation of the proposed model showed the effectiveness of the local and global features for the classification of these images. The proposed method achieved an accuracy of 95% and 89% on KMC and BreakHis datasets respectively, outperforming state-of-the-art classifiers.

R|Rashmi|R|
Prasad|Keerthana|K|
Udupa|Chethana Babu K|CBK|

Histopathological images
Image classification
Breast cancer
Image analysis
Computer - aided diagnosis
Convolution neural network
Deep learning


Target induced framework nucleic acid nanomachine with doxorubicin-spherical nucleic acid tags for electrochemical determination of human telomerase activity.

Abstract: A stable and enzyme-free method is described for highly sensitive determination of telomerase activity. It is based on the use of a framework nucleic acid (FNA) nanomachine and doxorubicin-spherical nucleic acid (DSNA) tags. Upon incubation with telomerase, the primer-tetrahedron becomes elongated to form the handed swing arm. The extended swing arm autonomously moves along the predefined track consisting of entropy-tetrahedron by consecutive strand displacement under the aid of fuel-tetrahedron. As a result, many (entropy-tetrahedron)-(fuel-tetrahedron) complexes are assembled for combining the DSNA tags. This results in an amplified electrochemical signal, typically measured at around -0.63 V (Ag/AgCl). The use of an enzyme-free FNA nanomachine and of DSNA tags warrants outstandingly high stability and sensitivity. The method shows a broad dynamic correlation of telomerase activity in cell extracts. The analytical range extends from 10 to 1.0 × 104 HeLa cells mL-1 with a lower detection limit of 2 cells mL-1. The differences in telomerase activity between different cancer cells can be easily evaluated. The method was further verified by quantifying telomerase activity of cancer cells in accumulated normal cells. Therefore, the sensing method has great potential for clinical application. Graphical abstractSchematic representation of the electrochemical biosensor based on target induced framework nucleic acid nanomachine with doxorubicin-spherical nucleic acids (DSNA) tags, which can be used to the determination of telomerase activity in accumulated normal cells. dNTP: Deoxynucleotide triphosphates; FT: Fuel-tetrahedron.

Shen|Yong|Y| Gong|Jiaomei|J| Xu|Qingxia|Q| Zhou|Lili|L| Sheng|Jiahe|J|

Biosensor
Cyclic voltammetry
Electrochemical impedance spectroscopy
Entropy-driven circuit
Isothermal signal amplification
Nucleic acid shell
Spherical nanoparticle core
Square wave voltammetry
Tetrahedron


A first glance into the nutritional properties of the sea cucumber Parastichopus regalis from the Mediterranean Sea (SE Spain).

Abstract: This work reports for the first time the nutritional profile, including proximate chemical composition, amino acids, fatty acids and minerals of Parastichopus regalis from the Mediterranean Sea (SE Spain). The studied species had a high moisture content, moderate protein and low lipid levels. The most abundant amino acids were glutamic acid, arginine and tyrosine. Polyunsaturated fatty acids, especially arachidonic acid, dominated the fatty acid profile. Iron, sodium, calcium and zinc were the most abundant mine rals. In general, P. regalis has a balanced nutritional quality suitable for human consumption.

D000596:Amino Acids
D000818:Animals
D005227:Fatty Acids
D005231:Fatty Acids, Unsaturated
D008522:Mediterranean Sea
D008903:Minerals
D009753:Nutritive Value
D012616:Sea Cucumbers
D013030:Spain

sea cucumbers
Nutritional profile
polyunsaturated fatty acids


Non-application of the nursing process at a hospital in Accra, Ghana: lessons from descriptive research.

Abstract:
Background
Registered nurses in Ghana are trained to plan the care that they provide to their patients in a systematic and organized manner. This scientific approach to care is known as the nursing process. There is evidence that the nursing process is not being practised by professional nurses in Ghana, as expected. This research seeks to explore what informs nursing interventions in the clinical area.

Methods
A qualitative study was conducted with ten registered nurses; and this was descriptive in nature. One-on-one interviews were conducted with the research participants, as a means of collecting the data. A semi-structured interview guide was used as the data-collecting tool. The collected data were analysed by using latent-content analysis. Three main themes emerged from the data analysis.

Results
It was found that registered nurses did not plan their nursing care. The care that the nurses provided was based on routine nursing care and doctors' orders, both verbal and non-verbal; or written communication were the means whereby the care was provided; and that was communicated among the nurses.

Conclusion
Registered nurses are taught the nursing process; and they are expected to implement the acquired knowledge in the clinical area. The failure of nurses to practise the expected standard of care results in their relying on the decision of other health-care professionals, such as doctors. This makes registered nurses appear to be assistants to doctors. We, therefore, conclude that nurse leaders must supervise nurses to put into practice what they were taught during their training; so that they can have professional autonomy in their practice as nurses. It is also suggested that nurses must show evidence of using the nursing process in their daily work by the use of the nursing care-plan form.

Nurses
Nursing process
Nursing care-plan
Non-usage


Monitoring of strain-dependent responsiveness to TLR activation in the mouse anterior segment using SD-OCT.

Abstract:
PURPOSE
To determine whether spectral-domain optical coherence tomography (SD-OCT) can be used to longitudinally monitor inflammation in the mouse anterior segment and to identify any strain-dependent differences in responsiveness to distinct toll-like receptor (TLR) ligands.

METHODS
Corneal inflammation was induced in BALB/c and C57BL/6 mice following central corneal abrasions and topical application of saline, TLR-4 ligand, lipopolysaccharide (LPS), or TLR-9 ligand, CpG-oligodeoxynucleotide (CpG-ODN; CpG). Anterior-segment images were captured using SD-OCT at baseline, 24 hours, and 1 week post treatment. Corneal thickness, stromal haze, and the number of keratic precipitates (KP) and anterior chamber (AC) cells were longitudinally compared to determine differences between mouse strains, time points, and TLR activation.

RESULTS
In both mouse strains, treatment with CpG, but not saline or LPS, resulted in a similar number of KPs and AC cells. In C57BL/6 mice, central corneal thickness (CCT) increased in CpG- and LPS-treated eyes at 24 hours, which normalized by 1 week. In BALB/c mice, a significant increase in CCT occurred in eyes treated with CpG at 1 week. Stromal haze peaked in C57BL/6 eyes treated with LPS- or CPG-treatment at 24 hours; however, BALB/c eyes showed persistent and marked increases in corneal haze compared with baseline at 1 week post treatment.

CONCLUSIONS
Spectral-domain OCT enables high-resolution, longitudinal, in vivo imaging of anterior segment inflammation in mice and revealed novel strain- and time-dependent differences in response to distinct TLR activation in the cornea.

Downie|Laura Elizabeth|LE|
Stainer|Matthew James|MJ|
Chinnery|Holly Rose|HR|

D000704:Analysis of Variance
D000818:Animals
D000867:Anterior Chamber
D000869:Anterior Eye Segment
D015715:Corneal Edema
D003319:Corneal Stroma
D004195:Disease Models, Animal
D005260:Female
D008070:Lipopolysaccharides
D008137:Longitudinal Studies
D051379:Mice
D008807:Mice, Inbred BALB C
D008810:Mice, Inbred C57BL
D009838:Oligodeoxyribonucleotides
D051197:Toll-Like Receptor 4
D051217:Toll-Like Receptor 9
D041623:Tomography, Optical Coherence

SD-OCT
inflammation
toll-like receptors
imaging
cornea


Sequence Capture versus Restriction Site Associated DNA Sequencing for Shallow Systematics.

Abstract: Sequence capture and restriction site associated DNA sequencing (RAD-Seq) are two genomic enrichment strategies for applying next-generation sequencing technologies to systematics studies. At shallow timescales, such as within species, RAD-Seq has been widely adopted among researchers, although there has been little discussion of the potential limitations and benefits of RAD-Seq and sequence capture. We discuss a series of issues that may impact the utility of sequence capture and RAD-Seq data for shallow systematics in non-model species. We review prior studies that used both methods, and investigate differences between the methods by re-analyzing existing RAD-Seq and sequence capture data sets from a Neotropical bird (Xenops minutus). We suggest that the strengths of RAD-Seq data sets for shallow systematics are the wide dispersion of markers across the genome, the relative ease and cost of laboratory work, the deep coverage and read overlap at recovered loci, and the high overall information that results. Sequence capture's benefits include flexibility and repeatability in the genomic regions targeted, success using low-quality samples, more straightforward read orthology assessment, and higher per-locus information content. The utility of a method in systematics, however, rests not only on its performance within a study, but on the comparability of data sets and inferences with those of prior work. In RAD-Seq data sets, comparability is compromised by low overlap of orthologous markers across species and the sensitivity of genetic diversity in a data set to an interaction between the level of natural heterozygosity in the samples examined and the parameters used for orthology assessment. In contrast, sequence capture of conserved genomic regions permits interrogation of the same loci across divergent species, which is preferable for maintaining comparability among data sets and studies for the purpose of drawing general conclusions about the impact of historical processes across biotas. We argue that sequence capture should be given greater attention as a method of obtaining data for studies in shallow systematics and comparative phylogeography.

Harvey|Michael G|MG|
Smith|Brian Tilston|BT|
Glenn|Travis C|TC|
Faircloth|Brant C|BC|
Brumfield|Robb T|RT|

next-generation sequencing
birds
Allele frequency spectrum
coalescent methods
concordance analysis
massively parallel sequencing
ultraconserved elements


The conundrum of indeterminate QuantiFERON-TB Gold results before anti-tumor necrosis factor initiation.

Abstract:
Background
Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI.

Methods
We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications.

Results
We included 107 and 89 patients with IBD and RA, respectively. We found that a higher proportion of IBD patients had indeterminate QFT-GIT result compared to RA patients. Furthermore, we found that the majority of patients with indeterminate results were tested during an acute flare of IBD (88%) and while taking corticosteroids. Of all patients receiving ≥20 mg equivalent prednisone dose (n=32), 63% resulted in indeterminate QFT-GIT, compared to only 6% indeterminate testing in patients receiving <20 mg of equivalent prednisone dose (n=164, P<0.001). There was no correlation between indeterminate results and age, gender, disease duration, or distribution, or smoking status within each population.

Conclusion
We observed that high-dose corticosteroids may affect QFT-GIT outcomes leading to a high proportion of indeterminate results. We propose that IBD patients should be tested prior to initiation of corticosteroids to avoid equivocal results and prevent potential delays in initiation of anti-TNF medications.

Hakimian|Shahrad|S|
Popov|Yevgeniy|Y|
Rupawala|Abbas H|AH|
Salomon-Escoto|Karen|K|
Hatch|Steven|S|
Pellish|Randall|R|

indeterminate QuantiFERON-TB Gold
inflammatory bowel disease
rheumatoid arthritis
latent TB infection
corticosteroids
IBD flare


SKF-10047, a prototype Sigma-1 receptor agonist, augmented the membrane trafficking and uptake activity of the serotonin transporter and its C-terminus-deleted mutant via a Sigma-1 receptor-independent mechanism.

Abstract: The serotonin transporter (SERT) is functionally regulated via membrane trafficking. Our previous studies have demonstrated that the SERT C-terminal deletion mutant (SERTΔCT) showed a robust decrease in its membrane trafficking and was retained in the endoplasmic reticulum (ER), suggesting that SERTΔCT is an unfolded protein that may cause ER stress. The Sigma-1 receptor (SigR1) has been reported to attenuate ER stress via its chaperone activity. In this study, we investigated the effects of SKF-10047, a prototype SigR1 agonist, on the membrane trafficking and uptake activity of SERT and SERTΔCT expressed in COS-7 cells. Twenty-four hours of SKF-10047 treatment (>200 μM) accelerated SERT membrane trafficking and robustly upregulated SERTΔCT activity. Interestingly, these effects of SKF-10047 on SERT functions were also found in cells in which SigR1 expression was knocked down by shRNA, suggesting that SKF-10047 exerted these effects on SERT via a mechanism independent of SigR1. A cDNA array study identified several candidate genes involved in the mechanism of action of SKF-10047. Among them, Syntaxin3, a member of the SNARE complex, was significantly upregulated by 48 h of SKF-10047 treatment. These results suggest that SKF-10047 is a candidate for ER stress relief.

Asano|Masaya|M| Motoike|Serika|S| Yokota|Chika|C| Usuki|Naoto|N| Yamamoto|Hikaru|H| Urabe|Tomoaki|T| Katarao|Kazusa|K| Hide|Izumi|I| Tanaka|Shigeru|S| Kawamoto|Masashi|M| Irifune|Masahiro|M| Sakai|Norio|N|

D050486:Serotonin Plasma Membrane Transport Proteins

SKF-10047
Sigma-1 receptor
Membrane trafficking
Serotonin transporter


Physical activity outcomes from a randomized trial of a theory- and technology-enhanced intervention for Latinas: the Seamos Activas II study.

Abstract: Latina women report disproportionately high and increasing prevalence of chronic health conditions (obesity, diabetes) related to low physical activity levels. Efforts to date at addressing high rates of physical inactivity in this at-risk population have shown modest success. The original Seamos Saludables (sample size N = 266) was a culturally and linguistically adapted, print-based physical activity intervention that showed significant increases in moderate to vigorous physical activity (MVPA) from baseline to 6 months. However, only 11% of intervention participants reached the national PA guidelines of ≥ 150 min/week of aerobic MVPA. The current study tests the original Seamos Saludables intervention (Original Intervention) against an enhanced iteration Seamos Activas II (Enhanced Intervention). Study aims and intervention refinements focus on increasing the percentage of Latinas meeting national aerobic PA guidelines. For the current study (Seamos Activas II), a randomized controlled trial with (N = 199 participants) of two PA interventions (original intervention, N = 102; vs. enhanced intervention, N = 97) was conducted. Intervention refinements involved further targeting key constructs of the Social Cognitive Theory and incorporating text-message-based strategies for self-monitoring, in response to participant feedback for greater interactivity and accountability. PA assessments were conducted at baseline and 6 months. The sample was predominantly Mexican American (89%) with average age of 43.8 years (SD = 10.11) and mean BMI at baseline was 30.6 (SD = 7.56). There were significant within group increases in MVPA from baseline to 6 months (p < .05) in both Original and Enhanced Intervention arms. However, quantile regression models did not indicate significant differences in 6-month outcomes between conditions controlling for baseline, p = 0.73. There were significant differences between conditions with respect to meeting national guidelines for aerobic MVPA at 6 months, with 57% of Enhanced Intervention participants meeting guidelines compared to 44% of Original Intervention participants, OR = 1.66, 95% CI: 1.09 -2.89. Models suggest trends favoring the enhanced condition for improvements in biomarkers over 6 months. Findings indicate that the intervention enhancements likely helped more Latinas achieve nationally recommended, health enhancing PA levels than the original intervention and showed promise for improving physiological response to exercise.Trial Registration ClinicalTrials.Gov; NCT02630953. Registered 14 December 2015. https://clinicaltrials.gov/ct2/show/NCT02630953 .

Physical activity
Intervention
Biomarkers


POR polymorphisms are associated with 21 hydroxylase deficiency.

Abstract:
PURPOSE
Genotype-phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450  oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiency METHODS: Sequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects.

RESULTS
Prevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4-29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138-1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78-3.92), higher ACTH levels, and younger age at diagnosis.

CONCLUSIONS
Polymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.

Pecori Giraldi|F|F|
Einaudi|S|S|
Sesta|A|A|
Verna|F|F|
Messina|M|M|
Manieri|C|C|
Menegatti|E|E|
Ghizzoni|L|L|

POR
CYP21A2
Congenital adrenal hyperplasia
Genotype–phenotype correlation
SNP


miR-146a interacting with lncRNA EPB41L4A-AS1 and lncRNA SNHG7 inhibits proliferation of bone marrow-derived mesenchymal stem cells.

Abstract: Emerging evidence suggests that microRNA plays a pivotal role in cell proliferation. Our previous research has certified that miR-146a attenuates osteoarthritis through the regulation of cartilage homeostasis. However, little information about the function of miR-146a in bone marrow-derived mesenchymal stem cells (BMSCs) proliferation and the underlying mechanism was available. Therefore, this study aims at investigating the role of miR-146a on the proliferation of BMSCs and the possible mechanisms involved. The function of miR-146a on BMSCs proliferation was studied through overexpression and knockdown of miR-146a or the indicated long noncoding RNAs (lncRNAs) in BMSCs and then the proliferation rate of the BMSCs were detected by Cell Counting Kit-8 assay, colony formation assay. Besides, flow cytometry was used to test the cell cycle state of BMSCs modified by overexpression or knockdown of miR-146a or lncRNA EPB41L4A-AS1 (EPB41L4A Antisense RNA 1) and small nucleolar RNA host gene 7 (SNHG7). The expression level of marker genes involved in modulating cell proliferation was evaluated by quantitative polymerase chain reaction and western blot analysis. We discovered that the knockdown of miR-146a significantly promoted BMSCs proliferation. Moreover, miR-146a could bind to and inhibit endogenous expression of EPB41L4A-AS1 and SNHG7. Further study demonstrated that overexpression of EPB41L4A-AS1 and SNHG7 significantly enhanced proliferation of BMSCs. For the first time, we certified that miR-146a suppressed BMSCs proliferation, but EPB41L4A-AS1 and SNHG7 promoted BMSCs proliferation in the present study. Mechanistically, miR-146a significantly inhibited BMSCs proliferation partly through miR-146a/EPB41L4A-AS1 SNHG7/cell proliferation signaling pathway axis.

Cui|Penglei|P|0000-0003-0319-9273 Zhao|Xiaoying|X| Liu|Jinlong|J| Chen|Xiaodong|X| Gao|Yuan|Y| Tao|Kun|K| Wang|Chuandong|C| Zhang|Xiaoling|X|0000-0002-0134-1347

D018507:Gene Expression Regulation, Developmental

D033681:Mitochondrial Membrane Transport Proteins

miR-146a
lncRNA EPB41L4A-AS1
lncRNA SNHG7
proliferation
BMSCs


Learning to Overexert Cognitive Control in a Stroop Task.

Abstract: How do people learn when to allocate how much cognitive control to which task? According to the Learned Value of Control (LVOC) model, people learn to predict the value of alternative control allocations from features of a situation. This suggests that people may generalize the value of control learned in one situation to others with shared features, even when demands for control are different. This makes the intriguing prediction that what a person learned in one setting could cause them to misestimate the need for, and potentially overexert, control in another setting, even if this harms their performance. To test this prediction, we had participants perform a novel variant of the Stroop task in which, on each trial, they could choose to either name the color (more control-demanding) or read the word (more automatic). Only one of these tasks was rewarded each trial and could be predicted by one or more stimulus features (the color and/or word). Participants first learned colors and then words that predicted the rewarded task. Then, we tested how these learned feature associations transferred to novel stimuli with some overlapping features. The stimulus-task-reward associations were designed so that for certain combinations of stimuli, transfer of learned feature associations would incorrectly predict that more highly rewarded task would be color-naming, even though the actually rewarded task was word-reading and therefore did not require engaging control. Our results demonstrated that participants overexerted control for these stimuli, providing support for the feature-based learning mechanism described by the LVOC model.

Bustamante|Laura|L|0000-0002-2539-0602 Lieder|Falk|F| Musslick|Sebastian|S| Shenhav|Amitai|A| Cohen|Jonathan|J|

Cognitive control
Cognitive plasticity
Metacognitive reinforcement learning
Self-control failure


Male, But Not Female, Alcohol-Dependent African Americans Discount Delayed Gains More Steeply than Propensity-Score Matched Controls.

Abstract:
RATIONALE
Alcohol dependence is known to be associated with steep discounting of delayed rewards, but its relation to the discounting of delayed losses and probabilistic rewards is unclear. Moreover, patterns of alcohol consumption vary considerably between communities, but previous research has not examined the relation between discounting and alcohol dependence in low-income African Americans.

OBJECTIVES
The goal of the present study was to determine whether low-income, alcohol-dependent African Americans differ from controls in the degree to which they discount delayed rewards, delayed losses, or probabilistic rewards.

METHODS
African-American participants, both cases and controls, were recruited from the same low-income neighborhoods, and propensity-score matching was used to further control for demographic differences. Participants performed three tasks that assessed their discounting of hypothetical monetary outcomes: delayed rewards, delayed losses, and probabilistic rewards.

RESULTS
Alcohol-dependent cases discounted delayed gains, but not delayed losses or probabilistic gains, more steeply than their matched controls. The difference in discounting of delayed gains was localized to the male cases, whose discounting was steeper than either the male controls or the female cases; no gender difference was observed between male and female controls.

CONCLUSIONS
The present results extend findings regarding discounting by substance abusers to a previously unstudied group, low-income African Americans, and suggest that in this group at least, alcohol dependence, particularly in males, may be more a reflection of choosing immediate rewards than of ignoring their delayed negative consequences.

Myerson|Joel|J|
Green|Leonard|L|
van den Berk-Clark|Carissa|C|
Grucza|Richard A|RA|

African Americans
Discounting
Delayed gains
Alcohol dependence
Delayed losses
Probabilistic gains
Gender
Income


The importance of seasonal influenza vaccination for people with disabilities during the COVID-19 pandemic.

Abstract: A large proportion of Americans have at least one disability and yet people with disabilities face inequities in health and health care access. Factors associated with underlying disability and health, how they perceive and interact with the world, and where they live, or work may increase the risk people with disabilities face for illness or severe outcomes from seasonal influenza. Given the need to reduce the burden of respiratory illness on a healthcare system already overwhelmed by the COVID-19 pandemic, maximizing seasonal influenza vaccination coverage is particularly important in 2020-2021. It is critical this season to ensure equitable access to influenza vaccination for people with disabilities. Providing influenza vaccination services in the unique places where people with disabilities are living, working, or receiving care during the COVID-19 pandemic is crucial, as well as communicating effectively to people with different types of disabilities.

Peacock|Georgina|G|
Ryerson|A Blythe|AB|
Koppaka|Ram|R|
Tschida|John|J|

Seasonal influenza vaccine
Disability
COVID-19


Hip kinematics and kinetics in persons with and without cam femoroacetabular impingement during a deep squat task.

Abstract:
BACKGROUND
Previous studies have indicated that hip and pelvis kinematics may be altered during functional tasks in persons with femoroacetabular impingement. The purpose of this study was to compare hip and pelvis kinematics and kinetics during a deep squat task between persons with cam femoroacetabular impingement and pain-free controls.

METHODS
Fifteen persons with cam femoroacetabular impingement and 15 persons without cam femoroacetabular impingement performed a deep squat task. Peak hip flexion, abduction, and internal rotation, and mean hip extensor, adductor, and external rotator moments were quantified. Independent t-tests (α<0.05) were used to evaluate between group differences.

FINDINGS
Compared to the control group, persons with cam femoroacetabular impingement demonstrated decreased peak hip internal rotation (15.2° (SD 9.5°) vs. 9.4° (SD 7.8°); P=0.041) and decreased mean hip extensor moments (0.56 (SD 0.12) Nm/kg vs. 0.45 (SD 0.15) Nm/kg; P=0.018). In addition persons in the cam femoroacetabular impingement group demonstrated decreased posterior pelvis tilt during squat descent compared to the control group, resulting in a more anteriorly tilted pelvis at the time peak hip flexion (12.5° (SD 17.1°) vs. 23.0° (SD 12.4°); P=0.024).

INTERPRETATION
The decreased hip internal rotation observed in persons with cam femoroacetabular impingement may be the result of bony impingement. Furthermore, the decrease in posterior pelvis tilt may contribute to impingement by further approximating the femoral head-neck junction with the acetabulum. Additionally, decreased hip extensor moments suggest that diminished hip extensor muscle activity may contribute to decreased posterior pelvis tilt.

Bagwell|Jennifer J|JJ|
Snibbe|Jason|J|
Gerhardt|Michael|M|
Powers|Christopher M|CM|

Hip
Kinematics
Kinetics
Femoroacetabular impingement
Squat
Pelvis


Comparison of 7 T and 3 T vessel wall MRI for the evaluation of intracranial aneurysm wall.

Abstract:
OBJECTIVES
To compare the visibility of intracranial aneurysm wall and thickness quantification between 7 and 3 T vessel wall imaging and evaluate the association between aneurysm size and wall thickness.

METHODS
Twenty-nine patients with 29 unruptured intracranial aneurysms were prospectively recruited for 3D T1-weighted vessel wall MRI at both 3 T and 7 T with 0.53 mm (3 T) and 0.4 mm (7 T) isotropic resolution, respectively. Two neuroradiologists independently evaluated wall visibility (0-5 Likert scale), quantified the apparent wall thickness (AWT) using a semi-automated full-width-half-maximum method, calculated wall sharpness, and measured the wall-to-lumen contrast ratio (CRwall/lumen).

RESULTS
Twenty-four patients with 24 aneurysms were included in this study. 7 T achieved significantly better aneurysm wall visibility than 3 T (3.6 ± 1.1 vs 2.7 ± 0.8, p = 0.003). AWT measured on 3 T and 7 T had a good correlation (averaged r = 0.63 ± 0.19). However, AWT on 3 T was 15% thicker than that on 7 T (0.52 ± 0.07 mm vs 0.45 ± 0.05 mm, p < 0.001). Wall sharpness on 7 T was 57% higher than that on 3 T (1.95 ± 0.32 mm-1 vs 1.24 ± 0.15 mm-1, p < 0.001). CRwall/lumen on 3 T and 7 T was comparable (p = 0.424). AWT on 7 T was positively correlated with aneurysm size (saccular: r = 0.58, q = 0.046; fusiform: r = 0.67, q = 0.049).

CONCLUSIONS
7 T provides better visualization of intracranial aneurysm wall with higher sharpness than 3 T. 3 T overestimates the wall thickness relative to 7 T. Aneurysm wall thickness is positively correlated with aneurysm size. 7 T MRI is a promising tool to evaluate aneurysm wall in vivo.

KEY POINTS
• 7 T provides better visualization of intracranial aneurysm wall with higher sharpness than 3 T. • 3 T overestimates the wall thickness comparing with 7 T. • Aneurysm wall thickness is positively correlated with aneurysm size.

MRI
Intracranial aneurysm
Wall thickness


Myxoid fibroadenomas differ from conventional fibroadenomas: a hypothesis-generating study.

Abstract:
AIMS
Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs.

METHODS AND RESULTS
Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture-microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon histological re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR1A somatic mutation was restricted to the stromal component.

CONCLUSION
MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers.

D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit


Persistent pharmacokinetic challenges to pediatric drug development.

Abstract: The development of new therapeutic agents for the mitigation of pediatric disorders is largely hindered by the inability for investigators to assess pediatric pharmacokinetics (PK) in healthy patients due to substantial safety concerns. Pediatric patients are a clinical moving target for drug delivery due to changes in absorption, distribution, metabolism and excretion (ADME) and the potential for PK related toxicological (T) events to occur throughout development. These changes in ADMET can have profound effects on drug delivery, and may lead to toxic or sub-therapeutic outcomes. Ethical, economical, logistical, and technical barriers have resulted in insufficient investigation of these changes by industrial, regulatory, and academic bodies, leading to the classification of pediatric patients as therapeutic orphans. In response to these concerns, regulatory agencies have incentivized investigation into these ontogenic changes and their effects on drug delivery in pediatric populations. The intent of this review is to briefly present a synopsis of the development changes that occur in pediatric patients, discuss the effects of these changes on ADME and drug delivery strategies, highlight the hurdles that are still being faced, and present some opportunities to overcome these challenges.

Sage|Daniel P|DP|
Kulczar|Christopher|C|
Roth|Wyatt|W|
Liu|Wanqing|W|
Knipp|Gregory T|GT|

pharmacokinetic pediatric ADME PBPK ontogeny


One-Dose Human Papillomavirus Vaccination and the Risk of Genital Warts: A Danish Nationwide Population-based Study.

Abstract:
BACKGROUND
Increasing evidence suggests that 1-dose human papillomavirus (HPV) vaccination may protect significantly against HPV-related disease. We provide nationwide, real-world data on the risk of genital warts (GWs) after <3 vaccine doses.

METHODS
All Danish women born in 1985-2003 were identified, and individual-level vaccination data were retrieved. The cohort was followed up for first occurrence of GWs until 31 December 2016. Using Poisson regression, we calculated incidence rates (IRs) of GWs per 100 000 person-years and IR ratios (IRRs) with corresponding 95% confidence intervals (CIs) for GWs, according to vaccination status, age at first dose, and calendar time.

RESULTS
The cohort comprised 1 076 945 girls and women, of whom 485 408 were vaccinated. For girls initiating vaccination at age 12-14 years and 15-16 years, 1-dose vaccine effectiveness (VE) was 71% (IRR = 0.29; 95% CI, .22-.38) and 62% (0.38; .29-.49), respectively, compared with unvaccinated girls. In the same age groups, 2-dose VE was 78% (IRR, 0.22; 95% CI, .18-.26) and 68% (0.32; .26-.38), respectively. After 2009, the IRRs for 3 versus 1 dose and 2 versus 1 dose increased towards unity over calendar time, being 0.69 (95% CI, .57-.84) and 0.86 (.68-1.08) in 2016, respectively.

CONCLUSIONS
In this study, 1 or 2 doses of quadrivalent HPV vaccine was associated with substantial protection against GWs in girls vaccinated at age ≤16 years. The 1-dose VE approached that of 3 or 2 doses over calendar time, probably reflecting the impact of herd protection.

Baandrup|Louise|L|
Dehlendorff|Christian|C|
Kjaer|Susanne K|SK|

genital warts
HPV
dose
vaccine effectiveness


Data-driven approaches in the investigation of social perception.

Abstract: The complexity of social perception poses a challenge to traditional approaches to understand its psychological and neurobiological underpinnings. Data-driven methods are particularly well suited to tackling the often high-dimensional nature of stimulus spaces and of neural representations that characterize social perception. Such methods are more exploratory, capitalize on rich and large datasets, and attempt to discover patterns often without strict hypothesis testing. We present four case studies here: behavioural studies on face judgements, two neuroimaging studies of movies, and eyetracking studies in autism. We conclude with suggestions for particular topics that seem ripe for data-driven approaches, as well as caveats and limitations.

Adolphs|Ralph|R|
Nummenmaa|Lauri|L|
Todorov|Alexander|A|
Haxby|James V|JV|

social perception
ecological validity
face space
intersubject brain correlation
social neuroscience


Effect of physiological determinants and cardiac disease on plasma adiponectin concentrations in dogs.

Abstract:
BACKGROUND
In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis.

HYPOTHESIS/OBJECTIVES
To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM).

ANIMALS
One hundred and fourteen client-owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège.

METHODS
We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine-specific sandwich ELISA kit.

RESULTS
An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014).

CONCLUSIONS AND CLINICAL IMPORTANCE
Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome.

Damoiseaux|C|C|
Merveille|A-C|AC|
Krafft|E|E|
Da Costa|A M|AM|
Gomart|S|S|
Jespers|P|P|
Michaux|C|C|
Clercx|C|C|
Verhoeven|C|C|
Mc Entee|K|K|

Myxomatous mitral valve disease
Dilated cardiomyopathy
Age
Neuter status
Adipokines


Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities.

Abstract: Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Beavers|Suzanne F|SF|
Pascopella|Lisa|L|
Davidow|Amy L|AL|
Mangan|Joan M|JM|
Hirsch-Moverman|Yael R|YR|
Golub|Jonathan E|JE|
Blumberg|Henry M|HM|
Webb|Risa M|RM|
Royce|Rachel A|RA|
Buskin|Susan E|SE|
Leonard|Michael K|MK|
Weinfurter|Paul C|PC|
Belknap|Robert W|RW|
Hughes|Stephen E|SE|
Warkentin|Jon V|JV|
Welbel|Sharon F|SF|
Miller|Thaddeus L|TL|
Kundipati|Saini R|SR|
Lauzardo|Michael|M|
Barry|Pennan M|PM|
Katz|Dolly J|DJ|
Garrett|Denise O|DO|
Graviss|Edward A|EA|
Flood|Jennifer M|JM|
|||

risk factors
cause of death
death certificates


Sparse Regression in Cancer Genomics: Comparing Variable Selection and Predictions in Real World Data.

Abstract:
Background
Evaluation of gene interaction models in cancer genomics is challenging, as the true distribution is uncertain. Previous analyses have benchmarked models using synthetic data or databases of experimentally verified interactions - approaches which are susceptible to misrepresentation and incompleteness, respectively. The objectives of this analysis are to (1) provide a real-world data-driven approach for comparing performance of genomic model inference algorithms, (2) compare the performance of LASSO, elastic net, best-subset selection,   penalisation and   penalisation in real genomic data and (3) compare algorithmic preselection according to performance in our benchmark datasets to algorithmic selection by internal cross-validation.

Methods
Five large  genomic datasets were extracted from Gene Expression Omnibus. 'Gold-standard' regression models were trained on subspaces of these datasets (  ,  ). Penalised regression models were trained on small samples from these subspaces (  ) and validated against the gold-standard models. Variable selection performance and out-of-sample prediction were assessed. Penalty 'preselection' according to test performance in the other 4 datasets was compared to selection internal cross-validation error minimisation.

Results
-penalisation achieved the highest cosine similarity between estimated coefficients and those of gold-standard models.   -penalised models explained the greatest proportion of variance in test responses, though performance was unreliable in low signal:noise conditions.   also attained the highest overall median variable selection F1 score. Penalty preselection significantly outperformed selection by internal cross-validation in each of 3 examined metrics.

Conclusions
This analysis explores a novel approach for comparisons of model selection approaches in real genomic data from 5 cancers. Our benchmarking datasets have been made publicly available for use in future research. Our findings support the use of   penalisation for structural selection and   penalisation for coefficient recovery in genomic data. Evaluation of learning algorithms according to observed test performance in external genomic datasets yields valuable insights into actual test performance, providing a data-driven complement to internal cross-validation in genomic regression tasks.

genomics
models
Artificial intelligence
computational biology
gene regulatory networks
statistical


Propofol-mediated cardioprotection dependent of microRNA-451/HMGB1 against myocardial ischemia-reperfusion injury.

Abstract: Administration of propofol at the time of reperfusion has shown to protect the heart from ischemia and reperfusion (I/R) injury. The aim of the present study was to investigate the molecular mechanism underling the cardioprotective effect of propofol against myocardial I/R injury (MIRI) in vivo and in vitro. Rat heart I/R injury was induced by ligation of the left anterior descending (LAD) artery for 30 min followed by 2-hr reperfusion. Propofol pretreatment (0.01 mg/g) was performed 10 min before reperfusion. In vitro MIRI was investigated in cultured cardiomyocytes H9C2 following hypoxia/reoxygenation (H/R) injuries. Propofol pretreatment in vitro was achieved in the medium supplemented with 25 μmol/L propofol before H/R injuries. Propofol pretreatment significantly increased miRNA-451 expression, decreased HMGB1 expression, reduced infarct size, and I/R-induced cardiomyocyte apoptosis in rat hearts undergoing I/R injuries. Knockdown of miRNA-451 48 hr before I/R injury was found to increase HMGB1 expression, infarct size, and I/R-induced cardiomyocyte apoptosis in rat hearts in the presence of propofol pretreatment. These in vivo findings were reproduced in vivo that knockdown of miRNA-451 48 hr before H/R injuries increased HMGB1 expression and H/R-induced apoptosis in cultured H9C2 supplemented with propofol. In addition, luciferase activity assays and gain-of-function studies found that propofol could decrease HMGB1, the target of miRNA-541. Taken together our findings provide a first demonstration that propofol-mediated cardioprotection against MIRI is dependent of microRNA-451/HMGB1. The study provides a novel target to prevent I/R injury during propofol anesthesia.

Li|Yu-Mei|YM| Sun|Jin-Guo|JG| Hu|Li-Hua|LH| Ma|Xian-Chun|XC| Zhou|Gang|G| Huang|Xi-Zhao|XZ|0000-0002-9394-4339

propofol-mediated cardioprotection
myocardial ischemia-reperfusion injury
miRNA-451


Point-to-Plane Nonhomogeneous Electric-Field-Induced Simultaneous Formation of Giant Unilamellar Vesicles (GUVs) and Lipid Tubes.

Abstract: It is well-known that homogeneous electric fields can be used to generate giant unilamellar vesicles (GUVs). Herein we report an interesting phenomenon of formation of GUVs and lipid tubes simultaneously using a nonhomogeneous electric field generated by point-to-plane electrodes. The underlying mechanism was analyzed using finite element analysis. The two forces play main roles, that is, the pulling force (F) to drag GUVs into lipid tubes induced by fluid flow, and the critical force (Fc) to prevent GUVs from deforming into lipid tubes induced by electric fields. In the center area underneath the needle electrode, the GUVs were found because F is less than Fc in that region, whereas in the edge area the lipid tubes were obtained because F is larger than Fc. The diffusion coefficient of lipid in the tubes was found to be 4.45 μm(2)  s(-1) using a fluorescence recovery after photobleaching (FRAP) technique. The method demonstrated here is superior to conventional GUV or lipid tube fabrication methods, and has great potential in cell mimic or hollow material fabrication using GUVs and tubes as templates.

Zhu|Chuntao|C| Zhang|Ying|Y| Wang|Yinan|Y| Li|Qingchuan|Q| Mu|Wei|W| Han|Xiaojun|X|


Sonographic patterns of renal lymphoma in B-mode imaging and in contrast-enhanced ultrasound (CEUS)--a retrospective evaluation.

Abstract:
INTRODUCTION
Retrospective analysis of sonographic patterns of renal lymphoma in B-mode imaging and contrast-enhanced ultrasound (CEUS).

PATIENTS/METHODS
From January 2000 to June 2014, 27 patients with clinical or histologically confirmed renal lymphoma were examined with B-mode imaging, followed by CEUS in 8 cases.

RESULTS
In B-mode imaging renal lymphoma were hypoechoic in all 27 cases (100%). 9 patients (33.3%) had a bilateral, 18 (66.7%) patients had an unilateral lymphoma infiltration of the kidneys. 8 (29.6%) cases of small nodular, 5 (18.5%) cases of large nodular and 6 (22.2%) cases of perirenal lymphoma infiltration of the kidney were observed in B-mode imaging. Bulky-formation of renal lymphoma was detected in 6 (22.2%) patients and 2 (7.4%) patients had a diffuse lymphoma infiltration of the kidneys. In CEUS an arterial isoechoic enhancement was observed in 5 (62.5%)- and, an arterial hypoechoic enhancement was observed in 3 (37.5%) cases of renal lymphoma. A hypoechoic enhancement in the parenchymal phase was observed in 8 (100%) cases of renal lymphoma infiltration.

CONCLUSION
In B-mode-imaging, nodular lymphoma infiltration of the kidneys is the most common of all renal lymphoma patterns in B-mode imaging. In CEUS, renal lymphoma presented an arterial iso- or hypoechoic enhancement, followed by a hypoechoic enhancement in the parenchymal phase. In regard to the differentiation of renal lymphoma to benign lesions of the kidney, CEUS may be helpful. However, the differentiation of renal lymphoma from other malignant lesions of the kidney like renal cell carcinoma is not feasible by CEUS.


Data analysis software package for radionuclide standardization with a digital coincidence counting system.

Abstract: The Nuclear Metrology Laboratory (LMN) - IPEN, São Paulo, Brazil - developed a Digital Coincidence System (DCS), based on the Coincidence Counting Methodology, in order to improve its capabilities in radionuclide primary-standardization. Digital process is implemented in two steps: data-acquisition (a set of measurements) and offline software data-analysis and calculation. The present work shows the basics of the data-acquisition unit (Software Coincidence System - SCS), describes the DCS' data-analysis process and the initial approaches chosen for the implementation of the software package (Coincidence Analyzing Task - CAT). 152Eu standardization, performed for DCS testing, software expansion and validation, is briefly discussed.

Brancaccio|F|F|
Dias|M S|MS|
Koskinas|M F|MF|
Moreira|D S|DS|
de Toledo|F|F|

Radionuclide standardization
Software coincidence
Coincidence method
Software tools


Psychometric evaluation of the youth eating disorder examination questionnaire in children with overweight or obesity.

Abstract: This study evaluated the psychometric properties of the Youth Eating Disorder Examination Questionnaire (YEDE-Q) and its utility for detecting loss of control (LOC) eating (i.e., eating episodes, regardless of size, involving a perceived inability to control what or how much one is eating) among school-age children with overweight or obesity. Identifying eating pathology, particularly LOC eating, in this population may facilitate treatment that improves weight outcomes and reduces eating disorder risk. Children with overweight or obesity (N = 241; 7-11 years) completed the YEDE-Q and abbreviated Child EDE (ChEDE) to assess LOC eating, prior to entering a weight management treatment trial. Confirmatory factor analyses (CFA) were conducted on children's YEDE-Q responses and compared to the standard adult EDE-Q factor structure and newer, alternate factor structures. CFA supported a three-factor structure, which distinguished youth with versus without LOC. The YEDE-Q showed low accuracy for detecting LOC eating as measured by the ChEDE, which served as the gold-standard benchmark (AUC = 0.69). Among children who endorsed LOC eating, more episodes per month were reported on the YEDE-Q than ChEDE (p < .001). The YEDE-Q may not have utility as a screener for identifying true cases of LOC eating among school-age children with overweight or obesity. Further evaluation of the YEDE-Q and the alternate three-factor structure is warranted.

Kass|Andrea E|AE|0000-0002-9736-8906
Theim Hurst|Kelly|K|
Kolko|Rachel P|RP|0000-0002-5107-1146
Ruzicka|Elizabeth B|EB|
Stein|Richard I|RI|
Saelens|Brian E|BE|
Welch|R Robinson|RR|
Perri|Michael G|MG|
Schechtman|Kenneth B|KB|
Epstein|Leonard H|LH|
Wilfley|Denise E|DE|

children
overweight
assessment
eating disorder pathology
loss of control eating


Older people and responses to COVID-19: A cross-sectional study of prevention practices and vaccination intention.

Abstract:
BACKGROUND
COVID-19 is a threat to everyone's health and can be especially devastating to older individuals.

AIM
This study examined the behavioural prevention practices against SARS-CoV-2 infection and the intention to vaccinate among older people when the COVID-19 vaccine is on the verge of becoming available.

METHOD
A cross-sectional, online survey was conducted between 14th July and 8th October 2020 among the older people in Malaysia. A questionnaire was designed to assess the practice towards measures preventing SARS-CoV-2 infection, and COVID-19 vaccination attitudes and intention. Socio-demographic characteristics, constructs of a health belief model (HBM), the 6-item state version of the State-Trait Anxiety Inventory (STAI-6) were correlates of the main outcomes.

FINDINGS
The mean score of total preventive measures scores was 13.4 ± 1.7 out of a maximum score of 15, indicating very good prevention practices. By demographics, females, having a tertiary education exhibited higher prevention practices in the univariable analyses. Components of the HBM and being female remain significant correlates of higher prevention practices in multivariable logistic regression analysis (MLRA). A total of 657 (87.1%) participants responded and intend to receive the COVID-19 vaccination. Provider recommendations may improve vaccination uptake (91.6%). MLRA revealed that having a positive vaccination attitude was 16 times more likely to accept the COVID-19 vaccination (OR = 16.10; 95% CI 8.97-28.91). Hearing of someone they know who has COVID-19 serves as a cue to action and significantly influences vaccination (OR = 4.25; 95% CI 1.80-10.03). Participants below 70 years old expressed higher vaccination intention (OR = 2.07; 95% CI 1.19-3.58).

CONCLUSION
The results provide the first evidence for public authorities to target older people vulnerable to compliance with recommended preventive measures against SARS-CoV-2 infections.

older people
COVID-19
prevention practices
vaccination intention


Deep Learning Applied on Next Generation Sequencing Data Analysis.

Abstract: Deep learning is defined as the group of computational techniques allowing for the discovery of latent information within large amounts of data. Recently, many fields have seen the immense potential of deep learning to solve various tasks in ways which outperformed many other traditional methods. Genomic research could be the next frontier to take advantage of deep learning, as it has the perfect combination of vast amounts of data and diverse tasks. Here we present the platform we generated to combine deep learning and genomic sequencing data. We tested the platform on publicly available sequencing data from the gut microbiome of cancer patients. We showed that our platform is capable of classifying patients with higher accuracy than other methods, with some caveats. Overall, we believe genomic research is the next frontline for deep learning as there are exciting avenues waiting to be explored. We think that our platform, presented here, could serve as the basis for such future research.

Deep learning
Computational techniques
Genomic research
Cancer detection


Untying the correlation between apolipoproteins and rheumatoid arthritis.

Abstract:
AIM AND OBJECTIVE
The concentration of lipoproteins and apolipoprotein are extremely low in the synovial fluid of any healthy person as compared to the concentrations in plasma. However, in the synovial fluid of any diseased patient the amount of cholesterol and lipids is sharply increased. The current review defines the role of various apolipoproteins and lipoproteins and their constituent subfractions in the synovial fluid embarking its principal role in rheumatoid arthritis. It also explains the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins in synovial fluid.

MATERIALS AND METHODS
Various research and review articles highlighting the role of apolipoproteins and lipoproteins were procured from medical websites mainly Pubmed, Medline, Science Direct, etc., and studied for the writing of the review paper.

CONCLUSION
Mainly apolipoproteins A-1, B and E are prominently increased in chronic inflammatory joint disorders. Several theories have been proposed to understand the source of increase of lipids and apolipoproteins in synovial fluid of the diseased patients compared to healthy individuals, yet the precise mechanism is still not lucid. Lipoproteins are believed to play both functional role and pathological role in the synovial fluid. The activated T-lymphocytes in patients of RA lead to activation of inflammatory cytokines such as tumor necrosis factor and interleukins which embark to be the principal mechanism for induction of the disease. It can be thus concluded that the apolipoproteins prevent the activation of monocytes by blocking their contact of activation and thus play critical role in management of RA by inhibiting the production of proinflammatory cytokines.

Apolipoproteins
Lipoproteins
Synovial fluid
Cholesterol
Lipids
Joint effusions


Mass spectrometric monitoring of oxidation of aliphatic C6-C8 hydrocarbons and ethanol in low pressure oxygen and air plasmas.

Abstract: Experimental and theoretical studies on the oxidation of saturated hydrocarbons (n-hexane, cyclohexane, n-heptane, n-octane and isooctane) and ethanol in 28 Torr O2 or air plasma generated by a hollow cathode discharge ion source were made. Ions corresponding to [M + 15]+ and [M + 13]+ in addition to [M - H]+ and [M - 3H]+ were detected as major ions where M is the sample molecule. The ions [M + 15]+ and [M + 13]+ were assigned as oxidation products, [M - H + O]+ and [M - 3H + O]+ , respectively. By the tandem mass spectrometry analysis of [M - H + O]+ and [M - 3H + O]+ , H2 O, olefins (and/or cycloalkanes) and oxygen-containing compounds were eliminated from these ions. Ozone as one of the terminal products in the O2 plasma was postulated as the oxidizing reagent. As an example, the reactions of C6 H14+• with O2 and of C6 H13+ (CH3 CH2 CH+ CH2 CH2 CH3 ) with ozone were examined by density functional theory calculations. Nucleophilic interaction of ozone with C6 H13+ leads to the formation of protonated ketone, CH3 CH2 C(=OH+ )CH2 CH2 CH3 . In air plasma, [M - H + O]+ became predominant over carbocations, [M - H]+ and [M - 3H]+ . For ethanol, the protonated acetic acid CH3 C(OH)2+ (m/z 61.03) was formed as the oxidation product. The peaks at m/z 75.04 and 75.08 are assigned as protonated ethyl formate and protonated diethyl ether, respectively, and that at m/z 89.06 as protonated ethyl acetate. Copyright © 2016 John Wiley & Sons, Ltd.

Usmanov|Dilshadbek T|DT|
Chen|Lee Chuin|LC|
Hiraoka|Kenzo|K|
Wada|Hiroshi|H|
Nonami|Hiroshi|H|
Yamabe|Shinichi|S|

oxidation
air plasma
hollow cathode discharge
ozone
DFT calculations
alkanes
oxygen plasma


The changes of T lymphocytes and cytokines in ICR mice fed with Fe3O4 magnetic nanoparticles.

Abstract: The aim of this article is to study the changes inhibited T lymphocytes and cytokines related to the cellular immunity in ICR (imprinting control region) mice fed with Fe(3)O(4) magnetic nanoparticles (Fe(3)O(4)-MNPs). The Fe(3)O(4)-MNPs were synthesized, and their characteristics such as particle size, zeta potential, and X-ray diffraction patterns were measured and determined. All ICR mice were sacrificed after being exposed to 0, 300, 600, and 1200 mg/kg of Fe(3)O(4)-MNPs by single gastric administration for 14 days. Splenocytes proliferation was indicated with stimulate index by MTT assay; release of cytokines in the serum of ICR mice was detected by enzyme-linked immunosorbent assay, and the phenotypic analyses of T-lymphocyte subsets were performed using flow cytometry. Our results indicated that there were no significant differences in splenocyte proliferation and release of cytokines between exposed and control groups. Furthermore, there was no significant difference in the proportions of T-lymphocyte subsets in the low-dose Fe(3)O(4)-MNPs group when compared to the control group, but the proportions of CD3(+)CD4(+) and CD3(+)CD8(+) T-lymphocyte subsets both in the medium- and high-dose Fe(3)O(4)-MNPs groups were higher than those in the control group. It is concluded that a high dose of Fe(3)O(4)-MNPs, to some extent, could influence in vivo immune function of normal ICR mice.

Wang|Jun|J| Chen|Baoan|B| Jin|Nan|N| Xia|Guohua|G| Chen|Yue|Y| Zhou|Ying|Y| Cai|Xiaohui|X| Ding|Jiahua|J| Li|Xiaomao|X| Wang|Xuemei|X|

ICR mice
Fe3O4
magnetic nanoparticles
splenocyte proliferation
release of cytokines
T-lymphocyte subsets


Correlation of clinical signs and symptoms of Behçet's disease with platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR).

Abstract: Behçet's disease (BD) is a chronic disorder that involves multiple organs and is pathologically considered as a form of vasculitis. The current study aims to assess the metric properties of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in assessing BD disease activity. Three-hundred-nineteen patients with BD were enrolled in this cross-sectional study. Demographic and epidemiological data, including IBDDAM, time since the onset, and medication and manifestation history were recorded. Complete blood counts (CBC), NLR, and PLR were assessed by analyzing blood samples. On the last visit, patients were assessed for active manifestations of disease. IBDDAM and ocular IBDAAM scores were calculated for activity of disease in each patient. Both PLR and NLR were higher in patients with active BD (Mann-Whitney U test, p-value < 0.05). Patients with active ocular manifestation had significantly higher NLR and PLR (Mann-Whitney U test, p-value < 0.05). These ratios, however, were not associated with other active BD manifestations. A value of NLR > 2.58 had 46% sensitivity and 85% specificity for the diagnosis of active ocular manifestations (AUC: 0.690). NLR had a significant, though, weak positive correlation with IBDDAM (Spearman's rho = 0.162; p-value < 0.05) and ocular IBDDAM (Spearman's rho = 0.159; p-value < 0.05). Active Behçet's presented with higher NLR and PLR ratios; however, there was only a modest correlation between NLR and BD activity (IBDDAM score). Also, NLR and PLR have significant relationship with ocular features of BD patients.

IBDDAM
Ocular manifestation
Behçet’s disease
Neutrophil to lymphocyte ratio
Platelet to lymphocyte ratio


Steps of care for adolescents with anorexia nervosa-A Delphi study.

Abstract:
OBJECTIVE
Anorexia nervosa (AN) commonly develops during adolescence. Existing literature offers some treatment guidelines, but clear clinical criteria for initial recommendations and steps of care are needed. The aim of the present study was to develop expert consensus for a stepped-care algorithm for treatment of adolescents with AN.

METHOD
The Delphi approach was used to identify clinical parameters that guide initial treatment recommendations and recommendations for transitions between levels of care. The Delphi approach provides a useful expert consensus when empirical data are limited. Individuals with at least 10 years of experience in the field of adolescent AN and membership in one of three professional organizations were recruited. Twenty-five panelists participated in three rounds of iterative online questionnaires.

RESULTS
Consensus was achieved on several features of a treatment algorithm. Hospitalization is recommended when medical instability, suicidality, or acute food refusal are present at any point in treatment. Family-based treatment (FBT) is recommended as the first-line treatment, with a few exceptions. Consensus was not reached on when to transition from a higher level of care to a lower level of care.

DISCUSSION
Expert opinion was used to develop a consensus-based algorithm for care of adolescents with AN. Future research is needed to test whether these recommendations can be used to optimize outcomes for adolescents with AN.

adolescent
Delphi
anorexia nervosa
treatment
algorithm


Seasonal reproductive tactics: annual timing and the capital-to-income breeder continuum.

Abstract: Tactics of resource use for reproduction are an important feature of life-history strategies. A distinction is made between 'capital' breeders, which finance reproduction using stored energy, and 'income' breeders, which pay for reproduction using concurrent energy intake. In reality, vertebrates use a continuum of capital-to-income tactics, and, for many species, the allocation of capital towards reproduction is a plastic trait. Here, we review how trophic interactions and the timing of life-history events are influenced by tactics of resource use in birds and mammals. We first examine how plasticity in the allocation of capital towards reproduction is linked to phenological flexibility via interactions between endocrine/neuroendocrine control systems and the sensory circuits that detect changes in endogenous state, and environmental cues. We then describe the ecological drivers of reproductive timing in species that vary in the degree to which they finance reproduction using capital. Capital can be used either as a mechanism to facilitate temporal synchrony between energy supply and demand or as a means of lessening the need for synchrony. Within many species, an individual's ability to cope with environmental change may be more tightly linked to plasticity in resource allocation than to absolute position on the capital-to-income breeder continuum.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.

life-history
phenology
resource allocation
capital breeding
income breeding


Spatial Period of Laser-Induced Surface Nanoripples on PET Determines Escherichia coli Repellence.

Abstract: Bacterial adhesion and biofilm formation on surfaces are associated with persistent microbial contamination, biofouling, and the emergence of resistance, thus, calling for new strategies to impede bacterial surface colonization. Using ns-UV laser treatment (wavelength 248 nm and a pulse duration of 20 ns), laser-induced periodic surface structures (LIPSS) featuring different sub-micrometric periods ranging from ~210 to ~610 nm were processed on commercial poly(ethylene terephthalate) (PET) foils. Bacterial adhesion tests revealed that these nanorippled surfaces exhibit a repellence for E. coli that decisively depends on the spatial periods of the LIPSS with the strongest reduction (~91%) in cell adhesion observed for LIPSS periods of 214 nm. Although chemical and structural analyses indicated a moderate laser-induced surface oxidation, a significant influence on the bacterial adhesion was ruled out. Scanning electron microscopy and additional biofilm studies using a pili-deficient E. coli TG1 strain revealed the role of extracellular appendages in the bacterial repellence observed here.


Overexpression of MIST1 reverses the epithelial-mesenchymal transition and reduces the tumorigenicity of pancreatic cancer cells via the Snail/E-cadherin pathway.

Abstract: The role of transcription factors in cancer has attracted significant attention. Although genetic models indicate MIST1 functions as a tumor suppressor in mice, its role in human pancreatic cancer is unclear. We explored the expression and function of MIST1 in pancreatic cancer. Analysis of three GEO datasets (GSE16515, GSE15471, and GSE62165) showed MIST1 mRNA was significantly downregulated in human pancreatic cancer compared to normal pancreatic tissues. Moreover, MIST1 protein and mRNA expression were downregulated in pancreatic cancer cell lines compared to normal cells. Immunohistochemistry confirmed MIST1 was downregulated in human pancreatic cancer tissues (n = 47) and associated with differentiation. In vitro, overexpression of MIST1 reduced pancreatic cancer cell growth, migration, and invasion. In vivo, overexpression of MIST1 retarded tumor xenograft growth and decreased tumor cell dissemination to the liver. Furthermore, MIST1 reversed the epithelial-mesenchymal transition by downregulating Snail and upregulating E-cadherin. Knockdown of E-cadherin promoted the migration and invasion of cancer cells overexpressing MIST1. In conclusion, this study indicates restoring the expression of MIST1 reversed the EMT and reduced the tumorigenicity of pancreatic cancer cells partly via the Snail/E-cadherin pathway.

Li|Xiaogang|X| Chen|Hengyu|H| Liu|Zhiqiang|Z| Ye|Zeng|Z| Gou|Shanmiao|S| Wang|Chunyou|C|

D051792:Basic Helix-Loop-Helix Transcription Factors

D015972:Gene Expression Regulation, Neoplastic

D000071250:Snail Family Transcription Factors


A vertical flow paper-microarray assay with isothermal DNA amplification for detection of Neisseria meningitidis.

Abstract: Paper-based biosensors offer a promising technology to be used at the point of care, enabled by good performance, convenience and low-cost. In this article, we describe a colorimetric vertical-flow DNA microarray (DNA-VFM) that takes advantage of the screening capability of DNA microarrays in a paper format together with isothermal amplification by means of Recombinase Polymerase Amplification (RPA). Different assay parameters such as hybridization buffer, flow rate, printing buffer and capture probe concentration were optimized. A limit of detection (LOD) of 4.4 nM was achieved as determined by tabletop scanning. The DNA-VFM was applied as a proof of concept for detection of Neisseria meningitidis, a primary cause of bacterial meningitis. The LOD was determined to be between 38 and 2.1 × 106 copies/VFMassay, depending on the choice of DNA capture probes. The presented approach provides multiplex capabilities of DNA microarrays in a paper-based format for future point-of-care applications.

Rivas|Lourdes|L| Reuterswärd|Philippa|P| Rasti|Reza|R| Herrmann|Björn|B| Mårtensson|Andreas|A| Alfvén|Tobias|T| Gantelius|Jesper|J| Andersson-Svahn|Helene|H|

D021141:Nucleic Acid Amplification Techniques

D020411:Oligonucleotide Array Sequence Analysis

Neisseria meningitidis
Paper-based biosensor
Microarray
Point-of-care
Gold nanoparticles


A rare case of acute pancreatitis caused by Candida Albicans.

Abstract: We experienced a rare case of acute pancreatitis caused by Candida infection. A 52-year-old man was admitted to our hospital with a chief complaint of abdominal pain. Blood tests revealed high amylase and hepatobiliary enzyme abnormalities, and the patient was hospitalized for acute pancreatitis. Abdominal computed tomography showed a 15-mm space-occupying lesion at the parenchyma of the pancreatic head. Endoscopic retrograde cholangiopancreatography was performed after conservative treatment, which revealed a cystic lesion with a suspected solid component inside involving both lower bile duct and pancreatic duct. Cytology of collected bile and pancreatic juice revealed innumerous hyphae and spores morphologically consistent with Candida spp., as did endoscopic ultrasound-guided fine needle aspiration biopsy of the tumor site. Empiric therapy with oral fluconazole resulted in reduction of the space-occupying lesion 3 months after discharge. However, acute pancreatitis recurred about 1 year and 6 months after discharge. After conservative treatment was carried out again, the same lesion was fenestrated by endoscopic sphincteroplasty, and its internal solid components were resected using a basket catheter. Pathological analysis confirmed the presence of fungus balls and degenerated substances. Candida Albicans was identified by fungal culture examination. After the excretion of the fungus balls, pancreatitis did not recur thereafter during outpatient follow-up.

Acute pancreatitis
Candida Albicans
Fungus ball


Cell-based skin substitutes accelerate regeneration of extensive burn wounds in rats.

Abstract:
BACKGROUND
This study investigated the effects of amniotic membrane combined with adipose-derived stem cells or fetal fibroblasts on regenerating extensive burns in rats.

METHODS
Third degree burns of 1100-1800 mm2 were induced on 32 Sprague-Dawley rats. Burned sites were excised and randomly covered with Vaseline gauze (control), human amniotic membrane (HAM), human fetal fibroblasts seeded on HAM (HAM-FF), or human adipose-derived stem cells seeded on HAM (HAM-ASC), and followed by wound closure and histological assessments.

RESULTS
Wound closure rates of HAM-FF, HAM-ASC, HAM and control groups at seven and 14 days after the treatment were 42.2% and 81.9%, 41.9% and 81.7%, 33.5% and 74.2%, and 16.5% and 69.7%, respectively. Wounds of HAM-FF, HAM-ASC, HAM and control groups were closed on 40, 40, 50 and 60 days after the treatment, respectively (P < 0.05). Histological assessments revealed lower inflammatory cell infiltration in HAM-ASC and HAM-FF groups.

CONCLUSIONS
Cell-based engineered skin substitutes seem to accelerate wound regeneration, especially within the first 14 days.

Motamed|Sadrollah|S|
Taghiabadi|Ehsan|E|
Molaei|Hojjat|H|
Sodeifi|Niloofar|N|
Hassanpour|Seyed Esmaeil|SE|
Shafieyan|Saeed|S|
Azargashb|Enzollah|E|
Farajzadeh-Vajari|Fatemeh|F|
Aghdami|Nasser|N|
Bajouri|Amir|A|

Burn
Stem cell
Tissue engineering
Wound healing


Ecological changes as a plausible explanation for differences in uptake of contaminants between European perch and eelpout in a coastal area of the Baltic Sea.

Abstract: Unexpected increasing trends in the concentration of contaminants in European perch (Perca fluviatilis) and in activity of ethoxyresorufin-O-deethylase (EROD) in European perch and eelpout (Zoarces viviparus) have been observed at a Swedish coastal reference site. This study uses data from different sources to investigate plausible explanations. The results showed that a change in diet and an improved overall condition coincide with an increase in mercury in European perch. Furthermore, an increase in several organic contaminants in European perch coincided with the introduction of an invasive deep-burrowing polychaete, which likely contributed to the release of contaminants through bioturbation. The increase in EROD-activity in both species seems to be related to contaminants that reach the fish through the water rather than the diet. The results show that for contaminants that are taken up via the diet, trends in contamination can be opposite for different species of fish in the same area.

Hanson|Niklas|N|
Larsson|Åke|Å|
Parkkonen|Jari|J|
Faxneld|Suzanne|S|
Nyberg|Elisabeth|E|
Bignert|Anders|A|
Henning|Helene Ek|HE|
Bryhn|Andreas|A|
Olsson|Jens|J|
Karlson|Agnes M L|AML|
Förlin|Lars|L|

Mercury EROD-activity Fish Biomarkers Biomonitoring PCB


Whole-genome sequencing to detect mutations associated with resistance to insecticides and Bt proteins in Spodoptera frugiperda.

Abstract: The fall armyworm (FAW), Spodoptera frugiperda, is a major pest native to the Americas that has recently invaded the Old World. Point mutations in the target-site proteins acetylcholinesterase-1 (ace-1), voltage-gated sodium channel (VGSC) and ryanodine receptor (RyR) have been identified in S. frugiperda as major resistance mechanisms to organophosphate, pyrethroid and diamide insecticides respectively. Mutations in the adenosine triphosphate-binding cassette transporter C2 gene (ABCC2) have also been identified to confer resistance to Cry1F protein. In this study, we applied a whole-genome sequencing (WGS) approach to identify point mutations in the target-site genes in 150 FAW individuals collected from China, Malawi, Uganda and Brazil. This approach revealed three amino acid substitutions (A201S, G227A and F290V) of S. frugiperda ace-1, which are known to be associated with organophosphate resistance. The Brazilian population had all three ace-1 point mutations and the 227A allele (mean frequency = 0.54) was the most common. Populations from China, Malawi and Uganda harbored two of the three ace-1 point mutations (A201S and F290V) with the 290V allele (0.47-0.58) as the dominant allele. Point mutations in VGSC (T929I, L932F and L1014F) and RyR (I4790M and G4946E) were not detected in any of the 150 individuals. A novel 12-bp insertion mutation in exon 15 of the ABCC2 gene was identified in some of the Brazilian individuals but absent in the invasive populations. Our results not only demonstrate robustness of the WGS-based genomic approach for detection of resistance mutations, but also provide insights for improvement of resistance management tactics in S. frugiperda.

D019837:Ryanodine Receptor Calcium Release Channel

whole-genome sequencing
Spodoptera frugiperda
Bt resistance
insecticide resistance
mutation detection


The effect of tactile feedback on gait initiation in people with Parkinson's disease: A pilot study.

Abstract:
BACKGROUND
Gait initiation and turning are common triggers for Freezing of Gait (FOG) in people with Parkinson's disease (PD). Recently, it has been shown that closed-loop tactile feedback (CLTF) can be effective to improve turning performance in people with FOG.

RESEARCH QUESTION
Does CLTF change the preparation and execution of the first step during gait initiation?

METHODS
People (n = 36) with PD with FOG (PD + FOG) (n = 18) and without FOG (PD-FOG) (n = 18) were included in the study and performed self-initiated gait with or without CLTF under single and dual task conditions. Anticipatory postural adjustments (APAs) and step kinematics were quantified with inertial measurement units (IMUs). Muscle activity of the right and left tensor fasciae latae (TFL) was measured via EMG recordings.

RESULTS
PD + FOG and PD-FOG did not differ in age, gender and disease duration and severity (p > 0.05). PD + FOG performed smaller APAs (F = 4.559, p = 0.04) with a higher amount of TFL co-contraction (F = 6.034, p = 0.02) compared to PD-FOG. CLTF had no effect on APAs but led to an increase in first step duration (F = 7.921, p = 0.008).

CONCLUSIONS
PD + FOG had smaller APAs and higher left and right TFL co-contraction during gait initiation. CLTF did not impact preparation of the first step but led to a slower execution of the first step. We speculate that, similarly to findings from turning, CLTF might result in the participant attending more closely to the first step compared to without CLTF. Whether increased attention on gait initiation is beneficial in diminishing FOG should be investigated in more detail.

Schlenstedt|Christian|C|
Peterson|Daniel S|DS|
Mancini|Martina|M|

Freezing of gait
Anticipatory postural adjustment
Posture
Cue
Electromyography
Parkinson’s disease
Postural balance
Postural control
Vibration


Multimodal Loading Environment Predicts Bioresorbable Vascular Scaffolds' Durability.

Abstract: Bioresorbable vascular scaffolds were considered the fourth generation of endovascular implants deemed to revolutionize cardiovascular interventions. Yet, unexpected high risk of scaffold thrombosis and post-procedural myocardial infractions quenched the early enthusiasm and highlighted the gap between benchtop predictions and clinical observations. To better understand scaffold behavior in the mechanical environment of vessels, animal, and benchtop tests with multimodal loading environment were conducted using industrial standard scaffolds. Finite element analysis was also performed to study the relationship among structural failure, scaffold design, and load types. We identified that applying the combination of bending, axial compression, and torsion better reflects incidence observed in-vivo, far more than tranditional single mode loads. Predication of fracture locations is also more accurate when at least bending and axial compression are applied during benchtop tests (>60% fractures at connected peak). These structural failures may be initiated by implantation-induced microstructural damages and worsened by cyclic loads from the beating heart. Ignoring the multi-modal loading environment in benchtop fatigue tests and computational platforms can lead to undetected potential design defects, calling for redefining consensus evaluation strategies for scaffold performance. With the robust evaluation strategy presented herein, which exploits the results of in-vivo, in-vitro and in-silico investigations, we may be able to compare alternative designs of prototypes at the early stages of device development and optimize the performance of endovascular implants according to patients-specific vessel dynamics and lesion configurations in the future.

Finite element
Animal study
Coronary stents/scaffolds
Design optimization
Patient-specific
Polylactic acid
Polymer mechanics
Scaffold fracture


Emodin inhibits human sperm functions by reducing sperm [Ca(2+)]i and tyrosine phosphorylation.

Abstract: Emodin, a bioactive anthraquinone widely used in Chinese traditional medicine, disrupts mouse testicular gene expression in vivo. In this study, we investigated the toxicity of emodin to human sperm in vitro. Different doses of emodin (25, 50, 100, 200 and 400μM) were applied to ejaculated human sperm. The results indicated that 100, 200 and 400μM emodin significantly inhibited the total motility, progressive motility and linear velocity of human sperm. In addition, sperm's ability to penetrate viscous medium together with progesterone induced capacitation and acrosome reaction was also adversely affected by emodin. In contrast, emodin did not affect sperm viability. Furthermore, intracellular Ca(2+) concentration ([Ca(2+)]i) and tyrosine phosphorylation, which serve as key regulators of sperm function, were dose-dependently reduced by emodin (50-400μM). These results suggest that emodin inhibits human sperm functions by reducing sperm [Ca(2+)]i and suppressing tyrosine phosphorylation in vitro.

Luo|Tao|T| Li|Na|N| He|Yuan-qiao|YQ| Weng|Shi-qi|SQ| Wang|Tao|T| Zou|Qian-xing|QX| Zeng|Xu-hui|XH|

Emodin
Human sperm functions
Tyrosine phosphorylation
Progesterone
CatSper
[Ca(2+)](i)


In situ assembly in confined spaces of coated particle scaffolds as thermal underfills with extraordinary thermal conductivity.

Abstract: In situ assembly of high thermal conductivity materials in severely confined spaces is an important problem bringing with it scientific challenges but also significant application relevance. Here we present a simple, affordable, and reproducible methodology for synthesizing such materials, composed of hierarchical diamond micro/nanoparticle scaffolds and an ethylenediamine coating. An important feature of the assembly process is the utilization of ethylenediamine as an immobilizing agent to secure the integrity of the microparticle scaffolds during and after each processing step. After other liquid components employed in the scaffolds assembly dry out, the immobilization agent solidifies forming a stable coated particle scaffold structure. Nanoparticles tend to concentrate in the shell and neck regions between adjacent microparticles. The interface between core and shell, along with the concentrated neck regions of nanoparticles, significantly enhance the thermal conductivity, making such materials an excellent candidate as thermal underfills in the electronics industry, where efficient heat removal is a major stumbling block toward increasing packing density. We show that the presented structures exhibit nearly 1 order of magnitude improvement in thermal conductivity, enhanced temperature uniformity, and reduced processing time compared to commercially available products for electronics cooling, which underpins their potential utility.

Hong|Guo|G|
Schutzius|Thomas M|TM|
Zimmermann|Severin|S|
Burg|Brian R|BR|
Zürcher|Jonas|J|
Brunschwiler|Thomas|T|
Tagliabue|Giulia|G|
Michel|Bruno|B|
Poulikakos|Dimos|D|

confined space
thermal conductivity
electronics cooling
hierarchical composite
liquid bridge