Characterizing the Symptoms of Patients with Persistent Post-Treatment Lyme Symptoms: A Survey of Patients at a Lyme Disease Clinic in Rhode Island.

Abstract:
BACKGROUND
10-20% of individuals diagnosed with Lyme disease develop chronic symptoms after antibiotic treatment.

METHODS
A convenience sample of adults with self- reported, persistent post-Lyme treatment symptoms seeking treatment at the Lifespan Lyme Disease Center in Rhode Island completed a demographic and medical survey, the Patient Reported Outcomes Measurement Information System (PROMIS)-29 v2.0, and other short-form PROMIS measures of cognitive function, sleep disturbance, and fatigue.

RESULTS
Compared to average standardized scale scores (T=50; SD=10), participants had mild impairments in physical (T=41) and social (T=42) functioning, mild symptoms of depression (T=56), anxiety (T=60), and sleep disturbance (T=57), and moderate pain interference (T=62), and fatigue (T=65). Participants reported greater symptoms than some other clinical samples including those with cancer and chronic pain. Post-hoc analyses revealed that women reported higher levels of fatigue than men.

CONCLUSIONS
People with persistent post-Lyme treatment symptoms report debilitating symptoms and functional impairments which must be considered in clinical care.

Vargas|Sara E|SE|
McCarthy|Meghan|M|
Boudreau|Matthew|M|
Canfield|Dylan|D|
Reece|Rebecca|R|
Flanigan|Timothy|T|

Lyme disease
patient-reported outcomes
chronic disease
quality of life


Diagnostic Impact of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and White Blood Cell SPECT/Computed Tomography in Patients With Suspected Cardiac Implantable Electronic Device Chronic Infection.

Abstract:
BACKGROUND
Cardiac implantable electronic devices (CIEDs) chronic infection diagnosis is challenging because the clinical presentation is frequently misleading and echocardiography may be inconclusive. The aim of this study was to evaluate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and radiolabeled white blood cells single photon emission CT/CT in a cohort of patients who underwent both scans for suspicion of CIED infection and inconclusive routine investigations.

METHODS
Forty-eight consecutive patients with suspicion of CIED infection who underwent both 18F-fluorodeoxyglucose positron emission tomography/CT and white blood cell single photon emission CT/CT in a time span ≤30 days were retrospectively included. The final diagnosis of CIED infection by the endocarditis expert team was based on the modified Duke-Li classification at the end of follow-up. 18F-Fluorodeoxyglucose positron emission tomography/CT and white blood cell single photon emission CT/CT scans were independently analyzed blinded to the patients' medical record.

RESULTS
In the overall study population, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were respectively 80%, 91%, 80%, and 91% for 18F-fluorodeoxyglucose positron emission tomography/CT and 60%, 100%, 100%, and 85% for white blood cell single photon emission CT/CT. Addition of a positive nuclear imaging scan as a major criterion markedly improved the Duke-Li classification at admission. Semiquantitative parameters did not allow to discriminate between definite and rejected CIED infection. Prolonged antibiotic therapy before imaging tended to decrease the sensitivity for both techniques.

CONCLUSIONS
Nuclear imaging can improve the diagnostic performances of the Duke-Li score at admission in a selected population of patients with suspected CIED infection, particularly when the infection was initially graded as possible. Whenever possible, imaging should be performed before or early after antibiotic initiation.

Calais|Jérémie|J|
Touati|Aziza|A|
Grall|Nathalie|N|
Laouénan|Cédric|C|
Benali|Khadija|K|
Mahida|Besma|B|
Vigne|Jonathan|J|
Hyafil|Fabien|F|
Iung|Bernard|B|
Duval|Xavier|X|
Lepage|Laurent|L|
Le Guludec|Dominique|D|
Rouzet|François|F|

D000072078:Positron Emission Tomography Computed Tomography

D000072098:Single Photon Emission Computed Tomography Computed Tomography

infection
diagnosis
cardiac pacemaker, artificial
implantable cardioverter-defibrillators
positron-emission tomography
radionuclide imaging


Comparison of multi-linear regression, particle swarm optimization artificial neural networks and genetic programming in the development of mini-tablets.

Abstract: In the present study, the preparation of pharmaceutical mini-tablets was attempted in the framework of Quality by Design (QbD) context, by comparing traditionally used multi-linear regression (MLR), with artificially-intelligence based regression techniques (such as standard artificial neural networks (ANNs), particle swarm optimization (PSO) ANNs and genetic programming (GP)) during Design of Experiment (DoE) implementation. Specifically, the effect of diluent type and particle size fraction for three commonly used direct compression diluents (lactose, pregelatinized starch and dibasic calcium phosphate dihydrate, DCPD) blended with either hydrophilic or hydrophobic flowing aids was evaluated in terms of: a) powder blend properties (such as bulk (Y1) and tapped (Y2) density, Carr's compressibility index (Y3, CCI), Kawakita's compaction fitting parameters a (Y4) and 1/b (Y5)), and b) mini-tablet's properties (such as relative density (Y6), average weight (Y7) and weight variation (Y8)). Results showed better flowing properties for pregelatinized starch and improved packing properties for lactose and DPCD. MLR analysis showed high goodness of fit for the Y1, Y2, Y4, Y6 and Y8 with RMSE values of Y1 = 0.028, Y2 = 0.032, Y4 = 0.019, Y6 = 0.015 and Y8 = 0.130; while for rest responses, high correlation was observed from both standard ANNs and GP. PSO-ANNs fitting was the only regression technique that was able to adequately fit all responses simultaneously (RMSE values of Y1 = 0.026, Y2 = 0.022, Y3 = 0.025, Y4 = 0.010, Y5 = 0.063, Y6 = 0.013, Y7 = 0.064 and Y8 = 0.104).

Barmpalexis|Panagiotis|P| Karagianni|Anna|A| Karasavvaides|Grigorios|G| Kachrimanis|Kyriakos|K|

Genetic programming
Mini-tablets
Quality by design (QbD)
Flow properties
DoE optimization
Particle swarm optimization ANNs


Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration.

Abstract: In collective cell migration, directional protrusions orient cells in response to external cues, which requires coordinated polarity among the migrating cohort. However, the molecular mechanism has not been well defined. Drosophila border cells (BCs) migrate collectively and invade via the confined space between nurse cells, offering an in vivo model to examine how group polarity is organized. Here, we show that the front/back polarity of BCs requires Rap1, hyperactivation of which disrupts cluster polarity and induces misoriented protrusions and loss of asymmetry in the actin network. Conversely, hypoactive Rap1 causes fewer protrusions and cluster spinning during migration. A forward genetic screen revealed that downregulation of the Hippo (Hpo) pathway core components hpo or mats enhances the Rap1V12-induced migration defect and misdirected protrusions. Mechanistically, association of Rap1V12 with the kinase domain of Hpo suppresses its activity, which releases Hpo signaling-mediated suppression of F-actin elongation, promoting cellular protrusions in collective cell migration.

Chang|Yu-Chiuan|YC|
Wu|Jhen-Wei|JW|
Hsieh|Yi-Chi|YC|
Huang|Tzu-Han|TH|
Liao|Zih-Min|ZM|
Huang|Yi-Shan|YS|
Mondo|James A|JA|
Montell|Denise|D|
Jang|Anna C-C|AC|

D047908:Intracellular Signaling Peptides and Proteins

Rap1
Border cells
group polarity
Hippo signaling


Clinically Unreported Salmonellosis Outbreak Detected via Comparative Genomic Analysis of Municipal Wastewater Salmonella Isolates.

Abstract: Municipal wastewater includes human waste that contains both commensal and pathogenic enteric microorganisms, and this collective community microbiome can be monitored for community diseases. In a previous study, we assessed the salmonellosis disease burden using municipal wastewater from Honolulu, Hawaii, which was monitored over a 54-week period. During that time, a strain of Salmonella enterica serovar Paratyphi B variant L(+) tartrate(+) (also known as Salmonella enterica serovar Paratyphi B variant Java) was identified; this strain was detected simultaneously with a clinically reported outbreak, and pulsed-field gel electrophoresis patterns were identical for clinical and municipal wastewater isolates. Months after the outbreak subsided, the same pulsotype was detected as the dominant pulsotype in municipal wastewater samples, with no corresponding clinical cases reported. Using genomic characterization (including core single-nucleotide polymorphism alignment, core genome multilocus sequence typing, and screening for virulence and antibiotic resistance genes), all S Java municipal wastewater isolates were determined to be clonal, indicating a resurgence of the original outbreak strain. This demonstrates the feasibility and utility of municipal wastewater surveillance for determining enteric disease outbreaks that may be missed by traditional clinical surveillance methods.IMPORTANCE Underdetection of microbial infectious disease outbreaks in human communities carries enormous health costs and is an ongoing problem in public health monitoring (which relies almost exclusively on data from health clinics). Surveillance of municipal wastewater for community-level monitoring of infectious disease burdens has the potential to fill this information gap, due to its easy access to the mixed community microbiome. In the present study, the genomes of 21 S Java isolates (collected from municipal wastewater in Honolulu) were analyzed; results showed that the same Salmonella strain that caused a known salmonellosis clinical outbreak in spring 2010 remerged as the most dominant strain in municipal wastewater in spring 2011, indicating a new outbreak that was not detected by health clinics. Our results show that wastewater monitoring holds great promise to inform the field of public health regarding outbreak status within communities.

salmonellosis
outbreaks
comparative genomics
wastewater


Targeted Phosphoproteome Analysis Using Selected/Multiple Reaction Monitoring (SRM/MRM).

Abstract: Mass spectrometry-based phosphoproteomics has been rapidly spread based on the advancement of mass spectrometry and development of efficient enrichment techniques for phosphorylated proteins or peptides. Non-targeted approach has been employed in most of the studies for phosphoproteome analysis. However, targeted approach using selected/multiple reaction monitoring (SRM/MRM) is an indispensible technique used for the quantitation of known targets especially when we have many samples to quantitate phosphorylation events on proteins in biological or clinical samples. We herein describe the application of a large-scale phosphoproteome analysis and SRM-based quantitation for the systematic discovery and validation of biomarkers.

Phosphoproteomics
Selected/multiple reaction monitoring
Biomarker
IMAC
Targeted proteomics


The Role of IFN-β during the Course of Sepsis Progression and Its Therapeutic Potential.

Abstract: Sepsis is a complex biphasic syndrome characterized by both pro- and anti-inflammatory immune states. Whereas early sepsis mortality is caused by an acute, deleterious pro-inflammatory response, the second sepsis phase is governed by acute immunosuppression, which predisposes patients to long-term risk for life-threatening secondary infections. Despite extensive basic research and clinical trials, there is to date no specific therapy for sepsis, and mortality rates are on the rise. Although IFN-β is one of the most-studied cytokines, its diverse effects are not fully understood. Depending on the disease or type of infection, it can have beneficial or detrimental effects. As IFN-β has been used successfully to treat diverse diseases, emphasis has been placed on understanding the role of IFN-β in sepsis. Analyses of mouse models of septic shock attribute a pro-inflammatory role to IFN-β in sepsis development. As anti-inflammatory treatments in humans with antibodies to TNF-α or IL1-β resulted disappointing, cytokine modulation approaches were discouraged and neutralization of IFN-β has not been pursued for sepsis treatment. In the case of patients with delayed sepsis and immunosuppression, there is a debate as to whether the use of specific cytokines would restore the deactivated immune response. Recent reports show an association of low IFN-β levels with the hyporesponsive state of monocytes from sepsis patients and after endotoxin tolerance induction. These data, discussed here, project a role for IFN-β in restoring monocyte function and reversing immunosuppression, and suggest IFN-β-based additive immunomodulatory therapy. The dichotomy in putative therapeutic approaches, involving reduction or an increase in IFN-β levels, mirrors the contrasting nature of the early hyperinflammatory state and the delayed immunosuppression phase.

Rackov|Gorjana|G|
Shokri|Rahman|R|
De Mon|Melchor Álvarez|MÁ|
Martínez-A|Carlos|C|
Balomenos|Dimitrios|D|

IFN-β
sepsis
immunosuppression
monocytes
IFN
M1–M2 polarization
macrophages
p21


Regulation of mammalian target of rapamycin complex 1 by Bcl-2 and Bcl-XL proteins.

Abstract: Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and metabolism. Its activity is controlled by various types of signals, including growth factors, nutrients, and stresses. In this study, we show that changes in expression levels of two antiapoptotic proteins, Bcl-2 and Bcl-XL, also affect mTORC1 signaling activity. In cells overexpressing Bcl-XL, mTORC1 activity is increased and becomes less sensitive to growth factor or nutrient conditions. In contrast, reduction in expression levels of the two antiapoptotic proteins inhibits mTORC1 signaling activity. Our results suggest that the effect of Bcl-2 and Bcl-XL on mTORC1 is mediated by FKBP38, an inhibitor of mTORC1. The two proteins compete with mTORC1 for FKBP38 binding and hence alter mTORC1 activity. This study reveals a novel cross-talk between Bcl-2/XL and mTORC1 signaling, which is likely to contribute to cancer development.

Zou|Huafei|H| Lai|Yumei|Y| Zhao|Xuwen|X| Yan|Gonghong|G| Ma|Dongzhu|D| Cardenes|Nayra|N| Shiva|Sruti|S| Liu|Yongjian|Y| Bai|Xiaochun|X| Jiang|Yong|Y| Jiang|Yu|Y|

D000076222:Mechanistic Target of Rapamycin Complex 1

D064549:Myeloid Cell Leukemia Sequence 1 Protein


Tumor grade-related language and control network reorganization in patients with left cerebral glioma.

Abstract: Language processing relies on both a functionally specialized language network and a domain-general cognitive control network. Yet, how the two networks reorganize after damage resulting from diffuse and progressive glioma remains largely unknown. To address this issue, 130 patients with left cerebral gliomas, including 77 patients with low-grade glioma (LGG, WHO grade Ⅰ/II), 53 patients with high-grade glioma (HGG, WHO grade III/IV) and 38 healthy controls (HC) were adopted. The changes in resting-state functional connectivity (rsFC) of the language network and the cingulo-opercular/fronto-parietal (CO-FP) network were examined using network-based statistics. We found that tumor grade negatively correlated with language scores and language network integrity. Compared with HCs, patients with LGGs exhibited slight language deficits, both decreased and increased changes in rsFC of language network, and nearly normal CO-FP network. Patients with HGGs had significantly lower language scores than those with LGG and exhibited more severe language and CO-FP network disruptions than HCs or patients with LGGs. Moreover, we found that in patients with HGGs, the decreased rsFCs of language network were positively correlated with language scores. Together, our findings suggest tumor grade-related network reorganization of both language and control networks underlie the different levels of language impairments observed in patients with gliomas.

Yuan|Binke|B| Zhang|Nan|N| Yan|Jing|J| Cheng|Jingliang|J| Lu|Junfeng|J| Wu|Jinsong|J|

Language
Glioma
Executive function
Plasticity
Resting-state fMRI


Programmed death-ligand 2 (PD-L2) expression in bladder cancer.

Abstract:
OBJECTIVE
Immune checkpoint blockade is an optional and effective therapy for bladder cancer. The present study was aimed to investigate the expression of programmed death ligand-2 (PD-L2) in patients with bladder cancer.

MATERIALS AND METHODS
Paraffin-embedded tissues of 92 patients with bladder cancer were obtained. Then immunohistochemistry of PD-L2 was performed. The expression intensity of PD-L2 was defined with score 0, 1, 2 and 3, in compliance with negative, weak, moderate, and strong, respectively. The association of PD-L2 expression with clinical characteristics was analyzed. A P < 0.05 was considered as significantly different.

RESULTS
By defining the expression intensity of PD-L2 with score 0 to 3, 73.9% of patients (68/92) had a positive expression of PD-L2, and 43.5% (40/92) had a mediate or strong expression. Furthermore, high expression PD-L2 (mediate or strong expression) was more common among patients ≤ 70 y (P = 0.038) and those with smoke history (P = 0.045). The univariate Kaplan-Meier analysis indicated that high expression of PD-L2 was associated with both shorter overall survival (OS) (78.3 vs. 60.3 months; P = 0.037) and shorter disease-free survival (44.3 vs. 22.5 months; P = 0.004). The multivariate COX regression model showed that high expression of PD-L2 was a poor factor of disease-free survival (hazard ratio = 0.537, 95%CI 0.322-0.898; P = 0.018), but not OS (hazard ratio = 0.565, 95%CI 0.253-1.262; P = 0.164).

CONCLUSION
Bladder cancer had a high expression of PD-L2. And high expression of PD-L2 may indicate worse prognosis. It may be a potential immunotherapeutic target of immune checkpoint blockade for bladder cancer.

Yang|Yubo|Y| Wang|Xiaoming|X| Bai|Yunjin|Y| Feng|Dechao|D| Li|Ao|A| Tang|Yin|Y| Wei|Xin|X| Han|Ping|P|

D061027:Programmed Cell Death 1 Ligand 2 Protein

Programmed death-ligand 2
Bladder cancer
Immune checkpoint blockade
Prognosis
Immunotherapy


Analyte-induced photoreduction method for visual and colorimetric detection of tyrosine.

Abstract: A new method based on photochemical formation of silver nanoparticles (AgNPs) was developed for detection of tyrosine (Tyr). To selectively detect Tyr and to simplify the detection procedure, the photoactivity of Tyr was utilized to trigger the photochemical reduction in production of AgNPs. The drastic change of solution color caused by the surface plasmon resonance (SPR) absorption band of the formed AgNPs was used to extract the quantitative information of Tyr. This developed method is simple in detection, while both the sensitivity and selectivity are significant improved. Meanwhile, the solution color was changed from colorless to dark yellow after the formation of AgNPs, which allows a much higher sensitivity in visual identification when compared with the SPR band shifting technique commonly, used in conventional colorimetric methods. To optimize the detection system and to understand the mechanism in this proposed method, parameters such as irradiation time, intensity of light source, and the concentration of Tyr were systematically examined. Results indicated that these factors mainly affected the reaction rate of photoreduction. The morphologies of the formed AgNPs were similar, but with small differences in particle sizes. In the examination of selectivity, sixteen other amino acids were examined. Results indicated that only amino acids of tryptophan, cysteine and histidine are photoactive and possess potential interferences in analysis of Tyr. Quantitative studies indicated that a linear response up to 10 μM with a detection limit of 100 nM could be obtained. For visually detection, color change could be observed with a concentration as low as 500 nM of Tyr.

Photoreduction
Tyrosine
Silver nanoparticles
Colorimetric method
Amino acids


Association between questionnaire- and accelerometer-assessed physical activity: the role of sociodemographic factors.

Abstract: The correlation between objective and self-reported measures of physical activity varies between studies. We examined this association and whether it differed by demographic factors or socioeconomic status (SES). Data were from 3,975 Whitehall II (United Kingdom, 2012-2013) participants aged 60-83 years, who completed a physical activity questionnaire and wore an accelerometer on their wrist for 9 days. There was a moderate correlation between questionnaire- and accelerometer-assessed physical activity (Spearman's r = 0.33, 95% confidence interval: 0.30, 0.36). The correlations were higher in high-SES groups than in low-SES groups (P 's = 0.02), as defined by education (r = 0.38 vs. r = 0.30) or occupational position (r = 0.37 vs. r = 0.29), but did not differ by age, sex, or marital status. Of the self-reported physical activity, 68.3% came from mild activities, 25% from moderate activities, and only 6.7% from vigorous activities, but their correlations with accelerometer-assessed total physical activity were comparable (range of r 's, 0.21-0.25). Self-reported physical activity from more energetic activities was more strongly associated with accelerometer data (for sports, r = 0.22; for gardening, r = 0.16; for housework, r = 0.09). High-SES persons reported more energetic activities, producing stronger accelerometer associations in these groups. Future studies should identify the aspects of physical activity that are most critical for health; this involves better understanding of the instruments being used.

Sabia|Séverine|S|
van Hees|Vincent T|VT|
Shipley|Martin J|MJ|
Trenell|Michael I|MI|
Hagger-Johnson|Gareth|G|
Elbaz|Alexis|A|
Kivimaki|Mika|M|
Singh-Manoux|Archana|A|

physical activity
questionnaires
accelerometry
cohort studies
elderly
epidemiologic methods


Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

Abstract: Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons.

Chao|Yu-Chieh|YC| Xie|Fang|F| Li|Xueyang|X| Guo|Ruijuan|R| Yang|Ning|N| Zhang|Chen|C| Shi|Rong|R| Guan|Yun|Y| Yue|Yun|Y| Wang|Yun|Y|

Dorsal root ganglion
Brain-derived neurotrophic factor
Epigenetics
Opioid-induced hyperalgesia


Influence of angle Kappa on the optimal intraocular orientation of asymmetric multifocal intraocular lenses.

Abstract:
PURPOSE
to evaluate the effects of kappa angle and intraocular orientation on the theoretical performance of asymmetric multifocal intraocular lenses (MIOL).

METHODS
For a total of 21 corneal aberrations, a computational analysis simulated the implantation of a computationally designed MIOL. An image quality parameter (IQ) (visually modulated transfer function metric) was calculated for a 5.0-mm pupil and for three conditions: distance, intermediate, and near vision. The procedure was repeated for each eye after a rotation of the MIOL with respect to the cornea from 0º to 360º in 5º steps. Kappa angles from 0 to 900 microns, in 150 microns steps, combined with two two variants of MIOL centration were tested: in the corneal apex or in the center of the entrance pupil. A p-value ≤ 0.05 was considered significant.

RESULTS
There were statistically significant differences of the IQ depending of the intraocular orientation of the MIOL. If kappa angle was increased, there was a statistically significant decrease of the IQ. The IQ maintained stable when the optimal intraocular orientation was re-calculated for each kappa angle. In general, the inter-variability of the results between subjects was very high. There were no strong evidences supporting that there exists a preferable centration point.

CONCLUSIONS
Our results suggest that kappa angle theoretically affects significantly the performance of asymmetric MIOL implantation. However, its negative effect can be compensated if a customized intraocular orientation is calculated taking into account the presence of the kappa angle.

Bonaque-González|Sergio|S|
Jaskulski|Matt T|MT|
Carmona-Ballester|David|D|
Pareja-Ríos|Alicia|A|
Trujillo-Sevilla|Juan M|JM|

Multifocal intraocular lenses
Kappa angle


Psychophysiological reactivity of currently dental phobic-, remitted dental phobic- and never-dental phobic individuals during exposure to dental-related and other affect-inducing materials.

Abstract: Psychophysiological responses indicating the preparation of defensive behaviour, such as heart rate (HR)-increase and startle-response (SR) potentiation, have often been reported amongst individuals suffering from phobic disorders when exposed to phobia-related information. Although exposure is widely considered the 'gold standard' for treatment of Specific Phobia, it is unclear to what extent psychophysiological defensive response patterns change following treatment, and whether any changes are maintained. We assessed the acoustic SR- and HR-response to neutral, positive, negative and phobia-related pictures and sounds in 41 individuals currently suffering from dental phobia, 22 formerly dental phobic individuals who had remitted following an exposure-based treatment eight months prior to assessment, and 29 control individuals with no history of dental phobia. We observed SR-potentiation to dental-related stimuli in controls combined with HR-deceleration. In contrast, amongst phobic individuals SR-potentiation was accompanied by HR-acceleration to dental pictures. Successfully treated individuals showed inhibited startle reactivity in combination with HR-deceleration to dental related materials of both modalities. Our findings suggest inappropriate fight-flight preparation amongst individuals with dental phobia, reflecting overactivation of the defensive system. However, successful treatment results in inhibited physiological defence preparation, with remitted individuals displaying a response pattern that differed from that of phobic individuals and controls.

Wannemueller|André|A|
Adolph|Dirk|D|
Joehren|Hans-Peter|HP|
Blackwell|Simon E|SE|
Margraf|Jürgen|J|

Specific phobia
Dental phobia
Defence preparation
Cardiac defensive responses
Dental fear
Startle potentiation


Examining the Implications of Social Anxiety in a Community Sample of Mainland Chinese Children.

Abstract:
OBJECTIVE
The purpose of this study was to examine the implications of social anxiety symptoms in a community sample of elementary school children in mainland China.

METHOD
Participants were N = 576 children (309 boys, 267 girls; mean age = 11.52 years, standard deviation = 1.21) attending public elementary schools in Shanghai, People's Republic of China. Multisource assessments included child self-reports, teacher ratings, and school records.

RESULTS
Confirmatory factor analyses replicated the previously established 3-factor solution for the Social Anxiety Scale for Children-Revised. Social anxiety symptoms were associated with indices of internalizing problems, peer difficulties, and poorer school adjustment.

CONCLUSION
Results are discussed in terms of the implications of social avoidance as a particularly maladaptive component of social anxiety in the collectivistic society of China.

Liu|Junsheng|J|
Coplan|Robert J|RJ|
Ooi|Laura L|LL|
Chen|Xinyin|X|
Li|Dan|D|


Nutritional properties of Tempranillo grapevine leaves are affected by clonal diversity, mycorrhizal symbiosis and air temperature regime.

Abstract: Tempranillo grapevine is widely cultivated in Spain and other countries over the world (Portugal, USA, France, Australia, and Argentina, among others) for its wine, but leaves are scarcely used for human or animal nutrition. Since high temperatures affect quality of fruits and leaves in grapevine and the association of Tempranillo with arbuscular mycorrhizal fungi (AMF) enhances the antioxidant properties of berries and leaves, we assessed the effect of elevated air temperature and mycorrhization, separately or combined, on the nutritional properties of Tempranillo leaves at the time of fruit harvest. Experimental assay included three clones (CL-260, CL-1048, and CL-1089) and two temperature regimes (24/14 °C or 28/18 °C day/night) during fruit ripening. Within each clone and temperature regime there were plants not inoculated or inoculated with AMF. The nutritional value of leaves increased under warming climate: elevated temperatures induced the accumulation of minerals, especially in CL-1089; antioxidant capacity and soluble sugars also increased in CL-1089; CL-260 showed enhanced amounts of pigments, and chlorophylls and soluble proteins increased in CL-1048. Results suggested the possibility of collecting leaves together with fruit harvest with different applications of every clone: those from CL-1089 would be adequate for an energetic diet and leaves from CL-260 and CL-1048 would be suitable for culinary processes. Mycorrhization improved the nutritional value of leaves by enhancing flavonols in all clones, hydroxycinnamic acids in CL-1089 and carotenoids in CL-260.

Torres|Nazareth|N|
Antolín|M Carmen|MC|
Garmendia|Idoia|I|
Goicoechea|Nieves|N|

Arbuscular mycorrhizal fungi
Minerals
Pigments
Global warming
Phenolic compounds
Vitis vinifera cv. Tempranillo


Current status of clinical pharmacy workforce, services and clinical pharmacist recruitment in Ho Chi Minh City, Vietnam.

Abstract:
OBJECTIVES
Clinical pharmacy practices in Vietnam have not been well studied. We aimed to describe clinical pharmacy practices in terms of workforce, activities and the recruitment demand for clinical pharmacists (CPs) in hospitals.

METHODS
A cross-sectional survey was conducted, and 123 questionnaires were distributed to Heads/Deputy heads of Pharmacy department and Boards of directors in all of hospitals in Ho Chi Minh City, Vietnam between August 2018 and June 2019.

RESULTS
There were 187 CPs in 79 participating hospitals, whereas the ratio of CPs per 100 patient beds was 0.67. The median number of CPs was 2 (1-4), with a significantly low median full time equivalent [0.4 (1, 2)]. The income of CPs was significantly low. Antibiotics were the most common medications that CPs discussed with physicians (93.06%). Interventions commonly performed by CPs were "Checking drug interactions" (77.78%), "Counseling physicians about the route of administration" (61.11%), "Checking drug allergies" (51.39%). The median number of CPs needed to recruit according to Heads/Deputy heads of Pharmacy Department and Boards of directors was 2 (1-3) and 2 (1-3.5), respectively.

CONCLUSION
The shortage of CPs, which was likely attributable to low income, might lead to numerous obstacles for delivering comprehensive healthcare services. Thus, the hospital recruitment strategies should focus on salary and benefits to attract more CPs, especially those with postgraduate degree.

D003430:Cross-Sectional Studies
D006801:Humans
D010560:Personnel Selection
D010595:Pharmacists
D010607:Pharmacy Service, Hospital
D011361:Professional Competence
D011795:Surveys and Questionnaires
D014505:Urban Population
D014744:Vietnam

clinical pharmacy
services
recruitment
Ho Chi Minh City
Vietnam


Short communication: Methicillin-resistant Staphylococcus aureus in conventional and organic dairy herds in Germany.

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) have been described repeatedly in dairy herds. In this study, we compared the prevalence and antimicrobial resistance of MRSA in bulk tank milk from conventional and organic dairy herds in Germany. Samples were collected from 372 conventional and 303 organic dairy herds throughout Germany. Bulk tank milk (25 mL) was tested for MRSA using an established double selective enrichment method. The MRSA isolates were typed using spa typing and tested for resistance to 19 antimicrobials using the broth microdilution method. Methicillin-resistant Staph. aureus was detected more frequently in bulk tank milk from conventional (9.7%) than from organic (1.7%) dairy herds. Herd size and region were associated with differences in prevalence. Most isolates (38/41) were from spa types associated with the livestock-associated clonal complex CC398. Isolates from conventional herds tended to be more resistant to antimicrobials; however, because of the limited number of isolates from organic herds, no statistical tests were performed. In conclusion, prevalence of MRSA in dairy herds in Germany seems to be increasing and is more prevalent in regions with high livestock density. Organic herds are also affected although at a lower level. Therefore, MRSA should be specifically included in biosecurity protocols for dairy herds, and effective control measures need to be investigated.

Tenhagen|Bernd-Alois|BA| Alt|Katja|K| Pfefferkorn|Beatrice|B| Wiehle|Lars|L| Käsbohrer|Annemarie|A| Fetsch|Alexandra|A|

methicillin-resistant Staphylococcus aureus (MRSA)


Enzyme-free Target Recycling and Double-Output Amplification System for Electrochemiluminescent Assay of Mucin 1 with MoS2 Nanoflowers as Co-reaction Accelerator.

Abstract: In this work, a sensitive electrochemiluminescent assay of mucin 1 (MUC1) was developed with the advantages of target recycling amplification strategy and effective MoS2 nanoflower (MoS2 NF)-based signal probe. Briefly, the target MUC1 triggered enzyme-free recycling and a double-output amplification process was executed to acquire masses of single-stranded DNA as a mimic target, which further participated in the catalytic hairpin assembly process for signal amplification. Meanwhile, MoS2 NFs were prepared as an effective co-reaction accelerator, which not only possessed excellent catalytic performance for H2O2 decomposition to largely enhance the luminous intensity of N-(aminobutyl)- N-(ethylisoluminol) (ABEI)-H2O2 electrochemiluminescence system but also offered a desirable platform for ABEI-functionalized Ag nanoparticles (ABEI-Ag complexes) loading via Ag-S binding. The experimental results showed the proposed aptasensor had a good linear relationship in the range of 1 fg/mL to 10 ng/mL for MUC1 detection and the limit of detection was 0.58 fg/mL (S/N = 3). In addition, the aptasensor had nice stability and selectivity and huge potential to be applied in clinical research.

double-output amplification
electrochemiluminescence
MoS2 nanoflowers
co-reaction accelerator
aptasensor


Resting-state functional network models for posttraumatic stress disorder.

Abstract: Four recent articles were examined for their use of resting-state functional magnetic resonance imaging on participants with posttraumatic symptoms. Theory-driven computations were complemented by the novel use of network metrics, which revealed reduced global centrality and higher efficiency within the default mode network for participants with posttraumatic symptoms. Data-driven methods from other studies revealed associations between functional networks and posttraumatic stress disorder (PTSD) symptoms and clusters of functional activation corresponding to different PTSD presentations.

resting-state
network models
PTSD
fMRI
functional connectivity


Carboxymethylcellulose-chitosan film modified magnetic alkaline Ca-bentonite for the efficient removal of Pb(II) and Cd(II) from aqueous solution.

Abstract: In order to endow alkaline Ca-bentonite (ACB) with magnetic separation ability, simultaneously obtain better magnetic stability and stronger removal capacity of heavy metal cations; magnetic alkaline Ca-bentonite/carboxymethylcellulose-chitosan film (MACB/C-C) was prepared by organic modification of magnetic alkaline Ca-bentonite (MACB) using non-toxic carboxymethylcellulose and chitosan. Textural characterization results revealed that magnetic Fe3O4 nanoparticles were successfully immobilized on ACB and modified with C-C. The functionalized layer of C-C concurrently enhanced the stability of Fe3O4 and removal performances of heavy metal cations. Adsorption results indicated that MACB/C-C exhibited thorough separation from aqueous solution and greater uptake ability for Pb(II) and Cd(II) (483 mg·g-1 and 123 mg·g-1) than the nascent MACB (335 mg·g-1 and 76 mg·g-1), respectively, at pH 5 and 25 °C temperature. The adsorption of Pb(II) and Cd(II) on MACB/C-C mainly occurred via surface precipitation and complexation when pH > 2. MACB/C-C could be efficiently recycled with marginal decrease in adsorption capacity. The current approach credited to the convenient operation, simplified synthesis, and high efficiency of MACB/C-C could be deemed as a promising alternative for the removal of heavy metal cations from wastewater.

Alkaline Ca-bentonite
Magnetic stability
Heavy metals
Carboxymethylcellulose
Adsorption isotherm


The nanostructuring of surfaces and films using interference lithography and chalcogenide photoresist.

Abstract: The reversible and transient photostimulated structural changes in annealed chalcogenide glass (ChG) layers were used to form interference periodic structures on semiconductor surfaces and metal films. It was shown that negative-action etchants based on amines dissolve illuminated parts of a chalcogenide film, i.e., act as positive etchants. The diffraction gratings and 2-D interference structures on germanium ChGs - more environmentally acceptable compounds than traditionally used arsenic chalcogenides - were recorded, and their characteristics were studied.

Dan'ko|Viktor|V| Indutnyi|Ivan|I| Myn'ko|Victor|V| Lukaniuk|Mariia|M| Shepeliavyi|Petro|P|


Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria vaccine design.

Abstract: With drug resistance to available therapeutics continuing to develop against Plasmodium falciparum malaria, the development of an effective vaccine candidate remains a major research goal. Successful interruption of invasion of parasites into erythrocytes during the blood stage of infection will prevent the severe clinical symptoms and complications associated with malaria. Previously studied blood stage antigens have highlighted the hurdles that are inherent to this life-cycle stage, namely that highly immunogenic antigens are also globally diverse, resulting in protection only against the vaccine strain, or that naturally acquired immunity to blood stage antigens do not always correlate with actual protection. The blood stage antigen reticulocyte binding homolog RH5 is essential for parasite viability, has globally limited diversity, and is associated with protection from disease. Here we summarize available information on this invasion ligand and recent findings that highlight its candidacy for inclusion in a blood-stage malaria vaccine.

Ord|Rosalynn L|RL|
Rodriguez|Marilis|M|
Lobo|Cheryl A|CA|

invasion
RH5
malaria vaccine
Plasmodium falciparum
vaccine development


Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: a controlled, blinded crossover study.

Abstract:
CONTEXT
Epidemiological studies and animal research have suggested that air pollution may negatively impact the central nervous system (CNS). Controlled human exposure studies of the effect of air pollution on the brain have potential to enhance our understanding of this relationship and to inform potential biological mechanisms.

OBJECTIVES
Biomarkers of systemic and CNS inflammation may address whether air pollution exposure induces inflammation, with potential for CNS negative effects.

MATERIALS AND METHODS
Twenty-seven healthy adults were exposed to two conditions: filtered air (FA) and diesel exhaust (DE) (300 μg PM2.5/m(3)) for 120 min, in a double-blinded crossover study with exposures separated by four weeks. Prior to and at 0, 3, and 24 h following each exposure, serum and plasma were collected and analyzed for inflammatory cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α), the astrocytic protein S100b, the neuronal cytoplasmic enzyme neuron-specific enolase (NSE), and serum brain-derived neurotrophic factor (BDNF). We hypothesized that IL-6, TNF-α, S100b and NSE would increase, and BDNF would decrease, following DE exposure.

RESULTS
At no time-point following exposure to DE was a significant increase in concentration from baseline seen for IL-6, TNF-α, S100b, or NSE relative to FA exposure. Similarly, no significant decrease in BDNF concentration from baseline was seen following DE exposure, relative to FA. Furthermore, the repeated measures ANOVA considered for all time-points and biomarkers revealed no significant time-exposure interaction.

DISCUSSION AND CONCLUSION
These results suggest that short-term exposure to DE amongst healthy adults does not acutely affect the systemic or CNS biomarkers that we measured.

Cliff|Rachel|R|
Curran|Jason|J|
Hirota|Jeremy A|JA|
Brauer|Michael|M|
Feldman|Howard|H|
Carlsten|Chris|C|

D064568:S100 Calcium Binding Protein beta Subunit

diesel exhaust
neurotoxicity
controlled human exposure
cognition


Impacts of Men's Gender-transformative Personal Narratives: A Qualitative Evaluation of the Men's Story Project.

Abstract: Gender-transformative interventions have been found to help ameliorate gender-inequitable norms and improve health outcomes for women and men. While narrative-based strategies are increasingly being used in public health programs, no evaluation publications exist to date for gender-transformative programming that employs men's public narrative-sharing as a central means for promoting healthy masculinities. The Men's Story Project (MSP) creates live productions in which diverse men publicly perform personal narratives that challenge hegemonic masculinity, promote gender equality, and highlight intersections of masculinity with other social identities. This study draws upon six focus groups with thirty-one audience members (AMs), two weeks after an MSP production at a US public university. The MSP led AMs to reevaluate key pillars of hegemonic masculinity, including a singular conception of masculinity, essentialist notions of gender, restricted emotional expression, and use of violence; AMs also gained an expanded understanding of intersectionality. Directions for future research are discussed.

Peretz|Tal|T|
Lehrer|Jocelyn|J|
Dworkin|Shari L|SL|

narrative
masculinities
performativity
hegemonic masculinity
gender equality
emotion
violence
culture
peer influence
pro-feminism
role models


Seeking natural capital projects: Forest fires, haze, and early-life exposure in Indonesia.

Abstract: Natural capital will be depleted rapidly and excessively if the long-term, offsite impacts of depletion are ignored. By examining the case of tropical forest burning, we illustrate such myopia: Pursuit of short-term economic gains results in air pollution that causes long-term, irreversible health impacts. We integrate longitudinal data on prenatal exposure to the 1997 Indonesian forest fires with child nutritional outcomes and find that mean exposure to air pollution during the prenatal stage is associated with a half-SD decrease in height-for-age z score at age 17, which is robust to several statistical checks. Because adult height is associated with income, this implies a loss of 4% of average monthly wages for approximately one million Indonesian workers born during this period. To put these human capital losses in the context of policy making, we conduct social cost-benefit analyses of oil palm plantations under different scenarios for clearing land and controlling fires. We find that clearing for oil palm plantations using mechanical methods generates higher social net benefits compared with clearing using fires. Oil palm producers, however, would be unwilling to bear the higher private costs of mechanical clearing. Therefore, we need more effective fire bans, fire suppression, and moratoriums on oil palm in Indonesia to protect natural and human capital, and increase social welfare.

D003247:Conservation of Natural Resources

oil palm
cost–benefit analysis
environmental health
health irreversibility
sustainable development


Patient and Surgeon Candidacy for Transoral Endoscopic Thyroid Surgery.

Abstract: The transoral thyroidectomy (TT) is a feasible novel surgical procedure that does not need visible incisions, a truly cutaneous scar-free surgery. Inclusion criteria are (a) patients who have a ultrasonographically (US) estimated thyroid diameter not larger than 10 cm, (b) US estimated gland volume ≤45 mL, (c) nodule size ≤50 mm, (d) a benign tumor, such as a thyroid cyst, single-nodular goiter, or multinodular goiter, (e) follicular neoplasm, and (f) papillary microcarcinoma without evidence of metastasis. The procedure is carried out through a three-port technique placed at the oral vestibule; one 10-mm port for a 30° endoscope and two additional 5-mm ports for dissecting and coagulating instruments. CO2 insufflation pressure is set at 6 mmHg. An anterior cervical subplatysmal space is created from the oral vestibule down to the sternal notch, laterally to the sternocleidomastoid muscle medial edges. TT is done fully endoscopically using conventional endoscopic instruments.

patient and surgeon candidacy
Transoral endoscopic thyroidectomy
learning curve
vestibular approach


Full validation of therapeutic antibody sequences by middle-up mass measurements and middle-down protein sequencing.

Abstract: The regulatory bodies request full sequence data assessment both for innovator and biosimilar monoclonal antibodies (mAbs). Full sequence coverage is typically used to verify the integrity of the analytical data obtained following the combination of multiple LC-MS/MS datasets from orthogonal protease digests (so called "bottom-up" approaches). Top-down or middle-down mass spectrometric approaches have the potential to minimize artifacts, reduce overall analysis time and provide orthogonality to this traditional approach. In this work we report a new combined approach involving middle-up LC-QTOF and middle-down LC-MALDI in-source decay (ISD) mass spectrometry. This was applied to cetuximab, panitumumab and natalizumab, selected as representative US Food and Drug Administration- and European Medicines Agency-approved mAbs. The goal was to unambiguously confirm their reference sequences and examine the general applicability of this approach. Furthermore, a new measure for assessing the integrity and validity of results from middle-down approaches is introduced - the "Sequence Validation Percentage." Full sequence data assessment of the 3 antibodies was achieved enabling all 3 sequences to be fully validated by a combination of middle-up molecular weight determination and middle-down protein sequencing. Three errors in the reference amino acid sequence of natalizumab, causing a cumulative mass shift of only -2 Da in the natalizumab Fd domain, were corrected as a result of this work.

Resemann|Anja|A| Jabs|Wolfgang|W| Wiechmann|Anja|A| Wagner|Elsa|E| Colas|Olivier|O| Evers|Waltraud|W| Belau|Eckhard|E| Vorwerg|Lars|L| Evans|Catherine|C| Beck|Alain|A| Suckau|Detlev|D|

middle-up
middle-down
cetuximab
panitumumab
natalizumab
sequence validation
Biotherapeutics
IgG
top-down protein sequencing


Colocalization of outflow segmentation and pores along the inner wall of Schlemm's canal.

Abstract: All aqueous humor draining through the conventional outflow pathway must cross the endothelium of Schlemm's canal (SC), likely by passing through micron-sized transendothelial pores. SC pores are non-uniformly distributed along the inner wall endothelium, but it is unclear how the distribution of pores relates to the non-uniform or segmental distribution of aqueous humor outflow through the trabecular meshwork. It is hypothesized that regions in the juxtacanalicular tissue (JCT) with higher local outflow should coincide with regions of greater inner wall pore density compared to JCT regions with lower outflow. Three pairs of non-glaucomatous human donor eyes were perfused at 8 mmHg with fluorescent tracer nanospheres to decorate local patterns of outflow segmentation through the JCT. The inner wall was stained for CD31 and/or vimentin and imaged en face using confocal and scanning electron microscopy (SEM). Confocal and SEM images were spatially registered to examine the spatial relationship between inner wall pore density and tracer intensity in the underlying JCT. For each eye, tracer intensity, pore density (n) and pore diameter (D) (for both transcellular "I" and paracellular "B" pores) were measured in 4-7 regions of interest (ROIs; 50 × 150 μm each). Analysis of covariance was used to examine the relationship between tracer intensity and pore density, as well as the relationship between tracer intensity and three pore metrics (nD, nD(2) and nD(3)) that represent the local hydraulic conductivity of the outflow pathway as predicted by various hydrodynamic models. Tracer intensity in the JCT correlated positively with local pore density when considering total pores (p = 0.044) and paracellular B pores on their own (p = 0.016), but not transcellular I-pores on their own (p = 0.54). Local hydraulic conductivity as predicted by the three hydrodynamic models all showed a significant positive correlation with tracer intensity when considering total pores and B-pores (p < 0.0015 and p < 10(-4)) but not I-pores (p > 0.38). These data suggest that aqueous humor passes through micron-sized pores in the inner wall endothelium of SC. Paracellular B-pores appear to have a dominant contribution towards transendothelial filtration across the inner wall relative to transcellular I-pores. Impaired pore formation, as previously described in glaucomatous SC cells, may thereby contribute to greater outflow heterogeneity, outflow obstruction, and IOP elevation in glaucoma.

Braakman|Sietse T|ST|
Read|A Thomas|AT|
Chan|Darren W-H|DW|
Ethier|C Ross|CR|
Overby|Darryl R|DR|

D019408:Platelet Endothelial Cell Adhesion Molecule-1

Segmentation
Pores
Inner wall
Schlemm's canal
Endothelium
Juxtacanalicular tissue
Perfusion
Human eyes


Grading Soft Tissue Involvement in Nasopharyngeal Carcinoma Using Network and Survival Analyses: A Two-Center Retrospective Study.

Abstract:
BACKGROUND
Soft tissue involvement (STI) indicates poor prognosis in nasopharyngeal carcinoma (NPC). However, only a few studies have systematically assessed this extension using network analysis.

PURPOSE
To investigate the prognostic value of STI and to propose an improved STI grading system for NPC therapy.

STUDY TYPE
Retrospective study.

POPULATION
A total of 1225 consecutive patients with pathologically confirmed NPC treated with intensive-modulated radiotherapy from January 2010 to March 2014 were enrolled from two centers.

FIELD STRENGTH/SEQUENCE
T1- and T2-weighted imaging and enhanced T1-weighted imaging with fast spin echo sequence at 1.5 or 3.0 T.

ASSESSMENT
The levator veli palatini and tensor veli palatini involvement were graded "mild," prevertebral muscle involvement, "moderate," medial pterygoid, lateral pterygoid, and the infratemporal fossa involvement, "severe" STI. The above STI sites were evaluated separately by three radiologists using MRI images and graded using network analysis. Overall survival (OS) and progression-free survival (PFS) were assessed.

STATISTICAL TESTS
Kaplan-Meier method, Cox's proportional hazards model, and concordance index (C-index) were used.

RESULTS
Five-year OS and PFS rates between mild and moderate groups (90.5% vs. 81.7%, P < 0.05 and 82.9% vs. 72.5%, P < 0.05, respectively) and between moderate and severe groups (81.7% vs. 70.4%, P < 0.05 and 72.5% vs. 61.2%, P < 0.05, respectively) revealed significant differences. The C-index of the nomogram with STI grading was higher compared with current T-classification (OS 0.641 vs. 0.604, P < 0.05 and PFS 0.605 vs. 0.581, P < 0.05, respectively). Significant OS differences were observed between patients with severe STI who underwent induction chemotherapy (IC) and those who did not (84.5% vs. 70.7%, P < 0.05).

DATA CONCLUSION
STI grading was an independent prognostic factor for OS and PFS in NPC patients and it may be help to improve the accuracy in predicting survival outcomes. Patients with severe STI might benefit from IC to improve OS.

LEVEL OF EVIDENCE
4 TECHNICAL EFFICACY: Stage 2.

Dong|Annan|A| Huang|Wenjie|W| Ma|Huali|H|0000-0003-1369-2897 Cui|Chunyan|C| Zhou|Jian|J| Ruan|Guangying|G| Liang|Shaobo|S| Liu|Lizhi|L|0000-0001-8578-6425 Li|Haojiang|H|0000-0001-5854-3989

nasopharyngeal carcinoma
survival analyses
magnetic resonance imaging
tumor staging


Endothelial Dysfunction Induced by Cadmium and Mercury and its Relationship to Hypertension.

Abstract: Hypertension is an important public health concern that affects millions globally, leading to a large number of morbidities and fatalities. The etiology of hypertension is complex and multifactorial, and it involves environmental factors, including heavy metals. Cadmium and mercury are toxic elements commonly found in the environment, contributing to hypertension. We aimed to assess the role of cadmium and mercury-induced endothelial dysfunction in the development of hypertension. A narrative review was carried out through database searches. In this review, we discussed the critical roles of cadmium and mercury in the etiology of hypertension and provided new insights into potential mechanisms of their effect, focusing primarily on endothelial dysfunction. Although the mechanisms by which cadmium and mercury induce hypertension have yet to be completely elucidated, evidence for both implicates impaired nitric oxide signaling in their hypertensive etiology.

Martins|Airton C|AC|
Santos|Alessanda A D|AAD|
Lopes|Ana C B A|ACBA|
Skalny|Anatoly V|AV|
Aschner|Michael|M|
Tinkov|Alexey A|AA|
Paoliello|Monica M B|MMB|

endothelial dysfunction
Cadmium
mercury
hypertension
heavy metals
nitric oxide


Source discrimination of drug residues in wastewater: The case of salbutamol.

Abstract: Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as "control" drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited number of samples had unexpectedly high concentrations where the EFrel was close to that observed of the un-metabolized, commercially available drug, supporting the idea of an external source of contamination, besides human metabolic excretion. Results showed that, when present, non-metabolic daily loads could be evaluated indicating an average of 4.12g/day of salbutamol extra load due to non-metabolic sources. The stereoselectivity in metabolism and enantiomeric ratio analysis appears to be a useful approach in WBE studies to identify different sources of drugs in the environment, when no metabolic products are present at useful analytical levels.

Depaolini|Andrea Re|AR|
Fattore|Elena|E|
Cappelli|Francesca|F|
Pellegrino|Raffaele|R|
Castiglioni|Sara|S|
Zuccato|Ettore|E|
Fanelli|Roberto|R|
Davoli|Enrico|E|

D000420:Albuterol
D002853:Chromatography, Liquid
D004784:Environmental Monitoring
D057230:Limit of Detection
D016014:Linear Models
D015203:Reproducibility of Results
D013237:Stereoisomerism
D053719:Tandem Mass Spectrometry
D062065:Waste Water
D014874:Water Pollutants, Chemical

Source discrimination
Salbutamol
Wastewater-based epidemiology
Chiral analysis


BMI is inversely correlated to the risk of mortality in patients with type 2 diabetes hospitalized for acute heart failure: Findings from the Gulf aCute heArt failuRE (Gulf-CARE) registry.

Abstract:
BACKGROUND
A U-shaped relationship has been reported between BMI and cardiovascular events among patients with acute heart failure (AHF). We hypothesized that an obesity paradox also governs the relationship between BMI and mortality in patients with type 2 diabetes (T2D) and AHF.

METHODS
We studied 3-month and 12-month mortality in patients with T2D hospitalized for AHF according to 5 BMI categories: Underweight (<20kg/m2), normal weight (referent group, 20-24.9kg/m2), overweight, (25-29.9kg/m2), obese (30-34.9kg/m2) and severely obese (≥35kg/m2), in the Gulf aCute heArt failuRe rEgistry (GULF-CARE).

RESULTS
Among the 5005 participants in this cohort, 2492 (49.8%) had T2D. Underweight patients had a higher 3-month and 12-month mortality risk (OR 2.04, 95% CI [1.02-4.08]; OR 2.44, 95% CI [1.35-4.3]; respectively), compared to normal weight. Severe obesity was associated with a lower 3-month and 12-month mortality risk (OR 0.53, 95% CI [0.34-0.83]; OR 0.58, 95% CI [0.42-0.81]; respectively). After adjustment for several risk variables in 2 different models, the primary outcome was still significantly increased in underweight patients, and decreased in severely obese patients, at 3months and 12months. Further, the odds of mortality decreases with increasing BMI by 0.38 at 3months and at 0.45 at 12months in a near-linear shape (p=0.007; p=0.037; respectively).

CONCLUSIONS
In this cohort of patients with AHF, BMI was inversely correlated to the risk of mortality in patients with T2D. Moreover, severe obesity was associated with less mortality risk.

Abi Khalil|Charbel|C|
Sulaiman|Kadhim|K|
Singh|Rajvir|R|
Jayyousi|Amin|A|
Asaad|Nidal|N|
AlHabib|Khalid F|KF|
Alsheikh-Ali|Alawi|A|
Al-Jarallah|Mohammed|M|
Bulbanat|Bassam|B|
AlMahmeed|Wael|W|
Dargham|Soha|S|
Ridha|Mustafa|M|
Bazargani|Nooshin|N|
Amin|Haitham|H|
Al-Motarreb|Ahmed|A|
AlFaleh|Husam|H|
Elasfar|Abdelfatah|A|
Panduranga|Prashanth|P|
Al Suwaidi|Jassim|J|

BMI
Diabetes
Heart failure
Cardiovascular mortality


Enhanced CO₂ Adsorption on Activated Carbon Fibers Grafted with Nitrogen-Doped Carbon Nanotubes.

Abstract: In this paper, multiscale composites formed by grafting N-doped carbon nanotubes (CNs) on the surface of polyamide (PAN)-based activated carbon fibers (ACFs) were investigated and their adsorption performance for CO₂ was determined. The spaghetti-like and randomly oriented CNs were homogeneously grown onto ACFs. The pre-immersion of cobalt(II) ions for ACFs made the CNs grow above with a large pore size distribution, decreased the oxidation resistance, and exhibited different predominant N-functionalities after chemical vapor deposition processes. Specifically, the CNs grafted on ACFs with or without pre-immersion of cobalt(II) ions were characterized by the pyridine-like structures of six-member rings or pyrrolic/amine moieties, respectively. In addition, the loss of microporosity on the specific surface area and pore volume exceeded the gain from the generation of the defects from CNs. The adsorption capacity of CO₂ decreased gradually with increasing temperature, implying that CO₂ adsorption was exothermic. The adsorption capacities of CO₂ at 25 °C and 1 atm were between 1.53 and 1.92 mmol/g and the Freundlich equation fit the adsorption data well. The isosteric enthalpy of adsorption, implying physical adsorption, indicated that the growth of CNTs on the ACFs benefit CO₂ adsorption.

Chiang|Yu-Chun|YC| Hsu|Wei-Lien|WL| Lin|Shih-Yu|SY| Juang|Ruey-Shin|RS|

adsorption
activated carbon fibers
carbon nanotubes
composites
carbon dioxide


Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies.

Abstract:
BACKGROUND
Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis.

METHODS
Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation.

RESULTS
MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death.

CONCLUSIONS
In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Sepsis
Resuscitation
Critical care outcomes
Lactic acid
Prognosis
Shock


Vitamin B12 Deficiency Observed in Children With First Afebrile Seizures.

Abstract:
OBJECTIVE
Vitamin B12 deficiency can lead to many different types of neurological symptoms and seizure can be seen as the first symptom. In the present study, we aimed to evaluate patients with seizures who were found to have vitamin B12 deficiency and whose seizures resolved with vitamin B12 treatment.

METHODS
A total of 26 infants were included in this retrospective study. The patients were evaluated in terms of clinical findings, laboratory tests including homocysteine, electrophysiological studies, neuroimaging studies, and other neurological examination findings.

RESULTS
Of 26 patients, 14 (53.8%) were male. The mean age of the patients was 8±4.8 months. Sixteen patients had generalized tonic-clonic seizures, and two patients had epileptic spasm (West syndrome)-type seizures. Six patients had abnormal discharge on electroencephalography. Twelve patients had abnormal findings in brain magnetic resonance imaging studies. Homocysteine level was high in all patients at admission.

CONCLUSION
The presence of seizures, including infantile spasm, is a very important and treatable manifestation of vitamin B12 deficiency. Considering the irreversible sequelae of increased homocysteine, vitamin B12 supplementation administered for an appropriate period and at an appropriate dose both prevents the use of unnecessary antiepileptic drugs and eliminates the need for unnecessary tests and examinations.

vitamin b12
seizure
homocysteine
infantile


Synthesis and characterization of electrospun nanofibrous tissue engineering scaffolds generated from in situ polymerization of ionomeric polyurethane composites.

Abstract: Tissue scaffolds need to be engineered to be cell compatible, have timely biodegradable character, be functional with respect to providing niche cell support for tissue repair and regeneration, readily accommodate multiple cell types, and have mechanical properties that enable the simulation of the native tissue. In this study, electrospun degradable polar hydrophobic ionic polyurethane (D-PHI) scaffolds were generated in order to yield an extracellular matrix-like structure for tissue engineering applications. D-PHI oligomers were synthesized, blended with a degradable linear polycarbonate polyurethane (PCNU), and electrospun with simultaneous in situ UV cross-linking in order to generate aligned nanofibrous scaffolds in the form of elastomeric composite materials. The D-PHI/PCNU scaffold fibre morphology, cross-linking efficiency, surface nature, mechanical properties, in vivo degradation and integration, as well as in vitro cell compatibility were characterized. The results showed that D-PHI/PCNU scaffolds had a high cross-linking efficiency, stronger polar nature, and lower stiffness relative to PCNU scaffolds. In vivo, the D-PHI/PCNU scaffold degraded relatively slowly, thereby enabling new tissue time to form and yielding very good integration with the latter tissue. Based on a study with A10 vascular smooth muscle cells, the D-PHI/PCNU scaffold was able to support high cell viability, adhesion, and expression of typical smooth muscle cell markers after a 7-day culture period, which was comparable to PCNU scaffolds. These characterization results demonstrate that the unique properties of a D-PHI/PCNU scaffold, combined with the benefits of electrospinning, could allow for the generation of a tissue engineered scaffold that mimics important aspects of the native extracellular matrix and could be used for functional tissue regeneration. STATEMENT OF SIGNIFICANCE: Tissue engineered scaffolds should recapitulate native extracellular matrix features. This study investigates the processing of a classical polycarbonate polyurethane (PCNU) with a cross-linked and degradable ionomeric polyurethane (D-PHI), polymerized via in situ rapid light curing to yield a 3-dimensional co-electrospun nanofibre matrix with chemical diversity and low modulus character. This research advances the use of D-PHI for tissue engineering applications by providing a facile means of changing physical and chemical properties in classical PCNUs without the need to adjust spinning viscosities of the base polymer. Further, the in vivo and cell culture findings set the stage for introducing unique elastic materials which inherently support wound healing, repair, and regeneration in tissues, for applications that require the recapitulation of native extracellular matrix physical features.

Chan|Jennifer P|JP|
Battiston|Kyle G|KG|
Santerre|J Paul|JP|

D057927:Hydrophobic and Hydrophilic Interactions

D017550:Spectroscopy, Fourier Transform Infrared

Polyurethane
Vascular smooth muscle cell
Tissue regeneration
Ionomer
Surface chemistry


Development of a Novel, Genome Subtraction-Derived, SARS-CoV-2-Specific COVID-19-nsp2 Real-Time RT-PCR Assay and Its Evaluation Using Clinical Specimens.

Abstract: The pandemic novel coronavirus infection, Coronavirus Disease 2019 (COVID-19), has affected at least 190 countries or territories, with 465,915 confirmed cases and 21,031 deaths. In a containment-based strategy, rapid, sensitive and specific testing is important in epidemiological control and clinical management. Using 96 SARS-CoV-2 and 104 non-SARS-CoV-2 coronavirus genomes and our in-house program, GolayMetaMiner, four specific regions longer than 50 nucleotides in the SARS-CoV-2 genome were identified. Primers were designed to target the longest and previously untargeted nsp2 region and optimized as a probe-free real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. The new COVID-19-nsp2 assay had a limit of detection (LOD) of 1.8 TCID50/mL and did not amplify other human-pathogenic coronaviruses and respiratory viruses. Assay reproducibility in terms of cycle threshold (Cp) values was satisfactory, with the total imprecision (% CV) values well below 5%. Evaluation of the new assay using 59 clinical specimens from 14 confirmed cases showed 100% concordance with our previously developed COVID-19-RdRp/Hel reference assay. A rapid, sensitive, SARS-CoV-2-specific real-time RT-PCR assay, COVID-19-nsp2, was developed.

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction

real-time RT-PCR
COVID-19
sensitivity
specificity
SARS-CoV-2
GolayMetaMiner
nsp2
COVID-19-nsp2 assay
clinical evaluation
genome subtraction


Comparison of Anti-Microbial Effects of Low-Level Laser Irradiation and Microwave Diathermy on Gram-Positive and Gram-Negative Bacteria in an In Vitro Model.

Abstract:
Background and Objectives: The aim of this study was to compare the effects of low-level laser therapy and continuous microwave diathermy on the growth of Gram-negative and Gram-positive bacteria and to establish their efficacy as an alternative therapeutic modality.

MATERIALS AND METHODS
Laser fluence of 13 Joules (J)/cm2, 18 J/cm2 and 30 J/cm2 were used against several bacterial strains. Microwave dosages of 25, 50 and 100 watts (W) were used, respectively.

RESULTS
A significant difference between the three groups was observed using repeated analysis of variance (RANOVA) (F value: 0.74, and p value: 0.001). The Greenhouse-Geisser correction (GG) revealed significant results for laser irradiation alone. However, effect size calculation showed effects with microwave diathermy as well as laser fluence.

CONCLUSIONS
Low-level laser therapy appears to be an effective modality of treatment when compared with continuous microwave diathermy on the Gram-negative and the Gram-positive bacterial strains tested. Microwave diathermy revealed large and medium effects on the bacterial cell counts with dominant effects on Gram-negative strains.

Dixit|Snehil|S|
Ahmad|Irfan|I|
Hakami|Abdulrahim|A|
Gular|Kumar|K|
Tedla|Jaya Shanker|JS|
Abohashrh|Mohammed|M|

D000704:Analysis of Variance
D000890:Anti-Infective Agents
D003972:Diathermy
D006090:Gram-Negative Bacteria
D006094:Gram-Positive Bacteria
D006801:Humans
D028022:Low-Level Light Therapy

microwave diathermy
low-level laser therapy
bacterial culture
electrotherapy
gram stain


Ectomycorrhizal fungal richness declines towards the host species' range edge.

Abstract: Plant range boundaries are generally considered to reflect abiotic conditions; however, a rise in negative or decline in positive species interactions at range margins may contribute to these stable boundaries. While evidence suggests that pollinator mutualisms may decline near range boundaries, little is known about other important plant mutualisms, including microbial root symbionts. Here, we used molecular methods to characterize root-associated fungal communities in populations of two related temperate tree species from across the species' range in the eastern United States. We found that ectomycorrhizal fungal richness on plant roots declined with distance from the centre of the host species range. These patterns were not evident in nonmycorrhizal fungal communities on roots nor in fungal communities in bulk soil. Climatic and soil chemical variables could not explain these biogeographic patterns, although these abiotic gradients affected other components of the bulk soil and rhizosphere fungal community. Depauperate ectomycorrhizal fungal communities may represent an underappreciated challenge to marginal tree populations, especially as rapid climate change pushes these populations outside their current climate niche.

Lankau|Richard A|RA|
Keymer|Daniel P|DP|

species range
Carpinus caroliniana
Ostrya virginiana
biogeography
ectomycorrhizae
range limit


Multi-Compartment Lymph-Node-on-a-Chip Enables Measurement of Immune Cell Motility in Response to Drugs.

Abstract: Organs On-a-Chip represent novel platforms for modelling human physiology and disease. The lymph node (LN) is a relevant immune organ in which B and T lymphocytes are spatially organized in a complex architecture, and it is the place where the immune response initiates. The present study addresses the utility of a recently designed LN-on-a-chip to dissect and understand the effect of drugs delivered to cells in a fluidic multicellular 3D setting that mimics the human LN. To do so, we analyzed the motility and viability of human B and T cells exposed to hydroxychloroquine (HCQ). We show that the innovative LN platform, which operates at a microscale level, allows real-time monitoring of co-cultured B and T cells by imaging, and supports cellular random movement. HCQ delivered to cells through a constant and continuous flow induces a reduction in T cell velocity while promotes persistent rotational motion. We also find that HCQ increases the production of reactive oxygen species in T cells. Taken together, these results highlight the potential of the LN-on-a-chip to be applied in drug screening and development, and in cellular dynamics studies.

Hallfors|Nicholas|N| Shanti|Aya|A| Sapudom|Jiranuwat|J|0000-0001-6627-7713 Teo|Jeremy|J| Petroianu|Georg|G| Lee|SungMun|S| Planelles|Lourdes|L| Stefanini|Cesare|C|

motility
hydroxychloroquine
rotational motion
reactive oxygen species
lymph node-on-a-chip


Determinants of per- and polyfluoroalkyl substances (PFAS) in midlife women: Evidence of racial/ethnic and geographic differences in PFAS exposure.

Abstract:
BACKGROUND
Per- and poly-fluoroalkyl substances (PFAS) are public health concerns because of widespread exposure through contaminated foods/drinking water. Although some determinants of PFAS exposure have been suggested, the role of geographic location and race/ethnicity in PFAS exposure has not been well characterized.

OBJECTIVES
We examined potential determinants of PFAS from the Study of Women's Health Across the Nation (SWAN).

METHODS
This study includes 1302 women aged 45-56 years from 5 SWAN sites where white women and women from one minority group were recruited (black from Southeast Michigan, Pittsburgh, Boston; Chinese from Oakland; Japanese from Los Angeles). We determined concentrations of 11 PFAS in serum samples collected in 1999-2000 and examined 7 PFAS detected in most women (>97%). Linear regression with backward elimination was used to identify important determinants of PFAS serum concentrations among a set of pre-specified variables (age, body mass index, site, race/ethnicity, education, financial hardship, occupation, born outside the United States (US), parity, menstrual bleeding within the past year, smoking status, alcohol consumption, and consumption of fish, dairy, pizza, salty snack, and French fries).

RESULTS
Site and race/ethnicity were two major determinants of PFAS. White women had higher concentrations of linear perfluorooctanoic acid (PFOA) compared with the Chinese in Oakland (p < 0.0001) and blacks in Pittsburgh (p = 0.048). Black women in Southeast Michigan and Boston (vs. white women) had higher concentrations of linear (p < 0.001 for Southeast Michigan; p < 0.0001 for Boston) and total perfluorooctane sulfonic acid (PFOS) (p < 0.001 for both Southeast Michigan and Boston) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (p = 0.02 for Southeast Michigan; p < 0.001 for Boston). Chinese (Oakland) and Japanese (Los Angeles) women had higher concentrations of perfluorononanoic acid (PFNA) compared with white women in each site (p < 0.01 for both). Within white women, those in Pittsburgh had relatively higher concentrations of PFAS. Within Chinese and Japanese women, those who were born outside the US had significantly lower concentrations of most PFAS but significantly higher PFNA concentrations. Menstrual bleeding and parity were significantly associated with lower PFAS concentrations. Higher intake of salty snacks including popcorn was significantly associated with higher concentrations of linear PFOA, PFOS and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid.

DISCUSSION
Geographic locations and race/ethnicity play an important role in differential exposure to PFAS, with racial/ethnic burdens differing between PFOS, PFOA and PFNA. Menstruation and parity were also determinants of PFAS concentrations possibly as an elimination route.

Park|Sung Kyun|SK|
Peng|Qing|Q|
Ding|Ning|N|
Mukherjee|Bhramar|B|
Harlow|Siobán D|SD|

Per- and polyfluoroalkyl substances (PFAS)


Compact dual-gas sensor for simultaneous measurement of atmospheric methane, and water vapor using a 3.38 μm antimonide-distributed feedback laser diode.

Abstract: A simple, compact sensor involving a continuous-wave 3.38 μm distributed feedback laser in combination with a novel compact dense-pattern multipass cell was demonstrated for simultaneous measurement of atmospheric methane and water vapor. The calibration-free direct absorption spectroscopy approach was adopted for data generation and processing. Allan deviation analysis indicates that minimum detection limits (1σ) of 11.0 ppb for CH4 and 100 ppm for H2O were achieved with a 1-s integration time at an optimum pressure of 50 Torr. Atmospheric environmental mixing ratios of these two gases were recorded and analyzed. This newly developed mid-infrared dual-gas sensor is very suitable for trace gas sensing in weight-limited unmanned aerial vehicle- or balloon-embedded field observations.

Ma|Hongliang|H| Sun|Mingguo|M| Zhan|Shengbao|S| Zhang|Qilei|Q| Zha|Shenlong|S| Wang|Guishi|G| Liu|Kun|K| Yi|Mingfang|M| Cao|Zhensong|Z|

Methane
Water vapor
Distributed feedback laser
Multipass cell
Laser absorption spectroscopy
Laser sensors


Pain and Spirituality Outcomes Among Women With Advanced Breast Cancer Participating in a Foot Reflexology Trial.

Abstract:
OBJECTIVES
To examine pain and spirituality, demographic and clinical factors associated with pain and spirituality, the contribution of spirituality to experiences of pain over time, and how pain and spirituality relate to engagement with a caregiver-delivered intervention.

SAMPLE & SETTING
Women with advanced breast cancer (N = 256) enrolled in a home-based randomized controlled trial of foot reflexology.

METHODS & VARIABLES
Secondary analyses were conducted with baseline and postintervention data. Stepwise model building, linear mixed-effects modeling, and negative binomial regression were used.

RESULTS
Participants who were younger, not married or partnered, not employed, or receiving hormonal therapy had increased odds of higher pain levels. Those who were older, non-White, or Christian had increased odds of higher spirituality. Spirituality's contribution to pain was not significant over time.

IMPLICATIONS FOR NURSING
Women in this sample experienced moderate pain, on average, at baseline. Women with specific demographic and clinical characteristics may require additional support with pain management and spiritual care.

Miller|Megan|M| Xu|Ding|D| Lehto|Rebecca|R| Moser|Jason|J| Wu|Horng-Shiuann|HS| Wyatt|Gwen|G|

pain
spirituality
breast cancer
pain management
integrative oncology


Superior oblique split lengthening procedure for brown syndrome, outcomes and complications.

Abstract:
INTRODUCTION
To evaluate the outcomes of the superior oblique split tendon lengthening (SOSL) procedure for Brown syndrome (BS).

METHODS
At a single institution, all patients who underwent SOSL surgery for BS from 2013 to 2019 were reviewed retrospectively. We looked at the surgical outcomes and complications in a total of 20 eyes of 18 patients. The superior oblique (SO) muscle was isolated and then extended. The tendon was then split centrally into equal halves. Two 6-0 polyglactin sutures were then placed on each end of the split tendon 6-10 mm apart. To complete the Z-cut, the split tendon was cut distal to the preplaced sutures. The sutures were then tied to produce the split Z-tendon lengthening.

RESULTS
Eleven (55%) out of 20 eyes were female patients. The mean age was 6.6 years (range 2-17 years). The mean follow-up was 26.8 months (range 5-72 months). The mean degree of preoperative limitation of elevation on adduction was -3.6±0.58 preoperatively and -0.75±1.25 postoperatively (p=0.0001). Preoperatively, the mean degree of vertical deviation at near was 3.5±7.62 and at distance was 3.10±7.84 prism diopters (PD), respectively. Postoperatively, the mean vertical deviation was 2.77±4.75 and 2.10±4.08 PD at near and distance, respectively. Postoperative complications included haematoma in one patient (5%), overcorrection in two patients (10%) and one patient required reoperation (5%).

CONCLUSION
SOSL is a safe procedure that surgeons can consider in managing patients with BS.

muscles
child health (paediatrics)
not applicable
treatment other
treatment surgery


A Bayesian approach for suppression of limited angular sampling artifacts in single particle 3D reconstruction.

Abstract: In the single particle reconstruction, the initial 3D structure often suffers from the limited angular sampling artifact. Selecting 2D class averages of particle images generally improves the accuracy and efficiency of the reference-free 3D angle estimation, but causes an insufficient angular sampling to fill the information of the target object in the 3D frequency space. Similarly, the initial 3D structure by the random-conical tilt reconstruction has the well-known "missing cone" artifact. Here, we attempted to solve the limited angular sampling problem by sequentially applying maximum a posteriori estimate with expectation maximization algorithm (sMAP-EM). Using both simulated and experimental cryo-electron microscope images, the sMAP-EM was compared to the direct Fourier method on the basis of reconstruction error and resolution. To establish selection criteria of the final regularization weight for the sMAP-EM, the effects of noise level and sampling sparseness on the reconstructions were examined with evenly distributed sampling simulations. The frequency information filled in the missing cone of the conical tilt sampling simulations was assessed by developing new quantitative measurements. All the results of visual and numerical evaluations showed the sMAP-EM performed better than the direct Fourier method, regardless of the sampling method, noise level, and sampling sparseness. Furthermore, the frequency domain analysis demonstrated that the sMAP-EM can fill the meaningful information in the unmeasured angular space without detailed a priori knowledge of the objects. The current research demonstrated that the sMAP-EM has a high potential to facilitate the determination of 3D protein structures at near atomic-resolution.

Moriya|Toshio|T|
Acar|Erman|E|
Cheng|R Holland|RH|
Ruotsalainen|Ulla|U|

Maximum a posteriori probability estimation


Heralds of global transparency: Remote sensing, nuclear fuel-cycle facilities, and the modularity of imagination.

Abstract: How has commercial remote sensing influenced the framing of public narratives about nuclear programs and weapons of mass destruction? This article examines an early and formative case: In 2002, a Washington-based nongovernmental organization used commercial satellite images to publicly identify the Natanz nuclear facility in Iran. The episode helped inaugurate the 'Iran nuclear crisis' as we have known it since. But it also played a role in fomenting a commercial market for remote sensing, adjusting the role of 'citizen scientist' in the nuclear arms-control community, visualizing a new television journalism beat of 'covering the intelligence community', legitimizing a transforming role of nuclear safeguards inspectors at the International Atomic Energy Agency, and solidifying Iran's nuclear program as 'clandestine'. This article follows the images as they pass through these social worlds and examines how heterogenous actors incorporated remote sensing into their identities and commitments to global transparency.

remote sensing
Iranian nuclear program
co-production
nuclear nonproliferation
sociotechnical imaginaries


What Is the Role of Dietary Inflammation in Severe Mental Illness? A Review of Observational and Experimental Findings.

Abstract: Severe mental illnesses (SMI), including major depressive disorder, bipolar disorder, and schizophrenia, are associated with increased inflammation. Given diet's role in modulating inflammatory processes, excessive calorie-dense, nutrient-deficient processed food intake may contribute toward the heightened inflammation observed in SMI. This review assesses the evidence from observational and experimental studies to investigate how diet may affect physical and mental health outcomes in SMI through inflammation-related pathways. Cross-sectional studies indicate that individuals with SMI, particularly schizophrenia, consume more pro-inflammatory foods and fewer anti-inflammatory nutrients than the general population. Cohort studies indicate that high levels of dietary inflammation are associated with increased risk of developing depression, but there is currently a lack of evidence for schizophrenia or bipolar disorder. Randomized controlled trials show that dietary interventions improve symptoms of depression, but none have tested the extent to which these benefits are due to changes in inflammation. This review summarizes evidence on dietary inflammation in SMI, explores the directionality of these links, and discusses the potential use of targeted nutritional interventions for improving psychological well-being and physical health outcomes in SMI. Establishing the extent to which diet explains elevated levels of inflammatory markers observed in SMI is a priority for future research.

Firth|Joseph|J|
Veronese|Nicola|N|
Cotter|Jack|J|
Shivappa|Nitin|N|
Hebert|James R|JR|
Ee|Carolyn|C|
Smith|Lee|L|
Stubbs|Brendon|B|
Jackson|Sarah E|SE|
Sarris|Jerome|J|

bipolar disorder
schizophrenia
nutrients
nutrition
vitamin


UDL and Intellectual Disability: What Do We Know and Where Do We Go?

Abstract: As an instructional design framework that can be used to design curriculum for students with and without disabilities, Universal Design for Learning (UDL) has the potential to support meaningful inclusion of students with intellectual disability (ID) in general educational settings. This article presents an overview of the existing set of research studies on UDL application for students with ID in PreK-12 settings. The current body of research illustrates that UDL is being applied to instructional activities for students with ID to examine a variety of interventions (e.g., adapted stories for individual students, inclusive general education curriculum) and outcomes (e.g., interaction, perceptions, knowledge gains) in self-contained and general educational settings. It also identifies important questions for consideration in future research as the field seeks to determine how UDL guidelines can be applied to curriculum, used with evidence-based and effective practices, and used to support schoolwide initiatives inclusive of students with ID.

Rao|Kavita|K|
Smith|Sean J|SJ|
Lowrey|K Alisa|KA|

D004495:Education of Intellectually Disabled

intellectual disability
Universal Design for Learning
research


Label-Free Sensing and Classification of Old Stored Blood.

Abstract: Transfusion is crucial in surgical operation and anemia treatment. However, several hemorheological properties of blood are adversely altered during blood storage. After transfusion, these adverse alterations are related with decrease of oxygen and ion transport in blood circulation, which increase the mortality of transfused patients. Therefore, accurate sensing of whether a blood supply is still viable for transfusion or not is extremely important. In this study, a H-shaped microfluidic device and digital in-line holographic microscopy were employed to measure temporal variations of blood viscosity and the optical focusing property of erythrocytes during blood storage. Stored rat blood samples separately preserved in citrate phosphate dextrose adenine-1 (CPDA-1) and ethylenediaminetetraacetic acid (EDTA) underwent considerable changes in their biophysical parameters after 2 weeks. Compared with EDTA, CPDA-1 preserves the hemorheological properties of stored blood more effectively. We propose new criteria for depository period of stored blood and indexes, such as viscosity and focal length of erythrocytes, to determine its appropriateness for transfusion. These criteria and indexes can be effectively used for high-throughput prescreening to reduce the risk of transfusion of aged blood or diagnose hematological diseases.

Park|Jun Hong|JH|
Go|Taesik|T|
Lee|Sang Joon|SJ|

Transfusion
Microfluidics
Holographic microscopy
Viscosity
Blood screening
Light scattering pattern


Effects of wireless packet loss in industrial process control systems.

Abstract: Timely and reliable sensing and actuation control are essential in networked control. This depends on not only the precision/quality of the sensors and actuators used but also on how well the communications links between the field instruments and the controller have been designed. Wireless networking offers simple deployment, reconfigurability, scalability, and reduced operational expenditure, and is easier to upgrade than wired solutions. However, the adoption of wireless networking has been slow in industrial process control due to the stochastic and less than 100% reliable nature of wireless communications and lack of a model to evaluate the effects of such communications imperfections on the overall control performance. In this paper, we study how control performance is affected by wireless link quality, which in turn is adversely affected by severe propagation loss in harsh industrial environments, co-channel interference, and unintended interference from other devices. We select the Tennessee Eastman Challenge Model (TE) for our study. A decentralized process control system, first proposed by N. Ricker, is adopted that employs 41 sensors and 12 actuators to manage the production process in the TE plant. We consider the scenario where wireless links are used to periodically transmit essential sensor measurement data, such as pressure, temperature and chemical composition to the controller as well as control commands to manipulate the actuators according to predetermined setpoints. We consider two models for packet loss in the wireless links, namely, an independent and identically distributed (IID) packet loss model and the two-state Gilbert-Elliot (GE) channel model. While the former is a random loss model, the latter can model bursty losses. With each channel model, the performance of the simulated decentralized controller using wireless links is compared with the one using wired links providing instant and 100% reliable communications. The sensitivity of the controller to the burstiness of packet loss is also characterized in different process stages. The performance results indicate that wireless links with redundant bandwidth reservation can meet the requirements of the TE process model under normal operational conditions. When disturbances are introduced in the TE plant model, wireless packet loss during transitions between process stages need further protection in severely impaired links. Techniques such as retransmission scheduling, multipath routing and enhanced physical layer design are discussed and the latest industrial wireless protocols are compared.

Chemical process control
Industrial control systems
Measurement science
Process performance
Process resilience
Safety
Testbed


Applying the Sport Commitment Model to Sport Injury Rehabilitation.

Abstract:
CONTEXT
Sustaining effort and persistence throughout injury rehabilitation are common goals for sport health care professionals. Considerable research in the sport domain has explored the issue of commitment to sport, as well as what predicts or influences an athlete's continued desire and resolve to continue participation. Scanlan and colleagues developed the sport commitment model (SCM) that places enjoyment as central construct influencing athletes' commitment. According to the model, perceptions of enjoyment, personal investments, involvement opportunities, attractive alternatives, social constraints, and social support should predict an athlete's level of sport commitment. One could argue the same may be true for commitment to sport injury rehabilitation. By applying the SCM to sport injury rehabilitation, practitioners may be able to enhance an athlete's commitment to their rehabilitation, prolong adherence, and increase other positive outcomes, such as increased enjoyment, motivation, and successful return to competition.

OBJECTIVE
The purpose of this pilot study was to explore the applicability of the SCM to the injury rehabilitation setting.

DESIGN
Correlational design was used.

SETTING
Division I, intercollegiate athletic training room.

PARTICIPANTS
51 injured intercollegiate male and female athletes, 5 certified athletic trainers, and 8 senior, athletic training students.

INTERVENTION
At the approximate midpoint of each athlete's injury rehabilitation, participants completed SCM measures. Certified athletic trainers and senior athletic training students independently assessed each injured athlete on effort, energy, and intensity during rehabilitation sessions.

MAIN OUTCOME MEASURES
Rehabilitation commitment, enjoyment, investments, attractive alternatives, social constraints, perceived costs, and rehabilitation behaviors.

RESULTS
Higher perceptions of investments predicted rehabilitation commitment. However, none of the SCM determinants predicted athletic trainer-rated rehabilitation behaviors.

CONCLUSIONS
Future research should continue to explore commitment constructs in relation to rehabilitation motivation.

enjoyment
motivation
rehabilitation behaviors
psychology


Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

Abstract: Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

Liang|Ya-Nan|YN| Liu|Yu|Y| Wang|Letian|L| Yao|Guodong|G| Li|Xiaobo|X| Meng|Xiangning|X| Wang|Fan|F| Li|Ming|M| Tong|Dandan|D| Geng|Jingshu|J|

caveolin-1
epidermal growth factor receptor
breast cancer
prognosis