Reduced microglial immunoreactivity for endogenous NMDA receptor agonist quinolinic acid in the hippocampus of schizophrenia patients.

Abstract: Postmortem and positron emission tomography studies have indicated the pathophysiological involvement of microglial cells in schizophrenia. We hypothesized that the microglial production of quinolinic acid (QUIN), an endogenous N-methyl-d-aspartate receptor (NMDAR) agonist, may be linked to the previously described glutamatergic deficits in the hippocampus of schizophrenia patients. We performed a semi-quantitative assessment of QUIN-immunoreactive microglial cells in schizophrenia patients and matched controls in the CA1, CA2/3, and dentate gyrus (DG) area of the posterior hippocampal formation. Complementary immunostaining of the commonly used microglial surface marker HLA-DR was performed in adjacent histological sections. Fewer QUIN-immunoreactive microglial cells were observed in the CA1 hippocampal subregion of schizophrenia patients compared to controls (left p=0.028, right p=0.018). No significant diagnosis-dependent changes were observed in the CA2/3 and DG regions. These results were controlled for potential confounds by age, duration of disease, autolysis time, psychotropic medication, and hippocampal volume. No diagnosis-related differences were observed for the overall density of microglial cells (HLA-DR expression). Our findings suggest that reduced microglial QUIN content in the hippocampal CA1 region is associated with schizophrenia. We hypothesize that this association may contribute to impaired glutamatergic neurotransmission in the hippocampus of schizophrenia patients.

Gos|Tomasz|T|
Myint|Aye-Mu|AM|
Schiltz|Kolja|K|
Meyer-Lotz|Gabriela|G|
Dobrowolny|Henrik|H|
Busse|Stefan|S|
Müller|Ulf J|UJ|
Mawrin|Christian|C|
Bernstein|Hans-Gert|HG|
Bogerts|Bernhard|B|
Steiner|Johann|J|

Quinolinic acid
Hippocampus
Schizophrenia
Hippocampal formation
Glutamate
Microglia


Correlation between aortic stiffness and left atrial volume index in hypertensive patients.

Abstract:
BACKGROUND
Both arterial stiffness and left atrial volume index are crucial predictors of cardiovascular outcomes in hypertensive patients. The correlation between these two factors has not been previously well established in hypertensive population.

OBJECTIVES
To determine the correlation between arterial stiffness and left atrial volume index in hypertensive patients.

METHODS AND RESULTS
The study was performed in 111 consecutive hypertensive patients (49.5% male, mean age 70.8 ± 10.3 years) undergoing cardiac magnetic resonance imaging (CMR). Arterial stiffness was determined by pulse wave velocity in the thoracic aorta by velocity-encoded imaging. Left atrial volume was assessed by biplane area-length method. Pulse wave velocity was significantly correlated with left atrial volume index in univariate analysis (r = 0.20, p = 0.032). In multivariate analysis, pulse wave velocity, coronary artery disease and left ventricular mass remain independent predictors (β = 1.01, p = 0.02).

CONCLUSION
Increased arterial stiffness correlates with left atrial enlargement in hypertensive patients. The prevention of left atrial enlargement and subsequent complications by specific antihypertensive drugs with positive effect on aortic stiffness warrants further studies.

Aortic stiffness
left atrial volume
hypertension
magnetic resonance imaging
pulse wave velocity
diastolic function


The erosion of the beaches on the coast of Alicante: Study of the mechanisms of weathering by accelerated laboratory tests.

Abstract: One of the main problems that coasts around the world present, is the regression and erosion of beaches. However, the factors involved in these processes are unclear. In this study, the influence of sediment erosion on beach regression has been analysed. In order to do that, a three-step investigation has been carried out. Firstly, coastline variations of four Spanish beaches have been analysed. Secondly, a study on sediment position along the beach profile has been developed. Finally, the process that beach sediments undergo along the surf zone when they are hit by the incident waves has been simulated by an accelerated particle weathering test. Samples of sand and shells were subjected to this accelerated particle weathering test. Results were supplemented with those from carbonate content test, XRD, SEM and granulometric analysis. Results shows a cross-shore classification of sediments along the beach profile in which finer particles move beyond offshore limit. Besides, it was observed that sediment erosion process is divided into three sages: i) particles wear due to crashes ii) dissolution of the carbonate fraction, and iii) breakage and separation of mineral and carbonate parts of particles. All these processes lead to a reduction of particle size. The mechanism responsible of beach erosion would consist of multiples and continuous particle location exchanges along the beach profile as a consequence of grain-size decrease due to erosion.

López|I|I|
López|M|M|
Aragonés|L|L|
García-Barba|J|J|
López|M P|MP|
Sánchez|I|I|

Dissolution of carbonates, median sediment size D(50)


Imaging Predictors for Endovascular Recanalization of Non-acute Occlusion of Internal Carotid Artery Based on 3D T1-SPACE MRI and DSA.

Abstract: Objectives: To investigate the predictive factors for successful recanalization based on digital subtraction angiography and three-dimensional T1W sampling perfection with application-optimized contrasts using different flip angle evolutions (3D T1-SPACE) high-resolution magnetic resonance imaging (MRI) signal features. Methods: Consecutive internal carotid artery occlusion cases with ipsilateral ischemic stroke refractory to therapy who visited our institution between February 2017 and August 2020 were retrospectively analyzed. Epidemiology, symptomatology, imaging morphology on angiography and MRI, peri-procedural complications, technical success rate, and follow-up results were summarized. Factors related to technical success were analyzed using univariate and multivariate analyses. Results: In total, 75 cases (53 men, mean age 57.51 ± 9.71 years) were included. The total successful recanalization rate was 72.00% (54/75), with a complication rate of 13.33% (9/75). Through multivariate analysis, first ischemic stroke in <3 months (OR: 2.57; 95% CI: 1.13-4.58), tapered stump (OR: 4.31; 95% CI: 1.37-13.55), reversed flow of the ophthalmic artery (OR: 2.99; 95% CI: 1.06-8.49), high intraluminal signal on unenhanced T1-SPACE sequence (OR: 16.15; 95% CI: 3.40-76.72), no vessel wall collapse (OR: 17.00; 95% CI: 3.57-81.02), short occlusion length (OR: 9.87; 95% CI: 2.09-46.64), and primary occlusion site at the cervical internal carotid artery (OR: 8.42; 95% CI: 1.04-68.19) were associated with successful recanalization. Conclusion: Besides traditional features such as short ischemic event time, tapered stump, and distal ICA reconstitution by the ophthalmic artery, our study demonstrates that luminal and mural changes determined by 3D SPACE high-resolution MRI could also predict successful endovascular recanalization. Endovascular recanalization for non-acute internal carotid artery occlusion is feasible, but prudent case selection is mandatory considering the high periprocedural complication rate.

Chao|Liu|L| Qingbin|Meng|M| Haowen|Xu|X| Shanshan|Xie|X| Qichang|Fu|F| Zhen|Chen|C| Sheng|Guan|G|

endovascular recanalization
non-acute occlusion
internal carotid artery
3D T1-SPACE
magnetic resonance imaging


Gene-based antiangiogenic applications for corneal neovascularization.

Abstract: Corneal avascularity is maintained by angiogenic privilege, an active process involving the production of higher level of angiostatic factors to offset the effect of angiogenic factors. A wide range of pathological insults to the cornea can disrupt this intricate equilibrium and promote angiogenesis and corneal neovascularization with resultant visual impairment. Corneal neovascularization is also a major risk factor for graft failure after keratoplasty. Current treatment options for corneal neovascularization are restricted by limited efficacy, adverse effects, and a short duration of action. The unique anatomical position and relative immune privilege of cornea make it an ideal tissue for gene-based therapies. Gene transfer vectors have been used to deliver or target genes involved in the pathogenesis of corneal neovascularization in animal models. Several proangiogenic and antiangiogenic factors have been targeted and assessed in experimentally induced corneal neovascularization. Antisense oligonucleotides targeting corneal neovascularization have entered human clinical trials and have not required vector delivery systems. The emergence of these RNA-based strategies heralds a new era in the management of corneal neovascularization and ocular therapeutics.

Liu|Siyin|S|
Romano|Vito|V|
Steger|Bernhard|B|
Kaye|Stephen B|SB|
Hamill|Kevin J|KJ|
Willoughby|Colin E|CE|

D042461:Vascular Endothelial Growth Factor A

neovascularization
cornea
angiogenesis
antisense oligonucleotide
gene therapy
miRNA
vascular endothelial growth factor


Delayed bleeding in a hemophilic patient after sinus floor elevation and multiple implant placements.

Abstract: Not required for clinical case letters.

de Mattos Carpena|Augusto Luis Mendes|ALM|

Dos Santos|Mateus Bertolini Fernandes|MBF|

sinus floor elevation
Dental Implants
complications
hemophilia A
inherited bleeding disorders


Anthropogenic 236U and Pu at remote sites of the South Pacific.

Abstract: Anthropogenic radionuclides, like 236U and 239,240Pu, are present in the environment as a result of global fallout from nuclear weapons tests conducted in the 1950s and 1960s and can potentially be used as tracers in soil erosion and sediment movement studies. Here, we report data on 236U and 239,240Pu in soil samples from the Motueka Valley (New Zealand) and for the first time from two remote islands Rarotonga and Atiu (Cook Islands) in the South Pacific. 236U and 239,240Pu were measured using Accelerator Mass Spectrometry (AMS) at the Australian National University. The 236U and 239Pu isotope concentrations versus soil depth and the 240Pu/239Pu and 236U/239Pu isotope ratios are discussed for each site. The radionuclide depth dependence revealed any soil disturbance, whereas the isotopic signatures indicated the source of the radionuclides' origin.

Froehlich|M B|MB|
Akber|A|A|
McNeil|S D|SD|
Tims|S G|SG|
Fifield|L K|LK|
Wallner|A|A|

South Pacific
Soil
Accelerator mass spectrometry
(236)U/(239)Pu
(240)Pu/(239)Pu
Southern Hemisphere


Why are you looking at me? It's because I'm talking, but mostly because I'm staring or not doing much.

Abstract: Our attention is particularly driven toward faces, especially the eyes, and there is much debate over the factors that modulate this social attentional orienting. Most of the previous research has presented faces in isolation, and we tried to address this shortcoming by measuring people's eye movements whilst they observe more naturalistic and varied social interactions. Participants' eye movements were monitored whilst they watched three different types of social interactions (monologue, manual activity, active attentional misdirection), which were either accompanied by the corresponding audio as speech or by silence. Our results showed that (1) participants spent more time looking at the face when the person was giving a monologue, than when he/she was carrying out manual activities, and in the latter case they spent more time fixating on the person's hands. (2) Hearing speech significantly increases the amount of time participants spent looking at the face (this effect was relatively small), although this was not accounted for by any increase in mouth-oriented gaze. (3) Participants spent significantly more time fixating on the face when direct eye contact was established, and this drive to establish eye contact was significantly stronger in the manual activities than during the monologue. These results highlight people's strategic top-down control over when they attend to faces and the eyes, and support the view that we use our eyes to signal non-verbal information.

Scott|Hannah|H|
Batten|Jonathan P|JP|
Kuhn|Gustav|G|

Attention
Social attention
Eye movements
Audio visual interaction
Direct eye gaze
Social cognition
Speech perception


Effects of pyrolysis temperature on the physicochemical properties of alfalfa-derived biochar for the adsorption of bisphenol A and sulfamethoxazole in water.

Abstract: The present study reports alfalfa (one of most abundant hays in U.S)-derived biochar for effective removal of emerging contaminants in water for the first time. The physicochemical properties of alfalfa-derived biochar (AF-BC) made at various pyrolysis temperatures were investigated, and correlated with the adsorption of bisphenol A (BPA) and sulfamethoxazole (SMX) in water. The increase in pyrolysis temperatures from 350 °C to 650 °C for the pyrolysis of AF led to a drastic increase in surface area and carbonization with the loss of functional groups. The AF-derived biochar made at 650 °C showed much higher adsorption capacities for BPA and SMX than those made at 350-550 °C, mainly owing to the hydrophobic and π-π interactions supported by its high surface area and degree of carbonization. The adsorption isotherms fitted the Freundlich for BPA and Temkin models for SMX well, respectively. The adsorption capacities of AF 650 for BPA and SMX were higher than those of other biochars but lower than those of commercial activated carbon. The pH-dependent desorption for AF 650 showed high efficiency for SMX, but low efficiency for BPA indicating needs for alternative regeneration methods for BPA.

Pyrolysis
Temperature
Biochar
Bisphenol A
Sulfamethoxazole
Alfalfa


Sexual Behavior Change Among Gay and Bisexual Men During the First COVID-19 Pandemic Wave in the United States.

Abstract:
Background
After decades of navigating HIV and other sexually transmitted infections, gay and bisexual men are responding to new and uncertain risks presented by the coronavirus (COVID-19) pandemic by adapting their sexual behavior.

Methods
This paper uses data from a national sample of 728 gay and bisexual men collected from April 10 to May 10, 2020, to examine changes to sexual behavior in response to the first wave of the pandemic in the USA. We also assess whether behavior modifications are associated with exposure to statewide public health measures, including Stay-at-Home orders.

Results
Sexual minority men report significant changes to their sexual behavior and partner selection during the first wave. Nine out of 10 men reported having either one sexual partner or no sexual partner in the last 30 days at the time of interview, a decrease compared to just before the pandemic for nearly half of men surveyed. Reporting no sexual partners in the last 30 days was significantly predicted by increased exposure to a Stay-at-Home order. Sexual minority men also reduced interactions with casual partners, increased no-contact sexual behaviors (e.g., masturbation and virtual sex), and engaged in new strategies to reduce their risks of infection from partners. HIV-positive men were particularly likely to adopt strategies including avoiding casual partners and avoiding public transportation to meet sexual partners.

Conclusion
Sexual minority men's behavior changes during the first wave may have reduced the impact of the coronavirus pandemic on their communities. Despite substantial changes in sexual behavior for most men in our sample during the initial first wave, we identify some concerns around the sustainability of certain behavioral changes over time and nondisclosure of COVID-19 symptoms to partners.

McKay|Tara|T|0000-0001-5076-6483
Henne|Jeff|J|
Gonzales|Gilbert|G|
Gavulic|Kyle A|KA|
Quarles|Rebecca|R|
Gallegos|Sergio Garcia|SG|

Sexual behavior
Gay and bisexual men
United States
Coronavirus
Stay-at-Home order
Sex
Men who have sex with men
Public health policy


Retinoic acid for treatment of systemic sclerosis and morphea: A literature review.

Abstract: Systemic sclerosis and morphea are connective tissue diseases characterized by tightening, thickening, and hardening of the skin, leading to significant morbidity. Unfortunately, current treatment options have limited efficacy for many patients. Cutaneous manifestations of these diseases arise from excess collagen deposition and fibrosis in the skin, through pathogenic mechanisms which have yet to be extensively detailed at the causal immune and cellular levels. Research elucidating the mechanism of action of retinoic acid on collagen production in the skin and case series highlighting the success of retinoic acid on the skin manifestations of systemic sclerosis and on morphea demonstrate its promise as a treatment. Herein they will briefly review the treatment options for both systemic sclerosis and morphea, and will discuss the potential of retinoic acid as a therapy and the supporting evidence from the literature, highlighting the previously published basic science and clinical studies investigating the role of retinoic acid in the treatment of sclerotic skin diseases.

Thomas|Renee M|RM|
Worswick|Scott|S|
Aleshin|Maria|M|

retinoic acid
systemic sclerosis
morphea
acitretin
etretinate
isotretinoin
localized scleroderma
scleroderma


Tissue Doppler assessment of diastolic function and relationship with mortality in critically ill septic patients: a systematic review and meta-analysis.

Abstract:
Background
Myocardial dysfunction may contribute to circulatory failure in sepsis. There is growing evidence of an association between left ventricular diastolic dysfunction (LVDD) and mortality in septic patients. Utilizing echocardiography, we know that tissue Doppler imaging (TDI) variables e' and E/e' are reliable predictors of LVDD and are useful measurements to estimate left ventricular (LV) filling pressures.

Methods
We conducted a systematic review and meta-analysis to investigate the association of e' and E/e' with mortality of patients with severe sepsis or septic shock. In the primary analysis, we included studies providing transthoracic TDI data for e' and E/e' and their association with mortality. Subgroup analyses were conducted according to myocardial regional focus of TDI assessment (septal, lateral or averaged). Three secondary analyses were performed: one included data from a transoesophageal study, another excluded studies reporting data at a very early (<6 h) or late (>48 h) stage following diagnosis, and the third pooled data only from studies excluding patients with heart valve disease.

Results
The primary analysis included 16 studies with 1507 patients with severe sepsis and/or septic shock. A significant association was found between mortality and both lower e' [standard mean difference (SMD) 0.33; 95% confidence interval (CI): 0.05, 0.62; P=0.02] and higher E/e' (SMD -0.33; 95% CI: -0.57, -0.10; P=0.006). In the subgroup analyses, only the lateral TDI values showed significant association with mortality (lower e' SMD 0.45; 95% CI: 0.11, 0.78; P=0.009; higher E/e' SMD -0.49; 95% CI: -0.76, -0.22; P=0.0003). The findings of the primary analysis were confirmed by all secondary analyses.

Conclusions
There is a strong association between both lower e' and higher E/e' and mortality in septic patients.

Sanfilippo|F|F| Corredor|C|C| Arcadipane|A|A| Landesberg|G|G| Vieillard-Baron|A|A| Cecconi|M|M| Fletcher|N|N|

diastolic dysfunction
echocardiography
severe sepsis
septic shock
intensive care


Is gill cortisol concentration a good acute stress indicator in fish? A study in rainbow trout and zebrafish.

Abstract: Cortisol is the main biomarker of physiological stress in fish. It is usually measured in plasma, which requires blood collection. Though cortisol is produced in the anterior kidney, it can diffuse easily through cell membranes due to its lipophilic nature. Taking advantage of that, some non-invasive techniques have been developed to measure cortisol directly in the water from fish-holding tanks, in skin mucus or in scales. In this study, we explored the possibility to analyze fish cortisol from gill filaments as a reliable acute stress marker. Our results show that gill cortisol levels correlate well with plasma cortisol levels in both rainbow trout and zebrafish exposed or not to an acute stress protocol. Measuring cortisol in gill filaments increases the available possibilities for stress assessment in fish. Although this approach should yet be tested for its use with other stressors, it has several advantages: In relatively large fish (i.e. above 30 g) gill cortisol levels could be measured in vivo. Sampling of gill biopsies is very fast and easy, and the procedure does not induce stress if properly performed, making it an ideal option for in vivo stress assessment. In small fish, the use of gill tissue to measure cortisol has important technical advantages with respect to the current methods using whole-body homogenates. Gill homogenates could be used directly for ELISA cortisol analysis, avoiding the need of tedious and expensive cortisol extraction protocols, and, since no organic solvent is required, contributing for a more environmentally friendly analysis.

Gesto|Manuel|M|
Hernández|Juan|J|
López-Patiño|Marcos A|MA|
Soengas|José L|JL|
Míguez|Jesús M|JM|

Gill Cortisol Stress Fish Trout Zebrafish


Factors Driving Live Discharge From Hospice: Provider Perspectives.

Abstract:
CONTEXT
The proportion of patients disenrolling from hospice before death has increased over the decade with significant variations across hospice types and regions. Such trends have raised concerns about live disenrollment's effect on care quality. Live disenrollment may be driven by factors other than patient preference and may create discontinuities in care, disrupting ongoing patient-provider relationships. Researchers have not explored when and how providers make this decision with patients.

OBJECTIVE
The objective of this study was to ascertain provider perspectives on key drivers of live discharge from the Medicare hospice program.

METHODS
We conducted semistructured telephone interviews with 18 individuals representing 14 hospice providers across the country. Transcriptions were coded and analyzed using a template analysis approach.

RESULTS
Analysis generated four themes: 1) difficulty estimating patient prognosis, 2) fear of Centers for Medicare & Medicaid Services audits, 3) rising market competition, and 4) challenges with inpatient contracting. Participants emphasized challenges underlying each decision to discharge patients alive, stressing that there often exists a gray line between appropriate and inappropriate discharges. Discussions also focused on scenarios in which financial motivations drive enrollment and disenrollment practices.

CONCLUSION
This study provides significant contributions to existing knowledge about hospice enrollment and disenrollment patterns. Results suggest that live discharge patterns are often susceptible to market and regulatory forces, which may have contributed to the rising national rate.

Dolin|Rachel|R|
Hanson|Laura C|LC|
Rosenblum|Sarah F|SF|
Stearns|Sally C|SC|
Holmes|George M|GM|
Silberman|Pam|P|

Medicare
Qualitative research
end-of-life care


A new species of the genus Megophrys Gunther, 1864 (Amphibia: Anura: Megophryidae) from Mount Wuyi, China.

Abstract: A new species of horned toad, Megophrys ombrophila sp. nov., is described based on specimens found from Guadun village from Mount Wuyi in northwestern Fujian Province, China. The species is distinguished from other described Megophrys by morphology, bioacoustics, and molecular data of the 12S and 16S mitochondrial loci. The species is characterized by its rotund stature, head length approximately equal to head width, canthus rostralis well developed, tympanum large and distinct, vomerine teeth absent, margin of tongue smooth, not notched from behind, heels of the feet not meeting when femurs are held at 90° to the axis of the body and tibias are depressed against the femur, toes weakly webbed at base, dorsal skin mostly smooth with scattered granules and ridges, usually the presence of two discontinuous dorsolateral ridges, supratympanic fold distinct and well-developed, and with females ranging from 32.8-35 mm snout-to-vent length, and males ranging from 27.4-34.5 mm SVL. In its type locality, the species is sympatric with M. boettgeri and M. kuatunensis; and phylogenetically, the most closely related described species is M. obesa from southwest Guangdong province. As more cryptic species are described within the subfamily Megophryinae, the more apparent becomes the need for fine-scale molecular and phenotypic assessment to capture the many forms of this hyper-diverse group.

Messenger|Kevin R|KR|
Dahn|Hollis A|HA|
Liang|Yuanrui|Y|
Xie|Peng|P|
Wang|Yong|Y|
Lu|Changhu|C|


Serum Biomarkers of Endothelial Dysfunction in Fabry Associated Cardiomyopathy.

Abstract: Background: Fabry disease (FD) is characterized by early development of vasculopathy and endothelial dysfunction. However, it is unclear whether these findings also play a pivotal role in cardiac manifestation. As Fabry cardiomyopathy (FC) is the leading cause of death in FD, we aimed to gather a better insight in pathological mechanisms of the disease. Methods: Serum samples were obtained from 17 healthy controls, 15 FD patients with and 7 without FC. FC was defined by LV wall thickening of >12 mm in cardiac magnetic resonance imaging and serum level of proBNP, high sensitive Troponin T (hsT), and globotriaosylsphingosine (lyso-GB3) were obtained. A multiplex ELISA-Assay for 23 different angiogenesis markers was performed in pooled samples. Markers showing significant differences among groups were further analyzed in single samples using specific Elisa antibody assays. L-homoarginine (hArg), L-arginine, asymmetric (ADMA), and symmetric Dimethylarginine (SDMA) were quantified by liquid chromatography-mass spectrometry. Results: Angiostatin and matrix metalloproteinase 9 (MMP-9) were elevated in FD patients compared to controls independently of the presence of FC (angiostatin: 98 ± 25 vs. 75 ± 15 ng/mL; p = 0.001; MMP-9: 8.0 ± 3.4 vs. 5.0 ± 2.4 μg/mL; p = 0.002). SDMA concentrations were highest in patients with FC (0.90 ± 0.64 μmol/l) compared to patients without (0.57 ± 0.10 μmol/l; p = 0.027) and vs. controls (0.58 ± 0.12 μmol/l; p = 0.006) and was positively correlated with indexed LV-mass (r = 0.61; p = 0.003), hsT (r = 0.56, p = 0.008), and lyso-Gb3 (r = 0.53, p = 0.013). Accordingly, the ratio of L-homoarginine to SDMA (hArg/SDMA) was lowest in patients with FC (2.63 ± 1.78) compared to controls (4.16 ± 1.44; p = 0.005). For L-arginine, hArg and ADMA no significant differences among groups could be detected, although a trend toward higher ADMA and lower hArg levels could be observed in the FC group. Furthermore, a significant relationship between kidney and cardiac function could be revealed (p = 0.045). Conclusion: Elevated MMP-9 and angiostatin levels suggest an increased extracellular matrix turnover in FD patients. Furthermore, endothelial dysfunction may also be involved in FC, as SDMA and hArg/SDMA are altered in these patients.

Loso|Jefferson|J| Lund|Natalie|N| Avanesov|Maxim|M| Muschol|Nicole|N| Lezius|Susanne|S| Cordts|Kathrin|K| Schwedhelm|Edzard|E| Patten|Monica|M|

endothelial dysfunction
Fabry disease
vasculopathy
Fabry cardiomyopathy
SDMA
angiostatins
matrix metalloproteinase 9
homoarginine


Cognitive Functioning and Health in Hispanic/Latina Breast Cancer Survivors.

Abstract: We examined the effect of waist-to-hip ratio, body mass index (BMI), diet, and physical activity on cognitive functioning among Hispanic/Latina breast cancer survivors in a cross-sectional design study. Participants were 54 Hispanic/Latina breast cancer survivors and completed the NIH Toolbox Cognition Battery. Linear Regression Models tested if statistically significant correlations held with covariates. After controlling for covariates, moderate and hard physical activity were not associated with cognition. However, very hard physical activity was positively associated with faster processing speed (β = 0.56, p < 0.001) and composite cognition score (β = 0.36, p < 0.05). Total time (minutes) of moderate to very hard physical activity was positively associated with cognitive flexibility (β = 0.52, p < 0.001). Total caloric intake was positively associated with episodic memory (β = 0.35 p < 0.05). BMI and WHR were not associated with cognition. These findings showed positive association with engagement in more MVPA and harder intensity physical activity to better cognitive functioning among Hispanic/Latina breast cancer survivors.ClinicalTrials.gov NCT02780271.

Cognition
Cancer survivors
Diet
Exercise
Hispanic Americans


Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics.

Abstract: Axonal damage is a prominent cause of disability and yet its pathogenesis is incompletely understood. Using a xenogeneic system, here we define the bioenergetic changes induced in rat neurons by exposure to cerebrospinal fluid samples from patients with multiple sclerosis compared to control subjects. A first discovery cohort of cerebrospinal fluid from 13 patients with multiple sclerosis and 10 control subjects showed that acute exposure to cerebrospinal fluid from patients with multiple sclerosis induced oxidative stress and decreased expression of neuroprotective genes, while increasing expression of genes involved in lipid signalling and in the response to oxidative stress. Protracted exposure of neurons to stress led to neurotoxicity and bioenergetics failure after cerebrospinal fluid exposure and positively correlated with the levels of neurofilament light chain. These findings were validated using a second independent cohort of cerebrospinal fluid samples (eight patients with multiple sclerosis and eight control subjects), collected at a different centre. The toxic effect of cerebrospinal fluid on neurons was not attributable to differences in IgG content, glucose, lactate or glutamate levels or differences in cytokine levels. A lipidomic profiling approach led to the identification of increased levels of ceramide C16:0 and C24:0 in the cerebrospinal fluid from patients with multiple sclerosis. Exposure of cultured neurons to micelles composed of these ceramide species was sufficient to recapitulate the bioenergetic dysfunction and oxidative damage induced by exposure to cerebrospinal fluid from patients with multiple sclerosis. Therefore, our data suggest that C16:0 and C24:0 ceramides are enriched in the cerebrospinal fluid of patients with multiple sclerosis and are sufficient to induce neuronal mitochondrial dysfunction and axonal damage.

Vidaurre|Oscar G|OG|
Haines|Jeffery D|JD|
Katz Sand|Ilana|I|
Adula|Kadidia P|KP|
Huynh|Jimmy L|JL|
McGraw|Corey A|CA|
Zhang|Fan|F|
Varghese|Merina|M|
Sotirchos|Elias|E|
Bhargava|Pavan|P|
Bandaru|Veera Venkata Ratnam|VV|
Pasinetti|Giulio|G|
Zhang|Weijia|W|
Inglese|Matilde|M|
Calabresi|Peter A|PA|
Wu|Gang|G|
Miller|Aaron E|AE|
Haughey|Norman J|NJ|
Lublin|Fred D|FD|
Casaccia|Patrizia|P|

axonal degeneration
demyelinating disease
lipid metabolism
mitochondria
neurodegenerative mechanism


Polyphenolic Profile and Varied Bioactivities of Processed Taiwanese Grown Broccoli: A Comparative Study of Edible and Non-Edible Parts.

Abstract: Broccoli contains a substantial amount of bioactive compounds such as glucosinolates, phenolics, and essential nutrients, which are positively linked to health-promoting effects. This work aimed to evaluate whether both edible and non-edible parts of broccoli could be effective by examining in vitro antioxidant, cytotoxic, apoptotic, and antibacterial properties of its floret, leaf, and seed extracts (FE, LE, and SE, correspondingly). High-performance liquid chromatography (HPLC) and various assays exhibited strong antioxidant activities of all samples. LE obtained the highest capacity, correlated to its polyphenolic contents. SE exerted significant cytotoxicity against A549, Caco-2, and HepG2 cancer cell lines at low inhibitory concentration (IC)50 values (0.134, 0.209, and 0.238 mg/mL, respectively), as tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry confirmed apoptosis induction of extracts in Caco-2 cells by revealing an increased subG1 population and a decreased mitochondrial membrane potential. The considerable antibacterial efficacy was observed in either LE and SE against Bacillus subtilis and Salmonella typhimurium (0.39-0.78 mg/mL) using well-agar diffusion and minimum inhibitory concentration (MIC) techniques, along with the weak activity against Staphylococcus aureus and Escherichia coli (1.56-3.13 mg/mL). The findings suggest that broccoli and its byproducts might serve as a promising source for further development of food or pharmaceutical products.

Le|Thanh Ninh|TN|
Sakulsataporn|Napat|N|
Chiu|Chiu-Hsia|CH|
Hsieh|And Pao-Chuan|AP|

broccoli
cytotoxicity
antioxidant activity
apoptosis
byproducts
antibacterial activity


Liquid-crystalline Metallomacrocycles Composed of Bis(hydroxypyridono)toluene Ligand and Cu2+ Ions.

Abstract: A series of π-extended chelating scaffolds incorporating two hydroxypyridone moieties were synthesized. X-ray crystallographic analysis revealed that a bis(hydroxypyridono)toluene ligand possessed a unique π-extended structure and exhibited efficient phase segregation from the aliphatic chains attached at the heterocyclic nitrogen. The bis-bidentate ligand formed a metal-coordination-induced macrocycle with Cu2+ ions. During the complexation, a spectral change in the visible region was induced. Furthermore, the successful development of a liquid crystal of the metallomacrocycle with appropriate side chains was achieved. Examples of liquid-crystalline macrocycles formed via metal-mediated self-assembly are still rare. Among them, the macrocycle described in this paper showed an obvious hexagonal columnar phase reflecting the three-fold symmetric planar structure of the mesogenic metal complex.

metallomacrocycles
liquid crystals
self-assembly
coordination
nanospace


Detection of Pneumonia in chest X-ray images.

Abstract: Pneumonia is the common type of infection found in the world. The infection spreads in the lungs area of a human body. The chest x-ray is performed to diagnose this infection. Physicians use this X-ray image to diagnose or monitor treatment for conditions of pneumonia. This type of chest X-ray is also used in the diagnosis of diseases like emphysema, lung cancer, line and tube placement and tuberculosis. Feature extraction methods like DWT, WFT, and WPT can also be used. In this paper, detection of pneumonia infection by unsupervised fuzzy c-means classification learning algorithm is used. This approach gives better result than the rest of the methods. In fuzzy c-means, each resultant pixel gives accurate value since it has a weight associated with it.

Parveen|N Ravia Shabnam|NR|
Sathik|M Mohamed|MM|

D011857:Radiographic Image Interpretation, Computer-Assisted

pneumonia
Feature extraction
fuzzy c-means classification
unsupervised learning


Assessing Representation and Perceived Inclusion among Members in the Society for Epidemiologic Research.

Abstract: Using web-based survey data collected June - August 2018 from the Society for Epidemiologic Research (SER) members, we characterized numerous dimensions of social identity and lived experience, and assessed relationships between these characteristics and perceptions of inclusion and society participation. We quantified associations between characteristics, feeling very welcomed, high (top 25th percentile) self-initiated participation, and any (top 10th percentile) society-initiated participation. Racial/ethnic and religious minority categories were blinded to preserve anonymity and we accounted for missing data. Most 2018 SER members (n = 1631) were white (62%) or female (66%). Females with racial/ethnic non-response were least likely, while white males were most likely to report feeling very welcomed. Members who did not report race, identified with a specific racial/ethnic minority, or were politically conservative/right-leaning were less likely than white or liberal/left-leaning members to have high self-initiated participation. Women and individuals of a specific racial/ethnic minority or minority religious affiliations were less likely to participate in events initiated by the society. These data represent a baseline for assessing trends and the impact of future initiatives aimed at improving diversity, inclusion, representation and participation within SER.

DeVilbiss|Elizabeth A|EA|
Weuve|Jennifer|J|
Fink|David S|DS|
Morris|Meghan D|MD|
Arah|Onyebuchi A|OA|
Radoc|Jeannie G|JG|
Datta|Geetanjali D|GD|
Abuelezam|Nadia N|NN|
Lopez|David S|DS|
Johnson|Dayna A|DA|
Branas|Charles C|CC|
Schisterman|Enrique F|EF|

societies
continental population groups
cultural diversity
demography
ethnic groups
sex
social participation


A validated LC-MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay.

Abstract: An accurate and sensitive LC-MS/MS method for determining thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in human plasma was developed and validated using umbelliferone as an internal standard. The analytes were extracted from plasma (100 μL) by liquid-liquid extraction with ethyl acetate and then separated on a BETASIL C18 column (4.6 × 150 mm, 5 μm) with mobile phase composed of methanol-water containing 0.1% formic acid (70:30, v/v) in isocratic mode at a flow rate of 0.5 mL/min. The detection was performed using an API triple quadrupole mass spectrometer in atmospheric pressure chemical ionization mode. The precursor-to-product ion transitions m/z 259.1 → 186.1 for thalidomide, m/z 273.2 → 161.3 for 5-hydroxy thalidomide, m/z 273.2 → 146.1 for 5'-hydroxy thalidomide and m/z 163.1 → 107.1 for umbelliferone (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentrations of 10.0-2000.0 ng/mL for thalidomide, 0.2-50.0 ng/mL for 5-hydroxy thalidomide and 1.0-200.0 ng/mL for 5'-hydroxy thalidomide. The method was validated with respect to linear, within- and between-batch precision and accuracy, extraction recovery, matrix effect and stability. Then it was successfully applied to estimate the concentration of thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in plasma samples collected from Crohn's disease patients after a single oral administration of thalidomide 100 mg.

D002853:Chromatography, Liquid
D004355:Drug Stability
D006801:Humans
D016014:Linear Models
D008297:Male
D015203:Reproducibility of Results
D012680:Sensitivity and Specificity
D053719:Tandem Mass Spectrometry
D013792:Thalidomide

LC-MS/MS thalidomide metabolites pharmacokinetics


Characterization of polyphenol oxidase activity in Ataulfo mango.

Abstract: Crude extracts of Ataulfo exhibited polyphenol oxidase (PPO) activity with pyrogallol, 3-methylcatechol, catechol, gallic acid, and protocatechuic acid. The substrate dependent pH optima ranged from pH 5.4 to 6.4 with Michaelis-Menten constants between 0.84 ± 0.09 and 4.6 ± 0.7 mM measured in MES or phosphate buffers. The use of acetate buffers resulted in larger Michaelis-Menten constants, up to 14.62 ± 2.03 mM. Sodium ascorbate, glutathione, and kojic acid are promising inhibitors to prevent enzymatic browning in Ataulfo. PPO activity increased with ripeness and was always higher in the skin compared to the pulp. Sodium dodecyl sulphate (SDS) enhanced PPO activity, with pulp showing a stronger increase than skin. SDS-PAGE gels stained for catecholase activity showed multiple bands, with the most prominent bands at apparent molecular weights of 53, 112, and 144 kDa.

Polyphenol oxidase
Ataulfo mango
Enzyme
Enzyme activity


Novel Strategy for Diagnosis of Focal Nodular Hyperplasia Using Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid: Enhanced Magnetic Resonance Imaging and Magnetic Resonance Elastography.

Abstract: Focal nodular hyperplasia (FNH) is the second most frequent benign liver tumor, and it is a fiber-rich stiff lesion. Typically, FNH can be diagnosed by imaging without biopsy. However, liver biopsy and diagnostic resection may be required to differentiate atypical FNH from other liver tumors, such as hepatocellular adenoma (HCA). Therefore, improved noninvasive diagnostic methods are needed. We experienced 2 cases where combination of magnetic resonance elastography (MRE) and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) helped diagnose FNH. A 36-year-old woman and 17-year-old boy with liver tumors measuring 40 mm in diameter each showed hypointense nodule centers, indicating a central scar, surrounded by hyperintense signals during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. To rule out HCA, we performed MRE and liver biopsy. On MRE, the mean stiffness of the mass was 11.6 kPa (mean stiffness of the background liver was 1.7 kPa) and 11.1 kPa (mean stiffness of the background liver was 2.4 kPa) in the first and second patients, respectively. Histological examination of both specimens showed CK7-positive bile-ductular proliferations, abundant fibrous tissue, and few Ki-67-positive cells. Based on these results, we diagnosed these tumors as FNH. Combination of Gd-EOB-DTPA-enhanced MRI and MRE can evaluate the character and stiffness of lesion and help in the diagnosis of FNH.

Takeda|Nobutaka|N| Tsuchiya|Atsunori|A| Natsui|Kazuki|K| Ishii|Yui|Y| Arao|Yoshihisa|Y| Kimura|Naruhiro|N| Tominaga|Kentaro|K| Takeuchi|Suguru|S| Hayashi|Kazunao|K| Takamura|Masaaki|M| Terai|Shuji|S|

Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging


Continuous-flow electrocoagulation (EC) process for iron removal from water: Experimental, statistical and economic study.

Abstract: The process of Electrocoagulation (EC), the in-situ production of coagulants by passing an electric current through sacrificial electrodes, is free of chemical additives and cost-effective. This makes it the most widely used water and wastewater treatment method. However, the literature highlights some significant drawbacks of this method including EC unit design limitations. This research therefore aimed to develop a new EC unit design using drilled plates (electrodes) to mix the solution being treated without using external mixers, this minimising power consumption. The performance of the new EC unit was validated by applying it to remove iron from water taking into account the effects of applied current density (ACD), the pH of the water (PoW), iron concentration (IC) and treatment time (TT). The effects of these parameters were optimised using the Box-Behnken model. Synthetic water samples containing different concentrations of iron (10-30 mg/l), were treated in a continuous flow, using the new EC reactor at different ACD (1.5-4.5 mA/cm2), PoW (4-10) and TT (10-50 min). The results revealed that the removal of 99.9% of iron was achieved by keeping PoW, ACD, IC and TT at 7, 3 mA/cm2, 10 mg/l and 50 min, respectively. The effects of ACD, POW, IC and TT on iron removal could be successfully simulated with R2 = 0.9788. The cost of removing iron using the proposed EC unit was 0.623 £/m3.

Abdulhadi|B|B| Kot|P|P| Hashim|K|K| Shaw|A|A| Muradov|M|M| Al-Khaddar|R|R|

Electrocoagulation
Aluminium electrodes
Heavy metals
Water treatment


Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer.

Abstract: Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.

Prager|Gerald W|GW|
Braemswig|Kira H|KH|
Martel|Alexandra|A|
Unseld|Matthias|M|
Heinze|Georg|G|
Brodowicz|Thomas|T|
Scheithauer|Werner|W|
Kornek|Gabriela|G|
Zielinski|Christoph C|CC|

D000971:Antineoplastic Combined Chemotherapy Protocols

carcinoembryonic antigen
colorectal cancer
bevacizumab
Angiogenesis inhibitors
biological markers


The phylogenetic origin and evolution of acellular bone in teleost fishes: insights into osteocyte function in bone metabolism.

Abstract: Vertebrate bone is composed of three main cell types: osteoblasts, osteoclasts and osteocytes, the latter being by far the most numerous. Osteocytes are thought to play a fundamental role in bone physiology and homeostasis, however they are entirely absent in most extant species of teleosts, a group that comprises the vast majority of bony 'fishes', and approximately half of vertebrates. Understanding how this acellular (anosteocytic) bone appeared and was maintained in such an important vertebrate group has important implications for our understanding of the function and evolution of osteocytes. Nevertheless, although it is clear that cellular bone is ancestral for teleosts, it has not been clear in which specific subgroup the osteocytes were lost. This review aims to clarify the phylogenetic distribution of cellular and acellular bone in teleosts, to identify its precise origin, reversals to cellularity, and their implications. We surveyed the bone type for more than 600 fossil and extant ray-finned fish species and optimised the results on recent large-scale molecular phylogenetic trees, estimating ancestral states. We find that acellular bone is a probable synapomorphy of Euteleostei, a group uniting approximately two-thirds of teleost species. We also confirm homoplasy in these traits: acellular bone occurs in some non-euteleosts (although rarely), and cellular bone was reacquired several times independently within euteleosts, in salmons and relatives, tunas and the opah (Lampris sp.). The occurrence of peculiar ecological (e.g. anadromous migration) and physiological (e.g. red-muscle endothermy) strategies in these lineages might explain the reacquisition of osteocytes. Our review supports that the main contribution of osteocytes in teleost bone is to mineral homeostasis (via osteocytic osteolysis) and not to strain detection or bone remodelling, helping to clarify their role in bone physiology.

acellular bone
osteocyte
endothermy
bone remodelling
Actinopterygii
Salmoniformes
Scombridae
Teleostei
ancestral state reconstruction
anosteocytic bone


Chiral HPLC Separation and Modeling of Four Stereomers of DL-Leucine-DL-Tryptophan Dipeptide on Amylose Chiral Column.

Abstract: Chiral high-performance liquid chromatography (HPLC) separation and modeling of four stereomers of DL-leucine-tryptophan DL-dipeptide on AmyCoat-RP column are described. The mobile phase applied was ammonium acetate (10 mM)-methanol-acetonitrile (50:5:45, v/v). The flow rate of the mobile phases was 0.8 mL/min with UV detection at 230 nm. The values of retention factors for LL-, DD-, DL-, and LD- stereomers were 2.25, 3.60, 5.00, and 6.50, respectively. The values of separation and resolution factors were 1.60, 1.39, and 1.30 and 7.76, 8.05, and 7.19. The limits of detection and quantitation were ranging from 1.0-2.3 and 5.6-14.0 μg/mL. The simulation studies established the elution orders and the mechanism of chiral recognition. It was seen that π-π connections and hydrogen bondings were the main forces for enantiomeric resolution. The reported chiral HPLC method may be applied for the enantiomeric separation of DL-leucine-DL-tryptophan in unknown matrices. Chirality 28:642-648, 2016. © 2016 Wiley Periodicals, Inc.

Alajmi|Mohammed F|MF|
Hussain|Afzal|A|
Suhail|Mohd|M|
Mukhtar|Sofi Danish|SD|
Sahoo|Dibya Ranjan|DR|
Asnin|Leonid|L|
Ali|Imran|I|

D002851:Chromatography, High Pressure Liquid

HPLC
DL-Leucine-DL-tryptophan
dipeptide
AmyCoat-RP
chiral resolution
modeling studies


IFN-γ gene loaded human umbilical mesenchymal stromal cells targeting therapy for Graft-versus-host disease.

Abstract: Graft-versus-host disease (GVHD) is a frequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The application of mesenchymal stromal cells (MSCs) to treat GVHD patients refractory to initial steroid treatment has led to impressive results. In this study, we explored the potential of human umbilical mesenchymal stem cells (HUMSCs) transfected with the IFN-γ gene of human (h)/mice (m) (HUMSCs + Ad-h/mIFN-γ) carried by a recombinant adenoviral vector in the prevention and treatment of GVHD. We demonstrated that HUMSCs + Ad-h/mIFN-γ efficiently suppressed T lymphocyte proliferation and activation, induced G1 cell cycle arrest and apoptosis in vitro. To assess the in vivo efficacy of HUMSCs + Ad-h/mIFN-γ, Balb/c mice were induced to develop GVHD symptoms by tail vein injection of C57BL/6 splenocytes after irradiation. Weight, hair, survival, hemogram, and chimera condition of GVHD model mice were monitored before and after treatment, respectively. The results showed that HUMSCs + Ad-h/mIFN-γ reduced GVHD's incidence and severity on the model mice and provided a significant survival benefit. In conclusion, this study may provide validated evidence that the introduction of IFN-γ into HUMSCs would help ameliorate GVHD after allo-HSCT.

Li|Hui|H| Liu|Qi|Q| Gao|Xiaofeng|X| Zhang|Di|D| Mao|Shengjun|S| Jia|Yongqian|Y|

D018380:Hematopoietic Stem Cell Transplantation

Graft-versus-host disease
Adenoviral vectors
Allogeneic bone marrow transplantation
Umbilical cord mesenchymal stem cells
γ-interferon


Highly Efficient Semitransparent Organic Solar Cells with Color Rendering Index Approaching 100.

Abstract: Neutral-colored semitransparent organic solar cells (ST-OSCs) have attracted considerable attention owing to their unique application in no-visual-obstacle building-integrated photovoltaics. Toward this promising potential application, a synergistic effect is first proposed by employing a dielectric mirror and ternary photoactive layer with near-infrared absorption to tune the color perception as well as ST-OSC performance precisely. As a result, a neutral-color ST-OSC with high average transmittance of over 21% is successfully constructed, and a remarkable color-rendering index approaching 100 and high power conversion efficiency (PCE) of 9.37% are simultaneously achieved. To the best of our knowledge, this is the highest PCE reported for neutral-color ST-OSCs to date. Importantly, this synergistic effect is demonstrated to be a universal strategy that is not only suitable for various photoactive layer systems, but can also be implanted in flexible substrate. The resulting neutral-color flexible ST-OSCs also show a promising PCE of 8.76%.

semitransparent organic solar cells
color rendering index
ternary photoactive layers
flexible solar cells
neutral color


Compression of environmental representations following interactions with objects.

Abstract: Previous work reveals that interacting with all objects in an environment can compress spatial memory for the entire group of objects. To assess the scope and magnitude of this effect, we tested whether interacting with a subset of objects compresses spatial memory for all objects in an environment. Participants inspected objects in one or two unmarked regions of space, then recalled the distances between pairs of objects from memory. One group of participants picked up objects in both regions, a second group picked up objects in one region and passively viewed objects in the other region, and a third group passively viewed objects in both regions. When participants manually interacted with objects, they recalled shorter object-pair distances throughout the environment. The magnitude of this effect was the same, regardless of whether participants interacted with all objects in the environment or just a subset of them. Together, these findings suggest that interacting with objects can compress environmental representations in memory, even when observers interact with a relatively small subset of objects.

Clement|Andrew|A|
Radvansky|Gabriel A|GA|
Brockmole|James R|JR|

Interaction
Environments
Spatial memory
Embodied cognition


Pandemics of COVID-19 and racism: how HBCUs are coping.

Abstract: Historically Black Colleges and Universities (HBCUs) are currently facing unique challenges to deal with parallel pandemics of COVID-19 and Racism, given the population they serve (mostly African American) are at high risk of these unprecedented crises. HBCU leaders are adopting various strategies to respond to both the pandemics in order to protect their stakeholders. This paper addresses various models that HBCUs have adopted or planned to adopt to cope with these pandemics, gleaning the data from various secondary sources and selected first-hand interviews with HBCU administrators.

Murty|Komanduri S|KS|
Payne|Tamara B|TB|

pandemics
COVID-19
racism
HBCUs
African American
Breonna Taylor
George Floyd
social justice
vaccine


Spatial patterns of pharmaceuticals and wastewater tracers in the Hudson River Estuary.

Abstract: The widespread use of pharmaceuticals by human populations results in their sustained discharge to surface waters via wastewater treatment plants (WWTPs). In this study, 16 highly prescribed pharmaceuticals were quantified along a 250 km transect of the Hudson River Estuary and New York Harbor to describe their sources and spatial patterns. Sampling was conducted over two dry weather periods in May and July 2016, at 72 sites which included mid-channel and nearshore sites, as well as locations influenced by tributaries and WWTP outfalls. The detection frequency of the study pharmaceuticals was almost identical between the May and July sampling periods at 55% and 52%, respectively. Six pharmaceuticals were measurable at 92% or more of the sites during both sampling periods, illustrating their ubiquitous presence throughout the study area. Individual pharmaceutical concentrations were highly variable spatially, ranging from non-detect to 3810 ng/L during the study. Major factors controlling concentrations were proximity and magnitude of WWTP discharges, inputs from tributaries and tidal mixing. Two compounds, sucralose and caffeine, were evaluated as tracers to identify wastewater sources and assess pharmaceutical behavior. Sucralose was useful in identifying wastewater inputs to the river and concentrations showed excellent correlations with numerous pharmaceuticals in the study. Caffeine-sucralose ratios showed potential in identifying discharges of untreated wastewater occurring during a combined sewage overflow event. Many of the study pharmaceuticals were present throughout the Hudson River Estuary as a consequence of sustained wastewater discharge. Whereas some concentrations were above published effects levels, a more complete risk assessment is needed to understand the potential for ecological impacts due to pharmaceuticals in the Hudson River Estuary.

Cantwell|Mark G|MG|
Katz|David R|DR|
Sullivan|Julia C|JC|
Shapley|Daniel|D|
Lipscomb|John|J|
Epstein|Jennifer|J|
Juhl|Andrew R|AR|
Knudson|Carol|C|
O'Mullan|Gregory D|GD|

Pharmaceuticals
Wastewater tracers
Hudson river
Emerging contaminants


Preparation of electrospun polyacrylonitrile/Ni-MOF-74 nanofibers for extraction of atenolol and captopril prior to HPLC-DAD.

Abstract: Electrospun nanofibers of polyacrylonitrile/Ni-metal-organic framework 74 (PAN/Ni-MOF-74) were prepared and utilized as a novel sorbent for spin-column micro-solid-phase extraction (SC-μSPE) of atenolol (ATN) and captopril (CAP). The electrospun nanofibers were characterized by field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. Ni-MOF-74 nanoparticles in the polymeric network of polyacrylonitrile considerably enhance the extraction efficiency of the electrospun sorbent due to providing hydrophobic, hydrogen bonding, and π-π interactions with the target analytes. The entire procedure, including sample loading, washing, and eluting of the target analytes was performed by centrifugation of the spin column. The extracted analytes were then quantified by high-performance liquid chromatography with a diode array detector. Various parameters affecting extraction efficiency were optimized using the one-variable-at-a-time method. Under optimum conditions, the calibration plots were linear in the range 0.5-500 ng mL-1 for ATN and 0.3-500 ng mL-1 for CAP with r2 > 0.999. Limits of detection of 0.15 and 0.13 ng mL-1 were obtained for ATN and CAP, respectively. The intra-assay relative standard deviation for five replicate measurements was ≤ 7.8. The relative recoveries for both drugs were within the range 82.6-98.9%. The applicability of the method was successfully investigated for measuring the target drugs in biological fluids and wastewater. The results indicate proper accuracy and analytical performance of the proposed method. Graphical abstract Schematic presentation of electrospun nanofibers of polyacrylonitrile/Ni-metal-organic framework 74 (PAN/Ni-MOF-74) which are used as the sorbent for spin-column microextraction (SC-μSPE) of atenolol (ATN) and captopril (CAP) prior to HPLC-DAD analysis.

Amini|Shima|S| Ebrahimzdeh|Homeira|H| Seidi|Shahram|S| Jalilian|Niloofar|N|


Discrepancies in the Brazilian tobacco production chain: raw inputs, international trade and legal cigarette production.

Abstract:
BACKGROUND
The significant market share of illicit cigarettes in Brazil is well established in the literature, nonetheless lacking clarity in terms of its actual size. Paraguay has a paramount role in this discussion, acting both as a supplier of illegal tobacco products to Brazil and as buyer of inputs from Brazil. A proper analysis of the illicit cigarette market in Brazil necessarily involves a deeper discussion of the Paraguayan production chain and its interaction with the Brazilian market.

METHODS
International data were used to establish the bilateral legal trade pattern of tobacco-related products between Paraguay and Brazil, including inputs and final outputs. Inspired by the technical requirements methodology, available unmanufactured tobacco within Brazil was obtained by adding-up domestic production with net imports. Its historical behaviour was compared with legal cigarette production patterns within Brazil. Supposing rational agents, these two links of the Brazilian cigarette production chain should behave similarly: for lower final usage, less domestically available supply. Any discrepancies would suggest something abnormal in the production chain.

RESULTS
Brazil is a relevant legal supplier of intermediate goods for the Paraguayan tobacco complex and has an irrelevant position as legal buyer of Paraguayan tobacco-related goods (either inputs or final goods). Paraguayan net imports of production inputs seem to be abnormally high for their legal needs. In Brazil, a clear discrepancy between domestically available unmanufactured tobacco (input) and tax-based cigarette production (output) emerged throughout the years and, even more striking, has been growing over the years.

CONCLUSIONS
Excessive cigarette production inputs in Paraguay suggest a potential oversupply of cigarettes in that country-likely diverted to illicit trade. Likewise, discrepancies in the Brazilian tobacco production chain are also evidence of illicit tobacco trading in Brazil-not necessarily of final products. A deeper analysis of the Brazil/Paraguay tobacco supply chain would be welcomed given the likely operation of these two countries as a single 'production/consumption hub' of both legal and illegal products (either inputs or final tobacco products). Public policies should foster controls not only on cigarettes but also on raw inputs for their production.

Ribeiro|Livio Santos de Leite|LSL|0000-0002-3413-5697

illegal tobacco products
public policy
economics
low
middle income country


High lactate dehydrogenase was associated with adverse outcomes in patients with acute ischemic stroke or transient ischemic attack.

Abstract:
BACKGROUND
Previous studies found that lactate dehydrogenase (LDH) levels predicted poor outcomes in hemorrhagic stroke, but the prognostic role of LDH in ischemic stroke (IS) remains unclear. The aim of this study is to investigate the association between LDH and adverse clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).

METHODS
All patients were enrolled from the Third China National Stroke Registry (CNSR-III). Adverse outcomes included all-cause death and poor functional outcomes [defined as modified Rankin Scale (mRS) score 3-6 and 2-6] at 3 months and 1 year. Multivariable Cox proportional hazards models and logistic regressions were used to evaluate the association of LDH with risk of all-cause death and poor functional outcomes, respectively.

RESULTS
Among 9,796 included patients, the median [interquartile range (IQR)] of LDH was 175.00 (151.00-205.40) U/L. After adjustment for confounding factors, patients in the highest LDH quartile had a higher risk of all-cause death [hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.27-3.90], and a higher proportion of mRS score 3-6 [odds ratio (OR), 1.54; 95% CI, 1.26-1.90] and mRS score 2-6 (OR, 1.56; 95% CI, 1.32-1.84) at 3 months. We also observed a J-shaped association between LDH and risk of each outcome. Consistent results were found at 1 year.

CONCLUSIONS
Higher LDH levels are independently associated with adverse outcomes in patients with AIS or TIA.

Wang|Anxin|A| Tian|Xue|X| Zuo|Yingting|Y| Wang|Xuechun|X| Xu|Qin|Q| Meng|Xia|X| Chen|Pan|P| Li|Hao|H| Wang|Yongjun|Y|

Lactate dehydrogenase (LDH)
acute ischemic stroke (AIS)
transient ischemic attack (TIA)
all-cause death
poor functional outcomes


Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial.

Abstract:
BACKGROUND
Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin.

METHODS
We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline.

RESULTS
Not applicable.

CONCLUSION
The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk.

TRIAL REGISTRATION
ClinicalTrials.gov NCT02967653 . Registered in February 2017.

Fotso Soh|Jocelyn|J|0000-0001-9706-995X
Torres-Platas|Susana G|SG|
Beaulieu|Serge|S|
Mantere|Outi|O|
Platt|Robert|R|
Mucsi|Istvan|I|
Saury|Sybille|S|
Renaud|Suzane|S|
Levinson|Andrea|A|
Andreazza|Ana C|AC|
Mulsant|Benoit H|BH|
Müller|Daniel|D|
Schaffer|Ayal|A|
Dols|Annemiek|A|
Cervantes|Pablo|P|
Low|Nancy Cp|NC|
Herrmann|Nathan|N|
Christensen|Birgitte M|BM|
Trepiccione|Francesco|F|
Rajji|Tarek|T|
Rej|Soham|S|

Atorvastatin
Nephrogenic diabetes insipidus
Lithium
Placebo
Kidney function
Randomized clinical trial
Urinary osmolality


Global Health, Geographical Contingency, and Contingent Geographies.

Abstract: Health geography has emerged from under the "shadow of the medical" to become one of the most vibrant of all the subdisciplines. Yet, this success has also meant that health research has become increasingly siloed within this subdisciplinary domain. As this article explores, this represents a potential lost opportunity with regard to the study of global health, which has instead come to be dominated by anthropology and political science. Chief among the former's concerns are exploring the gap between the programmatic intentions of global health and the unintended or unanticipated consequences of their deployment. This article asserts that recent work on contingency within geography offers significant conceptual potential for examining this gap. It therefore uses the example of alcohol taxation in Botswana, an emergent global health target and tool, to explore how geographical contingency and the emergent, contingent geographies that result might help counter the prevailing tendency for geography to be side-stepped within critical studies of global health. At the very least, then, this intervention aims to encourage reflection by geographers on how to make explicit the all-too-often implicit links between their research and global health debates located outside the discipline.

global health
contingency
geography
alcohol
Botswana
complexity


Phase II trial of pemetrexed continuation--maintenance after carboplatin-based induction in untreated non-squamous non-small cell lung cancer.

Abstract:
AIM
We conducted a phase II study to evaluate the efficacy and safety of pemetrexed continuation-maintenance after carboplatin-based induction for advanced non-squamous non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS
Thirty-four patients with advanced or recurrent non-squamous NSCLC received carboplatin (area under the concentration-time curve 6 mg/ml×min) plus pemetrexed (500 mg/m(2)) on day 1 tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity.

RESULTS
Twenty-five patients completed induction and 22 received maintenance. The 1-year survival, objective response and disease control rates were 70.3%, 32.4% and 88.2%, respectively. The median progression-free survival and overall survival of all patients were 5.2 and 23.3 months. The incidental rates of grade 3 or more severe adverse events were low.

CONCLUSION
This regimen appears to be an appropriate option for chemonaïve patients with advanced non-squamous NSCLC.

Minami|Seigo|S| Kijima|Takashi|T| Komuta|Kiyoshi|K| Kumagai|Toru|T| Imamura|Fumio|F| Yokota|Soichiro|S| Takeuchi|Yoshiko|Y| Nakatani|Takeshi|T| Tachibana|Isao|I| Kawase|Ichiro|I|

phase II trial
pemetrexed
non-squamous non-small cell lung cancer
Carboplatin


A Novel Neurosurgery Referral Course: Feasibility, Validation, and Inferences for Patient Care.

Abstract:
OBJECTIVE
The speciality of neurosurgery is under-represented in the majority of medical school curriculums, and those rotating within this specialty tend to be those with career aspirations within this field. Consequently, few emergency medicine trainees are exposed to this specialty. The aim of this educational project was to develop and validate a neurosurgery referral course for the target audience of emergency medics.

DESIGN
Development of a single day neurosurgery referral course, developed with accreditation from the Royal College of Surgeons England. The curriculum covered commonly referred pathologies. Content validity was assessed using a 5-point Likert Scale. Median Likert scores were compared to "indifferent" (3) (indifferent = 3 in this study Likert scale) using the Wilcoxon matched-pairs signed-rank test. Construct validity was assessed using a standardized pre and postcourse 10-single best answer exam and results compared using paired t tests.

SETTING
A pilot "Neurosurgery for Emergency Medics" referral course, hosted at a single UK based neurosurgery unit.

PARTICIPANTS
A cohort of 19 delegates, working in emergency departments various regions within the UK.

RESULTS
The subjective feedback showed significantly higher than the expected median Likert scale satisfaction scores (p = 0.0001). Construct validity was confirmed, with significant improvement in proportion of students getting the answers in the single best answer exam after the days training course (p = 0.017).

CONCLUSIONS
We demonstrate feasibility, content, and construct validity and conclude that this pilot "Neurosurgery for Emergency Medics" course was beneficial. Integration of this 1-day course into local doctor's induction programmes for emergency medicine and neurosurgery may advance both local and national standards for referrals and consults alike, with the ultimate goal of improving patient care.

Pradini-Santos|Laura|L|
Craven|Claudia L|CL|
Usher|Inga|I|
Mullins|Sophie|S|
D'Antona|Linda|L|
Al-Ahmad|Selma|S|
Abuhusain|Hazem|H|
Sayal|Parag P|PP|

referrals
validation
patient care
emergency department
medical education
neurosurgery training


Analysing the likelihood of caesarean birth after implementation of the two-childbirth policy in China, using the Ten Group Classification System.

Abstract: The aim of this study was to identify the main contributor to the high Caesarean section birth rate at a regional perinatal medical centre using the Robson Ten Group Classification System (TGCS). A total of 54,085 women were surveyed and were included in our study from 2015 to 2017 at the Women's Hospital at Zhejiang University School of Medicine in Hangzhou, China. The Caesarean birth rate was similar among the three years; although, the new two-childbirth policy in China has been in implementation since 2016. According to the TGCS, Group 5 was the largest contributor to the overall Caesarean birth rate (40.79%), followed by Group 2 (21.36%). The Caesarean birth rate of Group 5 and Group 2 decreased significantly from 2015 to 2017 (p < .05). The proportion of Group 7 contributing to the overall Caesarean birth rate increased significantly (p < .05). Future efforts should focus on increasing vaginal birth after Caesarean in Group 5 and external cephalic version in Group 7 to decrease the overall Caesarean birth rate.Impact statementWhat is already known on this subject? The Ten Group Classification System (TGCS) proposed by World Health Organisation was used in some countries such as Queensland, Singapore and Japan to assess and compare Caesarean section rates. The main contributor to the high Caesarean birth rate varies in different counties. However, it is not widely used in China.What the results of this study add? It was the first study using the TGCS to analyse the Caesarean birth rate and the changes after implementation of the two-childbirth policy in China. It identified that Group 5 (multiparous mothers with a previous Caesarean birth in a singleton, cephalic full-term pregnancy) constituted the most important determinant of overall Caesarean birth rates, followed by Group 2 (nulliparous mothers with a singleton, cephalic full-term pregnancy undergoing an induction of labour or prelabour Caesarean birth). The contribution of Group 5 and Group 7 (multiparous women with a single breech pregnancy) to the overall Caesarean birth rate has increased significantly since the new childbirth policy was implemented.What the implications are of these findings for clinical practice and/or further research? Future efforts should focus on increasing vaginal birth after Caesarean in Group 5 and external cephalic version in Group 7 to decrease the overall Caesarean birth rate in China.

China
Ten Group Classification System
childbirth policy
Caesarean delivery


Metabolome-based signature of disease pathology in MS.

Abstract:
BACKGROUND
Diagnostic delays are common for multiple sclerosis (MS) since diagnosis typically depends on the presentation of nonspecific clinical symptoms together with radiologically-determined central nervous system (CNS) lesions. It is important to reduce diagnostic delays as earlier initiation of disease modifying therapies mitigates long-term disability. Developing a metabolomic blood-based MS biomarker is attractive, but prior efforts have largely focused on specific subsets of metabolite classes or analytical platforms. Thus, there are opportunities to interrogate metabolite profiles using more expansive and comprehensive approaches for developing MS biomarkers and for advancing our understanding of MS pathogenesis.

METHODS
To identify putative blood-based MS biomarkers, we comprehensively interrogated the metabolite profiles in 12 non-Hispanic white, non-smoking, male MS cases who were drug naïve for 3 months prior to biospecimen collection and 13 non-Hispanic white, non-smoking male controls who were frequency matched to cases by age and body mass index. We performed untargeted two-dimensional gas chromatography and time-of-flight mass spectrometry (GCxGC-TOFMS) and targeted lipidomic and amino acid analysis on serum. 325 metabolites met quality control and supervised machine learning was used to identify metabolites most informative for MS status. The discrimination potential of these select metabolites were assessed using receiver operator characteristic curves based on logistic models; top candidate metabolites were defined as having area under the curves (AUC) >80%. The associations between whole-genome expression data and the top candidate metabolites were examined, followed by pathway enrichment analyses. Similar associations were examined for 175 putative MS risk variants and the top candidate metabolites.

RESULTS
12 metabolites were determined to be informative for MS status, of which 6 had AUCs >80%: pyroglutamate, laurate, acylcarnitine C14:1, N-methylmaleimide, and 2 phosphatidylcholines (PC ae 40:5, PC ae 42:5). These metabolites participate in glutathione metabolism, fatty acid metabolism/oxidation, cellular membrane composition, and transient receptor potential channel signaling. Pathway analyses based on the gene expression association for each metabolite suggested enrichment for pathways associated with apoptosis and mitochondrial dysfunction. Interestingly, the predominant MS genetic risk allele HLA-DRB1×15:01 was associated with one of the 6 top metabolites.

CONCLUSION
Our analysis represents the most comprehensive description of metabolic changes associated with MS in serum, to date, with the inclusion of genomic and genetic information. We identified atypical metabolic processes that differed between MS patients and controls, which may enable the development of biological targets for diagnosis and treatment.

Andersen|S L|SL|
Briggs|F B S|FBS|
Winnike|J H|JH|
Natanzon|Y|Y|
Maichle|S|S|
Knagge|K J|KJ|
Newby|L K|LK|
Gregory|S G|SG|

Multiple sclerosis
Metabolomics
Biomarker
Serum
Gene expression
Genotype


Combined ultrasound and nerve stimulator-guided deep nerve block may decrease the rate of local anesthetics systemic toxicity: a randomized clinical trial.

Abstract:
BACKGROUND
Ultrasound guidance might decrease the incidence of local anesthetics systemic toxicity (LAST) for many peripheral nerve blocks compared with nerve stimulator guidance. However, it remains uncertain whether ultrasound guidance is superior to nerve stimulator guidance for deep nerve block of the lower extremity. This study was designed to investigate whether deep nerve block with ultrasound guidance would decrease the incidence of LAST compared with that with nerve stimulator guidance, and to identify associated risk factors of LAST.

METHODS
Three hundred patients undergoing elective lower limb surgery and desiring lumbar plexus blocks (LPBs) and sciatic nerve blocks (SNBs) were enrolled in this study. The patients were randomly assigned to receive LPBs and SNBs with ultrasound guidance (group U), nerve stimulator guidance (group N) or dual guidance (group M). The primary outcome was the incidence of LAST. The secondary outcomes were the number of needle redirection, motor and sensory block onset and nerve distribution restoration time, as well as associated risk factors.

RESULTS
There were 18 patients with LAST, including 12 in group U, 4 in group N and 2 in group M. By multiple comparisons among the three groups, we found that the incidence of LAST in group U (12%) was significantly higher than that in group N (4%)(P = 0.037) and group M(2%)(P = 0.006). The OR of LAST with hepatitis B (HBV) infection and the female sex was 3.352 (95% CI,1.233-9.108, P = 0.013) and 9.488 (95% CI,2.142-42.093, P = 0.0004), respectively.

CONCLUSIONS
Ultrasound guidance, HBV infection and the female sex were risk factors of LAST with LPBs and SNBs. For patients infected with HBV or female patients receiving LPBs and SNBs, we recommended that combined ultrasound and nerve stimulator guidance should be used to improve the safety.

TRIAL REGISTRATION
This study was approved by the Ethical Committee of the First Affiliated Hospital of Army Medical University. The protocol was registered prospectively with the Chinese Clinical Trial Registry ( ChiCTR-IOR-16008099 ) on March 15, 2016.

Zhang|Xu-Hao|XH| Li|Yu-Jie|YJ| He|Wen-Quan|WQ| Yang|Chun-Yong|CY| Gu|Jian-Teng|JT| Lu|Kai-Zhi|KZ| Yi|Bin|B|0000-0001-5840-2086

Ultrasound
Nerve block
LAST
Nerve stimulation
HBV
Female


The role of Cymodocea nodosa on the dynamics of trace elements in different marine environmental compartments at the Mar Menor Lagoon (Spain).

Abstract: During mining activities historically developed at Sierra Minera (Cartagena-La Unión, Spain), high amounts of trace elements were discharged to the Mar Menor coastal lagoon mainly through El Beal Wadi. The objective of this study is to establish the role played by the Cymodocea nodosa in the coastal marine dynamics of trace elements at the mouth of the wadi. To this end, the content of nine trace elements (As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) in different marine environmental compartments (i.e. marine and coastal sediments, C. nodosa tissues collected from live seagrass and C. nodosa beach cast litter) at two different locations were determined by inductively coupled plasma atomic emission spectrometry. The results showed that the seagrass C. nodosa could mobilise part of the elements present in marine sediments and water, thereby causing their re-accumulation in the coastal sediments through the C. nodosa beach cast litter.

Serrano|Raquel|R| Gras|Luis|L| Giménez-Casalduero|Francisca|F| Del-Pilar-Ruso|Yoana|Y| Grindlay|Guillermo|G| Mora|Juan|J|

Mar Menor coastal lagoon
Analytical chemistry
Marine chemistry
Mining waste
Seagrass leaf litter beds
Trace metals mobilisation


Assessment of the toxic potential of engineered metal oxide nanomaterials using an acellular model: citrated rat blood plasma.

Abstract: Citrated Sprague-Dawley rat blood plasma was used as a biologically relevant exposure medium to assess the acellular toxic potential of two metal oxide engineered nanomaterials (ENMs), zinc oxide (nZnO), and cerium oxide (nCeO2). Plasma was incubated at 37 °C for up to 48 h with ENM concentrations ranging between 0 and 200 mg/L. The degree of ENM-induced oxidation was assessed by assaying for reactive oxygen species (ROS) levels using dichlorofluorescein (DCF), pH, ferric reducing ability of plasma (FRAP), lipase activity, malondialdehyde (MDA), and protein carbonyls (PC). Whereas previous in vitro studies showed linear-positive correlations between ENM concentration and oxidative damage, our results suggested that low concentrations were generally pro-oxidant and higher concentrations appeared antioxidant or protective, as indicated by DCF fluorescence trends. nZnO and nCeO2 also affected pH in a manner dependent on concentration and elemental composition; higher nZnO concentrations maintained a more alkaline pH, while nCeO2 tended to decrease pH. No other biomarkers of oxidative damage (FRAP, MDA, PC, lipase activity) showed changes at any ENM concentration or time-point tested. Differential dissolution of the two ENMs was also observed, where as much as ∼31.3% of nZnO was instantaneously dissolved to Zn2+ and only negligible nCeO2 was degraded. The results suggest that the direct oxidative potential of nZnO and nCeO2 in citrated rat blood plasma is low, and that a physiological or immune response is needed to generate appreciable damage biomarkers. The data also highlight the need for careful consideration when selecting a model for assessing ENM toxicity.

Gormley|Patrick Thomas|PT|
Callaghan|Neal Ingraham|NI|
MacCormack|Tyson James|TJ|
Dieni|Christopher Anthony|CA|

metal oxide
oxidation
Blood plasma
zinc oxide
cerium oxide
nanoparticles


Spontaneous middle cranial fossa cerebrospinal fluid otorrhea in adults.

Abstract:
OBJECTIVES/HYPOTHESIS
The goals of this study are to: 1) investigate the urgency for repair of middle cranial fossa spontaneous cerebrospinal fluid (CSF) leaks in adults, and 2) review the literature and treatment recommendations for adult spontaneous CSF otorrhea.

DATA SOURCES
1) All patients who were referred to a tertiary center with spontaneous CSF otorrhea, exposed middle cranial fossa dura, or encephalocele from 2004 to 2015; and 2) landmark references on spontaneous CSF leaks

REVIEW METHODS
Electronic medical records of patients with a documented spontaneous CSF leak, exposed dura, or encephalocele were reviewed. Subjects were excluded if they had a congenital, traumatic, or iatrogenic CSF leak. Main outcome measure was duration of CSF leak and development of meningitis after clinical presentation.

RESULTS
Twenty-two patients (27 ears) who were at risk for meningitis from spontaneous CSF otorrhea, encephalocele, or a dural breach with or without mastoiditis were evaluated. Duration of CSF leaks in patients who refused repair or who continued to have CSF leak after repair or prior to successful repair ranged from 4 months to 11 years. Duration of encephaloceles and dural exposure in an uninfected mastoid ranged from 24 months to 6 years. Only one patient presented with meningitis. None of these 22 patients developed meningitis during the time periods they were under our care.

CONCLUSION
Should patients with CSF otorrhea, exposed dura, or encephalocele refuse operation, it may be reasonable to follow them with close observation and education about warning signs for meningitis.

cerebrospinal fluid otorrhea
meningitis
cerebrospinal fluid leak


Early prediction of mortality risk among patients with severe COVID-19, using machine learning.

Abstract:
BACKGROUND
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, has been spreading globally. We aimed to develop a clinical model to predict the outcome of patients with severe COVID-19 infection early.

METHODS
Demographic, clinical and first laboratory findings after admission of 183 patients with severe COVID-19 infection (115 survivors and 68 non-survivors from the Sino-French New City Branch of Tongji Hospital, Wuhan) were used to develop the predictive models. Machine learning approaches were used to select the features and predict the patients' outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models' performance. A total of 64 with severe COVID-19 infection from the Optical Valley Branch of Tongji Hospital, Wuhan, were used to externally validate the final predictive model.

RESULTS
The baseline characteristics and laboratory tests were significantly different between the survivors and non-survivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the external validation sets were 0.881. The sensitivity and specificity were 0.839 and 0.794 for the validation set, when using a probability of death of 50% as the cutoff. Risk score based on the selected variables can be used to assess the mortality risk. The predictive model is available at [https://phenomics.fudan.edu.cn/risk_scores/].

CONCLUSIONS
Age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level of COVID-19 patients at admission are informative for the patients' outcomes.

Hu|Chuanyu|C|
Liu|Zhenqiu|Z|
Jiang|Yanfeng|Y|
Shi|Oumin|O|
Zhang|Xin|X|
Xu|Kelin|K|
Suo|Chen|C|
Wang|Qin|Q|
Song|Yujing|Y|
Yu|Kangkang|K|
Mao|Xianhua|X|
Wu|Xuefu|X|
Wu|Mingshan|M|
Shi|Tingting|T|
Jiang|Wei|W|
Mu|Lina|L|
Tully|Damien C|DC|
Xu|Lei|L|
Jin|Li|L|
Li|Shusheng|S|
Tao|Xuejin|X|
Zhang|Tiejun|T|
Chen|Xingdong|X|

COVID-19
machine learning
predictive model
death
fatality rate


Chemotherapy use in early stage anal canal squamous cell carcinoma and its impact on long-term overall survival,,.

Abstract:
BACKGROUND
The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy. It is postulated that chemotherapy could be omitted for the earliest stages without worsening outcomes.

METHODS
We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation, with and without chemotherapy, and at least two months of follow-up. Of the 2,959 patients meeting eligibility, 92% received chemotherapy (n = 2722) and 8% (n = 237) did not. Most patients were white (n = 2676), female (n = 2019), had private insurance (n = 1507) and were treated in a comprehensive cancer center (n = 1389). Average age was 58.5 years.

RESULTS
Predictors of chemotherapy omission were age > 58 years (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and treatment at the start of the study period (OR 1 for years 2004-2006). HR for single-agent chemotherapy was 0.70 (95% CI [0.50-0.96], P = 0.0288) and 0.48 for multi-agent (95% CI [0.38-0.62], P <0.0001). Overall survival was 86% in those that received chemotherapy vs 65% in those who did not (P <0.0001).

CONCLUSIONS
In conclusion, patients with early-stage squamous cell cancer of the anus who are treated with combination chemoradiation continue to demonstrate better overall survival than those who undergo radiotherapy alone.

Huffman|Deanna L|DL|
Jayakrishnan|Thejus T|TT|
Vannatter|Brittany L|BL|
Monga|Dulabh K|DK|
Finley|Gene G|GG|
McCormick|James T|JT|
Kirichenko|Alexander V|AV|
Wegner|Rodney E|RE|

Chemotherapy
Survival
Radiotherapy
Anal cancer
National cancer database


Evaluation of oral health-related quality of life in patients with temporomandibular disorders.

Abstract: Objective: To evaluate oral health-related quality of life (OHRQoL) in patients with temporomandibular disorders (TMDs).Methods: Subjects included 56 patients diagnosed with TMD. Control subjects consisted of 30 individuals without temporomandibular joint symptoms. OHRQoL was evaluated using the Japanese version of the Oral Health Impact Profile (OHIP-J54) before and 4 months after treatment.Results: Total score and all subscale scores of the OHIP-J54 in patients before treatment were significantly higher than those of the control subjects and were significantly improved after treatment, except for social disability. Gender and NRS pain scores had statistically significant effects on OHRQoL, which was low in females and patients with severe pain.Conclusion: OHIP-J54 appeared to be useful for understanding psychological and social problems as a screening tool and for assessing the extent of changes in the well-being of patients with TMD.


Enhancing CO2 Electroreduction with Au/Pyridine/Carbon Nanotubes Hybrid Structures.

Abstract: Selective electrochemical reduction of CO2 by using renewable electricity has received considerable attention because of the potential to convert a harmful greenhouse gas into useful chemicals. A high-performance electrocatalyst for CO2 reduction is constructed based on metal nanoparticles/organic molecule hybrid materials. On the nanoscale, Au nanoparticles are uniformly anchored on carbon nanotubes to afford substantially increased current density, improved selectivity for CO, and enhanced stability. On the molecular level, the catalytic performance is further enhanced by introducing axial pyridine groups to the surface of the carbon nanotubes. The resulting hybrid catalyst exhibits around 93 % faradaic efficiency for CO production over a wide potential range (-0.58 to -0.98 V), a high mass activity of 251 A gAu -1 at -0.98 V in aqueous solution at near-neutral pH, and strong stability with continuous electrolysis for 10 h at -0.58 V. DFT calculations indicate that the synergistic effects of Au and axial pyridine could dramatically stabilize the key intermediate (*COOH) formed in the rate-limiting step of CO2 reduction, which effectively lowers the overpotential.

carbon dioxide
density function calculations
electrocatalysis
gold
reactive intermediates


Determination of tetrabromobisphenol-A/S and their eight derivatives in abiotic (soil/dust) samples using ultra-high performance liquid chromatography-tandem mass spectrometry.

Abstract: Tetrabromobisphenol-A and Tetrabromobisphenol-S (TBBPA/S) and their derivatives have attracted widespread attention owing to their environmental risks and adverse effects on human health. In this study, we developed an analytical method based on ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of TBBPA/S and their eight derivatives in soil samples. After ultrasonic extraction, TBBPA/S and their derivatives were purified using an LC-Si cartridge with 1 mL acetone and 30 mL dichloromethane/n-hexane (1/1, v/v) as the eluent. In the multiple reaction monitoring (MRM) mode, TBBPA and TBBPS were quantified with electrospray ionization (ESI), whereas their derivatives were quantified with atmospheric pressure chemical ionization (APCI). The proposed method was verified with blank spiking and matrix spiking experiments. All target compounds were recovered at the range of 78-124% and the average recoveries of surrogate standard 13C12-labeled TBBPA were 103% and 99% in spiked blank and soil samples, respectively. The method quantitative limits (MQLs) of TBBPA/S and their derivatives in soil samples ranged from 0.22 to 8.8 pg/g dw. These results indicated that an effective method was provided for the analysis of TBBPA/S and their derivatives in abiotic matrices.

Yang|Hui|H| Luo|Xiao-Jun|XJ| Zeng|Yan-Hong|YH| Mai|Bi-Xian|BX|

Derivatives
Analytical method
Abiotic samples
Tetrabromobisphenol A
Tetrabromobisphenol S


Triclosan inhibits the activation of human periodontal ligament fibroblasts induced by lipopolysaccharide from Porphyromonas gingivalis.

Abstract: Periodontitis is a highly prevalent, chronic, non-specific, and immunologically devastating disease of periodontal tissues, caused by microbial infection. This study aims to examine the efficacy and protective mechanism of triclosan (TCS), a bisphenolic, non-cationic component of oral care products, against periodontal inflammation induced by lipopolysaccharide purified from Porphyromonas gingivalis (LPS-PG). TCS markedly downregulated interleukin-6 (IL-6), IL-8, and IL-15 in human periodontal ligament fibroblasts (HPDLFs) treated with LPS-PG. By using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach, 318 differentially expressed proteins (161 upregulated and 157 downregulated) were identified in TCS-pretreated HPDLFs. TCS upregulated HSPA5 and HSP90B1 but downregulated HSPA2. Besides, TCS upregulated miR-548i in HPDLFs, which downregulated IL-15. These results indicate that TCS attenuates the activation of HPDLFs and downregulates the inflammatory cytokines through various mechanisms, thus highlighting its protective role in periodontal inflammation.

Shu|Wei|W| Zhang|Yanman|Y| Zhang|Chen|C| You|Qiang|Q| Zhou|Hong|H| Wen|Shuang|S|

triclosan
human periodontal ligament fibroblasts
lipopolysaccharide
heat shock protein


Execution of julolidine based derivative as bifunctional chemosensor for Zn2+ and Cu2+ ions: Applications in bio-imaging and molecular logic gate.

Abstract: A simple julolidine based chemosensor (JT) was designed and synthesized by single condensation step. JT displayed excellent selectivity and sensitivity with on-off responses towards Zn2+ and Cu2+ over other biologically relevant metal ions in aqueous media. Upon addition of Zn2+ ions, JT exhibited a significant blue shift in emission followed by turn-on enhancement while with Cu2+, the fluorescence intensity of JT was completely vanished. The 1:1 binding affinity between JT and Zn2+/Cu2+ was proposed by Job's plot analysis. The detection limit for Zn2+ and Cu2+ ions reached at 3.5 × 10-8 M and 1.46 × 10-6 M, respectively. The sensing mechanism of JT with Zn2+/Cu2+ was supported by DFT calculations. Based on photophysical studies and its reversibility environment with EDTA, molecular logic gates were fabricated. Furthermore, JT was successfully established to detect intracellular Zn2+ ions in live cells by turn-on response.

Ganesan|Jeya Shree|JS|
Gandhi|Sivaraman|S|
Radhakrishnan|K|K|
Balasubramaniem|Ashokkumar|A|
Sepperumal|Murugesan|M|
Ayyanar|Siva|S|

Julolidine
Molecular logic gate
Live cell imaging
Zn(2+) and Cu(2+) sensor


"You think it's hard now … It gets much harder for our children": Youth with autism and their caregiver's perspectives of health care transition services.

Abstract: Adolescents with Autism Spectrum Disorder diagnosis often have complex comorbid physical and mental health conditions. These youth rely heavily on their medical providers and struggle through the often rocky transition out of pediatric care into adulthood and adult-centered care. This study is among the first to qualitatively examine the health care transition experiences of youth with Autism Spectrum Disorder and their caregivers. We conducted four focus groups with youth with Autism Spectrum Disorder (n = 13) and their caregivers (n = 19) and used thematic analysis strategies to identify key themes. Parents' discussions emphasized (a) loss of relationship with provider and lack of support transitioning from pediatric to adult care, (b) providers' lack of knowledge about Autism Spectrum Disorder, and (c) concerns about losing guardianship. Youth emphasized their confusion and anxiety around (a) medical providers' role, especially in the transition to adulthood; and (b) managing their medical lives independently. Our findings are important because they not only improve our understanding of health care transition needs among youth with Autism Spectrum Disorder and their caregivers but demonstrate a sound methodological procedure to facilitate input from youth with Autism Spectrum Disorder.

autism
caregiving
health care transition
adolescence/youth


A community-based sleep educational intervention for children with autism spectrum disorder.

Abstract:
Background
Sleep problems are common in children with autism spectrum disorder (ASD). Sleep education, effective in improving sleep in ASD, may be difficult to access. We determined if community-based pediatric therapists could successfully deliver sleep educational interventions to caregivers of children with ASD.

Methods
A seven-week feasibility study was conducted consisting of 10 children and caregivers. This feasibility study informed the development of a 16-week preliminary effectiveness study, which consisted of 33 children and caregivers. Children, ages 2-12 years, with a clinical diagnosis of autism and caregiver-reported sleep onset delay of 30 min were included. Community therapists underwent comprehensive training in sleep education and then met with caregiver participants to provide sleep education to each family. Semi-structured qualitative interviews were conducted with all families who completed study procedures.In the feasibility and preliminary effectiveness studies, child participants wore an actigraphy watch (at baseline and after sleep education) and caregivers completed the Child Sleep Habits Questionnaire and Family Inventory of Sleep Habits at baseline and after sleep education; the Child Behavior Checklist was also completed by caregivers in the preliminary effectiveness study.

Results
Educator fidelity to the manualized curriculum was maintained. Caregivers showed appropriate understanding, comfort, and implementation of the curriculum. Qualitative and quantitative measures, including caregiver surveys and actigraphy, showed improvements in child sleep and behavior.

Conclusions
Community-based therapists can successfully deliver sleep education to families of children with ASD, which has favorable implications for improving access to care in this population.

MacDonald|Lydia L|LL|
Gray|Laura|L|
Loring|Whitney|W|
Wyatt|Amanda|A|
Bonnet|Kemberlee|K|
Schlund|David|D|
Gaston|Mary Landis|ML|
Malow|Beth A|BA|

Sleep education
Autism spectrum disorder
Community
Children’s Sleep Habits Questionnaire