bluuebunny/crossref_metadata_2025 huggingface dataset:
Zonulin antagonist protects against tight junction disruption by Pseudomonas aeruginosa in airway epithelial cells
Authors: Kalsi Kameljit Kaur , Jackson Sonya , Baines Deborah Louise
Published: April 2020

Zonulin is known as a regulator of barrier function in both epithelial and endothelial cells in the intestine and kidney by acting through EGFR (epidermal growth factor receptor) and PAR2 (Proteinase activated receptors) to cause the dissociation of ZO‐1 from occludin and claudin‐1 from the cell junctions. Respiratory infection is characterized by increased lung permeability caused by the reduction in the abundance and/or distribution of proteins at the tight junction. Here the effect of the zonulin antagonist, larazotide acetate (LA) on airway epithelial cell barrier function after the addition of lipopolysaccharide (LPS) from Pseudomonas aeruginosa or undiluted P.aeruginosa filtrate isolated from an overnight culture was investigated. Two human airway epithelial cell models were used, H441 cells grown at air‐liquid interface and 16HBE14o‐cells grown as submerged monolayers. Cells were incubated with 10 μg/ml LPS and 12 mM larazotide acetate. Transepithelial electrical resistance (TEER) and permeability was measured after 1h and 6h. TEER was decreased with LPS which was prevented by LA, (p<0.05, n=3) LPS vs LPS/LA at 1 hour. Permeability was increased with LPS after 6h (p<0.05, n=3) LPS vs control. Cells were immunostained for ZO‐1 and E‐cadherin, LPS caused the disappearance of ZO‐1 staining at the apical surface which was conserved with LA. E‐cadherin localization did not change with either LPS or LPS/LA treatment. Total protein abundance assessed by western blot showed no changes. Exposure of 16HBE14o‐ cells to P.aeruginosa filtrate for 24 h lead to a 61% decrease in TEER compared to control (p<0.0001, n=3). P.aeruginosa filtrate/LA increased TEER by 39% (p<0.02, n=3). Tight junction localization of E‐cadherin and claudin‐1 were both disrupted with P.aeruginosa filtrate while incubation with LA attenuated this rearrangement. This study shows that larazotide acetate helped to counteract the damage to tight junctions caused by LPS and P.aeruginosa filtrate, this supports a role for zonulin as a regulator of lung epithelial barrier function.

Support or Funding Information

Funded by Astra Zeneca
Remediation of Nitrate in Drinking Water and Accumulation of Lipids using Microalgae
Authors: Hankore Wihib D. , Behrens Mark , Black Paul , DiRusso Concetta
Published: April 2020

The use of fertilizers in agriculture, and especially nitrogen to improve crop yield has resulted in the accumulation of high levels of nitrates in the groundwater (wells) throughout the mid‐western US states. This can lead to high levels of nitrates in drinking water, which exceeds the Safe Drinking Water Act, which the EPA limits at 10 mg/L. Drinking water containing nitrate levels above 10 mg/L is associated with significant health risks, particularly to unborn infants, as it can cause blue‐baby syndrome, a condition caused reduced capacity of hemoglobin to carry oxygen. Our laboratory has been employing microalgae to remediate nitrates to reduce this burden on water supplies. Two of the algal strains we have used were able to reduce Bold Basal Media (BBM) level nitrate (42mg/L) down to below 1 mg/L in 4 days, with an optical density (OD550) absorbance of around 3.0. In addition to remediating nitrate from contaminated sources, these microorganisms also accumulate lipids (triglycerides) under certain nutrient conditions and have been promoted as a feedstock for biofuels. Our lab has discovered several small compounds including WD30030 and WD20067 that induce lipid accumulation in algae without reducing growth and biomass in Chlamydomonas reinhardtii. In the present studies, we evaluated the impact of the compounds on several algal strains that have shown good growth in large bioreactors, Coccomyxia subellipsoidea – C169, Scenedesmus acutus f. alternans (UTEX B72), Chlorella kessleri (UTEX 2229) and Bumilleriopsis filiformis. Both nitrate removal and lipid accumulation during growth were monitored to assess whether or not these organisms can be used to couple nitrate remediation to production of high value lipid products.

Support or Funding Information

Nebraska Department of Economic Development and Vestal W2O, LLC
Angiotensin‐(1‐7) Actions in Animal Models of Metabolic Syndrome: a Systematic Review
Authors: Cordeiro Beatriz , Hilgemberg-Junior Romel , Guimaraes Priscila
Published: April 2020

This systematic review aims to collect all available data of Ang‐(1‐7) in animal models to study metabolic syndrome (MetS). The following electronic bibliographic databases have been searched: PubMed, EMBASE, Web of Science, and Scopus. The full search strategy was based on the search components “animal models”, “metabolic syndrome” and “angiotensin‐(1‐7)”. No publication date or language restrictions have been applied. The protocol of this study is available online in PROSPERO. The comprehensive search retrieved a total of 2056 citations (EMBASE, n = 816; PubMed, n = 285; SCOPUS, n = 290; Web of Science, n = 665). All citations were saved into one file in reference software. After removing duplications (n = 891), a total of 1419 citations were screened considering title and abstract, resulting in 149 citations selected as potentially relevant articles. These were then screened considering the full text content, resulting in 54 citations for data extraction. The other citations were either duplications (n = 4), conference abstracts (n = 66), or did not match inclusion criteria for disease and/or intervention (n = 25). Data extraction revealed that 31 of 54 studies, besides evaluating metabolism, have performed in vivo and/or ex vivo protocols to analyze the effects of increasing Ang‐(1‐7) availability (n = 27) or Mas receptor blockade (n = 4) on cardiovascular system. Among the other 23 citations that did not study cardiovascular parameters, 20 evaluated Ang‐(1‐7) effects on metabolism, and 3, the blockade or knockout of Mas recector. Outcomes are still being extracted and categorized for reporting. All database searches have been performed in July, 2019. This systematic review may gather all available data of Ang‐(1‐7) in animal models to study MetS, based on original full text articles, and categorize it by type of interventions, animal models, MetS induction method, and outcome measures. These results may contribute to highlight the efficacy of Ang‐(1‐7) on MetS risk factors as well as possible related gaps in the literature in this concern.

Support or Funding Information

FAPEAL, CAPES, CNPq
Effects of exercise training on metabolic and cardiovascular dysfunctions in offspring of fructose animals: role of cholinergic anti‐inflammatory reflex.
Authors: Dias Danielle Silva , Dos Santos Camila Silva , Araujo Amanda , Ferreira Maycon , Shecaira Tânia , Carmo Gabriel , Bernardes Nathalia , Irigoyen Maria Cláudia , De Angelis Kátia
Published: April 2020

Aim

To evaluate the effects of aerobic ET on metabolic and cardiovascular parameters in offspring of fructose‐consuming animals, testing the role of cholinergic anti‐inflammatory reflex in this condition by splenectomy.

Methods

Offspring of Wistar genitor rats treated with fructose or placebo (water) were divided into 4 groups: sedentary‐water (W), sedentary‐fructose (F), trained‐fructose (TF) and trained‐splenectomized‐fructose (TSF). Fructose overload (10%) was started 30 days after weaning only for the parents and continued until the end of lactation. The offspring received standard feeding and 30 days after weaning the spleen was removed (splenectomy) and the ET was started on treadmill (1h/d, 5d/week, 4 weeks, moderate intensity). After 30 days, the glycemia, blood triglycerides (TG) and insulin tolerance were evaluated. Blood pressure (BP) and heart rate (HR) signals were directly recorded in awake animals through an acquisition system.

Results

Although no differences in glycemia and insulin tolerance were observed, the TSF group showed an increase in TG compared to W, F and TF groups (166 ± 12 vs. 100±6; 113±11; 110±4 mg/dL). Regarding cardiovascular changes, the F group had increased systolic blood pressure (SBP) compared to W group (F: 127±4 vs. W: 117±2 mmHg). ET prevented the increase in SBP (TF: 118 ± 2 mmHg); however, this benefit was not observed in the TSF group (129±5 mmHg). In addition, diastolic BP was higher in the TSF group (100±6 mmHg) compared to W and TF groups (91 ± 3 and 87 ± 2 mmHg). There was no difference in HR between the groups studied. BP variability was increased in F group in relation to TSF group.

Conclusion

The consumption of fructose by parents induced early BP changes in offspring, which were prevented by exercise training. In addition, splenectomy abolished the cardiovascular benefits of ET in offspring of fructose rats, suggesting participation of the anti‐inflammatory cholinergic reflex in these adaptations.

Support or Funding Information

FAPESP: 2018/17183‐4, CNPq (157746/2018‐6) and UNINOVE
Age‐Related Increase in Extra‐Media Thickness is Associated with Arterial Stiffening and Carotid Blood Pressure
Authors: Carlini Nicholas A. , Harber Matthew P. , Fleenor Bradley S.
Published: April 2020

Older age is a primary risk factor associated with future cardiovascular disease (CVD) related events. Age‐related changes in perivascular adipose tissue (PVAT) and vascular remodeling both contribute to arterial stiffening and increased blood pressure which are established CVD risk factors. The non‐invasively measured extra‐media thickness (EMT) is a novel and composite measure, which includes PVAT, arterial adventitia, and the jugular vein that may provide translational insight for these factors contributing to age‐related arterial stiffening and higher blood pressure. However, it is unknown if aging increases EMT and is associated with arterial stiffness and blood pressure. We hypothesized that age‐related increases in EMT will be associated with higher arterial stiffness and blood pressure. Forty participants (young: 8M/12F, 23.2 ± 1.1 yrs and middle‐aged/older: 7M/13F, 60.7 ± 9.4 yrs) underwent measures of blood pressure (brachial; carotid), arterial stiffness (carotid b‐stiffness), EMT via ultrasonography and body composition with dual x‐ray absorptiometry. All measurements were taken in the supine position. Group mean differences between young and middle‐aged/older participants were analyzed with unpaired t‐tests and Pearson correlations were used to assess relations between EMT and arterial stiffness and blood pressure endpoints. Compared to younger participants, middle‐aged/older participants had higher EMT (0.80 ± 0.03 vs. 0.69 ± 0.02 mm), carotid beta stiffness (3.24 ± 0.08 vs. 2.60 ± 0.04), carotid SBP (116.5 ± 4.9 vs. 99.1 ± 2.3 mmHg), and carotid PP (44.6 ± 4.2 vs. 34.8 ± 1.5 mmHg) (all, p<0.05). Brachial SBP was not different between groups (p>0.05). Carotid beta stiffness (r= 0.410), carotid SBP (r= 0.501), and carotid PP (r= 0.5037) were all positively correlated with EMT for the entire cohort (all, p<0.05). Our findings indicate that there is an age‐related increase in EMT that is associated with both carotid arterial stiffness and pressure. These data suggest that increases in arterial stiffness and blood pressure with advancing age may be attributable, in part, to increases in EMT, which may be due to changes in PVAT and arterial adventitial remodeling. Therefore, EMT, a potential surrogate for PVAT and arterial remodeling, may provide novel insight into age‐related arterial stiffening, higher blood pressure and increased CVD risk with aging.
Ultra‐processed Food Consumption and Vascular Health
Authors: Smiljanec Katarina
Published: April 2020

Ultra‐processed (UP) foods are ready‐to‐eat foods formulated from industrial sources of dietary energy and nutrients, containing little or no whole foods. These products are typically high in saturated fats, added sugar, salt, and food additives, and low in protein, fiber, and micronutrients. UP foods are associated with an increase in energy intake (EI), weight gain, obesity, and cardiovascular disease. The objective of this study was to test the hypothesis that UP food consumption is associated with increased blood pressure (BP), arterial stiffness, and pressure wave reflection. Habitual dietary intake was assessed via 3‐day food records in 22–45 year old non‐hypertensive adults. Food items were categorized to non‐processed and/or minimally processed (NP) and UP groups by using the NOVA system of food classification. Bivariate and partial Pearson correlation was used to identify relations between NP and UP foods with systolic (SBP) and diastolic BP (DBP), pulse wave velocity (PWV), and augmentation index normalized for heart rate at 75 beats per minute (AIx75). Thirty eight healthy subjects (17M, 21F; 29±7 yrs; BMI 23.9±3.3 kg/m2) were included in the study. Average UP food consumption was 45±18% of daily EI. UP food consumption was positively associated with AIx75 (r=0.45, p<0.001), and trended to be positively associated with peripheral SBP (r=0.32, p=0.05) and peripheral DBP (r=0.29, p=0.07). When controlled for BMI, UP food consumption was positively associated with peripheral DBP (r=0.47, p=0.02), AIx75 (r=0.50, p=0.01), central SBP (r=0.44, p=0.03), and remained trending with peripheral SBP (r=0.40, p=0.05). When only women were analyzed, UP food consumption was positively associated with peripheral SBP (r=0.48, p=0.03), central SBP (r=0.57, p=0.03), AIx75 (r=0.54, p=0.01), and trended to be positively associated with peripheral DBP (r=0.41, p=0.06), even after controlling for BMI. There were no associations with UP food consumption and BP, PWV, or AIx75 in men. These findings suggest that UP food consumption is associated with increased BP and pressure wave reflection in healthy individuals and that these relations are more pronounced in women.

Support or Funding Information

Supported by NIGMS P20GM113125
The Effect of EGF Inhibition on Diurnal Variation of Blood Pressure in Mice
Authors: Arroyave Juan Sebastian , King-Medina Keyona N. , Lim Heeju , Hoover Robert S.
Published: April 2020

There are 78 million adults in the United States, who have hypertension also known as the “silent killer” because most individuals are unaware of their diagnosis. High blood pressure (BP) is a serious medical condition that serves as risk factor for cardiovascular disease (CVD), diabetes, and chronic kidney disease (CKD). Blood pressure normally declines about 10% during sleep. This nocturnal decline in blood pressure is called “dipping”. Studies have demonstrated that an attenuated decline in nocturnal blood pressure (“non‐dipping”) is associated with increased cardiovascular risks. Investigations by our group and others have demonstrated an effect of the epidermal growth factor (EGF) on sodium transport proteins and blood pressure. However, an association between EGF and “dipping” has not been described. We hypothesized that the inhibition of EGF will attenuate the sleep time (daytime for mice) decline of BP in mice. Using radio‐telemetry, in five male mice ages 6–7 weeks old, we collected the systolic blood pressure (SBP) measurements over 24‐hours daily for two weeks. These animals received a low Na+ diet (0.4% Na chow) for 6 days and high Na+ diet (4% Na chow) for 8 days. Only the experimental (E) group (n=3) received gefitinib (an EGF receptor tyrosine kinase inhibitor) at a regimen of 100 mg/kg/d given orally while the control (C) group (n=2) received a placebo. The change in SBP for sleep (9am–9pm) versus awake (9pm–9am), while receiving low salt diet (0.4% Na chow), showed the experimental group had less of a decrease in their SBP compared to the control group (E group: −9.7 ± 0.016 vs. C group: −14.4 ± 0.34 mmHg, p<0.001). The change (delta, Δ) in SBP was 4.7 mmHg, p<0.001 where the control group had a greater decrease in their SBP. When increasing the dietary Na+ intake by giving the high salt diet (4% Na+ chow), once again the experimental group demonstrated an attenuation of their ability to lower their SBP during sleep time compared to the control group (E group: −7.3 ± 0.18 vs. C group: −13.5 ± 0.38 mmHg, p<0.001). Here the Δ is 6.1 mmHg, p<0.001, which shows that the control group maintained a greater decrease in their resting SBP compared to the experimental group. Overall, our results suggest that inhibition of EGF leads to decreased dipping in SBP regardless of the dietary Na+ intake. This effect is greater with high Na+ in the diet. Our data is the first to suggest that EGF may play a role in the nocturnal dipping of blood pressure. This could have potential implications for hypertension‐related cardiovascular disease.

Support or Funding Information

NIH T32:5T32DK007656‐28 (King‐Medina) and VA Merit Awards: I01BX002322‐01 (Hoover)
Short‐term Physiological Knowledge Retention in Nursing Students.
Authors: Narnaware Raj , Neumeier Melanie
Published: April 2020

Despite anatomy and physiology being foundational courses in medical, nursing and allied ‐ health care programs, there is growing concern that the essential bioscience knowledge in these courses is not being retained by students over time. Numerous studies have demonstrated the difficulty of medical, nursing and allied health care students to retain and apply anatomical knowledge as they progress through their programs of study (Doomernik et al., 2017). However, physiological knowledge retention has not been studied as extensively as anatomical knowledge retention in health care disciplines, with very few studies focusing on nursing students (Aari et al., 2004). Of those studies most are carried out after graduation (Aari et al., 2004), or are focused on a single or limited number of organ systems (Pourshanazari et al., 2013). The present study aims to determine the level of physiological knowledge retained by nursing students in the four month time period between the completion of their physiology course in first‐year nursing and enrollment in the second‐year pathophysiology course. To answer this question, nursing students were quizzed on eight organ systems using the on‐line quizzing system Kahoot. Each Kahoot quiz included nine to eleven knowledge and comprehension level multiple‐choice questions. These scores were compared to first year quiz scores on the same content to determine overall knowledge retention over time. Data were statistically analyzed using SPSS II, and means were compared using 2‐sample t‐tests. The scores are described for each organ system by reporting the mean and standard deviation (SD). Statistical significance was set at P ≤ 0.05 for all tests. The mean score of questions from all organ systems in year one was 64.72 ± 9.3 (SD). Comparing that score to matched test items evaluated in the pathophysiology course, there is a decrease in the overall mean score from 64.72 ± 9.3 (SD) to 53.33 ± 25.8 (SD). This equates to an 86.6% retention rate, or 13.6% knowledge loss within four months. Organ‐specific knowledge retention was highest for renal physiology (99.0%), digestive physiology (97.8%), immunity (89.9%), vascular physiology (88.6%), and reproductive physiology (84.2%). Retention was comparatively lower for endocrine physiology (80.7%), inflammation (79.8%), and blood (79.4%). These results demonstrate a high level of knowledge retention overall with variations in retention being system specific. The level of knowledge retention in this study was significantly higher than previous rates reported in medical and allied‐health students (Pourshanazari et al., 2013) and is significantly higher than anatomical knowledge retention levels in the same population (Narnaware and Neumeier, 2019 a,b).

Support or Funding Information

None
A Novel Tumor Microenvironment Model that Combines Bioprinting and Tissue Culture to Investigate Cancer Cell and Microvascular Interactions
Authors: Suarez-Martinez Ariana D. , Sole-Gras Marc , Dykes Samantha S. , Wakefield Zachary R. , Bauer Kevin , Lampejo Arinola , Siemann Dietmar W. , Huang Yong , Murfee Walter L.
Published: April 2020

A challenge in cancer research is the lack of a physiologically responsive in vitro model that allows for the investigation of cancer cells in a tissue‐like environment. A model that enables real‐time investigation of cancer cell migration, fate, and function during microvascular network growth does not currently exist. While current models such as 2D in vitro models or microfluidic systems incorporate real‐time cell tracking and multiple cell types, they do not mimic the complexity of intact networks and tissue environments. The objective of this study was to establish a novel tumor‐microvasculature model by demonstrating the feasibility of bioprinting cancer cells onto excised mouse mesometrium tissues. Pre‐labeled DiI mouse breast cancer (4T1) cells were inkjet‐printed onto mouse mesometrium tissues. The cell ink for printing comprised of 2% Na‐alginate mixed in minimum essential media with 1% PenStrep (MEM) containing 15 million 4T1 cells. A single cancer cell spot per tissue was created by printing 10 drops of cell ink in the same location. MEM was added on top of tissue 30 seconds after printing and then incubated for 5 minutes before being plated into 6‐well plates containing MEM supplemented with 20% serum. Tissues were cultured for 5 days with media being changed every day. The spot of DiI+ cells was imaged every 24 hours to then quantify cell number and area for Day 0, 1, and 2. At Day 2 or 5, tissues were fixed in methanol and labeled with platelet endothelial cell adhesion molecule (PECAM), and E‐cadherin, to identify endothelial cells and cancer cells, respectively. Co‐localization of DAPI+ nuclei confirmed that DiI+ cells remained intact post‐printing. Printed DiI+ 4T1 cells also remained viable after printing on Day 0 and after culture on Day 5. Time‐lapse imaging over 5 days in culture enabled tracking of cell motility and proliferation. The number of cells (Day 0: 159 ± 40, Day 1: 370 ± 78, Day 2: 889 ± 184, Day 5: 18,031 ± 1,695) and cell area (Day 0: 0.72 ± 0.19, Day 1: 1.89 ± 0.33, Day 2: 2.92 ± 0.44, Day 5: 5.93 ± 0.75 mm2) were significantly increased over time. Moreover, a proliferation assay of anti‐BrdU on Day 2 also highlighted that a subset of E‐cadherin+ cells are in the S‐phase of the cell cycle contributing to the increase in cell number and cell area. Also, microvessels in the tissue were angiogenic evident by PECAM+ sprouts. These results corroborate that cancer cells are mobile and proliferative in this novel ex vivo model. Further, it demonstrates the potential for bioprinting cancer cells onto live, intact tissues to investigate cancer dynamics within a physiologically relevant microenvironment.

Support or Funding Information

NIH R01AG049821
Characterizing the circular RNA circPCNX through BaseScope RNA FISH
Authors: Harris Sophia , Tsitsipatis Dimitrios , Indig Fred , Gorospe Myriam
Published: April 2020

In eukaryotic cells, a transcribed pre‐mRNA is spliced by the spliceosome, a catalytic machinery comprising proteins and noncoding RNAs. Splicing typically removes introns, but it can also generate circular RNAs (circRNAs). The body of the circRNA is fully present in the parent pre‐mRNA; the only unique sequence is found where the ends of the linear RNA are ligated—the junction. Initially, circRNAs were thought to be inert byproducts of this splicing process. However, in recent years, it has been discovered that circRNAs may have important functions within the cell, including acting as a microRNA “sponge” that limits the functions of the miRNA. Through this and other functions, circRNAs have been implicated in many diseases including cancer.

The goal of this study is to visualize a particular circRNA in the cell. We have adopted the BaseScope technology (Advanced Cell Diagnostics, Newark, CA) to locate and visualize a circRNA via in situ hybridization. This technology utilizes a “ZZ”‐shaped probe to target specific sequences in RNA and greatly amplify a chromogenic signal. This method allows for probe hybridization to small RNA sequences, which is essential for visualization of circRNA, as the probe is specific to the circRNA junction sequence and will not hybridize to the pre‐mRNA. We have performed this method in HeLa cells to identify the circRNA circPCNX, a circRNA that associates with the cancer‐related RNA‐binding protein AUF1. We have also visualized PCNX mRNA, the linear counterpart of circPCNX. Ongoing BaseScope analysis reveals punctate dots, each representing a single instance of circPCNX, which allows for quantification of RNA copy numbers as well as visualization of their subcellular localization. Preliminary findings suggest that circPCNX exists in low abundancy in HeLa cells, while PCNX mRNA is found to be more abundant, and exists in both the cytoplasm and nucleus of HeLa cells. This method provides both descriptive and quantitative analyses of circPCNX that complement computational strategies to investigate circPCNX levels and localization in HeLa cells. Efforts to visualize circPCNX and other circRNAs shed light on the dynamics and functions of circRNAs and allow us to harness their therapeutic potential.

Support or Funding Information

This work was supported by the National Institute on Aging Intramural Research Program of the NIH.
Insomnia is Associated with an Increased Carotid‐Femoral Pulse Wave Velocity in Healthy Young Adults during Awake Hours
Authors: Gagnon Madison K. , Dempster Kylie S. , Wade Terrance J. , O’Leary Deborah D.
Published: April 2020

Current literature indicates that those living with insomnia have an increased risk of developing and dying from cardiovascular disease (CVD). Previous studies have investigated cardiovascular measures such as baroreflex sensitivity (cvBRS), heart rate (HR), blood pressure (BP) and serum lipid levels in those with insomnia, however these studies focus on older adults and do not investigate early cardiovascular changes occurring in a young population. The purpose of this study was to examine differences across multiple cardiovascular measures that may be associated with insomnia in a young, healthy adult population. This cross‐sectional analysis of the midpoint sample of the Niagara Longitudinal Heart Study used data from 156 participants aged 19–25 years. Insomnia was classified using the SLEEP‐50 questionnaire and was compared across measures of BP, HR, cvBRS, and carotid‐femoral pulse wave velocity (cfPWV). HR and BP were measured using an automatic oscillometric device, cvBRS was measured using a beat‐by‐beat systolic BP and RR intervals, and cfPWV was measured using a hand‐held tonometer which measured pressure waveforms. Significantly higher cfPWV was found in those with insomnia (M=6.00± 0.89) versus those without (M=5.57 ±0.88) (p=0.013). There were no significant differences between those with and without insomnia for BP, HR or cvBRS (p>0.05), however, a non‐significant trend in HR was found between those with insomnia (M=79.93± 11.92) and those without (M=75.91± 11.18) (p=0.058). Literature suggests that insomnia may lead to CVD through mechanisms including changes in autonomic activity, systemic inflammation, and hormonal dysregulation. Previous insomnia studies have not investigated cfPWV, therefore these findings suggest that arterial stiffness may be an early indicator of CVD risk in those with insomnia. These results are especially novel since they are being detected in a young, otherwise healthy population suggesting that CVD risk may begin to develop early in those suffering with insomnia. The identification of these differences at a young age suggests that significant cardiovascular change occurs earlier than previously expected in those living with insomnia, thus prompting early intervention to help reduce the physiological burden of this sleeping disorder.

Support or Funding Information

Funding source: The NLHS is funded by the Canadian Institutes of Health Research (CIHR #s 363774, 399332). KSD is funded by a CIHR Doctoral Research Award – Frederick Banting and Charles Best Canada Graduate Scholarship (RFN#167014)
Biological Sex Mediates Cancer Cachexia Associated Muscle Weakness
Authors: Blackburn George , Swan Zachary , Brantley T.J. , Tichy Louisa , Parry Traci
Published: April 2020

Cancer cachexia is a complex metabolic and wasting disease that results in death in up to one‐third of cancer patients and affects up to 80%. Currently, there are no clear diagnostic criteria, its effects are irreversible, and it cannot be treated. Therefore, a great need exists to better understand this disease. Furthermore, recent evidence states that cancer cachexia presents in a sexually dimorphic manner. Therefore, the purpose of this study was to determine whether cancer cachexia alters skeletal muscle function in a sexually dimorphic manner and to determine underlying mechanisms responsible for muscle wasting. Male and female mice underwent a 3 week period of tumor bearing (1×106 LLC cells in flank). Both male and female tumor bearing mice exhibited a loss in grip strength compared to baseline values. Interestingly, males exhibited a significantly greater loss in grip strength compared females (−17% vs −13%, P < 0.05). Male mice also exhibited significantly larger tumors compared to female mice (P < 0.01). Next, possible mechanisms responsible for cancer cachexia‐mediated muscle wasting were investigated. Since protein degratory pathways are known to play an important role in pathological muscle wasting, autophagy was investigated. Interestingly, while both male and female gastrocnemius exhibited an increase in LC3‐II protein levels (increased autophagy) compared to non‐tumor bearing controls, only female gastrocnemius LC3‐II levels were significantly increased (P<0.05). Since inflammation is thought to exacerbate pathological muscle wasting, IL‐1beta was investigated. Both male and female gastrocnemius exhibited increased IL‐1beta compared to non‐tumor bearing controls, though only male gastrocnemius exhibited a significant increase in IL‐1beta protein levels (P < 0.05). These data indicate that cancer cachexia does result in skeletal muscle weakness in a sexually dimprophic manner and that possible underlying mechanisms may differ by biological sex. Such data are critical in elucidating how cancer cachexia variably presents and progresses by biological sex, and in the identification of therapeutic targets aimed at muscle wasting in a sex specific manner.
Fecal-Oral Transmission of SARS-CoV-2 In Children
Authors: Donà Daniele , Minotti Chiara , Costenaro Paola , Da Dalt Liviana , Giaquinto Carlo
Published: April 2020

Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.
Conjunctival Implantation Cyst in the Orbicularis Oculi Muscle: Review of a Possible Origin From Displaced Stem Cells With a Differential Diagnosis
Authors: Jakobiec Frederick A. , Hanbazazh Mehenaz , Barrantes Paula Cortes , Yoon Michael K.
Published: April 2020

Purpose:

To document a unique case of a corneal/conjunctival epithelial inclusion cyst located in the orbicularis oculi muscle with a comprehensive review of variant conjunctival cysts and simulating conditions.

Methods:

Clinicopathologic case report with detailed histopathologic and immunohistochemical evaluation for cytokeratins combined with a tabulation of mimicking lesions and relevant literature citations.

Results:

A 59-year-old man experienced severe blunt left periorbital trauma that resulted in a limbal partial-thickness corneal wound with an associated epithelial abrasion and a full-thickness eyelid laceration extending from the superior fornix to the margin. Several months after surgical repair of the eyelid a cyst appeared in the superior pretarsal skin. Histopathologic and immunohistochemical investigations supplied data suggesting that the cyst had a high probability of a corneoscleral limbal stem cell origin. Distinctive features of the lesion are contrasted with those of allied or simulating cysts.

Conclusions:

Stem cells are now believed to be located at the corneoscleral limbus, in the inferior fornix, in the medial canthal region, and at the eyelid margin where transitions from conjunctival epithelium to epidermal epithelium occur. Due to their replicative, hardy and robust nature, stem cells displaced to alien environments are most likely to survive and produce cysts. The cyst’s corneal-type cytologic characteristics, the absence of goblet cells, and the expression of a broad spectrum of cytokeratin biomarkers in the current case give support to the proposal that limbal stem cells in the region of the corneal laceration were displaced to the eyelid orbicularis muscle and were responsible for this most extraordinary cyst. Comparison with other epithelial cystic linings lends further evidence for this conclusion.
Building Your Brand: Analysis of Successful Oculoplastic Surgeons on Social Media
Authors: Park Sally S. E. , Akella Sruti S. , Moon Jee-Young , Zarrin Bryan , Patel Sheel , Doshi Hiten , Barmettler Anne
Published: April 2020

The influence of social media is rapidly growing and can be strategically harnessed by oculoplastic surgeons to educate both patients and healthcare providers, collaborate with colleagues, and for referrals and marketing.

Supplemental Digital Content is available in the text.

Purpose:

To determine the impact of social media content from oculoplastic surgeon-held accounts on public engagement.

Methods:

This study analyzed successful Instagram accounts (defined by >500 followers as of May 2019) held by American Society of Ophthalmic Plastic Reconstruction Surgery members. Each account’s 20 most and 20 least successful posts (based on number of likes) were characterized by the post’s subject, location, media type, and tag usage. Posts were then analyzed using a web-based application that calculates the engagement level of Instagram users with the selected post.

Results:

A total of 4,812 posts were analyzed from 37 Instagram accounts. Of these American Society of Ophthalmic Plastic Reconstruction Surgery members, the majority were men (67.6%, n = 25) in private practice solely (70.3%, n = 26). Numerous post characteristics, like content and media type, impacted success in a statistically significant manner; for example, public engagement rose when featuring the posting doctor, especially when smiling and wearing a white coat. Meanwhile, posts featuring an office procedure had a negative effect. Formatting was also found to contribute to success. For example, photographs were preferred over videos, while multiple images were best presented sequentially as a carousel (with the viewer swiping through the series) rather than in a large collage. Use of tags (hashtags, accounts, and locations) were associated with increased engagement.

Conclusions:

Social media is an important communication and marketing tool, especially in esthetic fields like oculoplastics. Guidelines for success are presented in this study; content, location, subject, media type, and tags statistically significantly impact public engagement.
Effects of breastfeeding education based on the self-efficacy theory on women with gestational diabetes mellitus
Authors: You Huaxuan , Lei Anjiang , Xiang Jie , Wang Yan , Luo Biru , Hu Juan
Published: April 2020

Background:

Women with gestational diabetes mellitus (GDM) face big challenges of breastfeeding. In order to improve breastfeeding self-efficacy and breastfeeding rate of them, we formulated perinatal individualized interventions based on self-efficacy theory and conducted a randomized controlled trial to verify the effectiveness.

Methods:

We conducted a randomized controlled trial. The perinatal individualized interventions based on the self-efficacy theory including 4 phases were led by the International Board Certified Lactation Consultant (IBCLC). Women allocated to the control group received usual care for lactation support during the antenatal and postnatal period. Data collection occurred at admission, discharge, 6 weeks postpartum, 4 months postpartum, and 6 months postpartum.

Results:

We enrolled 226 women with GDM, 113 in the intervention group and 113 in the control group. The scores of breastfeeding self-efficacy in the intervention group were significantly higher than those in the control group at discharge, at 6 weeks, 4 months, and 6 months postpartum (P < .05). We found higher rates of exclusive and any breastfeeding in the intervention group at discharge (Exclusive: 25.2% vs 13.5%, P < .05; Any: 94.4% vs 89.4%, P > .05), at 6 weeks postpartum (Exclusive: 75.5% vs 62.5%, P < .05; Any: 100.0% vs 96.2%, P > .05), at 4 months postpartum (Exclusive: 68.9% vs 43.3%, P < .05; Any: 94.3% vs 83.7%, P < .05) and at 6 months postpartum (Exclusive: 55.8% vs 36.9%, P < .05; Any: 88.5% vs 64.1%, P < .05).

Conclusion:

Perinatal individualized breastfeeding education based on the self-efficacy theory had positive effects on breastfeeding self-efficacy and breastfeeding rate of women with GDM.
Open abdomen treatment for complicated intra-abdominal infection patients with gastrointestinal fistula can reduce the mortality
Authors: Li Xuzhao , Wei Jiangpeng , Zhang Ying , Wang Weizhong , Wu Guosheng , Zhao Qingchuan , Li Xiaohua
Published: April 2020

To evaluate the effect of the open abdomen (OA) and closed abdomen (CA) approaches for treating intestinal fistula with complicated intra-abdominal infection (IFWCIAI), and analyze the risk factors in OA treatment.

IFWCIAI is associated with high mortality rates and healthcare costs, as well as longer postoperative hospital stay. However, OA treatment has also been linked with increased mortality and development of secondary intestinal fistula.

A total of 195 IFWCIAI patients who were operated over a period of 7 years at our hospital were retrospectively analyzed. These patients were divided into the OA group (n = 112) and CA group (n = 83) accordingly, and the mortality rates, hospital costs, and hospital stay duration of both groups were compared. In addition, the risk factors in OA treatment were also analyzed.

OA resulted in significantly lower mortality rates (9.8% vs 30.1%, P < .001) and hospital costs ($11721.40 ± $9368.86 vs $20365.36 ± $21789.06, P < .001) compared with the CA group. No incidences of secondary intestinal fistula was recorded and the duration of hospital stay was similar for both groups (P = .151). Delayed OA was an independent risk factor of death following OA treatment (hazard ratio [HR] = 1.316; 95% confidence interval [CI] = 1.068–1.623, P = .010), whereas early enteral nutrition (EN) exceeding 666.67 mL was a protective factor (HR = 0.996; 95% CI = 0.993–0.999, P = .018). In addition, Acinetobacter baumannii, Pseudomonas aeruginosa, and Candida albicans were the main pathogens responsible for the death of patients after OA treatment.

OA decreased mortality rates and hospital costs of IFWCIAI patients, and did not lead to any secondary fistulas. Early OA and EN also reduced mortality rates.
Impact of cardiac rehabilitation programs on left ventricular remodeling after acute myocardial infarction
Authors: Susca Mihaela Ghircau , Hodas Roxana , Benedek Theodora , Benedek Imre , Chitu Monica , Opincariu Diana , Chiotoroiu Andreea , Rezus Ciprian
Published: April 2020

Introduction:

While the role of early mobilization in the immediate postinfarction period has been well demonstrated, little is known in present about the link between early mobilization and reduction of systemic inflammation. At the same time, the impact of early mobilization on regression of left ventricular remodeling has not been elucidated so far.

Material and methods:

Here we present the study protocol of the REHAB trial, a clinical descriptive, prospective study, conducted in a single-center, with the purpose to analyze the impact of early mobilization in reducing left ventricular remodeling, the complication rates and mortality in patients who had suffered a recent acute myocardial infarction (AMI). At the same time, the study aims to demonstrate the contribution of early mobilization to reduction of systemic inflammation, thus reducing the inflammation-mediated ventricular remodeling. 100 patients with AMI in the last 12 hours, and successful revascularization of the culprit artery within the first 12 hours after the onset of symptoms in ST-segment elevation acute myocardial infarction or within first 48 hours in non ST-segment elevation AMI will be enrolled in the study. Based on the moment of mobilization after AMI patients will be distributed in 2 groups: group 1 – patients with early mobilization (<2 days after the onset of symptoms) and; group 2 – subjects with delayed mobilization after AMI (>2 days after the onset of symptoms). Study outcomes will consist in the impact of early mobilization after AMI on the ventricular remodeling in the post-infarction period, as assessed by cardiac magnetic resonance imaging, the rate of in-hospital mortality, the rate of repeated revascularization or MACE and the effect of early mobilization on systemic inflammation in the immediate postinfarction phase.

Conclusion:

In conclusion, REHAB will be the first trial that will elucidate the impact of early mobilization in the first period after AMI, as a first step of a complex cardiac rehabilitation program, to reduce systemic inflammation and prevent deleterious ventricular remodeling in patients who suffered a recent AMI.
Current status of normothermic ex-vivo perfusion of cardiac allografts
Authors: Ragalie William S. , Ardehali Abbas
Published: April 2020

Purpose of review

Ex-vivo perfusion has emerged in recent years as an alternative to cold static preservation of organs harvested for transplant. Normothermic ex-vivo perfusion, the subject of this review, maintains the donor heart in a near physiologic state, and allows the transplant team to monitor and control perfusion to the organ prior to implantation. A growing body of evidence has established the safety and viability of this technique, which may improve on current standards of donor management.

Recent findings

Following initial single-arm studies over a decade ago, ex-vivo perfusion has been studied in a prospective, randomized fashion in standard donor hearts (PROCEED II trial). The short and intermediate-term results demonstrated similar outcomes compared with cold storage with significantly shorter cold ischemic time. Since then, ex-vivo perfusion has been studied in extended-criteria donor hearts, first in observational studies, and currently in randomized, prospective fashion in the recently completed EXPAND-Heart trial, which is anticipated to be reported in 2020.

Normothermic ex-vivo perfusion has an established literature base and holds promise for changing current practices of heart preservation. Results of forthcoming pivotal studies will help determine its role in more widespread clinical adoption.
Novel insights into pathophysiology and therapeutic possibilities reveal further differences between AQP4-IgG- and MOG-IgG-associated diseases
Authors: Mader Simone , Kümpfel Tania , Meinl Edgar
Published: April 2020

Purpose of review

This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies.

Recent findings

Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a broader clinical spectrum of autoimmune diseases of the central nervous system (CNS). Details of membrane assembly of AQP4-IgG required for complement activation have been uncovered. Affinity-purified MOG-IgG from patients were shown to be pathogenic by induction of demyelination when the blood--brain barrier (BBB) was breached and by enhancement of activation of cognate T cells. A high-affinity AQP4-IgG, given peripherally, could induce NMOSD-like lesions in rats in the absence of BBB breach. Circulating AQP4-specific and MOG-specific B cells were identified and suggest differences in origin of MOG-antibodies or AQP4-antibodies. Patients with MOG-IgG show a dichotomy concerning circulating MOG-specific B cells; whether this is related to differences in clinical response of anti-CD20 therapy remains to be analyzed. Clinical trials of AQP4-IgG-positive NMOSD patients showed success with eculizumab (preventing cleavage of complement factor C5, thereby blocking formation of chemotactic C5a and membrane attack complex C9neo), inebilizumab (depleting CD19 + B cells), and satralizumab (anti-IL-6R blocking IL-6 actions).

New insights into pathological mechanisms and therapeutic responses argue to consider NMOSD with AQP4-IgG and MOGAD as separate disease entities.
prewas: data pre-processing for more informative bacterial GWAS
Authors: Saund Katie , Lapp Zena , Thiede Stephanie N. , Pirani Ali , Snitkin Evan S.
Published: April 2020

While variant identification pipelines are becoming increasingly standardized, less attention has been paid to the pre-processing of variants prior to their use in bacterial genome-wide association studies (bGWAS). Three nuances of variant pre-processing that impact downstream identification of genetic associations include the separation of variants at multiallelic sites, separation of variants in overlapping genes, and referencing of variants relative to ancestral alleles. Here we demonstrate the importance of these variant pre-processing steps on diverse bacterial genomic datasets and present prewas, an R package, that standardizes the pre-processing of multiallelic sites, overlapping genes, and reference alleles before bGWAS. This package facilitates improved reproducibility and interpretability of bGWAS results. prewas enables users to extract maximal information from bGWAS by implementing multi-line representation for multiallelic sites and variants in overlapping genes. prewas outputs a binary SNP matrix that can be used for SNP-based bGWAS and will prevent the masking of minor alleles during bGWAS analysis. The optional binary gene matrix output can be used for gene-based bGWAS, which will enable users to maximize the power and evolutionary interpretability of their bGWAS studies. prewas is available for download from GitHub.
Coronavirus PPE: a positive pressure hood assembled from ubiquitous, low-cost materials
Authors: Crawford Mark
Published: April 2020

A positive pressure protective hood system was purposefully constructed only from materials commonly found worldwide, including bendable aluminum mesh, elastic head straps, velcro tape, a plastic sheet, a furnace filter and two computer central processing unit (CPU) cooling fans. The practical advantages of this system are that the materials are readily available in the inventories of most electronics and hardware outlets, ease of assembly (particularly if choosing to employ 3D printing for the fan enclosure and/or making several units at once with a defined workflow), and high probability of the materials being available in current or prospective personal protective equipment (PPE)-deplete regions. An experiment with identical fire detectors showed adequate inner isolation of the hood prototype from paper combustion particulates, which have a size range slightly smaller than putative coronavirus aerosols, for at least 90 seconds. The theoretical advantages of this system include significant reduction in healthcare provider exposure to coronavirus-containing respiratory fomites, respiratory droplets and aerosols (vs. traditional static masks and shields) during high risk procedures such as endotracheal intubation or routine care of an upright and coughing patient. Additionally, the assembly eliminates contact exposure to coronavirus fomites due to whole-head coverage from a hood system.
Estimation of true number of COVID-19 infected people in Japan using LINE questionnaire
Authors: Tanaka Shin-ichoro , Oku Shinya
Published: April 2020

The authors estimated the true number of COVID-19 infected people in Japan using the LINE questionnaire data and the PCR test results. A statistically significant correlation was observed between the infection rate per prefecture with PCR test and the rate of high fever. Using this correlation, true number of COVID-19 infected people in Japan was estimated approximately twenty thousand (±ten thousand) as of April 1, 2020.