bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal P2X receptors mediating pressure‐natriuresis, oxygenation and injury susceptibility (LB721)
Authors: Menzies Robert , Mullins John , Bailey Matthew
Published: June 2021

Chronic kidney disease (CKD) affects an estimated 1 in 10 individuals and therefore presents a profound socioeconomic burden. The etiology of CKD is undoubtedly multifaceted, remaining largely elusive in spite of a significant focus of basic and translational research, resulting in fibrosis and renal function decline. We have developed models to investigate the pathology of CKD following over‐activation of the renin angiotensin system. In the Cyp1a1‐Ren2 transgenic rat hypertension causes renal injury, predominantly in the preglomerular vasculature. In this model renal injury is characterized by both blood pressure dependent (owing to the antihypertensive affect of Losartan), and blood pressure independent (amelioration of renal injury but not hypertension by spironolactone), mechanisms.

Consomic/congenic strain variants identified angiotensin converting enzyme (Ace) as an important gene modifier. Comparative studies of F344 (susceptible) and Lewis (relatively protected) strains by renal microarray revealed the purinergic receptors P2x7 and P2x4 as further candidate modifiers. Gene and protein expression of these P2X receptors were both higher in F344 compared with Lewis. Immunohistochemistry localized P2X7 and P2X4 to the renal vascular endothelium, vasa recta and tubules: between strains the expression pattern only became architecturally distinct in the medulla. Renal functional studies indicated that F344, but not Lewis, responded to acute antagonism of P2X7 and P2X4. F344 showed a significant drop in blood pressure but maintained renal blood flow, indicative of tonic renal vasoconstriction by the vasa recta.

Following chronic ANG II infusion into F344 rats, pressure‐natriuresis was impaired and there was a modest increase in blood pressure but no overt injury. Similarly, macrophage infiltration was not significantly increased. Blood oxygenation‐level dependent (BOLD) magnetic resonance imaging (MRI) of the kidney identified a decrease in renal R2* signal following P2X7 and P2X4 antagonism in ANG II infused F344 rats. Together these results suggest that P2X4/7 activation tonically suppress renal perfusion which impairs pressure‐natriuresis and reduces oxygenation. These effects are pro‐fibrotic and may underpin susceptibility to renal injury.

Grant Funding Source: British Heart Foundation Centre of Research Excellence (CoRE) Award
Methacholine (M) and resistance exercise training (RET) increase human myofibrillar protein absolute synthetic rate (MPASR) in proportion to increased nutritively perfused mass, belied by steady myofibrillar protein fractional synthetic rates (MPFSR) (LB760)
Authors: Rennie Michael
Published: June 2021

Michael Clark identified the metabolic power of switching from non nutritive to nutritive flow but for aminoacids (AA) in human leg the situation is complex e.g. leg has ≍35% non muscle lean and fat tissue draining into femoral vein blood. Thus, measures derived from tracer exchange, including Ra, Rd and Net Protein Balance (NPB, ([AAa]‐[AAv]xF)) and MPFSR, are too imprecise to surely detect increases in MPASR unless the % increase in microvascularly perfused muscle is dominant and, or the true muscle mass is known. To research this we measured leg femoral flow (FBF, Doppler) and microvascular blood volume (MBV, CEUS) and components of MPASR groups: 10 men (23 y) fed IV D5W‐AA mix, infused with M (AJP doi: 10.1152); 10 men (72 y) studied postabsorptively and IV fed, pre and post RET (20 w). Unilateral arterial M raised fed state FBF and MBV (126±12% P<0.05; 79±30% P<0.05) causing large but non significant increases (+ ≍50% P=0.26) in NPB. Post RET men showed greater leg strength (+39% P<0.0001) and leg, appendicular and whole body muscle masses (median +1.3‐2.3%, CI 1.1‐16%; RM‐ANOVA, P<0.0001). They also showed greater fed state FBF and MBV than before (+40±11% P<0.05; +44±15% P<0.001) and NPB was larger (+40±16%, P<0.05) despite identical basal FBF and MBV. MPFSR always increased on feeding, but its doubling (P<0.001) and final value (≍0.072%/h) were constant. However for post RET men, knowledge of true DXA muscle mass, corrected for non muscle, revealed significant increases in MPASR (MPFSR x mass x [muscle protein] of 3.2 (2.5‐11.2)%, (median (CI) P<0.01). Thus, likely for M, and certainly for RET, the adaptive response to M and RET is to service fed perfused muscle by increasing AA delivery and thus MPASR.

Grant Funding Source: Supported by the Dunhill Medical Trust; I acknowledge my collaborators, K Sjøberg, J P Williams and S Heymsfield, and the technical assistance of P Atherton, M Limb, B E Phillips, A Selby, K Smith and K Varadhan.
Gender and epithelial sodium channel genotype influence the lung fluid response to hypoxic exercise (LB791)
Authors: Baker Sarah , Wheatley Courtney , Taylor Bryan , Johnson Bruce , Snyder Eric
Published: June 2021

Fluid clearance from the alveolar space is critically dependent on epithelial sodium channels (ENaC). A common polymorphism in the gene encoding the ENaC alpha subunit results in an alanine to threonine substitution (A663T), with higher ENaC channel activity. This variant influences ion and fluid regulation in the lung during exercise and in response to albuterol. We investigated the influence of the threonine variant (T663; AT/TT group) on the lung fluid response to exercise in conditions of normobaric hypoxia, which challenges lung fluid balance. Lung fluid balance was assessed using Exhaled Na+ (ENa+) and the diffusing capacity for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) to determine alveolar‐capillary membrane conductance (Dm). 19 healthy subjects were grouped by ENaC genotype (n=8 vs. 11 for AA and AT/TT, %female=50 vs. 62%, age=27±1 vs. 28±2yrs., ht=171±3 vs. 173±2cm, wt=69±6 vs.72±3kg , BMI=23±1 vs.24±1kg/m2) and completed two overnight visits in a hypoxic tent simulating just over 5,400m. The visits were randomized to inhaled placebo or inhaled amiloride (1.5mg in 5ml normal saline, used to inhibit ENaC activity) with ENa+, DLCO, and Dm assessed at baseline, following 12 hours of hypoxic exposure, and following hypoxic exercise at 65% peak power on a cycle ergometer. We found significant effects of the interaction between gender and ENaC genotype on DLCO, Dm, and Dm corrected for pulmonary capillary blood volume (p<0.05). Specifically, females with the more active T663 variant had a greater diffusing capacity and less ENa+ under placebo conditions, suggesting a greater removal of Na+ and fluid from the airspace. These results suggest that genetic variation of ENaC may influence lung fluid balance during hypoxia and hypoxic exercise.

Grant Funding Source: Supported by HL71478, HL108962‐03, and HL007249
Interaction between genetic background and training intensity influences training responses (LB802)
Authors: Avila Joshua , Kim Seung , Massett Michael
Published: June 2021

The aim of this study was to determine the intensity of exercise training that is required to maximize training adaptations in low responding mice. Male mice from three inbred strains: SJL/J, C57BL/6J, and NON/ShiLtJ completed a graded exercise test before and after four weeks of treadmill running. Mice from each strain were assigned to one of three groups (n=6/group): sedentary control (SED), continuous running (65% of max) and high‐intensity interval training (HIT) (6 x 85% of max for 8 min, 50% of max for 2 min). Exercise capacity was improved by continuous running compared with SED in mice from all strains (P < 0.05). For HIT, only NON/ShiLtJ mice showed a significant improvement in exercise capacity relative to SED mice from that strain. Protein content for PGC‐1alpha, NRF‐1 and mtTFA was examined in plantaris muscle to assess the metabolic adaptation to the different intensities of exercise training. Overall, exercise training induced relatively small changes in protein content in the plantaris. For SJL/J and NON/ShiLtJ, PGC‐1alpha tended to be double in plantaris from HIT compared with sedentary and unchanged in plantaris from C57BL/6J. Tfam protein content was also nearly double in muscle for HIT in SJL/J and C57BL/6J strains compared with sedentary. These data indicate that adaptations to training in skeletal muscle proteins are not directly related to changes in exercise capacity.

Grant Funding Source: Supported by NIH grant HL085918 to MPM
Skin blood flow response following repeated local heating (LB803)
Authors: Herron Robert , Collins Ann , Carter Stephen , Mitchell Jermaine , Bishop Phillip
Published: June 2021

Dynamic control of skin blood flow is necessary to maintain thermoregulatory homeostasis in humans through reflexive and local mechanisms. Local heating of the skin elicits vasodilation via local sensory nerves and nitric oxide (NO). However, research investigating the desensitization of the cutaneous vasculature to repeated heating remains equivocal. Eight healthy‐young participants (6 males, 2 females, age 21 ± 2 yr) completed a heat (H1) and reheat (H2) protocol. Females were tested in the follicular or low hormone phase of their menstrual cycle (2‐7 days post menses). Participants rested supine as their dominant forearm was instrumented with a laser Doppler flowmetry probe (LDF) and local skin heater. Baseline skin blood flow (in arbitrary units; au) and blood pressure were assessed during a 5‐min period during which local skin temperature was clamped at 34 °C. The heater was increased by 0.2 °C•10 s‐1 to a temperature of 42 °C. Skin blood flow continued to be measured for at least 30 min to attain a max NO‐driven plateau. Blood pressure was measured every 10 min via automated oscillometry. Mean arterial pressure (MAP) was used to calculate cutaneous vascular conductance (CVC; LDF/MAP). The heating protocol was repeated after 1 hour of quiet rest. A paired‐samples t‐test found no difference in CVC at baseline (p = 0.20, H1 = 0.19 ± 0.04 au/mm Hg vs H2 = 0.25 ± 0.13 au/mm Hg) nor any difference detected in maximum skin blood flow as expressed in %∆CVC (p = 0.41, H1 = 938 ± 350 au/mm Hg vs H2 = 779 ± 404 au/mm Hg). The results indicate that maximal skin blood flow can be achieved during repeated bouts of local heating separated by 1 hour.
Relation of genetic polymorphisms and nutrient with bone density and skeletal muscle mass in Japanese young women (LB805)
Authors: Kondo Hiroyo , Fujino Hidemi , Nagatomo Fumiko , Ishihara Akihiko
Published: June 2021

Osteoporosis and sarcopenia are complex diseases characterized by low bone density and muscle mass, respectively, The purpose of this study was to assess the interactive effects of habitual exercise, nutrient intake and gene polymorphisms of Vitamin D receptor (VDR), estrogen receptor alpha (ESR1) and ciliary neurotrophic factor (CNTF) on bone density and skeletal muscle mass. 240 Japanese healthy young women (20‐23 yr) were recruited in this study. Habitual exercise and nutrient intake were assessed using a questionnaire. Bone density and muscle mass were measured by a quantitative ultrasound method and whole body impedance, respectively. In addition, the polymorphisms of ESR1, VDR and CNTF were genotyped using a TaqMan based real‐time PCR method. The skeletal muscle mass was correlated with calcium intake although there was no relationship between protein intake. Interestingly, the subjects with ESR1 allele A and VDR allele C in the habitual exercise subjects had significantly higher bone density than those in the non‐habitual exercise subjects . In addition, the skeletal muscle mass in non‐habitual exercise subjects with AA homozygote in CNTF was higher than that in TT. Thus, habitual exercise and calcium intake are more important for bone metabolism and skeletal muscle mass carrying ESR1 A and VDR C, allele. These results suggest that genetic polymorphisms were significantly associated with bone density and muscle mass in young women. Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Grant Funding Source: Supported by Japanese MEXT
Effect of Whey Protein Form on Physiological Response to Chronic Resistance Exercise in Trained Men (LB806)
Authors: Lockwood Christopher , Roberts Michael , Dalbo Vincent , Kendall Kristina , Smith‐Ryan Abbie , Moon Jordan , Stout Jeffrey
Published: June 2021

Fifty‐six men (21.4±0.4 yrs) were randomly assigned to one of four double‐blinded treatments: 60 g/d maltodextrin (PLA) or 60 g/d whey protein from either a) 80% whey protein concentrate (WPC80), b) high lactoferrin WPC80 (WPC80+), or c) hydrolyzed WPC80 (WPH). All subjects participated in an 8‐week resistance training program. Two‐way repeated measures ANCOVAs were used for statistical analyses. No between‐ or within‐group (p>0.05 and p>0.0125, respectively) changes were observed for 12‐hour fasted blood lipids, glucose, WBC, CK or other clinical chemistry markers of safety; however, all groups reduced (p<0.0125) creatinine. Urea nitrogen decreased in WPH (‐18.06%, p<0.0125), which differed (p<0.05) from WPC80 (+16.91%). All groups similarly increased (p<0.0125) upper‐ and lower‐body 1RM strength and 80RM muscular endurance. LBM and total body muscle mass increased (p<0.0125) in all groups, as did BM in all groups except WPH (+0.64 kg; p=0.114). Only WPH significantly reduced FM (‐5.94%) and %FAT (‐1.60%), which was significantly different from PLA (+9.10% and +0.64%, respectively). Therefore, in trained men, whey protein form provides similar responses to an 8‐week heavy resistance training program on measures of total body muscle mass, strength, anaerobic endurance, blood lipids and clinical safety markers. However, WPH appears to significantly augment fat loss and may increase nitrogen retention.
Inflammation following muscle injury promotes myoblast proliferation (LB808)
Authors: Lees Simon , Niccoli Sarah , Hawdon Nicole , Sarvas Jessica , Frye Melinda , Chicco Adam , Otis Jeffrey
Published: June 2021

Objective: To determine the expression of IL‐1β and IL‐6 at several time points following injury, and their effects on myoblast proliferation. Experimental Design: Skeletal muscle was injured using BaCl2 in mice and tissue was collected 1, 5, 10, and 28 days following injury. Cytokine expression was determined using real time RT‐PCR. Mechanisms of cytokine‐induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. Results: ~20‐fold increase in IL‐1β (p<0.05) and IL‐6 (p=0.06) expression was observed 5 days following injury. IL‐1β increased proliferation of both primary and C2C12 myoblasts ~25%. It was determined that IL‐1β not only stimulated NF‐B activation, but this signalling was required for the mitogenic effect of IL‐1β. These data demonstrate for the first time that IL‐1β alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offers insight into the mechanisms dictating satellite cell function following injury.

Grant Funding Source: Supported by NIH‐NIA (R03 AG‐034352, P.I., SJL), NIH‐NIAAA (K01 017190, P.I., JSO), NOHFC (P.I., SJL
Electron microscopy studies elucidate morphological forms of Chlamydia pneumoniae in blood samples from patients diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (LB81)
Authors: Brandt James , Cader Ahmad , Semler Lauren , Hammond Christine , Bell Marcus , Devins Morgan , Smith Jenayle , Joseph Nicol , Velez Marisol , Galluzzi Katherine , Balin Balin , Appelt Denah
Published: June 2021

Our previous studies of brain tissues obtained at autopsy have established an association of Chlamydia pneumoniae (Cpn) infection with late‐onset Alzheimer’s disease (AD). Given these findings, we have designed a study using electron microscopy (EM) to determine if various forms of Cpn from geriatric patient’s blood samples could be identified and correlated with cognitive decline associated with AD.

Patients, >65 years old, and who participated in this IRB approved study, met well‐defined exclusion criteria prior to being evaluated for cognitive status using the SLUMS and FAST testing assessments. After psychometric testing, blood was drawn from the patients and these samples were prepared for EM and assessed for the presence of Cpn.

Our ultrastructural analysis revealed evidence for the presence of Cpn in peripheral blood cells from 12 patients correlated with MCI and AD. Intravacuolar reticulate bodies, elementary bodies, and intermediate bodies characteristic of Cpn were observed in leukocytes from the buffy coat. More specifically, we observed the classical “pear‐shaped” elementary bodies characteristic of Cpn. Immuno‐ EM was performed for positive identification of these various forms of Cpn.

Our data indicate that screening for Cpn from blood samples may prove to be a viable biomarker in differentiating cognitive change consistent with stages associated with MCI and AD. Investigating the distinct morphologies of Cpn in human blood samples from the geriatric population by EM, with other frontline diagnostic procedures, may clarify the diagnosis of MCI and late onset AD.

Grant Funding Source: Center for Chronic Disorders of Aging
Ontogeny of genetic networks underlying central appetite‐controlling systems in the teleost Atlantic cod (LB830)
Authors: Rønnestad Ivar , Le MTDH , Ebbesson Lars , Karlsen Ørjan , Angotzi Anna Rita
Published: June 2021

We examined the distribution of Neuropeptide Y (NPY), cocaine‐ and amphetamine‐regulated transcript (CART) and prepro‐orexin (pOX) in the brain of Atlantic cod by in situ hybridization from onset of exogenous feeding (4days post hatch, dph) to postlarval stage (76dph). All examined genes were expressed from 4dph and displayed temporal and spatial differences in expression during development. pOX mRNA was only expressed in hypothalamus. NPY and CART mRNA expressions had broad distributions in the brain, including telencephalon, diencephalon, and optic tectum. In addition, NPY transcripts were found in the preoptic region, while CART was found in medulla oblongata. New populations of CART positive neurons appeared in olfactory bulb, in the region of the nucleus of medial longitudinal fascicle, and later in midbrain tegmentum. We found several examples of co‐expression (NPY‐CART) and (CART‐pOX). Distributions of NPY and pOX transcripts suggest that telencephalon and hypothalamus are involved in stimulation of feeding in cod. Expression of CART indicates that “satiety centers” are located in hypothalamus, thalamus and medulla oblongata.

Grant Funding Source: Supported by Research Council of Norway‐ CODE 199482
CXCR4‐CXCL12 axis in proliferation, migration, and invasion of endometriosis (LB850)
Authors: Ruiz‐Rivera Abigail , Monteiro Janice , Colon Mariano , Echevarria Martha , Fazleabas Asgerally , Flores Idhaliz
Published: June 2021

Endometriosis a benign gynaecological disease, associated with chronic inflammation and increased levels of chemokines. Lesions are composed of endometrial stroma and glands localized outside the uterus. In a rat model of endometriosis, we showed high CXCR4 mRNA levels in endometriotic lesions and in high protein expression levels in human endometriosis tissues compared to control endometrium . The CXCR4‐CXCL12 axis plays roles in proliferation, migration, and cell invasion. Endometriotic epithelial cells expressed CXCR4. We hypothesized that CXCL12 may induce proliferation, migration, and invasion of endometriotic cells (12Z) compared to a non‐invasive breast cancer cells, expressing endometrial markers (EEC), and the induction may be blocked by the CXCR4 inhibitor, AMD3100. Cell proliferation in response to CXCL12 was analyzed by BrdU assay. We also studied cell invasion and migration in response to CXCL12 and AMD3100 by invasion and migration chambers. Rat model of endometriosis was used to identify the effect of AMD3100 in lesions regression. CXCL12 increased proliferation and migration of EEC, and invasion in 12Z cells, compared to media (p<0.05). AMD3100 reduced migration in EEC; reduced migration and increased invasion in 12Z cells (p<0.05). These data suggest that the CXCR4‐CXCL12 axis can be activated in endometrial cells to promote cell proliferation, migration, and invasion, and application of cancer treatments to endometriosis disease requires additional studies. These biological functions have been previously shown to be dysregulated in endometriosis, by still undefined mechanisms, leading to survival and growth of ectopic endometrium.

Grant Funding Source: Supported by F31HD072594, RCMI G12‐MD007579, R25GM082406, R25GM096955, R01‐HD050509
LYP's implications cause both increased or decreased susceptibility towards autoimmune and acquired diseases (LB96)
Authors: Babinski Alexander , Fernandez Michelle , Georgieva Darina , Gui Michael , Huettl Maggie , Prebble Lara , Roselle Anna , Schultz Eric , Shukla Neehal , Fassler Amy , Schrodi Steve
Published: June 2021

When functioning properly, the immune system protects the body from foreign invaders with the help of T‐cells. An error in the formation of T‐cells in the thymus can lead to autoimmune diseases in which the T‐cells attack normal body tissues. When a T‐cell binds to an antigen, a signal transduction pathway is activated, forming a multimeric signaling complex known as the TCR signalosome. LCK, part of the signalosome, is a lymphocyte‐specific protein tyrosine kinase that phosphorylates a variety of proteins in order to activate the T‐cell receptor pathway. TCR stimulation also leads to the activation of LYP, a lymphoid tyrosine phosphatase that down regulates TCR signaling by removing phosphates from the signaling intermediates of the TCR signalosome. LYP also dephosphorylates Y394 of LCK, thus inactivating the kinase and inhibiting TCR signaling. The LYP R620W mutation prevents LYP from binding to the signalosome, resulting in a gain‐of‐function, leading to increased inhibition of TCR signaling. The LYP R620W mutation has been linked to a wide spectrum of human diseases, including a decreased risk in Crohn’s disease and increased risk to rheumatoid arthritis, and possible links to non‐autoimmune disorders such as cardiovascular disease. The Marshfield SMART (Students Modeling A Research Topic) Team modeled the mutated protein LYP R620W using 3D technology.

Grant Funding Source: Supported by grants from NIH‐CTSA and NIH‐SEPA.
Inhibition of Polyamine Biosynthesis Using Difluoromethylornithine Acts as a Potent Immune Modulator and Displays Therapeutic Synergy With PD-1-blockade
Authors: Dryja Parker , Fisher Carrie , Woster Patrick M. , Bartee Eric
Published: June 2021

Polyamines are known to play a significant role in cancer progression and treatment using difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, has shown some clinical promise. It is interesting to note that, while DFMO is directly cytostatic in vitro, recent work has suggested that it achieves its antitumor efficacy in vivo by enhancing adaptive antitumor immune responses. On the basis of these data, we hypothesized that DFMO might act as an immune sensitizer to increase tumor responsiveness to checkpoint blockade. To test this hypothesis, we treated tumors with DFMO, in either the presence or absence of additional PD-1 blockade, and subsequently analyzed their immunological and therapeutic responses. Our data demonstrates that treatment with DFMO significantly enhances both the viability and activation status of intratumoral CD8+ T cells, most likely through an indirect mechanism. When combined with PD-1 blockade, this increased viability resulted in unique proinflammatory cytokine profiles and transcriptomes within the tumor microenvironment and improved therapeutic outcomes. Taken together, these data suggest that DFMO might represent a potential immunomodulatory agent that can enhance current PD-1-based checkpoint therapies.
Calcium channel blockers improve prognosis of patients with coronavirus disease 2019 and hypertension
Authors: Peng Chi , Wang Hao , Guo Yu-Feng , Qi Ge-Yao , Zhang Chen-Xu , Chen Ting , He Jia , Jin Zhi-Chao
Published: June 2021

Background:

Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.

Methods:

We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.

Results:

Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13–0.76, χ
2 = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13–1.43, χ
2 = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53–2.69, χ
2 = 0.17, P = 0.6777).

Conclusions:

In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.
A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy
Authors: Xia Hai-Zhui , Bi Hai , Yan Ye , Yang Bin , Ma Ruo-Zhuo , He Wei , Zhu Xue-Hua , Zhang Zhi-Ying , Zhang Yu-Ting , Ma Lu-Lin , Hou Xiao-Fei , Wirth Gregory J. , Lu Jian
Published: June 2021

Background:

Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS).

Methods:

A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score.

Results:

A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.

Conclusions:

PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.
Ginkgo Biloba Extract EGB761 Alleviates Warfarin-induced Aortic Valve Calcification Through the BMP2/Smad1/5/Runx2 Signaling Pathway
Authors: Liu Jing , Liu Cuiying , Qian Chunqi , Abela George , Sun Wei , Kong Xiangqing
Published: June 2021

Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.
Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study
Authors: Dixon Dave L. , Billingsley Hayley E. , Canada Justin M. , Trankle Cory R. , Kadariya Dinesh , Cooke Richard , Hart Linda , Van Tassell Benjamin , Abbate Antonio , Carbone Salvatore
Published: June 2021

The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF). The CANA-HF trial was a prospective, randomized controlled study that compared the effects of canagliflozin 100 mg daily to sitagliptin 100 mg daily on cardiorespiratory fitness in patients with HFrEF and T2DM. Of the 36 patients enrolled in CANA-HF, 35 patients had both baseline and 12-weeks serum lipids obtained via venipuncture. The change in LDL-C from baseline to 12 weeks was 5 (−12.5 to 19.5) mg/dL versus −8 (−19 to −1) mg/dL (P = 0.82) and triglyceride levels was −4 (−26 to 9) mg/dL and −10.5 (−50 to 29.3) mg/dL (P = 0.52) for canagliflozin and sitagliptin, respectively. No significant differences were found between canagliflozin and sitagliptin for total cholesterol, high-density lipoprotein cholesterol or non-HDL-C (P > 0.5 for all). These data suggest that compared with sitagliptin, canagliflozin may not increase LDL-C in patients with T2DM and HFrEF.
Fournier's Gangrene with Edwardsiella tarda: A Gas Production Case by Bacterial Synergism with Streptococcus anginosus
Authors: Tsuge Itaru , Matsui Miho , Kanno Toru , Kaisho Junichi , Takahashi Toshifumi , Yamanaka Hiroki , Katsube Motoki , Sakamoto Michiharu , Morimoto Naoki
Published: June 2021

Edwardsiella tarda is an anaerobe associated with freshwater and marine life. Necrotizing soft tissue infection caused by E. tarda is rare, but its mortality rate is extremely high (61.1%). We experienced a survival case of Fournier’s gangrene with E. tarda. A key clinical feature for the diagnosis was gas production; however, there have been no previous reports of such a phenomenon in relation to E. tarda. A 64-year-old man was admitted with a 3-day history of a high fever. His medical history, which included paraplegia from the Th6 level down, made the focus of inflammation at the perineum difficult to notice. Whole-body CT revealed subcutaneous gas from the posterior scrotum around the entire circumference of the anus. During emergency surgery, an incision at the posterior scrotum revealed extensive fascia necrosis, and E. tarda and Streptococcus anginosus were identified. We speculated the gas production in this case to be the product of a mixed infection of aerobes and anaerobes, which acted synergistically to induce bacterial growth. Timely surgical debridement and antibiotic therapy led to the patient’s survival.
Applying Unsterile Microporous Tape onto Surgical Wounds: Tape Contamination and Clinical Rationale
Authors: Ausen Kjersti , Kroknes Marthe L. , Gunnarson Gudjon , Radtke Andreas
Published: June 2021

Background:

Fomites are surfaces that carry contaminants and may cause infection. We wanted to assess the bacterial load on rolls of nonsterile microporous tape in a hospital setting and explore the scientific rationale behind the existing practice of applying unsterile adhesives onto a surgical wound.

Methods:

We analyzed the aerobic bacterial contamination in rolls of microporous tape collected from surgical theaters, outpatient clinics, and storage rooms at St. Olav’s University Hospital, Trondheim, Norway between 2018 and 2020. We also reviewed the literature for relevant publications.

Results:

A total of 58 rolls were collected; 55 were included for final analysis. Exposed tape surfaces were significantly more contaminated than unexposed surfaces. Tape rolls from outpatient clinics were significantly more contaminated and contained a significantly greater variety of microbes than rolls from operation theaters and storage rooms. Unexposed surfaces from both operation theaters and storage rooms demonstrated very little contamination.

Conclusions:

Rolls of tape may act as fomites, but widespread use of adhesives is inevitable in hospital settings. Removing the outer layer of a tape roll before use may significantly reduce bacterial contamination. Given sufficient vigilance to avoid cross-contamination, inner layers of tape may represent a close-to-sterile alternative as surgical dressing. However, the economic savings constitute a negligible fraction of the total costs of the surgery, and the risk of contamination seems apparent. Scientific support of dressing a fresh surgical wound with unsterile microporous tape is lacking, and we therefore do not recommend the practice except in situations with very limited resources.
Results From the German Fungal Keratitis Registry: Significant Differences Between Cases With and Without a History of Contact Lens Use
Authors: Roth Mathias , Holtmann Christoph , Daas Loay , Kakkassery Vinodh , Kurzai Oliver , Geerling Gerd ,   and German Fungal Keratitis Registry Study Group
Published: June 2021

Purpose:

Fungal keratitis (FK) is a serious ophthalmic disease with a potentially devastating outcome that seems to be increasing in recent years. The use of contact lenses (CLs) was evaluated as a risk factor for FK to determine possible differences in course and outcome.

Methods:

Data from 173 cases reported in the German FK registry until August 2019 were evaluated regarding CL behavior, other ophthalmological and general risk factors, age, sex, identified pathogens, conservative and surgical therapy, visual acuity, and findings at admission and follow-up.

Results:

One hundred seventy-four eyes from 173 patients between 2000 and 2019 were included [64.4% women, median age 54 (39; 72) years]; 49.7% wore CL, of which 81.3% were soft CL, and 50.3% had no history of contact lens use (NCL). CL users were significantly more often women and otherwise healthy (CL: 80.2% vs. NCL: 48.9%; P < 0.0001). The spectrum of pathogens among CL users showed a significantly higher proportion of infections with filamentous pathogens, in particular Fusarium sp. (total filament: CL 69.8% vs. NCL 27.3%; P = 0.0001; Fusarium sp.: CL 50.0% vs. NCL 14.8%; P < 0.0001). Overall, 54.6% required keratoplasty and 8.6% enucleation.

Conclusions:

CLS are the most important risk factor for FK in Germany. With CLs, typically, the infection is caused by molds, and patients are comparably younger and otherwise healthy. Often, extensive surgery is needed. To evaluate changes in the pathogen and resistance spectrum and to further monitor possible CL-related risk factors, a consistent collection of data remains paramount.
The Role of Corneal Donor Rim Fungal Cultures: Pro Side
Authors: Ritterband David
Published: June 2021

Fungal infection after corneal transplantation is a rare but potentially devastating complication. It is of paramount concern for transplant surgeons and the eye banking community. The value of universal corneal rim cultures for keratoplasty remains controversial. In 2016, The Eye Bank Association for America reported an increasing trend in the incidence of post keratoplasty fungal infections and a higher incidence of post keratoplasty [penetrating keratoplasty and endothelial keratoplasty (EK)] fungal endophthalmitis cases. This increasing trend in rate over time from previous Eye Bank Association for America reports was disproportionately associated with EK and Candida species. Additionally, several studies confirmed a high correlation between positive corneoscleral donor rim fungal cultures and postoperative infections, and a higher risk to the mate eye of a cornea that had the positive fungal corneal rim culture and developed an infection. Positive fungal donor rim cultures-especially in the setting of interface keratitis after EK surgery-can raise the index of suspicion for a fungal cause and may help direct therapy, especially in the early stages, where the symptoms and signs of spread may not be obvious and obtaining direct cultures is inherently difficult without surgical intervention.
Scheimpflug Corneal Densitometry Values and Severity of Guttae in Relation to Visual Acuity in Fuchs Endothelial Corneal Dystrophy
Authors: Shah Khushali , Eghrari Allen O. , Vanner Elizabeth A. , O'Brien Terrence P. , Koo Ellen H.
Published: June 2021

Purpose:

The purpose of this study was to investigate the association between corneal densitometry (CD) values from Scheimpflug tomography imaging, severity of guttae, and visual acuity in eyes with Fuchs endothelial corneal dystrophy (FECD).

Methods:

This was a retrospective, cross-sectional study. Patients with FECD were examined at the Bascom Palmer Eye Institute from January 2015 to September 2019. We extracted CD values at central annuli of 0-2, 2-6, 6-10 and 10-12 mm from Scheimpflug tomography images. We investigated the association of corrected distance visual acuity (CDVA) with CD values, severity of guttae, central corneal thickness (CCT), cataract grade, refractive error, corneal edema grade, age, and gender using multivariate generalized estimating equation regression models.

Results:

One hundred ninety-two eyes from 110 patients were included in this study. Increase in central CD values at the 0 to 2 mm zone (P < 0.001), severity of guttae (P = 0.046), age (P < 0.001), cataract grade (P < 0.001), corneal edema grade (P < 0.001), and type of refractive error (P = 0.008) were significantly associated with decreased CDVA. Central corneal thickness, sex, and the peripheral CD values (2–6, 6–10, and 10–12 mm) were not significantly associated with CDVA (P > 0.05) in the final multivariate regression model.

Conclusions:

Our study demonstrates that central CD values at 0 to 2 mm and severity of guttae are each associated with decreased CDVA in FECD. These findings carry implications for patients with FECD considering surgical intervention for phacoemulsification alone, Descemet stripping only, or endothelial cell transplantation and provide a multifactorial perspective on vision loss in FECD.
Multicountry clinical outcomes of a new nondiffractive presbyopia-correcting IOL
Authors: Bala Chandra , Poyales Francisco , Guarro Mercè , Mesa Ramón Ruiz , Mearza Ali , Varma Devesh Kumar , Jasti Srichand , Lemp-Hull Jessie
Published: June 2021

Purpose:

To evaluate the effectiveness and safety of a new presbyopia-correcting intraocular lens (IOL) with a nondiffractive design, DFT015, compared with an aspheric monofocal IOL, SN60WF.

Setting:

19 investigational sites in 4 countries: Australia, Canada, Spain, and the United Kingdom.

Design:

Prospective, randomized, parallel-group, controlled, assessor- and patient-masked clinical study.

Methods:

Participants aged ≥22 years with bilateral cataracts were randomized to DFT015 or SN60WF in a 5:4 ratio and masked until final postoperative follow-up at month 6. The primary effectiveness objective was superiority of DFT015 over SN60WF in mean monocular photopic distance-corrected intermediate visual acuity (DCIVA) at month 3. Secondary effectiveness objectives included noninferiority of DFT015 to SN60WF in mean monocular photopic corrected distance visual acuity (CDVA) and superiority in the mean monocular photopic distance-corrected near visual acuity (DCNVA) at month 3. Visual disturbances were assessed at month 6.

Results:

282 patients were randomized to DFT015 (n = 159) or SN60WF (n = 123). All effectiveness objectives were achieved at month 3 in first eyes. For monocular photopic results in first eyes, DFT015 demonstrated superior mean DCIVA (least squares means of −0.139 logMAR in favor of DFT015, P < .001), noninferior mean CDVA (97.5% upper confidence limit [UCL] of the difference was <0.1 logMAR) and superior mean DCNVA (95% UCL of the difference was <0.0 logMAR) compared with SN60WF at month 6. DFT015 exhibited a similar visual disturbance profile to that of SN60WF.

Conclusions:

DFT015 provided superior intermediate and near vision and a similar visual disturbance profile compared with an aspheric monofocal IOL.
Endothermal pupilloplasty to optimize pupil centration, size, and contour
Authors: De Francesco Ticiana , Ma Jingyi , Ahmed Iqbal Ike K.
Published: June 2021

Iris defects and distorted pupils are commonly managed with iris suturing techniques that aim to close the defect and/or reform the physiological pupil. The re-creation of an optimally sized and centered pupil is often challenging because of missing iris, asymmetrical iris damage, or variable tension around the pupil. Current options include removing or cutting iris tissue using microscissors or the vitreous cutter, instrument stretching, or postoperative laser photocoagulation. Iris microendodiathermy is a simple technique that is minimally traumatic, titratable, and controlled, avoids excessive tissue manipulation, and is able to create a round cosmetically pleasing pupil. A bipolar endodiathermy cautery is applied to the iris stroma to induce tissue contraction and to gently pull the pupil in the meridian to which probe is applied. Endothermal pupilloplasty (EDP) may be used to recenter or enlarge a small pupil, thereby avoiding additional trauma inflicted by a vitrector or microscissors that physically cuts the iris.
The Implementation of the Sexual Assault Forensic Examination Telehealth Center: A Program Evaluation
Authors: Miyamoto Sheridan , Thiede Elizabeth , Wright Elizabeth N. , Berish Diane , Perkins Daniel F. , Bittner Cynthia , Dorn Lorah , Scanlon Dennis
Published: June 2021

Introduction

Substantial disparities in the quality of post-sexual-assault (SA) care exist in the United States, particularly in rural areas. This study evaluates the implementation of the Sexual Assault Forensic Examination Telehealth Center, a program to improve SA care by increasing access to experienced sexual assault nurse examiners via telehealth, in three rural hospitals.

Materials and Methods

The Dynamic Sustainability Framework (DSF) guided the implementation of the intervention. Survey and implementation data were evaluated 1 year after implementation using a nonexperimental pre–post design. Outcomes include patient and nurse perceptions of telehealth, local site nurse (LSN) confidence, and hospital protocol/policy changes.

Results

Forty-one telehealth consultations were completed in the program's first year. An average of 34 system-level protocol changes were made per site. LSNs demonstrated statistically significant increases in confidence to provide SA care at 1 year. LSNs and telehealth sexual assault nurse examiners (expert consultants) reported that quality of SA care improved (87% and 83%, respectively). Patients highly rated the care they received (83%), reported telehealth improved care (78%), and reported feeling better after the examination (74%).

Discussion

Using the DSF for implementation supported a tailored approach and successful adoption and also allowed for program iteration based on lessons learned.

Conclusions

The Sexual Assault Forensic Examination Telehealth model resulted in improved local nurse confidence in provision of SA care, nurse perception of improvement in care quality, and high patient care experience ratings. These findings and the use of the DSF have implications for SA specialty care implementation in rural communities.