bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced carotid artery blood flow of spontaneously hypertensive rats is unaffected by aging from 20 weeks (young adulthood) to 65 weeks (upper middle age) (LB690)
Authors: Denniss Steven , Smith Christopher , Rush James 
Published: June 2021

The objective of this study was to quantify blood flow (using a perivascular flowprobe) and pressure (using a catheter‐tip transducer) in the common carotid artery (CCA) of anesthetized young adult (~20 week old) and upper middle aged (~65 week old) Wistar Kyoto rats (WKY) and Spontaneously Hypertensive rats (SHR). In young adult SHR vs. WKY, mean (172±10 vs. 82±2 mmHg), systolic (198±13 vs. 92±4), diastolic (151±9 vs. 72±5), and pulse pressure (48±5 vs. 20±2), and heart rate (371±12 vs. 277±19 beats/min), were each elevated (p<0.01). In SHR, aging had no effect on these pressure parameters, or heart rate; whereas, in WKY, aging was associated with a significant increase in pulse pressure (31±1 mmHg; p=0.04) but no other pressure parameter. Mean (4.94±0.29 vs. 3.80±0.54 ml/min), maximum systolic (11.58±1.08 vs. 19.00±2.18), and minimum diastolic blood flow (0.62±0.73 vs. 1.90±0.34) were each reduced in young adult SHR vs. WKY (p<0.05), while flow pulsatility was no different (3.23±0.73 vs. 3.43±0.44). Aging had no effect on these flow parameters in either SHR or WKY. Together, these data demonstrate that CCA blood flow is >20% reduced in young adult SHR, and that this reduction is neither exacerbated nor attenuated at upper middle age. Given the important contribution of the internal branches of the CCAs to the total perfusion of the brain, these findings may be of pathophysiological and clinical relevance.Grant Funding Source: Supported by NSERC Canada
Lubiprostone reduces murine colitis principally in a ClC‐2‐dependent manner. (LB750)
Authors: Jin Younggeon , Pridgeon Tiffany , Blikslager Anthony 
Published: June 2021

Lubiprostone, a ClC‐2 chloride channel activator, induces intestinal secretion and is used in the management of idiopathic chronic constipation. Recent studies have suggested that lubiprostone has multiple targets and mechanisms of action in the intestine. However, we have previously reported that lubiprostone initiates intestinal barrier repair in ischemic‐injured intestine via its principal target, the chloride channel ClC‐2. Thus, we hypothesized that lubiprostone would have a protective or therapeutic effect in an in vivo colitis model. We administrated lubiprostone in a dextran sulfate sodium (DSS)‐induced colitis model in wild type and ClC‐2‐/‐ mice. We determined the severity of colitis based on body weight, disease activity index (DAI), histology scores, and levels of cytokine production. Additionally, intestinal permeability was measured in vivo to evaluate barrier function. Administration of DSS in the drinking water initiated symptoms of experimental IBD, including weight loos and elevation in DAI. Oral preventive or therapeutic administration of lubiprostone significantly reduced weight loss, DAI, histology scores, colon shortening, and intestinal permeability in a dose‐dependent manner as compared to DSS‐treated wild type mice that were not treated with lubiprostone. We also observed that the lubiprostone caused a significant elevation of the sealing tight junction protein expression for occludin and claudin‐1, while significant reduction of the pore‐forming tight junction protein claudin‐2. When administered to ClC‐2‐/‐ mice, the oral preventive lubiprostone treatment had a limited protective effect against DSS colitis. Specifically, loss of body weight, DAI, and intestinal permeability were significantly reduced in the high dose (100 μg/kg) lubiprostone treatment group of ClC‐2‐/‐ mice, but they showed no difference in colon length and histology score. In conclusion, lubiprostone might possess potential therapeutic interest for the treatment of IBD in a ClC‐2 dependent, but it also has some alternative mechanisms of action at high dosages. Additional investigation is required to determine the detailed mechanisms of action of lubiprostone in experimental colitis model.Grant Funding Source: Supported by Sucampo Pharmaceuticals inc. and Takeda Pharmaceuticals inc
Role of IL‐4 and IL‐13 in Schistosoma‐induced pulmonary hypertension (LB780)
Authors: Kumar Rahul , Chabon Jacob , Gebreab Liya , Rodriguez Garcia Alexandra , Koyanangi Dan , Sanders Linda , Tuder Rubin , Graham Brian 
Published: June 2021

Background: Schistosomiasis‐associated pulmonary arterial hypertension (PAH) occurs in the context of Th2 inflammation, which is induced by IL‐4 and IL‐13. We had previously observed that TGF‐β signaling is necessary for Schistosoma‐induced pulmonary hypertension (PH) in the mouse. We hypothesized that IL‐4 and IL‐13 were necessary for the TGF‐β‐induced pulmonary vascular disease induced by Schistosoma.Methods: Wild type, IL‐13YFP, IL‐4GFP, IL‐4‐/‐, IL‐13‐/‐ and IL‐4‐/‐IL‐13‐/‐ mice (N=5‐17 per group) were intraperitoneally (IP) sensitized with 175 S. mansoni eggs/gram body weight, two weeks later intravenously (IV) challenged via tail vein with the same dose of eggs, and one week thereafter underwent right ventricular catheterization followed by quantitative histologic and protein analysis, or lung digestion and flow cytometry. Lung tissue from patients who died of schistosomiasis‐associated PAH was studied by immunostaining.Results: The lungs of patients with schistosomiasis‐associated PAH and mice with experimental disease had an increase in IL‐13, IL‐4Rα, phospho‐STAT6 and periostin, a target of IL‐13 signaling. Flow cytometry with IL‐13YFP and IL‐4GFP mice identified both of these cytokines were produced by CD4+ T‐cells. IL‐4‐/‐IL‐13‐/‐ mice, but not IL‐4‐/‐IL13+/+ or IL4+/+IL‐13‐/‐ mice, were protected from Schistosoma‐induced vascular remodeling, although the elevated right ventricular pressure persisted. Immunostaining of Schistosoma‐exposed mice demonstrated decreased phospho‐STAT6, perivascular TGF‐β ligand, and intravascular nuclear phospho‐Smad2/3 in IL4/IL13 double‐deficient mice only.Conclusions: Combined IL‐4 and IL‐13 deficiency are required for protection against Schistosoma‐induced pulmonary vascular remodeling.
Leukocyte subpopulation responses to resistance exercise are different in men and women and affected by protein supplementation (LB800)
Authors: Freidenreich Daniel , Hiester Kevin , Mastro Andrea , Volk Brittanie , Aristizabal Juan , Kraemer William , Volek Jeff 
Published: June 2021

Immune cells are integral to the recovery from exercise, but little is known about the effects of supplementation and sex on the immune response. Untrained men (M) (N=88) and women (W) (N=54) performed a squat exercise protocol (6 sets, 10 repetitions, 2 minutes rest between sets at 65% of 1 RM) and randomly received a supplement immediately post exercise of carbohydrate (CHO) (M=27, W=16), whey (WHY) (M=25, W=18) or soy (SOY) (M=27, W=19). Immunophenotypic analysis of leukocytes was performed before (Pre) and 15 and 60 min post exercise (PE). Comparison of sexes disregarding supplementation indicated lower CD4 T cell counts at all time points in women. CD4 T cells continuously declined in men at 15 and 60 min PE while women only decreased below Pre at 60 min PE. Monocytes increased significantly at 15 min PE in women only (M=+11%, W=+17%) but decreased significantly in both sexes at 60 min PE (M=‐21%, W=‐11%). After division by sex and supplement, monocytes were not different from Pre to 60 min PE in women in all groups, but in men monocytes decreased below Pre at 60 min PE in both CHO and SOY. B cells decreased below Pre at 60 min PE in men in all groups, but only decreased below Pre at 60 min PE in women in SOY. Granulocytes continuously increased PE in men in WHY and CHO, and in women in CHO and SOY. Sex and supplementation differentially affect leukocyte compartmentalization with the most apparent effects on monocytes.Grant Funding Source: Supported by the Dairy Research Institute
Antioxidative effects of allopurinol and sodium ascorbate increase posfatigue tension in avian skeletal muscle (LB809)
Authors: Sánchez‐Duarte Elizabeth , Guzmán‐Ambriz Ana , Trujillo Xóchitl , Huerta Miguel , Cortés‐Rojo Christian , Saavedra‐Molina Alfredo , Meza‐Carmen Víctor , Montoya‐Pérez Rocío 
Published: June 2021

Muscle fatigue is conceived as a decrease in force development after periods of intense activity, and is considered a multifactorial process. Reactive oxygen species (ROS) could play an important role in the regulation of the signaling pathways involved in the proper functioning of muscles, particularly during fatigue. It has previously been reported that the use of antioxidants can reduce the development of fatigue and reverse the decline of force induced by ROS. Moreover, it has been reported that low concentrations of antioxidants are beneficial to the cells, while high concentrations may become detrimental. Although several studies indicate that mitochondria are the predominant site for ROS generation during activity, there has been considerable speculation concerning the role of xanthine oxidase in generation of ROS by skeletal muscle. The aim of this study was to determine the effect of Allopurinol (inhibitor of xanthine oxidase) and sodium ascorbate (ageneral antioxidant) during the muscle fatigue.Anterior Latissimus Dorsi (ALD) muscle of chicken was dissected and mounted on an experimental recording chamber by placing the proximal end to the bottom of the chamber and the distal end to the hook of a mechanic‐electric transducer (Grass FT03), which through an amplifier and a 320 CyberAmp analog‐digital interface (Digidata 1322A) allowed to acquire the muscle tension generated in a computer (Pentium 4) and a “software” of data acquisition (AXOTAPE, pCLAMP 9.2). We performed a fatigue protocol by twitches (pulses of 100 V, 300 ms duration, 0.5 Hz). The bundle was stimulated until the force decreased by 60 %, then was applied the study drug for 6 min to observe its effect. We used concentrations of Allopurinol (1uM, 10uM and 100 µM) and sodium ascorbate (10, 30 and 100 uM).In dose response curves the mayor effect for Allopurinol was 100 uM and 10 uM by sodium ascorbate. In combination of Allopurinol and sodium ascorbate the tension post‐fatigue increased to 27.24% ± 8.47% in peak tension, while in total tension was an increase by 53.38% ± 18.60% compared with fatigue. The post‐fatigue increase was similar in combination of both drugs that separately, this suggested us the necessity of certain amount of ROS for the normal behavior of the muscle, since both Allopurinol and sodium ascorbate might act as antioxidants.Grant Funding Source: Supported by CIC2014‐RMP
Melatonin combined with treadmill exercise suppresses aberrant chondrocyte behavior in osteoarthritic cartilage via TGF‐β1 upregulation (LB834)
Authors: Choi Jeonghyun , Hong Yunkyung , Hong Yonggeun 
Published: June 2021

There is no curative treatment that modifies the structure of the damaged articular cartilage. This study examined the effect of melatonin (MT) with or without treadmill exercise (Ex) on aberrant chondrocyte behavior. MT was injected twice/day subcutaneously and Ex was conducted for 1 h/day. The interventions were initiated 4 weeks after an intra‐articular collagenase injection, and were maintained for 4 weeks. Vehicle treatment (Veh) elevated the joint parameters, while MT with or without Ex restored them to the control levels. Intervention reduced the levels of both serum TNF‐α and its downstream molecules Hif‐2a and Runx2. COL2A1 was over‐expressed and cleaved in the Veh and MT alone groups, while active MMP‐13 was the same in all groups. Intervention decreased the cleaved caspase‐3 level regardless of the type, whereas LC3 II expression was abolished in MT+Ex only. Combined intervention induced the upregulation of TGF‐β1 gene expression, with lower ALP levels. Consistent with this, histological repair was stimulated in the MT+Ex group. These findings suggest that melatonin combined with exercise blocks the TNF‐α‐mediated death signal via TGF‐β1 upregulation, leading to cartilage recovery in the osteoarthritic rats.Key words : Osteoarthritic cartilage, Melatonin, Treadmill exercise, Cell death, TGF‐β1
Dopamine Reuptake Inhibition as the Means of Antidepressant Mechanism of Function (LB92)
Authors: Deng Helend , Luo Thomas , Vorperian Sevahn , Petzold Christine , Nelson David 
Published: June 2021

Maintaining the equilibrium of neurotransmitters (NT) at neural synapses is essential for normal brain functioning. Lack of regulation of NT levels is associated with disorders including depression, Parkinson’s disease, ADHD, and epilepsy. The dopamine transporter (DAT) is the primary removal mechanism of the NT, dopamine, from the synaptic cleft. The regulation of NT reuptake is critical for preventing chemical imbalance and the inhibition of reuptake has become the primary target for antidepressants. The Drosophila melanogaster DAT was crystallized in complex with a tricyclic antidepressant (TCA) and found induced in an outward‐open conformation towards the synaptic cleft. Three factors contribute to inhibiting the inward‐facing conformation required for DAT activity: the antidepressant nortriptyline bound at the substrate‐binding site blocks important helix movement, a cholesterol molecule stabilizes the outward conformation, and lastly the C‐terminus caps the cytoplasmic gate. The Madison West SMART (Students Modeling a Research Topic) modeled the DAT structure using 3D printing technology. The structure of TCA‐bound DAT provides new knowledge of eukaryotic transporters and enables a better understanding of the critical factors and conformational changes associated with NT transport inhibition to allow for targeted drug research.Grant Funding Source: Supported by grants from the NIH‐SEPA and NIH‐CTSA.
Trigger Site Deactivation Surgery for Headaches is Associated with Decreased Postoperative Medication Use
Authors: Amador Ricardo O. , Gfrerer Lisa , Panzenbeck Paul , Hansdorfer Marek A. , Austen William G. 
Published: June 2021

Background:
Patients with chronic headaches suffer debilitating pain, which often leads to the use of numerous medications. Trigger site deactivation surgery has emerged as an effective treatment for select headache patients. This study aims to describe the preoperative and postoperative medication use among patients undergoing trigger site deactivation.

Methods:
One-hundred sixty patients undergoing trigger site deactivation surgery between September 2012 and November 2017 were prospectively enrolled. Information on medication use, including type, dose, and frequency of use, was collected. Follow-up surveys were sent to all patients 12 months postoperatively.

Results:
One-hundred twenty-nine patients met the inclusion criteria. At the time of screening, 96% of patients described taking prescription medication for their headache pain. The type of medication varied among patients but included preventative in 55%, abortive in 52%, rescue in 54%, and antiemetic in 18%. Thirty-one percent of patients reported using opioid medication for their headache pain. At 12 months postoperatively, 68% of patients reported decreased prescription medication use. Patients reported a 67% decrease in the number of days they took medication. Twenty-three percent stopped medications altogether. Fifty percent of patients reported that their migraine medication helped them more compared with preoperatively.

Conclusions:
Trigger site deactivation surgery has been associated with improvements in headache symptoms. We now show that it is also associated with a significant decrease in medication use.
Comparison of 30-day Clinical Outcomes with SimpliDerm and AlloDerm RTU in Immediate Breast Reconstruction
Authors: Tierney Brian P. 
Published: June 2021

Background:
Acellular dermal matrix (ADM) is widely used in breast reconstruction, and outcomes of these procedures may be improved through optimized product design. SimpliDerm is a new human ADM designed to closely preserve the architecture of native dermis, with the goal of improving surgical outcomes. This study reports the initial (30-day) clinical experience with SimpliDerm compared with AlloDerm Ready-To-Use (RTU) in ADM-assisted breast reconstruction.

Methods:
Clinical characteristics and outcomes of 59 consecutive patients who underwent immediate 2-stage reconstruction with SimpliDerm (n = 28) or AlloDerm RTU (n = 31) following mastectomy are reported.

Results:
Fifty-nine women (108 breasts) underwent posmastectomy breast reconstruction with SimpliDerm or AlloDerm RTU. Mean patient age was 51.1 years, and mean body mass index was 28.2 kg/m2. Reconstructions were predominantly prepectoral (95.4%), used tissue expanders (100%), and followed a skin-sparing (64%) approach to mastectomy. Mean time to final drain removal did not differ between groups (17.0 days, SimpliDerm versus 17.7 days, AlloDerm RTU). Adverse events occurred in 13 (22%) patients; none considered serious—all were mild or moderate in intensity. Adverse event rates did not differ between groups. The observed adverse event profiles and rates are similar to those published for other ADMs in immediate breast reconstruction.

Conclusions:
There remains a clinical need for ADMs with more optimal characteristics. This case series describes comparable outcomes with SimpliDerm and AlloDerm RTU over 30 days after immediate 2-stage breast reconstruction.
CorNeat KPro: Ocular Implantation Study in Rabbits
Authors: Litvin Gilad , Klein Ido , Litvin Yoav , Klaiman Guy , Nyska Abraham 
Published: June 2021

Purpose:
The purpose of this study was to evaluate surgical feasibility and long-term integration of the CorNeat Keratoprosthesis (KPro), a novel synthetic cornea, in rabbits.

Methods:
The CorNeat KPro is a synthetic corneal implant designed to treat corneal blindness by using a polymeric scaffold for biointegration, consequently assimilating synthetic optics within ocular tissues. Eight New Zealand White rabbits were implanted unilaterally with the CorNeat KPro and observed for 6 months. Animals were regularly monitored by a certified ophthalmologist using slit-lamp biomicroscopy. One animal developed postoperative endophthalmitis and was removed from the study 7 weeks postsurgery. At termination, eyes were enucleated and evaluated histologically to assess local tissue integration and inflammatory response.

Results:
The surgical procedure was found feasible. The CorNeat KPro integrated into all operated eyes, resulting in a retention rate of 87.5% at the conclusion of the 6-month follow-up period. We observed minimal-to-mild conjunctival and iridial congestion and did not find additional inflammatory indicators, such as anterior chamber fibrin, flare, or cells. The optical element of the device remained clear with zero incidence of retroprosthetic membrane formation. Histopathological evaluation revealed comparable tissue and cellular reaction in all eyes, consisting of the presence of fibroblasts and associated collagen fibrils within the device's skirt component. Some eyes showed a mild foreign body reaction surrounding the skirt.

Conclusions:
Clinical and histological findings indicate the integration of the implanted device into the surrounding tissue, evident by the retention rate and the diffuse infiltration of fibroblasts with collagen deposition among the device's fibrils. These data hold promise for clinical application in humans.
Household wealth and HIV incidence over time, rural Uganda, 1994–2018
Authors: Santelli John S. , Chen Ivy , Makumbi Fred , Wei Ying , Nalugoda Fred , Lutalo Tom , Spindler Esther , Grilo Stephanie A. , Deisher Andrea , Grabowski Katherine , Hoffman Susie , Kagaayi Joseph , Chang Larry W. , Gray Ronald , Wawer Maria , Serwadda David 
Published: June 2021

Objective:
To examine the relationship between household wealth and HIV incidence in rural Uganda over time from 1994 to 2018. In research conducted early in the epidemic, greater wealth (i.e. higher socioeconomic status, SES) was associated with higher HIV prevalence in sub-Saharan Africa (SSA); this relationship reversed in some settings in later years.

Design:
Analysis of associations over time in a population-based open cohort of persons 15–49 years from 17 survey-rounds in 28 continuously followed communities of the Rakai Community Cohort Study (RCCS).

Methods:
The RCCS sample averaged 8622 individuals and 5387 households per round. Principal components analysis was used to create a nine-item asset-based measure of household wealth. Poisson regression with generalized estimating equation (GEE) and exchangeable correlation structure was used to estimate HIV incidence rate ratios (IRRs) by SES quartile, survey-round, sex, and age group.

Results:
From 1994 to 2018, SES rose considerably, and HIV incidence declined from 1.45 to 0.40 per 100 person-years (IRR = 0.39, 95% CI = 0.32--0.47, P < 0.001). HIV incidence was similar by SES category in the initial survey intervals (1994–1997); however, higher SES groups showed greater declines in HIV incidence over time. Multivariable analyses showed significant associations between HIV incidence and SES (IRR = 0.55 for highest compared with lowest quartile, 95% CI = 0.45--0.66, P < 0.001) controlling for time, sex, and age group.

Conclusion:
Beyond the early years of the RCCS, higher SES was associated with lower HIV incidence and SES gradients widened over time. The poor, like other key populations, should be targeted for HIV prevention, including treatment as prevention.
Relapsed Breast Implant–Associated Anaplastic Large-Cell Lymphoma Presenting as Refractory Fluid Collections With Low Uptake on FDG PET/CT Scan
Authors: Alsa’di Hussein S. , Donald Joseph S. 
Published: June 2021

Abstract
Breast implant–associated anaplastic large-cell lymphoma is a rare type of non-Hodgkin lymphoma that occurs years after placement of textured surface breast implants. Patients typically present after the development of pain, a palpable mass, or swelling. We present a case of a 45-year-old woman with recurrent breast implant–associated anaplastic large-cell lymphoma presenting as refractory fluid collections, and the unusual finding of low uptake on FDG PET/CT scan despite being confirmed by cytology.
Solitary Contralateral Adrenal Metastasis of Renal Cell Carcinoma
Authors: Filizoglu Nuh , Ozguven Salih 
Published: June 2021

Abstract

68Ga-DOTATATE PET/CT is an imaging technique used in the diagnosis of neuroendocrine tumors. Since renal cell carcinoma (RCC) expresses the somatostatin receptors, 68Ga-DOTATATE PET/CT could be used in the surveillance of RCC. However, limited cases showing 68Ga-DOTATATE uptake in the metastases of RCC have been reported before. Herein, we report a case of a 55-year-old woman with a history of left nephrectomy for clear cell renal cell carcinoma 2 years before, and referred to 68Ga-DOTATATE PET/CT for the evaluation of adrenal mass. 68Ga-DOTATATE PET/CT showed intense 68Ga-DOTATATE uptake on the adrenal mass. Histopathology of the adrenal mass confirmed the diagnosis of clear cell renal cell carcinoma metastasis.