bluuebunny/crossref_metadata_2025_split huggingface dataset:
Femoral Condyle Curvature and the Chondral Modeling Theory
Authors: Harris Emma , Sylvester Adam 
Published: June 2021

The chondral modeling theory argues that the cartilage of a developing joint surface responds to mechanical loading during ontogeny, resulting in regions of low curvature where the joint is heavily loaded. This theory has been used to explain the relatively lower curvature exhibited by the anterior portions of human femoral condyles. In contrast, it has been argued that the femoral condyles of non‐human primates have constant curvatures, potentially in conflict with the chondral modeling theory, although this has never been rigorously quantified. The goal of this study was to measure the curvature across the medial femoral condyles of chimpanzees and gorillas, comparing them with humans.Three‐dimensional surface models of human (n=9), chimpanzee (n=9) and gorilla (n=9) femora were created using a white light surface scanner. Landmarks were collected on the attachment point for the collateral ligaments and across the femoral head. These points were used to estimate functional/mechanical axes of the femur which were then used to align all bones to a standardized orientation. The profile of each medial condyle, relative to the axis of knee flexion/extension, was extracted from digital images of the models and curvature was quantified across the profile.Measurements of curvature across the human profile match previous work, demonstrating a region of low curvature at the anterior portion of the condyle. While gorilla femora did not appear to exhibit an obvious low curvature region, the chimpanzee medial femoral condyle was found to show a consistent region of relatively low curvature. Furthermore, in support of the chondral modeling hypothesis, the position of low curvature regions appears to be associated with knee positions used during the stance phase of chimpanzee walking.
A Novel Infant Nutrition System Precisely Delivers Hygienic Reconstituted Formula
Authors: Yan Jian , Pecquet Sophie , Wyss Heinz , Steenhout Philippe 
Published: June 2021

Powdered infant formula is conventionally supplied in multi‐serve packaging and reconstituted following multiple manual preparation steps. An advanced infant nutrition system, combining a dedicated dispenser with single‐serve capsules of powdered formula, was designed to precisely deliver hygienic reconstituted formula in < 1 min. To test the performance (technical reliability and quality of reconstituted formula), a field study was conducted at three hospitals in Switzerland with a prototype system, where hospital staff used the system (n = 4) to reconstitute formula when needed by infants. Only 22 (0.9%) of the 2445 bottles prepared over the 4‐mo period encountered preparation difficulties. After reconstitution, 93% of the 2445 capsules showed no solid residue, and 5% had only a few small lumps, suggesting good solubility. Additional preparations were conducted in hospitals to assess the dilution precision and microbiological quality of reconstitutes. The target for reconstituted formula weight (±3g) was met by 89% of the 252 bottles tested, suggesting good technical precision of formula dilution. 100% of the reconstituted formula tested negative for Enterobacteriaceae (n=281) and Salmonella (n=262), and Aerobic Mesophilic Count was <100 cfu/ml in 83% and <1000 cfu/ml in 98% of 276 bottles, which met CODEX good quality specification after reconstitution. Interviews with hospital staff (n=74) revealed that the system was preferred over conventional formula preparation partially due to its ease of use. In sum, these data indicate that the new infant nutrition system ensures a hygienic, safe, precise and convenient preparation for each feeding.Funded by Nestec S.A.
Effects of a Unique Vitamin C Ingredient on Chronic Knee Complaints
Authors: Mitmesser Susan , Zhang Zhiyling , Ye Qian 
Published: June 2021

BackgroundChronic knee complaints are very common in athletes. Overuse injury can cause pain in the patellar tendon. Vitamin C is required for collagen synthesis, which is an important component of tendons. It has been reported that vitamin C can suppress cytokine production, which is indicative of an inflammatory response. Ester‐C®, calcium ascorbate plus vitamin C metabolites, has been clinically studied and may have a higher biological availability in body tissues than ascorbic acid.ObjectiveTo examine the effect of Ester‐C® on the improvement of injury complaints in athletes with patella tendonitis (also known as “jumper's knee”).MethodsBasketball players with patella tendonitis were recruited to participate in this study. Each athlete received Ester‐C® in increasing daily doses for 6 weeks (Week 1: 1000 mg, Week 2: 2000 mg, Weeks 3‐6: 3000 mg). Improvement scores of six complaints ‐ pain, power, mobility, speed, jumping ability, and general condition ‐ were assessed on a scale of 0‐3 (0=no improvement; 1=noticeable improvement; 2=full improvement at rest; 3=full athletic improvement). The percentage of subjects that showed improvement in each category and the average improvement scores (AIS) were calculated.ResultsA total of 16 basketball players completed the study. Most complaints started to show improvement after Week 2. Dramatic improvements were observed in all injury criteria during Week 5 and were maintained at the end of Week 6. The greatest improvements were in pain reduction (AIS 1.75) and jumping ability (AIS 1.5), with the least improvement observed in mobility (AIS 0.38).ConclusionEster‐C® has a positive effect on chronic knee complaints caused by overuse in high‐impact sports, such as basketball.
Induction of Mindin is Associated with Pathological Changes in the Kidney of Cd151‐/‐ Mice
Authors: Naudin Crystal , Weidenhofer Judith , Roselli Severine , Keely Simon 
Published: June 2021

The presence of CD151, a transmembrane protein involved in cell adhesion complexes with α3β1 integrins, is essential for glomerular function. We have identified significant increases in mindin in the glomeruli of CD151 knock‐out mice (Cd151‐/‐)compared to wild‐types (Cd151+/+). Due to mindins known role in actin cytoskeleton and cell adhesion signalling, we hypothesised that aberrant expression of mindin in the glomerulus leads to the abnormal extracellular matrix deposition, and disruption to podocyte actin cytoskeleton structure, which occurs in this disease model.Immunofluorescent labelling of mindin in 3‐week‐old Cd151+/+ and Cd151‐/‐ kidneys demonstrated specific accumulation in Cd151‐/‐ glomeruli, (absent in Cd151+/+). No expression of mindin was observed in 5 day old mice (when Cd151‐/‐ glomeruli first exhibit pathology) indicating it is unlikely to be involved in initial pathology.As mindin is also an immune cell activator, we examined whether the induction of mindin leads to immune‐mediated glomerular injury as part of disease progression in the Cd151‐/‐ kidney. We also investigated mindin as a potential biomarker of glomerular disease in the broader sense and characterised immune cell infiltrates in Cd151‐/‐ kidneys.Infiltration of lymphocytes, neutrophils, macrophages and eosinophils was observed as early as 3 weeks of age in Cd151‐/‐ but not Cd151+/+ kidneys by differential histological staining. This infiltration was progressive and more pronounced in 12 week old Cd151‐/‐ mice, associated with extensive inflammatory lesions. Together, these data suggest that in the absence of CD151, mindin is induced early in disease, associated with disruption to podocyte actin cytoskeleton homeostasis, and immune‐mediated glomerular damage.
The Effect of Croton lechleri on Prostate Cancer Progression
Authors: Glasscock Laura , Webb Stefanie 
Published: June 2021

Prostate cancer (CaP) continues to be the second leading cause of cancer deaths in men in the US (Siegel 2014). Many of the cancer drugs currently on the market are from or are structurally similar to compounds found in natural plant products. We investigated the effect of a tree bark native to the Peruvian Amazon, Croton lechleri on the proliferation and invasion of two prostate cancer cell lines, DU‐145 and PC‐3. C. lechleri is commonly used by Peruvian healers to treat prostate conditions and is one of the most popular treatments purchased from herbal markets (Bussmann 2007). C. lechleri has antioxidant capabilities as a free radical scavenger (DeMarino 2008) and species in the same genus as C. lechleri decrease cell adhesion and induce apoptosis in stomach and colon cancer cell lines (Sandoval 2002). We used C. lechleri latex extracts, the form used by Peruvian Shaman for therapeutic use, to treat PC‐3 and DU‐145 CaP cell lines and evaluate their ability to proliferate using CellTiter 96® and invade using a modified Boyden Chamber. C. lechleri, at concentrations equal to and less than those used as Peruvian therapeutic treatments, significantly reduced proliferation of both PC‐3 and DU‐145 cells in a dose dependent manner. C. lechleri reduced invasion of DU‐145 cells but not the more invasive PC‐3 cells. Studies of the effect of C. lechleri on cancer progression have been contradictory, depending on the type of cancer under investigation. Here, we describe that in prostate cancer, C. lechleri decreases both the ability of prostate tumor cells to proliferate and invade. We are currently investigating the effect of C. lechleri on CaP cell apoptosis.This project was funded NIH‐INBRE Grant from the National Center for Research Resources and Winthrop University Research Council
Using Protein Microarray Technology to Screen Anti‐E‐Cadherin (ECAD) Monoclonal Antibodies for Specificity and Applications in Pathology
Authors: Chen Caiwei , Wei Haitao , Yuan Kehu , Ma Donghui , He Wei‐wu 
Published: June 2021

E‐cadherin (ECAD) is a calcium‐dependent cell‐cell adhesion molecule playing a crucial role in establishing epithelial architecture and maintaining cell polarity and differentiation. Reports showed that decreased ECAD expression has been associated with more advanced tumor stage and grade for lung tumors, gastric tumors, breast tumors and etc. Other research discovered that staining for ECAD may be useful for the differentiation between ductal and lobular breast carcinomas. Thus, a high quality monoclonal antibody validated for immunohistochemistry (IHC) is required to evaluate ECAD protein levels in formalin‐fixed paraffin‐embedded tissue samples.To develop the a suitable monoclonal antibody for ECAD IHC analysis, 49 monoclonal antibodies were generated, of which 10 were selected for screening in IHC on breast and prostate cancer tissues. Further evaluation with a high density protein microarray chip containing 17,000 human proteins indicated that clone 3C11 is highly specific and only detected ECAD. Comparison to the monoclonal 4A2C7, showed that 3C11 is more sensitive on breast, prostate, and prostate cancer tissues. The new monoclonal antibody 3C11 will be a promising candidate to detect the expression and aberrant alterations of ECAD for the diagnosis, prognosis, and therapy of cancer.
Targeting The Laminin Receptor / PEDF Interface to Treat Prostate Cancer Cells
Authors: Umbaugh Charles , Diaz‐Quiñones Adriana , Zhou Jia , Cheng Xiaodong , Figueiredo Marxa 
Published: June 2021

The non‐integrin laminin receptor (LAMR1) is a multifunctional protein localized in the cytosol and at the membrane. Recently, the potent antiangiogenic protein required for retinal development and maintenance, pigment epithelium derived factor (PEDF), was confirmed as a binding partner for LAMR1. LAMR1 is frequently overexpressed in cancer cells. Our lab and others have demonstrated that PEDF abolishes neo‐vasculature in prostate tumors, resulting in decreased tumor growth and burden and abatement of metastatic potential.Using crystal structures for PEDF and LAMR1, we mapped the interaction interface and screened the Maybridge HitFinder Database in silico (>14,000 compounds) using Docking@UTMB and AutoDock Vina. We selected seven hits and conducted a medium throughput screen in multiple cell lines. IC50s were generated using a six point dose curve and a four parameter non‐linear regression. Orthogonal validation was performed using luciferase assays against cancer specific promoters. Finally, we identified the 67 kDa species of LAMR1 and successfully knocked endogenous protein down using siRNA duplexes.Our phenotypic screen revealed three putative laminin antagonists, two agonists, and two ineffective compounds. We established that PEDF and the peptide P18 can mediate changes in gene expression. One compound significantly reduced Fas Ligand promoter activity and phenocopied PEDF, suggesting that these compounds may modify the tumor microenvironment. Next, we will confirm LamR specificity using cell‐surface binding assays and siRNA.Funding: UTMB CAR P50DA033935 Pilot Grant and Startup Funds
Redox‐sensitive Sp‐3 Transcription Factor via Renal AT1 Receptor Contributes to Age‐related Hypertension
Authors: Saleem Mohammad , Asghar Mohammad 
Published: June 2021

Renal angiotensin II type 1 receptor (AT1R) plays pivotal role in blood pressure control. We recently reported an exaggerated AT1 receptor function and hypertension in aged (21 month) Fisher 344 X Brown Norway (FBN) rats. Antioxidant tempol treatment reduced AT1R function and blood pressure in these rats suggesting a role of oxidative stress in this phenomenon. However, oxidative stress mechanism for higher AT1R function is not known. Therefore, we became interested in delineating the mechanism of oxidative stress induced up‐regulation of AT1R in aging kidney. mRNA levels of renal AT1R were measured by qRT‐PCR while nuclear Sp‐3 and AT1R protein levels were measured by western blot. To further examine whether oxidative stress increases nuclear translocation of Sp‐3 and up‐regulation of renal AT1R expression, we treated human kidney 2 (HK2) cells with pro‐oxidants diethyldithiocarbamate (DDC) and hydrogen peroxide (H2O2). Acute treatment of DDC (30min) and H2O2 (20min)increased nuclear levels of Sp‐3 which was attenuated with tempol treatment. DDC chronic treatment (2.5 hour) increased the expression of AT1R while tempol treatment attenuated this effect. Moreover, Sp‐3 plasmid increased and Sp‐3 siRNA decreased the levels of AT1R protein in HK2 cells. Our results suggest that redox‐sensitive Sp‐3 transcription factor up‐regulates renal AT1 receptor and may contribute to age‐related hypertension.Source of research support: NIH/NIA AG039856
Behavioral, Biochemical and Molecular modulation in Brain and Spinal cord : A potential antinociceptive‐antidepressant mechanism of Xanthophylls
Authors: Badgujar Lohit , Saraf Madhusudan 
Published: June 2021

AimThe present study was designed to investigate the antinociceptive‐antidepressant effects of xanthophylls, Lutein and in chronic pain‐depression dyed.MethodsSD rats (230‐250 g) were anesthetized under ketamine‐xylazine (80 ‐ 20 mg/kg, intraperitoneally) and chronic constriction injury (CCI) was performed (Bennett and Xie, 1988). Vehicle‐olive oil (0.5 ml), Lutein (LT 20 & 40 mg/kg), Zeaxanthin (ZX 20 & 40 mg/kg) and Lutein‐Zeaxanthin (LZ 25 & 50 mg/kg) were administered from day 14 to day 38. Behavioural observations were recorded on 0, 7, 14, 21, 28 & 35th day. Animals were sacrificed on 36th day; sciatic nerve, spinal cord and brain were isolated for biochemical estimations (Brain monoamines, spinal GABA, total ROS in brain, spinal cord and sciatic nerve)and molecular expression.ResultPain, anxiety and depression (increased immobility at expenses of climbing behaviour) were significantly increased in CCI animals. Decreased brain noradrenalin and increased spinal ROS was observed in CCI animals compared to sham. LT 40, ZX 40 and LZ 25 and 50 decreased the mechanical allodynia, thermal hyperalgesia and allodynia. Similarly, LT (40 mg/kg), ZX (40 mg/kg) and their combination LZ (25 and 50 mg/kg) showed reduction in depression behaviour i.e. decreased time of immobility and increased climbing in FST. Modulation in brain monoamine levels and decreased spinal ROS were observed in LT 40, ZX 40, LZ 25 and LZ 50 treated animals. Similarly, modulation in protein and mRNA expression at Spinal cord were observed.Conclusionxanthophylls LT, ZX and LZ play their antinociceptive‐antidepressant role by modulating ROS & monoamines level at brain along with the protein and mRNA expression and ROS at spinal cord.
Knockout of the Ergothioneine Transporter ETT in Zebrafish Results in Increased 8‐Oxoguanine Levels
Authors: Krueger Johanna , Pfeiffer Carolin , Gruendemann Dirk 
Published: June 2021

Ergothioneine (ET) is expected to provide antioxidative properties due to its double‐bonded sulfur. It is acquired by plants and vertebrates solely through dietary means. However, the precise physiological function of ET remains unclear. Case‐control studies suggest an association of polymorphisms in the human ET transporter (ETT) gene with chronic inflammatory diseases like rheumatoid arthritis [Nat Genet 35, 341‐348], Crohn's disease [Nat Genet 36, 471‐475] and diabetes [Biochem J 25, 171]. MethodsHere we have procured, based on retroviral insertion [Genes Dev 13:2713‐24], an ETT knock‐out zebrafish (Danio rerio). The expression profile of ETT in wild‐type zebrafish was analyzed by RT‐PCR and real‐time RT‐PCR and validated by measuring ET tissue content.ResultsStrong signals were obtained with kidney, intestine, skin, brain and eye. In whole‐fish lysates of homozygous knock‐out animals, ET content (0.06 ± 0.01 ng/g wet mass; n=3) was reduced more than 1000‐fold compared to wild‐type (138 ± 61 ng/g wet mass; n = 3). Similarly, all examined organs contained virtually no ET. Carnitine and acetylcarnitine were reduced across all examined tissues of knock‐out fish by a factor of 2.0 ± 0.2, and 1.7 ± 0.1, respectively. Incubation in sublethal concentrations of Pb2+ and Cu2+ led to an increase of the lipid peroxidation markers 4‐hydroxy‐2,3‐trans‐nonenal (HNE) and malondialdehyde (MDA) in knock‐out versus wild‐type zebrafish. Comparison of unstressed fish at the level of small molecules by LC‐MS difference shading [Proc. Natl. Acad. Sci. U.S.A. 102:5256‐61] revealed a 3.8‐fold increase of 8‐oxoguanine in the skin of ETT knockout fish.ConclusionBased on this phenotype we propose that the universal and specific purpose of ET is to eliminate singlet oxygen.
Prevention of Cardiovascular Disease at Outpatient Clinic Service in Kazakhstan
Authors: Turlybekova K.D. , Khismetova Z.A. , Rakhypbekov T.K. 
Published: June 2021

High public and medical importance of diseases of the circulatory system (hereinafter ‐ SBR) due to their wide distribution, poor prognosis and significant social and economic losses. Components of the study for the prevention of coronary heart disease (CHD) were: detection and dynamic monitoring of individual groups (CHD) risk; training of patients with diseases of the circulatory system in the school, “Coronary heart disease”; adherence to the principles of continuity in the monitoring of patients with coronary artery disease between general practitioners (GPs), cardiologist and physician day hospital; empowerment of day hospitals; active health education outreach.During the period from 2010‐2012 to in the medical preventive institution surveyed 1,852 people. Among examined patients 42.3% had a SBR requiring active interventions for secondary prevention, while 48% of them have never consulted a doctor, and the pathology was revealed during questioning and subsequently the active examination. 64.5% ‐ are at the ages of 50‐59 years. At risk group the largest share (30.5%) were in people aged 45‐54 years; 25.7% ‐ 44 years; 23.4% ‐ 50‐54 years; 17.8% of those at risk group in the age 55‐59 years and 21.6% ‐ 35‐40 years. Healthy people predominated in the age group 35‐39 years (55.3%).Thus, considering that if hypertension is a strong risk of vascular events: stroke, myocardial infarction, treatment costs are significantly was higher (8‐12 times), than the costs of preventive measures for hypertension, it is necessary to develop ways of improving economic approach to the development of the above diseases.
Systemic and Microcirculatory Vasoactive Effects of a Third Generation Perfluorocarbon in a Rodent Top‐Load Model
Authors: Crossland Randy , Macko Antoni , Song Bjorn , Sheppard Forest 
Published: June 2021

BackgroundRestoration of oxygen carrying capacity (OCC) is essential to adequately treat hemorrhagic shock. Multifunctional resuscitation fluids (MRFs) containing oxygen carrier (OC) molecules are being developed to improve OCC. However, adverse vasoactivity of previous generations of OCs has limited MRF development. Newer, third generation PFCs have garnered interest as potential OCs for use in MRFs. Here, as part of an evaluation as a potential OC for use in a MRF, we tested a third generation PFC for systemic and microvascular vasoactivity in a rodent model.MethodsMale Sprague‐Dawley rats (250‐350 grams) were randomly assigned to receive four sequential intravenous infusions (1.5 mL/kg each) of either PFC (Oxycyte®; n=10) or 0.9% NaCl (control; n=10). At the conclusion of each study, phenylephrine (PE; 1 mg/kg) was infused to confirm physiological intactness of the animal. Heart rate (HR) and mean arterial pressure (MAP) were continuously monitored. Vasoactivity was assessed by intravital microscopy of spinotrapezius arcade arterioles. Statistical comparisons were made by ANOVA. Results reported as mean ± SEM.ResultsNo observed differences were seen in MAP, HR, or microvascular arteriole diameters between groups at baseline or throughout the study (Table 1). In both PFC and control groups, PE constricted arterioles by 50% (p<0.001) and elevated MAP 2‐fold (p<0.001).

PFC (n=10)
Control (n=10)

Baseline
Final Dose
PE
Baseline
Final Dose
PE

MAP (mmHg)
94 ± 4
99 ± 5
198 ± 3
95 ± 2
90 ± 4
199 ± 5

HR (bpm)
362 ± 6
344 ± 36
326 ± 10
364 ± 9
359 ± 10
314 ± 11

Arteriole Diameter (µm)
58 ± 4
58 ± 4
26 ± 4
57 ± 2
62 ± 4
24 ± 4

Funding: DoD Hemorrhage and Resuscitation Research and Development Program (WUN G1018)ConclusionAlthough these data demonstrate no adverse systemic or microcirculatory vasoactive effects, further evaluation of the third generation PFC in a clinically relevant hemorrhage model is warranted.
Repeatability of Reactive Hyperemia Flow‐Mediated Dilation in the Superficial Femoral Artery
Authors: Schmitter Sarah , King Trevor , Pyke Kyra 
Published: June 2021

Reactive hyperemia (RH) is induced via the release of a temporary limb occlusion and causes a transient increase in artery shear stress. Flow‐mediated dilation stimulated by RH (RH‐FMD) is a standard index of endothelial function in the brachial artery however, relatively few studies have assessed RH‐FMD in the superficial femoral artery (SFA). The purpose of this study was to determine the repeatability of RH‐FMD in the SFA. SFA RH‐FMD was measured in 19 subjects (10 males and 9 females; age: 24 ± 2 years). Subjects performed four 5‐minute occlusion RH trials in a seated position with the cuff placed above the knee. Six minutes of recovery followed cuff release. SFA diameter and blood velocity were assessed using echo and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = mean blood velocity/SFA diameter). RH‐FMD was calculated as the % increase from baseline diameter to the peak 3 second diameter measurement post occlusion release. Results are expressed as mean ± SD. The RH SR area under the curve (AUC) for the 30 seconds following cuff release was higher in trial 1 versus trial 2 and 3 (p < 0.001 and p = 0.021). There were no differences in %RH‐FMD across trials (RH trial 1: 5.2 ± 2.6%, trial 2: 5.0 ± 2.3%, trial 3: 4.5 ± 2.2%, and trial 4: 5.0 ± 2.9%, p = 0.465). FMD normalized to the SR AUC also did not differ between trials (p = 0.879). In conclusion, despite some variability in the SR stimulus, there was no systematic change in %RH‐FMD over four repeated trials.Funded by NSERC and CFI