bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an FM interferential electrical stimulator for swallowing rehabilitation
Authors: Morimoto In 
Published: May 2022

Dysphagia (disorder of swallowing) can develop due to structural, functional, psychological, and/or medical causes. The prevalence of dysphagia in the elderly is 7%~22% per 100,000 people, and its incidence increases with age. In Japan, pneumonia is the fifth leading cause of death, with aspiration pneumonia accounting for 70% of these cases. Treatment options for dysphagia have been proposed, including transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (rTMS), peripheral neuromuscular stimulation (NMES), pharyngeal electrical stimulation (PES), and drug therapy. Among other things, an electrical stimulator using peripheral neuromuscular stimulation has been developed in the USA and is the most commonly used therapy in medical practice. This device aims to improve the muscle strength required for swallowing by applying a low‐frequency electric current to the muscles. In addition, a rehabilitation device using transcutaneous electrical sensory stimulation (TESS) without muscle contraction has been developed in Japan, which can increase the frequency of swallowing without discomfort by activating the sensation in the throat with a medium frequency.In this study, a rehabilitation device will be developed using burst modulated square waves, which are high‐frequency square waves modulated by low‐frequency, devised by Hernández Arrieta. The high‐frequency component of burst‐modulated square waves can lower the impedance of the skin and induce muscle contraction with less pain than direct current or low‐frequency stimulation.In our study, we developed a multi‐point stimulation electrode for the forearm. We applied 125 patterns of electrical stimulation with 25 electrodes to five healthy subjects and were able to produce 69 different hand postures. However, because different hand postures were sometimes expressed in each experiment even when the stimulus position was the same, we sought to use machine learning models to robustly estimate the stimulus position and hand posture. The results show that the Gaussian naïve Bayes classifier has the best prediction accuracy for the thumb and index finger, where the number of bends is low, and the decision tree algorithms LightGBM and GradientBoosting classifiers for the middle, ring, and little fingers, where the number of bends is high.In the future, to use this electrical stimulator for swallowing, it is necessary to consider the shape of the electrodes to improve discomfort during stimulation, the stimulation position to stimulate appropriate muscles, and sufficient stimulation parameters to activate the swallowing muscle groups.
Anatomical Gift Programs Continue to Meet Donor Demands of Anatomy Educators During the COVID‐19 Pandemic: Here’s How
Authors: Cope Janet , Bennett Cynthia M. , Zimmerman Monica , Balilionis Gytis , Person Dianne 
Published: May 2022

INTRODUCTIONSchools of higher education across the US closed all operations and in‐person classes during the COVID ‐19 pandemic, significantly affecting laboratory‐based anatomy dissection courses and the anatomical gift programs (AGP) that support them. The purpose of this study was to investigate how the COVID‐19 pandemic affected AGP operations in the US. The researchers hypothesized that programs would modify donation acceptance criteria and that anatomy education demands for donors would be reduced during the first year of the pandemic.METHODS/ RESULTSThe researchers sent a Qualtrics survey to 135 AGP directors with a response rate of 28% (n=38). Respondents were from 26 states and included 28 AGPs operating for 25 years or longer and ten programs operational for 15 years or less. Six AGP’s (16%) stopped accepting donors for varying lengths of time secondary to the COVID‐19 pandemic during its first year, while 32 programs (84%) continued operations. Of the programs that remained operational, 81% (n=26) made modifications to donor acceptance policies, while 19% (n=6) maintained existing acceptance policies. Schools that made policy modifications for donor acceptance criteria reported changes, including heightened screening for symptoms of COVID‐19 at the time of donor registration and upon death and requiring a negative COVID test for the anatomical donor near the time of death. In addition, COVID‐19 infection was added to the existing list of disqualifying conditions for many programs. Some sites excluded donors from large group facilities (hospitals, long‐term care), and some declined any donors with respiratory infections at the time of death. Several programs (13%) stopped accepting those donors who were not registered with their AGP prior to the onset of the COVID pandemic.During COVID‐19, the demand for donors in anatomy education decreased significantly (p<0.05). Reasons for the reduced donor demand as reported by respondents included school closings and adjusted (smaller, shorter in time) laboratory sessions. These actions were taken because of concern for student/staff safety, reduced availability of appropriate personal protective equipment, and safety‐related student/faculty spacing needs.CONCLUSIONMost AGPs were operational during COVID‐19 and able to maintain donor needs for anatomy education. Further research is warranted into the long‐term effects on AGPs as the pandemic persists.
Effects of Dietary Pattern on Average Cortical Bone Density and Estimated Thickness of the Proximal Ulna
Authors: Armon Austin , Erceg Fayja , Lochner Bailey , Rodgers Hannah , Zelazny Kaya G. 
Published: May 2022

There is an established relationship between diet and phenotype in various human body systems. Vegetarian diets may contain lower quantities of calcium and protein compared to other diets, causing speculation that this dietary pattern may contribute to lower bone mineral density (BMD) or osteoporosis. Nutritional intake is a major element in a person’s overall Bone Mineral Density (BMD), but little is known about how the upper extremity responds to changes in dietary pattern. There is also conflicting evidence for the effects of a vegetarian diet on bone, with some studies suggesting that lower quantities of calcium and protein compared to other diets contributes to lower bone mineral density (BMD), while others find that the lower acidic load found in the vegetarian diet combined with a higher intake of potassium have a calcium‐sparing effect with positive effects on bone health. This study tests how vegetarian and convenience diets affect Cortical Bone Thickness (CBT) and Average Cortical Density (ACD) of the olecranon process in humans, a site of fracture in the upper limb.Computed tomography (CT) scans with varying dietary pattern were obtained from the New Mexico Decedent Image Database and segmented in 3D Slicer. Cortical thickness was measured by calculating the difference between periosteal and endosteal section contours. Density was approximated by comparing the average radiodensity after applying a threshold of 500 HU to isolate cortical bone. MANOVA and post‐hoc ANOVA testing were conducted in R Studio to test differences between dietary groups. There was a statistically significant effect of bone length (p = 0.001) and diet (p = 0.014) on both proximal ulnar bone properties measured (approximated cortical thickness and density). Post‐hoc testing found that only bone length had a significant effect on cortical thickness (p = 0.003) while diet, but not bone length or sex, had a significant effect on average cortical density (p = 0.008).These results provide evidence of detrimental effects of a convenience diet on bone density, and possible evidence for beneficial effects of a vegetarian diet. Convenience foods are high in saturated fats, sodium, and refined sugars, which have been shown to have negative effects on bone mass and bone microarchitecture in rodents. Our results suggest that similar effects may be seen in the cortical bone of humans, providing additional evidence for the negative effects of convenience food on health. Previous studies have found that nutritional acidic load, which may be lowered by a vegetarian diet, is positively correlated with fracture risk and negatively correlated with BMD. Our results support these findings and add to the growing evidence for the benefits of a vegetarian diet.
Role of Potassium Channel Function and Long‐term Exercise Training in Soleus Resistance Arterioles
Authors: Caldwell Jacob , Reid‐Foley Emily , Ballehr Kelsey , Restrepro Alexis , Wahl John , Maraj Joshua , Park Hyerim , Delp Michael , Muller‐Delp Judy 
Published: May 2022

IntroductionNuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) expression has been linked to potassium (K+) channel function. We hypothesized that myogenic responses are enhanced by exercise training and also modulated by K+ channel function but would be impaired in arterioles from skeletal muscle of trained rats in which Nrf2 (Nrf2 KO) is deleted.MethodsExercise training was performed in male wildtype (WT) Sprague‐Dawley rats, and their littermates lacking the Nrf2 gene (Nrf2 KO). Rats were exercise trained using a mixed moderate and high‐intensity interval treadmill program for 10‐12 weeks. A WT cage‐confined control group was also studied to compare the impact of exercise training. After exercise training or sedentary cage‐confinement, soleus resistance arterioles were isolated and cannulated for the assessment of vascular reactivity. Vasodilatory responses to low concentrations of KCl [10 and 20mM} were assessed. Vasoconstrictor responses to higher concentrations of KCl [30–100mM] and myogenic responses to increasing intraluminal pressure (pressure 0cm H2O – 130cm H2O) were also assessed. The contribution of inward rectifying K+ channels (Kir) to vasodilation during low concentrations of KCl was assessed by treatment with barium chloride (BaCl2, 100mM).ResultsSoleus resistance arteriole myogenic responsiveness was reduced in trained Nrf2 KO as compared to WT (p<0.01). Trained WT rats produced a significantly higher myogenic responsiveness than sedentary WT controls (p<0.05). Vasodilation to low concentrations of KCl was reduced in soleus arterioles from trained Nrf2 KO rats as compared to arterioles from trained WT rats (p<0.01). Exercise training did not alter vasodilation to low KCl concentrations in WT rats (p>0.05). Constriction to higher concentrations of KCl was similar in arterioles from trained WT and Nrf2 KO rats. Inhibiting Kir channels with BaCl2 eliminated the genotype‐ and training‐related differences in myogenic responses and vasodilation to KCl.ConclusionOur data indicate that Nrf2 may be a critical regulator of vascular adaptation that occurs in skeletal muscle arterioles in response to long‐term exercise training. Elimination of differences in myogenic responsiveness by BaCl2 suggest that Nrf2‐mediated adaptation of the myogenic responsiveness may involve Kir channels.
The Role of Sex in the Effects of Cigarette Smoke in Vascular Smooth Muscle Cells
Authors: Centner Ann M. 
Published: May 2022

Cigarette smoke (CS) damages the vasculature and causes atherosclerosis or arterial plaque build‐up. While mechanistic differences in males and females likely exist, this area is largely unexplored. In fact, our lab observed that male atherosclerotic mice exposed to CS for 4 months had less severe plaque build‐up than their female counterparts. Thus, we hypothesized that male cells had a protective mechanism against the adverse effects of CS.To test our hypothesis and fill the gap in the literature, we treated male and female vascular smooth muscle cells (VSMCs) with cigarette smoke extract (CSE). Using increasing concentrations of CSE (10‐50%), we observed that in female cells mortality increased significantly at 40% and 50% CSE, while in males’ significant mortality only occurred at 50% CSE. Female cells treated with CSE (30%) had higher levels of reactive oxygen species (ROS) and cellular senescence than male cells. Increased resistance of male cells to CSE correlated with a decrease in phosphorylated AKT, which drove an upregulation of endogenous antioxidants (catalase, superoxide dismutase 1 – SOD1) as well as levels of autophagy markers including Sequestosome 1/p62 (SQSTM1) and microtubule‐associated protein light chain 3 II (LC3‐II). This mechanism was not seen in female cells. Sqstm1‐/‐ VSMCs express lower levels of catalase and SOD1, increased ROS levels and showed a higher mortality to CSE compared with wild type cells, suggesting that the upregulation of SQSTM1 is required for male cell’s protective effects. Differences in cellular and secreted ECM‐regulators, metalloproteinases (MMPs), were also observed between sexes, suggesting that plaque stability is different between males and females exposed to CS.Altogether, these data show that intrinsic sex‐dependent differences regulate the Akt/SQSTM1 pathway in response to CS and that SQSTM1 is a possible target to reduce the effects of CS in the cardiovascular system.
Loop‐Diuretics Increase Pendrin through alpha‐ketoglutarate receptor, Oxgr1
Authors: Tahaei Seyedmohammad E. , Wall Susan , Welling Paul A. 
Published: May 2022

IntroductionIt is well appreciated that loop diuretic resistance is governed by pendrin and activation of the thiazide‐sensitive sodium chloride cotransporter, NCC. Recently, our lab discovered pendrin increases as the natriuretic response wanes, coincident with the activation of a‐ketoglutarate (AKG) synthesis, secretion of a‐KG into the pro‐urine, and increased gene expression of the AKG GPCR, Oxgr1. Here we test the hypothesis that activation of Oxgr1 is necessary for the development of loop diuretic resistance.Methods10 week old male OXGR1 KO and WT (C57B6J) mice were challenged with furosemide (100 mg/kg) for 4 days. Urine was collected over 24 hours, daily, and urinary electrolytes were measured. Mice were euthanized at the end of the experiment and plasma electrolytes and aldosterone levels were measured using standard methods. Cortical protein and RNA abundances were measured using western blot and qRT‐PCR, respectively.ResultsWT and OXGR1 KO displayed distinguishing phenotypes only after furosemide administration. The loop‐diuretic challenge increased pendrin protein in WT mice but not in the OXGR1 KO mice despite identical increases in the chief pendrin stimulators, aldosterone and metabolic alkalosis. Pendrin transcript increased to the same extent in both genotypes, indicating OXGR1 augments pendrin via a post‐translational mechanism. Even with compromised upregulation of pendrin, OXGR1 KO mice exhibited the same diuretic response as WT mice. Upregulation of NCC was not compromised in the OXGR1 mice.ConclusionOXGR1 is required for post‐translational upregulation of pendrin protein post diuretic challenge, consistent with activation of a aKG‐OXGR1‐pendrin signaling axis. Upregulation of NCC and residual pendrin activity may be sufficient to brake the loop‐diuretic response.
Eight Weeks of Daily Cannabidiol Ingestion Does Not Alter Peripheral Blood Mononuclear Cell Profile or Natural Killer Cell Cytotoxicity
Authors: Kisiolek Jacob N. , Haughian James M. , Flores Victoria A. , Ramani Arjun H. , Stewart Laura K. 
Published: May 2022

ObjectiveThe purpose of this randomized placebo‐controlled trial was to determine the effects of an 8‐week cannabidiol (CBD) intervention on peripheral blood mononuclear cells (PBMCs) profile and natural killer cell (NKC) cytotoxicity.HypothesisFollowing an 8‐week CBD intervention, participants consuming CBD will have an increased percentage of NKC in peripheral blood, as well as decreased NKC cytotoxicity determined by a measure of K562 cell viability.MethodsPhysically active men and women (18‐45 y), currently meeting the American College of Sports Medicine (ACSM) guidelines for physical activity were randomly assigned to placebo (CN, n=5) or CBD (CB, n=9) groups. Participants consumed capsulized control; coconut derived medium chain triglycerides (MCT; 225mg/day) or CBD (50mg/day with 175mg of MCT) daily for 8 weeks. Participants completed measures of body size, body composition (BodPod) and fitness (VO2max), and peripheral blood was drawn before and after the intervention. Ficoll‐isolated PBMCs were co‐incubated for 4h with K562 human leukemia cells before cytotoxicity analysis by flow cytometry. Before co‐culture, PBMCs were stained with T cell marker CD3, and NKC marker, CD56, for immune profiling. K562 cells were pre‐stained with cell‐specific CD71 (transferrin receptor) and the cell viability dye Calcein AM. Data are presented as mean ± standard deviation with significance set at a=0.05. At the pre intervention time point, data was not normally distributed, so a Welch’s t‐test was preformed to determine group differences. A 2 (group) x 2 (time) analysis of variance (ANOVA) was used to identify any interactions or main effects.ResultsAt the pre‐intervention time points, there were no significant differences between groups with respect to participant characteristics (age: 27.1 ± 6.1 y; height: 169 ± 9.7 cm; weight: 73.8 ± 15.5 kg; lean body mass: 57.5 ± 12.0 kg; body fat: 21.5 ± 8.3%; VO2Peak: 45.2 ± 7.6 ml/kg/min). There were no significant differences in percentage of NKC (Pre: 8.8 ± 5.8%; Post:7.4 ± 5.7%), natural killer T‐cells (NKT; Pre: 1.7 ±1.1; Post: 1.5 ±1.1%), or T‐cells (Pre: 47.37±13.3; Post: 46.29±10.17%) when CN was compared to CB following the intervention. Furthermore, there were no differences in K562 cell mean or median fluorescence intensity of Calcein AM when CN was compared to CB following the intervention.ConclusionEight weeks of CBD (50mg/day) did not alter NKC, NKT, or T‐cell distribution in PBMCs. In line with these findings, NKC showed similar cytolytic function through no change in mean or median fluorescence intensity of Calcein AM expression of K562 human leukemia cells, indicating no change in cell viability following CBD supplementation. This preliminary study suggests that CBD does not alter the distribution of circulating mononuclear immune cells or NKC cytolytic function.
Insulin is Not Driving Urinary Bladder Enlargement in Rodent Models of Diabetes
Authors: Michel Martin C. , Beltrans‐Ornelas Jesus H. , Silva‐Velasco Diana L. , Castañeda Tamara R. , Elvert Ralf , Kannt Aimo , Xia Ning , Li Huige , Arioglu‐Inan Ebru , Centurion David 
Published: May 2022

The urinary bladder is enlarged in all models of type 1 and several of type 2 diabetes (doi 10.1002/nau.23786). We have previously reported that such enlargement is correlated to insulin, but not glucose levels in fructose‐fed rats (doi 10.1096/fasebj.2020.34.s1.00542). Because this was surprising, we have now repeated that study and expanded our analysis to other models of diabetes and obesity.Five studies were performed in models of type 2 diabetes and obesity, one in fructose‐fed rats (n = 16), one each in ZSF1 rats at age 20 and 28 weeks (a cross between a female Zucker Diabetic Fatty and a male spontaneously hypertensive SHHF rat; n = 30 and 45, respectively), and two in mice on a high‐fat diet (n = 23 and 24, respectively). Bladder weight at study end and blood insulin concentrations were subjected to linear correlation analysis based on individual animal data, and data expressed a squared Pearsson correlation coefficient (r2).Animals in the diabetic/obese groups were hyperinsulinemic, whereas bladder enlargement was observed in both studies with ZSF1 rats, the old but not the new in fructose‐fed rats, and in neither study with mice on a high‐fat diet. Bladder weight and insulin levels were not correlated in the new study in fructose‐fed rats or any of the other four studies; the numerical correlation coefficient was negative in two of these studies. When data from all six studies were pooled, a very weak inverse correlation was observed (r2 0.0682, descriptive p‐value 0.0094; Figure 1).We conclude that, contrary to our previous observation, bladder weight is not positively correlated with insulin levels in rodent models of type 2 diabetes and obesity.
The Bile Acid Receptor Tgr5 and High Fat, High Sugar‐Induced Liver Injury
Authors: Ferrell Jessica M. , Dilts Matthew , Stahl Zachary , Pokhrel Sabita , Boehme Shannon , Chiang John Y. L. 
Published: May 2022

BackgroundProgression of fatty liver disease to NASH/fibrosis is a major health concern. Bile acids regulate metabolic homeostasis and inflammation in the liver and gut via the activation of nuclear farnesoid‐X‐receptor (Fxr) and the membrane G protein‐coupled bile acid receptor 1 (Gpbar1, aka Tgr5). Tgr5 is expressed in the gut and skeletal muscle, and in cholangiocytes and Kupffer cells of the liver. Activation of Tgr5 reduces inflammation through suppression of NFκB. Tgr5 also induces GLP‐1 secretion from enterocytes to improve insulin sensitivity. Here, we fed Tgr5‐/‐ mice a high fat, high fructose, and high sucrose diet to test the hypothesis that lack of Tgr5 would exacerbate the progression from fatty liver to NASH/fibrosis.MethodsFemale C57Bl/6J control wild type mice (WT) and Tgr5 knockout mice (Tgr5‐/‐) were fed a high fat (40% kcal), high fructose diet + 20% sucrose water (HFS) for 20 weeks. Metabolic phenotypes were characterized through examination of lipid and cholesterol metabolism pathways, and fibrosis and inflammation pathways.ResultsTgr5‐/‐ mice fed HFS were more glucose intolerant compared to WT mice, despite gaining the same amount of weight. Tgr5‐/‐ mice fed HFS accumulated significantly more hepatic cholesterol and triglycerides compared to WT mice on the same diet, and gene expression of Acc and Fasn were significantly upregulated. Surprisingly, hepatic expression of genes involved in inflammation and fibrosis were significantly reduced in Tgr5‐/‐ mice fed HFS diet. Tgr‐/‐mice had significantly reduced expression of Col1a1, Col1a2, Tgfb, and Sma. Tgr5‐/‐ also had significantly reduced liver hydroxyproline, a measure of collagen production. Liver fibrosis is partly mediated through serotonin signaling. Tgr5‐/‐mice had significantly reduced expression of Maoa and the serotonin receptors Htr2a and Htr2b, which may have protected against the development of liver fibrosis in these mice.ConclusionAltered serotonin metabolism may protect Tgr5‐/‐ mice from the progression of steatosis to NASH/fibrosis induced by a high fat, high sugar diet.