bluuebunny/crossref_metadata_2025 huggingface dataset:
Weddell seals (Leptonychotes weddellii) respond less to inflammatory stimuli to evade ischemic‐reperfusion injury
Authors: Klink Amy , Bagchi Aranya , Hindle Allyson G.
Published: May 2022

During diving, Weddell seals (Leptonychotes weddellii) experience repeated hypoxemia. To mediate hypoxic tissue damage, Weddell seals employ vasoconstriction favoring vital organs (e.g. brain, lung, adrenals) resulting in reduced oxygen delivery to visceral and peripheral tissues. Weddell seals therefore experience periods of local ischemia associated with vasoconstriction followed by reoxygenation and return of perfusion at the surface. Ischemia‐reperfusion injury (IRI) is the expected result from reduced blood flow and localized hypoxia, followed by reoxygenation and reperfusion. A typical human response to IRI induces inflammation. We studied the inflammatory response of Weddell seals to determine whether its downregulation could be a mechanism by which seals avoid hypoxic and IRI injury. Weddell seal white blood cells (n=12) demonstrate a reduced immune reaction (mean ± stdev 247± 200 fold induction of IL‐6 from baseline) compared to human monocytes (n=6 replicates, THP‐1 cells 3091 ± 1126 fold IL‐6 induction, t‐test p<0.0001) when exposed to an inflammatory stimulus in vitro (10 ng/mL lipopolysaccharide). To evaluate species differences in gene pathways associated with the immune response, we conducted RNA‐seq and identified distinct transcriptomic profiles between species. We next evaluated the inflammatory response of Weddell seal primary cells (monocytes and pulmonary endothelial cells) resulting from hypoxia and reoxygenation. By simulating this natural stressor, we aim to discover whether the response of immune cells is an important component of molecular protection against IRI inflammatory sequelae in diving seals.
Metabolic Cooperation Between Adipose Tissue and Skeletal Muscle Mediates the Prevention of NAFLD Through Aerobic Physical Exercise
Authors: Evangelista Fabiana S. , Ferreira Marilia M. , Fortunato‐Lima Vanessa C. , Correa Saulo M. , Vecchiatto Bruno , Martucci Luiz F. , Muller Cynthia R. , Américo Anna Laura V.
Published: May 2022

Increased energy expenditure influences lipid handling by the liver. Aerobic exercise training (AET) has been widely used for the prevention and treatment of liver disorders especially non‐alcoholic fatty liver disease (NAFLD). In the present study, we evaluated the contribution of visceral white and brown adipose tissue (WAT and BAT, respectively) and the skeletal muscle to prevent NAFLD through aerobic physical exercise (APE). Adult male C57BL6/J mice were assigned into groups (n=10/group): chow‐fed controls (C), chow‐fed trained (T), cafeteria diet (CAF), and cafeteria diet and trained (CAFT). AET was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (002/2015) and from School of Arts, Science and Humanities, University of Sao Paulo (002/2018). The CAF group presented higher body weight gain, glucose intolerance, insulin resistance while AET prevented such damages in the CAFT group. In the liver, lipid deposition was higher in CAF (10.7 ± 1.9 %/area) compared to C, T and CAFT groups (6.4 ± 1.4, 0.5 ± 0.2 and 5.3 ± 1.1 %/area, respectively), the protein expression of DGAT2 did not differ but the expression of FAS enzyme and the content of IL‐6 was lower in CAFT compared to CAF. The CAF group increased periepididymal WAT weight compared to C and T groups, and the protein expressions of p‐HSL and ATGL, which are markers of lipolysis, increased in both CAF and CAFT compared to C and T groups. In addition, interscapular BAT weight did not change among groups, however the protein expression of UCP1 and PGC1a, which are markers of thermogenesis, increased in both CAF and CAFT compared to C and T groups. The activity of oxidative enzymes citrate synthase and β‐HAD in the soleus muscle increased in the T (352 ± 21.5 and 80.1 ± 6.6 mmol/min/mg) and CAFT (350 ± 22.4 and 87.9 ± 7.3 mmol/min/mg) groups compared to C (272.7 ± 9.5 and 62.7 ± 3.9 mmol/min/mg) and CAF (254.6 ± 15.7 and 46.7 ± 1.6 mmol/min/mg) groups. In conclusion, for the prevention of NAFLD, the AET increased the metabolic activation of WAT and BAT that favors fat oxidation as well as improved the oxidative capacity of skeletal muscle to deal with excess lipids.
Expression of rhodopsin and opsin in late‐stage epigean and hypogean salamander embryos
Authors: Delcid‐Morales Evelyn E. , Wiebe Diana E. , Tovar Ruben , Hillis David M. , Garcia Dana M.
Published: May 2022

Evolutionarily, sensory systems have undergone extreme diversifications that have allowed vertebrates to survive diverse environments. The salamander clade Eurycea of Central Texas has branched out of its epigean ancestral roots and has successfully invaded subterranean environments. The San Marcos salamander (E. nana) and the Barton Springs salamander (E. sosorum) live above ground in springs and streams whereas the Texas blind salamander (E. rathbuni) occupies caves and recesses in the Edwards Aquifer. From an evolutionary perspective, it is thought that the hypogeal state is derived, but what remains a mystery is the developmental adaption of its sensory system to life under ground. The habitational broadening of the Eurycea salamander has been associated with the phenotype of reduced eyes exhibited in the Texas blind salamander. It is not clear whether this phenotype represents incomplete development, regression, or a combination of both. The clade of Eurycea is a prime model for comparing the molecular mechanisms that are involved in diverging neural systems, since species within the same clade present two extremes of phenotypes that are associated with their environment. Retinal development in embryonic E. rathbuni has been observed; however, the extent to which the retina develops is unknown. We identify retinal rod and cone photoreceptor cells along with their associated visual proteins (rhodopsin and opsin, respectively) in blind species and in epigean salamanders with fully developed eyes. Immunohistochemistry followed by confocal microscopy was applied for the investigation of sections of late embryonic stages of these salamander species. The results suggest opsin is expressed in the retina of E. nana and E. sosorum, and rhodopsin is expressed in all three species. Based on previous work indicating absence of visual pigments in adult Texas blind salamanders, we conclude expression of rhodopsin is transient or variable in this species. In future studies we will examine the expression of visual pigments at other stages to get a clearer picture of the time course and species‐level variability in expression.
Endocrine and osmotic responses to tidally‐changing salinities in Mozambique tilapia, Oreochromis mossambicus
Authors: Seale Andre P.
Published: May 2022

Variations in salinity are among the main physical parameters that drive the capacity of fish to survive and thrive in a range of environments. Acclimation to changes in environmental salinity is regulated by the interplay of local osmotically‐induced cellular responses and the systemic regulation by the neuroendocrine system, which together, direct ion extrusion or uptake responses via the gill and other osmoregulatory tissues. Many euryhaline teleost fish are native to waters in which salinity varies tidally between that of fresh water (FW) and seawater (SW), such as estuaries. The physiology of salinity acclimation of euryhaline teleosts has been studied extensively in steady‐state salinities, and after one‐way transfers between steady‐state salinities. Fewer studies, however, have addressed salinity regimes that reflect or simulate the continuous dynamic changes by which euryhaline fishes may be subject to in a native environment. Experimentally, the simulation of a changing environment was obtained by rearing fish in salinities that changed between those of FW and SW every six hours, in a tidal regime (TR). An overview of the main differences in the regulation of transcripts involved in ion balance between euryhaline Mozambique tilapia, Oreochromis mossambicus, responding to TR and those acclimating to steady‐state salinities is provided. Transcripts analyzed include branchial Na+/K+‐ATPase (nka), Na+, Cl‐ co‐transporter (ncc), Na+/H+ antiporter 3 (nhe3), 2Cl‐ co‐transporter (nkcc), cystic fibrosis transmembrane conductance regulator (cftr), and aquaporin 3 (aqp3). In particular, both cftrand aqp3were highly sensitive to changes in salinity in fish acclimated to a TR, indicating indispensable roles in rapidly maintaining hydromineral balance. The pituitary hormones, prolactin and growth hormone, known to play osmoregulatory roles in Mozambique tilapia, were also compared along with their receptors between TR and steady‐state salinity paradigms. Specifically, through the dynamic changes in hormone receptor transcription observed in the TR rearing paradigm, the endocrine control of osmoregulatory outcomes appears shifted from systemic to local regulation at the level of target tissues. Together, these studies indicate that fish are able to compensate for broad and frequent changes in external salinity while keeping osmoregulatory parameters within a narrow range.
Sentiment Analysis Machine Learning Model Congruence: A Case Study Using Neuroscience Module Evaluations
Authors: Plochocki Jeffrey , Kibble Jonathan
Published: May 2022

Introduction

Medical school faculty and administrators regularly assess sentiment in student‐generated textual data, such as instructor and course evaluations. Machine learning models (MLMs) that automate and systematize sentiment analysis are commercially available. However, the congruency of MLMs has not been extensively tested. We compare sentiment polarity derived from human analysis and five MLMs to test the hypothesis they yield significantly correlated output.

Methods

Student evaluations (n=116) of the neuroscience module at the UCF College of Medicine were collected and anonymized. Students were asked to evaluate the strengths of the module (n=108) and provide suggestions for improvement (n=102). Responses were subjected to sentiment analysis by five commercially available MLMs and two module faculty reviewers. Sentiment was classified as either positive (1), neutral (0), or negative (‐1).

Results

Sentiment polarity as assessed by the reviewers was significantly correlated (r=0.66, p<0.05). Reviewer assessments were congruent for 73.8% (n=155) of responses. Congruence was greatest for responses on strengths of the module (92.6%, n=100) compared to suggestions for improvement (54.4%, n=103). Congruency among the MLMs was 38.1% (n=80) for all responses, 60.1% (n=80) for module strengths (n=65), and 14.7% (n=15) for suggestions for improvement. Correlation matrix showed moderate correlations among the reviewers and MLMs (range of r=0.41‐0.62, p<0.05). Congruence among all reviewers and MLMs occurred for 34.3% (n=72) responses, with maximal incongruence occurring for only 2.4% (n=5) of responses. Again, congruence was greatest for responses on module strengths (58.3%, n=63) compared to suggestions for improvement (8.8%, n=9). All methods assessed the responses on strength of the module to be more positive than suggestions for improvement. With all methods combined, responses on strengths of the module scored an average of 0.79 compared to suggestions for improvement, which scored ‐0.34.

Conclusion

Sentiment polarity derived from human analysis and MLMs is significantly correlated, although the coefficients reflect only modest linear relationships. MLMs are less congruent than the human observers. All methods demonstrate greater congruence when assessing responses as more positive (i.e., module strengths) than negative (i.e., suggestions for improvement). Additional refinement of MLMs may be necessary before for they can be applied with consistency in medical education settings.
Effects of 5‐hydroxytryptophan on Glucose Tolerance and Lactation in Dairy Cows
Authors: Pszczolkowski Virginia L. , Connelly Meghan K. , Beard Adam D. , Laporta Jimena , Hernandez Laura L. , Arriola Apelo Sebastian I.
Published: May 2022

Introduction

Peripheral serotonin is an important regulator of many aspects of lactation. Administration of the serotonin precursor, 5‐hydroxytryptophan (5‐HTP), has been shown to alter some aspects of energy metabolism and endocrine signals in dairy cattle. However, neither the effect of 5‐HTP on insulin sensitivity nor the long‐term effect on milk production have been studied in ruminants.

The objectives of this study were to determine the effects of intravenous (IV) infusion of 5‐HTP on response to an IV glucose tolerance test (GTT) and on lactation performance in dairy cows. We hypothesized that 5‐HTP would alter insulin sensitivity and improve lactation performance.

Twenty‐four Holstein cows were assigned to IV infusion of either 5‐HTP (1 mg/kg/day) or saline in a 2‐period crossover design. Treatments were infused via jugular catheters for 1 h/day, with 3 days of infusion followed by 4 days of rest, repeated through the 21‐day period. The GTT was performed immediately after IV infusion on day 3.

For the GTT, differential effects were observed for glucose, insulin, and free fatty acids (FFA). Neither maximal glucose nor area under the curve (AUC) were affected by 5‐HTP (P≥0.15). On the other hand, basal insulin (difference of 0.116 µg/L, P=0.004) and AUC (P=0.04) were both decreased for 5‐HTP, with maximal insulin tending to be decreased by 0.35 µg/L (P=0.06). Basal FFA concentration was unaffected by treatment (P =0.55), but both minimal (difference of 82 µmol/L, P=0.015) and AUC (P=0.034) FFA were increased by 5‐HTP treatment. During the final 7 days of the period, feed intake was decreased by 4.0 kg/day during infusion days for 5‐HTP cows (P<0.01), but not on rest days (P=0.34). Milk yield was decreased for 5‐HTP cows only during infusion days (4.4 kg/day, P<0.01), returning to control levels on rest days (P=0.69). Similarly, milk protein yield was decreased (80 g/day, P<0.01) and milk fat yield tended to be decreased (140 g/day, P=0.06) by 5‐HTP on infusion days, recovering on rest days. Over the 21‐day period, 5‐HTP cows lost 0.87 kg/day of body weight, while control cows gained 0.45 kg/day (P<0.01).

Given the glucose and insulin responses during the GTT, it is evident that less insulin was required to clear the same glucose load for cows receiving 5‐HTP. However, it is unclear if the lack of responsiveness in FFA to glucose challenge is due to effects of serotonin on the adipose tissue, or if there is a relationship between these FFA and decreased synthetic capacity of the mammary glands. Overall, this level of 5‐HTP altered insulin sensitivity, and acutely but transiently depressed production. More work is needed to delineate the effects of 5‐HTP on energy metabolism and production.
Influence of High‐Polyphenol Sorghum on Benzo[a]pyrene‐Metabolizing Enzymes
Authors: Lascarez Cynthia , Kamagate Zeguela , Smolensky Dmitriy , Tsuji Petra
Published: May 2022

Colorectal cancer ranks among the top five most common types of cancer in the United States. Lifestyle, diet, and environmental factors are correlated to the increased risk of colon cancer. One of those environmental factors is the polycyclic aromatic hydrocarbon (PAHs) Benzo[a]pyrene (BaP), formed by the incomplete combustion of organic material. Human exposure to BaP occurs through air pollution, tobacco smoke, engine exhaust, and the consumption of BaP‐exposed foods. BaP crosses cellular membranes, and it becomes metabolically activated by Phase I enzymes, primarily cytochrome P450s (CYPs) and Epoxide Hydrolase, and subsequently has the potential to bind to DNA. The binding of BaP to DNA may result in adverse genotypic alterations, which may result in tumorigenesis. On the other hand, cellular Phase II enzymes play a role in the inactivation of BaP and its metabolites, which can facilitate the excretion of these molecules. Polyphenols, a group of plant micronutrients known for their antioxidant and anti‐inflammatory properties, have been suggested to contribute to the prevention of colon cancer. Extracts from two types of Sorghum bicolor were provided by the USDA ARS Kansas. Preliminary studies in our lab suggest that polyphenol‐rich varietals of the grain Sorghumaffect pathways in carcinogenesis. Specifically, mRNA expression of UDP‐glucuronosyl transferase (UGT) 1A1, a Phase II PAH‐bioinactivating enzyme, is significantly increased in high‐polyphenol sorghum treated HCT116 cells. Therefore, we propose to investigate the impact of high‐polyphenol sorghum on BaP‐exposed colon cancer cells, assessing the expression and activity of Phase I and Phase II enzymes in particular. Our hypothesis is that compared to controls, high polyphenol sorghum extracts will decrease expression and activity of Phase I, and increase expression and activity of Phase II enzymes in BaP‐treated colon cancer cells.

Human colorectal cancer HCT116 cells were incubated with either 0, 1, 2, or 5 µM BaP alone, Sorghum extracts alone, or in the presence of high‐polyphenol sorghum and Benzo[a] pyrene for up to 48 hours. RNA was extracted and reverse‐transcribed to cDNA. mRNA expression of carcinogen activating and inactivating enzymes was measured using qPCR. BaP alone increased mRNA expression of CYP1A1 as expected. Our high polyphenol Sorghum extract dramatically decreased mRNA expression of the Phase I enzyme CYP1B1, but also moderately increased mRNA expression of Epoxide Hydrolase. We plan to complete assessment of the expression and catalytic activity of Phase I and Phase II enzymes in the presence of high‐polyphenol sorghum and Benzo[a] pyrene. Our initial results suggest that high‐polyphenol Sorghum may be able to shift the balance of Phase I and Phase II enzymes in BaP‐exposed cells, and thus provide an avenue of a dietary approach to support chemoprevention.
AT1R‐mediated neurodegeneration is part of the etiology of hypertension‐associated cognitive impairment
Authors: Wu Hanxue , Zhuang Jinzhu , Wang Jiawei , Yuan Shenglan , Sun Hui , Xu Jiaxi
Published: May 2022

Hypertension has now been closely associated to cognitive impairment, due to its contribution to cerebrovascular dysfunction. To investigate whether there is neuronal mechanism, hypertension was induced in C57BL/6j male mice (6 months) by DOCA‐salt treatment (1.5 mg/g, s.c., 28 days). Firstly, behavioral study, which contains object location behavioral task, novel object recognition, Barnes maze, and nesting score test, was performed to assess cognitive function, meanwhile, blood pressure (BP) was monitored by tail‐cuff device. In NT (non‐transgenic) mice, DOCA+1%NaCl increases BP significantly, before vs. after DOCA (systolic BP): 114.8 ±0.94 vs. 133.7 ±3.3 mmHg. In whole, compared to sham controls, the treated NT mice performed worse in all four behavioral tests, indicating cognition decline after DOCA‐salt treatment. Later, brain tissues were collected to evaluate possible degenerative alterations in neurons by transmission electron microscope (TEM) imaging, Golgi‐Cox staining, fluorescence‐activated cell sorting (FACS) and qRT‐PCR. It was shown via the TEM that DOCA‐salt hypertension induces mitochondrial damage and morphological changes in prefrontal cortical neurons, meanwhile, Golgi‐Cox staining revealed decreased numbers of dendritic spines, suggesting the onset of neurodegeneration in DOCA‐salt hypertension. In both prefrontal cortex and hippocampus, the mRNA levels of BDNF (brain‐derived neurotrophic factor) and PI4KIIIβ (phosphatidylinositol 4‐kinase IIIβ) were found to be significantly lower in hypertensive NT mice. Using FACS, neurons were sorted from those regions, then analyzed via qRT‐PCR, which identified that the downregulated expression of PI4KIIIβ takes place in neurons. Using laser speckle contrast imaging system, we detected only decreased functional hyperemia, but no impairment in basal cerebral blood flow of the hypertensive mice, suggesting that the neurodegeneration is not caused by cerebral ischemia. We previously demonstrated that neuronal angiotensin type 1 receptors (AT1R) plays a pivotal role in the maintenance of neurogenic hypertension, and here we hypothesized that activation of AT1R could also exacerbate hypertension‐induced reduction in neuronal function. Particularly, in the hippocampal CA1 of adult mice, treatment of angiotensin II (Ang‐II, 500 nM, bath application) induces a significant inhibition in the induction of long‐term potentiation (LTP), while pre‐treatment with losartan (5 μM, 15 min), the AT1R antagonist, can efficiently block this Ang‐II‐induced inhibition, supporting the involvement of neuronal AT1R. Indeed, in mice with selective deletion of neuronal AT1aR, DOCA‐salt‐induced neurodegeneration was attenuated, as evidenced by significantly higher mRNA levels of cortical BDNF and PI4KIIIβ, compared with the NT. In summary, our data suggest that neuron‐expressing AT1R participates in the development of hypertension‐associated cognitive impairment, independently of vascular AT1R.
The Efficacy of Digital Media in Teaching Anatomy During the COVID‐19 Pandemic
Authors: Gheysari Aryan , Chang Lucas , Xu Wendy , Kianpoor Kiana , Doroudi Majid
Published: May 2022

Introduction

The traditional method of teaching anatomy has been through live in person lectures and dissection labs as well as textbooks and other course materials. However, during the COVID‐19 pandemic, these resources were no longer available due to health and safety protocols. With the advancement of technology, it was possible to create anatomy walkthrough videos for the students to supplement the traditional methods of teaching anatomy.

Goal

To investigate the effectiveness of a video based guide to learning gross anatomy of the boney pelvis and the viscera.

Methods

Two videos were created covering the boney pelvis and the viscera for the first and second year medical students. The videos were presented by an anatomy professor and filmed and edited by Medical Students. The video covers the curriculum outline, labels relevant parts of the anatomy, and provides extra information relating to form and function. The videos included a quiz at the end for students to test their knowledge. The videos were made available online on Youtube to an international audience, along with a feedback survey.

Results

Feedback was collected on the boney pelvis and the viscera videos. The respondents watched the videos for the purpose of preparing for anatomy labs and dissections, preparing for anatomy lectures and preparing for examinations. The majority of respondents agreed or strongly agreed that the videos presented assisted them in fulfilling their indicated purpose (89.1%), that a combination of video and written materials should be used for effective learning of anatomy (95.7%), and that they would like to see videos for other anatomical regions (95.7%).

Conclusion

In summary, digital media in the form of video‐based anatomy guides may be useful in instances when in person teaching is not possible and may be a useful tool to be incorporated into the educational curriculum in combination with traditional teaching methods. Future goals include implementing student feedback and reaching a broader audience.
Importance of Probe Substrate Selection in Assessing Interactions of Tyrosine Kinase Inhibitors with Polyspecific Organic Cation Transporters
Authors: Tsang Yik Pui , López Quiñones Antonio J. , Wang Joanne
Published: May 2022

The organic cation transporters 1‐3 (hOCT1‐3) and multidrug and toxin extrusion proteins 1 and 2‐K (hMATE1/2‐K) are important polyspecific transporters involved in the disposition of many clinically used therapeutics. Evaluation of transporter‐mediated drug‐drug interactions (DDIs) is a critical step during drug development. Tyrosine kinase inhibitors (TKIs) are a rapidly growing class of targeted anticancer agents designed to target specific tyrosine kinases that are fused, mutated, or overexpressed in cancer. Previously, using known inhibitors, we and others have shown that the inhibition of hOCT2 and hMATEs is substrate‐dependent, with hOCT2 exhibiting greater substrate‐dependence than hMATEs. The goal of this study is to characterize the interactions of TKIs with polyspecific organic cation transporters and determine if TKI inhibition of hOCT1‐3 and hMATE1/2‐K is substrate‐ and isoform‐dependent. Using HEK293 cell lines stably transfected with hOCT1‐3 and hMATE1/2‐K, we determined the inhibitory potency of selected TKIs (erlotinib, lorlatinib, crizotinib, and brigatinib) using three different substrates (meta‐iodobenzylguanidine (mIBG), metformin, and 1‐methyl‐4‐phenylpyridinium (MPP+)). Among the tested TKIs, brigatinib potently inhibited mIBG, metformin and MPP+ uptake by hOCT3 and hMATE1, and metformin uptake by hOCT1, with their half maximal inhibitory concentration (IC50) being in the low micromolar range. Crizotinib also potently inhibited metformin and MPP+ uptake by hOCT3 and hMATE1 and metformin uptake by hOCT1, hOCT2 and hMATE2‐K. Except for hMATE1, substantial substrate‐dependent inhibition of transporters was observed for both crizotinib and brigatinib, with metformin being the most sensitive to inhibition among the three tested substrates. Brigatinib was approximately 23‐, 18‐, 4‐, and 11‐fold more potent towards hOCT1, hOCT2, hOCT3 and hMATE2‐K, respectively, when metformin is used as the substrate instead of MPP+, while crizotinib was approximately 17‐, 16‐, 5‐, and 12‐ fold more potent, respectively, when metformin is used. Interestingly and consistent with our previous observation, hMATE1 inhibition by both TKIs is influenced minimally by the choice of substrate, with similar IC50 values of less than 1.5‐fold differences across substrates. Together, our results demonstrated that TKI inhibition of hOCTs and hMATE2‐K is substrate‐dependent, which underscore the importance of selecting clinically relevant probe substrates when assessing the DDI potential for these transporters using in vitro systems.
Evaluation and adjustment of screening algorithms for HBV, HCV, HIV and syphilis in an anatomical donation program for undergraduate education
Authors: Willaert Wouter , D'Herde Katharina
Published: May 2022

Study objective

Undergraduates and other users of anatomical donors are at risk of exposure to bloodborne pathogens. This study evaluated screening algorithms for hepatitis B and C virus, human immunodeficiency virus and Treponema pallidum during donor allocation and assessed the impact of postmortem time on hemolysis and how hemolysis affects test results and donor discard rate.

Methods

From 2011‐2018, demographic data of donors, time of postmortem blood sampling, presence of sample hemolysis, serological test results (negative; active infection; false reactive screening test; historic infection; inconclusive; technically impracticable) and the actual donor allocation were collected.

Results

Donors (n=537) had a mean age of 77.53±13.67 year. Nine (1.68%) had test results indicative for active infection for hepatitis B (n=1) and C virus (n=2), human immunodeficiency virus (n=5) and Treponema pallidum (n=1). Negative screenings ranged from 74.67 to 97.58%, depending on the pathogen. Based on the screening algorithms, 479 (89.20%) donors should have been accepted. In practice, a donor acceptance rate of 91.20% was found. Analysis of potential donor allocation interpretation obstacles resulted in simplification of the testing algorithms and addition of a nucleic acid test to increase the reliability for identification of active (acute) human immunodeficiency virus infection. Hemolysis was more common when sampling was performed more than 24 hours after death (p<0.001). Hemolytic samples more frequently showed a reactive or indeterminate human immunodeficiency virus test result (p<0.001). Screening for human immunodeficiency virus and Treponema pallidum was technically more impracticable when hemolysis was present (p=0.042 and p=0.003, respectively). Donors with hemolytic blood samples were more often discarded (46.88%) compared to bodies with non‐hemolytic samples (6.32%) (p<0.001).

Conclusions

Despite the use of screening algorithms, many bodies used for undergraduate education have an inconsistent allocation. Simplified algorithms were made and are currently prospectively assessed. Early postmortem blood sampling is key as hemolysis can influence certain test results and donor allocation.
Comparison of Excess Post‐exercise Oxygen Consumption between Continuous, Interval, and Accumulated Workout with Equalized Exercise Volume in Healthy Women
Authors: Sun Yerin , Jung Won‐Sang , Kim Sung‐Woo , Kim Jisu , Park Hun‐Young , Lim Kiwon
Published: May 2022

Purpose

The primary purpose of the present study was to compare the EPOC during different exercise modalities including continuous exercise (CE), interval exercise (IE), and accumulated exercise (AE) that spent the equalized energy expenditure during exercise in healthy women.

Methods

Forty‐four healthy women (36.09 ± 11.73 years), who did not participate regular exercise, were included in the present study. All participants visited the laboratory four times at intervals of one week during experimental period. During the first visit, they underwent body composition test and graded exercise test. On the second, third, and fourth occasions, the participants underwent a randomized crossover experimental trial consisted of CE, IE, and AE with equalized energy expenditure. CE was performed for 30 min at 60%VO2max and AE was conducted 3 times for 10 min at 60%VO2max. IE was performed for 26 min and exercise protocol was structured as follows: 6 times of 80%VO2max for 3 min + 40%VO2max for 1 min and 1 time of 80%VO2max for 2 min. Heart rate (HR), minute ventilation (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), and respiratory exchange ratio (RER), carbohydrate oxidation (CHO), fatty acid oxidation (FAO), and energy expenditure (EE) were measured during exercise and after exercise.

Results

In exercise session, IE showed a significantly higher RER, CHO and a lower HR, FAO than CE. AE showed a significantly lower RER and a higher FAO than IE, and it showed a significantly lower VE than CE. In addition, there was no significant difference in EE between the three trial sessions, confirming that exercise volume homogenization was well performed. In EPOC session, IE showed a significantly higher HR, VE, VO2, VCO2, CHO, FAO, EE than CE. AE showed a significantly a higher HR, VE, VO2, VCO2, RER, CHO, EE than CE and IE, and it also showed a higher FAO than CE. In total (exercise plus EPOC session), IE and CE have a similar EE, but IE showed a significantly higher RER, CHO and a lower FAO than CE. AE showed a significantly higher HR, VE, VO2, VCO2, CHO and EE than CE and IE. In addition, AE showed a significantly higher RER than CE and AE showed a significantly higher FAO than IE.

Conclusion

The present study confirmed that the EE in EPOC session after three types workout using a ergometer with homogenized exercise volume was showed in the order AE, IE, and CE, in particular, AE showed a higher EE in total than CE and IE. Therefore, we suggest that AE is the most effective strategies in maximize EE compared to CE and IE, and IE is also effective than CE in increasing EE via EPOC.
Oxidative stress targets Kir2.1 channel in a model of aging neuroglia
Authors: Remigante Alessia , Morabito Rossana , Spinelli Sara , Marino Angela , Sarikas Antonio , Pusch Michael , Dossena Silvia
Published: May 2022

Oxidative stress (OS) has a main role in the pathogenesis of central nervous system disorders. In this regard, epilepsy is a highly prevalent serious brain disease and its prevalence increases with age. Strikingly, about 50% of all epilepsy cases diagnosed in elderly patients (>65 years) are idiopathic. Metabolic changes, including the production of reactive oxygen species (ROS), are regarded to as possible mechanism involved in epileptogenesis. The neuronal glia plays a crucial role in epilepsy by controlling neuronal hyperexcitability. One of the key roles of glial cells is the spatial buffering of extracellular K+ ions that are released by excited neurons and transported through glial inwardly rectifying potassium (Kir) channels from extracellular regions of high K+ to those of low K+ to inhibit epileptogenesis. Among experimental OS‐related aging models, long‐term (24 hours) exposure to D‐Galactose (D‐Gal, 100 mM) is considered the most similar to natural aging. In the present study, we investigated the effect of D‐Gal‐induced aging on Kir channel activity in glioblastoma U87‐MG cells. Screening of all fifteen Kir isoforms revealed that the predominant transcript corresponds to Kir2.1, with minor contribution of Kir4.1. D‐Galactose had no obvious cytotoxicity, but strongly promoted OS, namely increased lipoperoxidation levels and decreased the membrane protein sulfhydryl group abundance. Interestingly, D‐Gal exposure was associated with a decrease of inwardly rectifying K+ currents sensitive to ML‐133, a specific inhibitor of Kir2.1 channels. Our findings reveal a novel Kir2.1 channel modulation that is likely to occur in OS. We suggest that inhibition of Kir2.1 channels in glia cells may alter extracellular K+ buffering and contribute to OS‐related neuronal hyperexcitability and epileptogenesis during aging.
The Effect of the Klim Feed Additive on Cortisol Levels in Cows During Stress
Authors: Aleksandrova Ekaterina , Lukoyanova Lubov , Kriyachko Oksana , Gaponova Viktoriya , Shafiev Aleksei , Anisimova Kseniya
Published: May 2022

Currently, intensive animal breeding techniques are actively applied. It is absolutely impossible to avoid a technology stress under such conditions. Therefore, development of methods of correction of animal stress levels (especially during critical periods of animal life) is crucial.

The objectiveof this research is to determine the effect of the Klim feed additive based on organic acids on cortisol levels during different technological periods.

In the course of this research, 2 groups of cows (n=10 heads) were selected in one of livestock enterprises of the Leningrad region. Each cow had an average productivity, age of 3.5 to 4 years and second pregnancy; each cow was apparently healthy. By the moment of 21 days before the estimated calving date, each cow from the experimental group has been receiving the Klim feed additive mixed with a feed (dosage of 10 g per head: 5 g of active substance and 5 g of vanilla filling) daily for 50 days (the drug has been administered in an individual manner). Before administering the drug, each animal has undergone a clinical examination, blood sample of each animal has been collected for further research. No valid difference between parameters of the experimental and control groups has been identified at the moment of the research initial phase.

Research results. One day after calving, in order to determine the stress level, the level of cortisol in blood has been identified for cows from the experimental and control groups. The research results prove that the level of cortisol in blood of the cows from the group that received the Klim feed additive was 62.72 ± 12.1 nmol/l, and the level of cortisol in blood of the cows from the control group was 96.62 ± 19.3 nmol/l. Such cortisol level shows that the animals from the control group have a high level of stress, which ultimately can result in negative effect on productivity and clinical status of these cows. Meanwhile, the cortisol level of the cows from the experimental group did not exceed standard limit values (20 – 80 nmol/l) – this verifies our assumption that the Klim feed additive relieves the manifestations of stress at early stage. One day after the rearrangement of cows (25 days after calving), the level of cortisol in blood of the animals from both groups has been identified. The level for the cows from the experimental group was 36.3 ± 8.4 nmol/l, the level for the cows from the control group was 50.18±11.7 nmol/l – this proves that these cows have a higher level of stress.

In view of the above, it has been identified that the Klim feed additive had a positive effect on the adaptation capabilities of animals during stressful situations (pregnancy period and change of environment (rearrangement)).
Role of CRF1 and CRF2 receptors in the lateral hypothalamus in anxiogenic response evoked by acute and repeated restraint stress in rats
Authors: de Souza Lucas B. , Silva Lilian Liz R. , Crestani Carlos C.
Published: May 2022

The lateral hypothalamus (LH) is an important hypothalamic area that has been implicated in the integration of behavioral and physiological responses to stress. The corticotropin‐releasing factor (CRF) system has been shown to be an important neurochemical mechanism in the central nervous system involved in the etiology of the behavioral changes evoked by exposure to aversive situations. The exposure to chronic stress affects the expression of CRF neurotransmission components in brain regions controlling stress responses. However, the role of CRF neurotransmission within the LH in the anxiogenic responses evoked by acute and repeated restraint stress (RS) has not been investigated. Here, was investigated the effect of bilateral microinjection into the LH of the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine‐30 (ASV‐30) in the anxiogenic responses following the first and the 10th session of restraint stress (RS) in male rats. For this, male Wistar rats (250g) had cannula‐guide bilaterally implanted within the LH. The RS was realized by placing the animals in a plastic cylindrical tube for 60 minutes. Independent sets of animals received CP376395 (0.01 mol/100nL), ASV‐30 (0.01 mol/100nL) or vehicle into the LH 10 minutes before the onset of the first or 10th session of RS. Immediately after the end of the stress session, the animals were individually placed in the elevated plus maze (EPM) for 5 minutes to assess anxiety‐related behaviors. The behavioral analysis revealed that an acute RS session decreased the % of entries and time in the open arms of the EPM in vehicle‐treated animals, when compared to animals that were not submitted to restraint stress (i.e., naïve group) (P<0.05). Bilateral microinjection of either CP376395 or ASV‐30 into the LH inhibited the decreased open‐arms exploration caused by acute restraint stress (P<0.05). We did not identify behavioral changes in the EPM in animals repeatedly subjected to restraint stress, and pharmacological treatments also had no behavioral effect when administered before the 10th RS session (P>0.05). Taken together, the results indicates that the CRFergic neurotransmission in the LH, acting through activation of both CRF1 and CRF2 receptors, is involved in the generation of anxiety‐like behaviors induced by acute restraint stress, and the previous repeated exposure to this stressor affect this control.
Is there a Role of Anti‐platelet Aggregation Agents in the Management of Primary Hypertension: An In‐Vivo Study
Authors: Goyal Manjeet K. , Vuthaluru Ashita R. , Lal Mahesh
Published: May 2022

INTRODUCTION

Hypertension is a leading identifiable and reversible risk factor for myocardial infarction, heart failure, atrial fibrillation, aortic dissection, peripheral arterial disease, stroke, kidney failure, etc with thrombus being the culprit lesion. South Asian ethnicity predisposes to higher mortality and morbidity from cardiovascular disease than other ethnic groups and is estimated to cause 7.5 million deaths, which accounts for 57 million disability‐adjusted life years (DALYs).

Hypertension causes changes in platelets (shape, size, expression of P‐selectin, and sensitivity to catecholamines,) However, the data on platelet aggregation is sparse, inconclusive, and has shown contradictory results in Asian Indians. Therefore, this study is designed to study the platelet aggregation in Indian hypertensives and to investigate if platelet aggregation is determined by the level of blood pressure.

MATERIALS AND METHODS

The study was conducted at the tertiary health center in 50 primary hypertensives & compared with age & sex‐matched healthy controls. After ethics approval from IRB, an informed and written consent was taken. All subjects completed a physical and cardiovascular system examination. Blood pressure recordings were done as per JNC‐VIII Guidelines and were further divided into sub‐groups as per the JNC‐VIII classification. Platelet rich plasma was used to estimate aggregation using a Chronolog aggregometer based on the principle of light transmission. ADP (5 µM) & Epinephrine (2µM) were added to PRP to induce platelet aggregation. The normal value of platelet aggregation was compared between study subjects and controls using Independent t test and Mann‐Whitney Test.

RESULTS

After comparing platelet aggregation to ADP and epinephrine in primary hypertensives and healthy controls, 28 cases had stage I and 22 had stage II hypertension. The mean platelet aggregation to ADP in normotensives and primary hypertensives was 31.32±6.64 and 73±10.07, respectively (p value<0.0001). Similarly, the mean platelet aggregation to Epinephrine in normotensives and primary hypertensives was 24.82±5.51and 50.94±12.19, respectively (p value<0.0001). (Fig 1) Furthermore, platelet aggregability was found to be significantly increased in primary hypertensives as compared to controls. Moreover, it was further raised in stage II hypertensives in comparison to stage I hypertensives.(Fig 2)

CONCLUSIONS

This study is the largest prospective study conducted on plasma from hypertensives and implicates platelet aggregation as a the causative factor leading to cerebrovascular accidents, ischemic heart diseases in primary hypertensives. Hence, any anti‐hypertensive drug which confers additional anti‐platelet aggregation properties may benefit in the management of hypertension especially in the Indian population. However, further larger studies are recommended to verify the same.
Response of Trypanosoma brucei to Exogenous Fatty Acids in Low Lipid Conditions
Authors: Saliutama Joshua , Paul Kimberly
Published: May 2022

Trypanosoma brucei is an extracellular parasite that causes African Sleeping Sickness and is endemic to the sub‐Saharan African region. The parasite's extracellular nature forces the parasite to adapt to its host's environment. One of the regulatory mechanisms is to regulate fatty acid synthesis enzymes in response to exogenous fatty acids. Our previous study showed that the insect‐host procyclic form (PF) T. brucei regulates the activity and expression level of acetyl‐CoA carboxylase (ACC) when grown in media containing different lipid levels. PF in low lipid media has an elevated ACC activity but lower ACC protein level than in high lipid media. We also observed that the addition of C18:0 to PF in low lipid media reduced ACC activity and increased growth rate, which showed an environmental response to the exogenous fatty acid level. Here, we observe the growth and the ACC level of low lipid‐adapted PF T. brucei after treatment with fatty acids of different chain lengths. We did not observe a significant change in the ACC protein level; however, we observed significant growth differences with the addition of different fatty acids, and some of these effects were cell density‐dependent. These data suggested that adding fatty acids changes ACC's activity and pattern of PF growth in low lipid but does not change PF's ACC expression level. Future studies will investigate whether different fatty acids regulate ACC activity by phosphorylation, allosteric regulation, or a combination of both mechanisms.
Evaluation of the cellular and extracellular fluid of the body of calves using bio impedancemetry
Authors: Nikitina Anastasia , Trushkin Vyacheslav , Kovalev Sergey , Vasilev Roman , Vasileva Svetlana , Gaponova Viktoriya , Nikitin Georgy
Published: May 2022

Currently, non‐invasive animal research methods continue to develop, one of which is bioelectrical impedance analysis to determine the body's water, fat, fat‐free, and cell mass, which reflects the assessment of the body's liquids. The electrical and biological significance of impedance analysis lies in the fact that the measurement of the resistance (impedance) of the body's tissues or fluids changes during exposure to alternating currents of different frequencies and makes it possible to take into account the totality of resistance or the actual difference between two measurements taken in succession. The research object was newborn calves, healthy (G1) and with enteritis (G2), selected according to the principle of analogs, 15 animals in each group. The impedance measurements were studied using the “BICA” device (body impedance composition analyzer). Enteritis in calves is accompanied by a significant loss of electrolytes and free fluid, affecting normal metabolic processes. In this regard, the study of the liquids of the body of healthy and enteritis‐sick calves was the main goal of the research. The first signs of enteritis appeared more often on the second and third days of life. In G2: a decrease in motor activity, hunchback (calves do not lean well on the chest limbs, the head is lowered down) were shown, a decrease in the sucking reflex, retraction of the eyeballs into the orbits, low skin turgor, a red border on the gums under the arcade of the incisors. Feces in sick calves are unformed, watery, gray‐yellow in color, with a pungent, sour odor. On the tenth day of life in calves with enteritis, the total body fluid decreased, and this indicator was 1.5 times lower than in healthy calves (P <0.01). The decrease in the total body fluid volume mainly occurred due to a decrease in the level of intracellular fluid, which in sick animals was 2.8 times lower than in healthy animals (p <0.001). At the same time, the level of extracellular fluid in calves from the G1 and the G2 did not differ significantly and amounted to 7.9 ± 0.8% and 6.28 ± 1.0%, respectively. After the treatment (diet therapy and enroxil 5%, intramuscularly, at a dose of 1 ml per 20 kg of body weight once a day for 3 days) by the age of twenty days, the volume of total body fluid in calves with enteritis recovered and did not significantly differ from the level in healthy animals. There were no significant differences in the volume of extracellular fluid in the calves of both groups. However, as for the intracellular fluid volume, this indicator in recovered calves was still significantly lower (P <0.05) than in healthy animals and amounted to 12.14 ± 1.0% and 15.48 ± 0, 7% respectively. Thus, from the data obtained, it can be seen that fluid loss occurs mainly due to the intracellular fluid with enteritis in calves. Complete recovery of the liquid sectors in calves was observed only by the age of one month.