bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the Effects of 30‐ and 60‐min of Acute Whole‐Body Passive Heat Stress on Peripheral Vascular Function in Older Adults
Authors: Pizzey Faith K. , Ruediger Stefanie L. , Koep Jodie L. , Askew Christopher D. , Coombes Jeff S. , Bailey Tom G. 
Published: May 2022

IntroductionMacro‐ and microvascular dysfunction elevate the risk of cardiovascular disease (CVD). Heat therapy has the potential to improve vascular health and reduce CVD risk, but the optimal length of heat stress exposure is unknown. We hypothesized that 1) acute whole body heat stress (WBHS) would increase vascular function and 2) a longer WBHS period (30‐ vs 60‐min) would elicit a greater effect.Methods20 older adults (10 female; 64±7 y) underwent two separate periods of WBHS (30‐ vs 60‐min) via water perfused suit (48°C) in a randomized, counterbalanced design. Macrovascular function via flow‐mediated dilation (FMD) and microvascular function via skin reactive hyperemia (SKBF RH) were assessed before (PRE) and after (POST) WBHS. Core (Tcore; rectal) and skin (Tskin; 6‐site average) temperatures were monitored throughout. Repeated measures ANOVA were used to assess the effect of time (PRE vs POST) and visit (30‐ vs 60‐min) on all outcomes.ResultsTcore and Tskin increased after both WBHS periods (Tcore: 30‐min, PRE: 36.4±0.3, POST: 36.6±0.3°C; 60‐min, PRE: 36.4±0.3, POST: 36.8±0.2°C, p=0.001; Tskin: 30‐min, PRE: 33.5±0.6, POST: 36.3±0.4°C, p<0.0005; 60‐min, PRE: 33.2±0.5°C, POST: 36.6±0.5°C, p<0.0005). FMD% was unchanged (30‐min, PRE: 8.5±5.1%, POST: 7.1±4.2%; 60‐min, PRE: 7.7±3.9%, POST: 6.6±4.3%; p=0.10) after both WBHS periods. During RH, brachial artery shear rate area under the curve was higher after 30‐ (PRE: 17.08±9.57, POST: 26.34±13.06·10‐3 AUC; p=0.003) but not 60‐min (PRE: 21.06±12.30, POST: 27.83±19.32·10‐3 AUC; p=0.186). Total SKBFAUC increased following both 30‐ (PRE: 6.31±3.22, POST: 12.82±6.44·10‐3 AUC; p<0.0005) and 60‐min (PRE: 6.01±3.24, POST: 9.609±4.882·10‐3 AUC; p=0.037), whereas peak SKBF fluxAUC increased following 30‐ (PRE: 1.86±1.54, POST: 4.15±3.07·10‐3 AUC; p=0.001) but not 60‐min (PRE: 1.58±1.31, POST: 2.93±2.77·10‐3 AUC; p=0.1113) of WBHS.DiscussionUp to 60‐min of acute WBHS does not change macrovascular function in older adults. Interestingly, WBHS might increase downstream microvascular functional capacity. The changes in microvascular function following 30‐min of WBHS may reflect early markers of the benefits of repeated whole body heat stress.
Augmented and Virtual Reality in Anatomical Education and its Evaluation: Quality Matters
Authors: Swic Sebastian , Alkhammash Leena , Krebs Claudia 
Published: May 2022

Introduction and ObjectiveMany studies have described augmented and virtual reality (AR/VR) teaching in anatomy as having great potential. However, for this potential to be realized, deeper exploration of the offered evidence in AR/VR tool evaluation is required. While the body of evidence may be increasing to support the use of AR/VR, the purpose of this review is to examine the gaps in implementing and evaluating AR/VR anatomical education. The focus of many reviews is on the technology with less emphasis on instructional design. This review aims to pave the way for future researchers to provide evidence based, rigorously evaluated and validated anatomical educational tools that will truly be helpful.Materials and MethodsA literature search was conducted using search terms related to AR/VR anatomical educational tool evaluation. Included studies were evaluated for quality of research.ResultsGaps in AR/VR anatomy education evaluation studies included lack of user‐focused design process, minimal to no re‐iterations of AR/VR anatomy educational methods, high risk of bias, low validity, and lack of standardized protocols.ConclusionIn order to successfully and sustainably incorporate AR/VR into institutional educational curricula, high quality, comprehensive, standardized protocols of evaluation and user‐centred design approaches to meet instructional and curricular goals are required.Significance/ImplicationAR/VR is becoming increasingly available as a tool in anatomy education. It is a promising but relatively new frontier, and as such there is an increased pressure to seek out high quality evidence regarding its efficacy. These protocols must reflect a user‐centered, iterative process that begets high quality anatomical educational tools which would reliably and reproducibly lead to higher quality educational outcomes.
Extension of the isogravimetric method for the determination of the capillary filtration coefficient CFC
Authors: Petrow Jordan M. 
Published: May 2022

In 1948, J.R. Pappenheimer made the decision to allow blood pressure to act from the capillary toward the interstitium in CFC determination. With this decision, he was inevitably confronted with the fact that an interstitium with unknown properties stood in his way during CFC determination. Depending on how these properties turn out, the experimental conditions change drastically and the measurements give a wrong result. In the example of muscle tissue, contrary to expectations, the effective fitration pressure (EFP) across the capillary membrane does not remain constant in this method, but quickly drops to zero. As a result, the measurement result is calculated to be much smaller than the actual permeability of the capillary membrane.When this problem was recognized in the method of Pappenheimer and Soto Rivera, the simpler way was chosen by allowing the pressure to act in the opposite direction, coming from the interstitium and going outward. As a first step, the tissue was flooded with fluid and then squeezed outward in a pletysmograph. A tissue model was first used to demonstrate that the EFP remained constant in this case. The new method for CFC determination has shown that the CFC in the muscle tissue can be estimated to be many times larger than the CFC measured in the past using the method of Pappenheimer and Soto Rivera.For the muscle tissue in the rabbit experiment, a CFC= 0.130±0.012 ml/mmHg.100g was determined at that time, which was considerably larger than the data known from the literature around 0.008 ml/mmHg.100g
Teaching Essay Writing: When Good Intentions Lead to Bad Outcomes
Authors: Witchel Harry J. 
Published: May 2022

This warning narrative explores the tension in student‐centered learning between attempting to teach individual students the skills of scientific writing in good faith versus encouraging student responsibility. There are often protocols to facilitate student learning that systematically apportion tasks between different members of staff. These protocols are reliable and well‐established, but in the face of a failing student, plainly some aspect of the protocol has gone wrong. Has the student fallen through a gap in the system, has a busy instructor given insufficiently personalized teaching, or has the student failed to take responsibility for their student‐centered learning? We conclude that deviating from protocols, even with due caution and substantive teaching experience, can still lead to conflicts.In this narrative example, the author, a physiology educator, failed to follow protocol and ended up creating predictable problems for his colleagues. The author made this mistake despite the fact that he has also been awarded a National Teaching Fellowship (UK) and has also written a book “Writing for Biomedical Sciences Students” for Macmillan Study Skills. The tension between the student needing skills and the student needing to take responsibility highlights how learning in good faith (and teaching in good faith) is at the core of student‐centered learning. The case study looks at an anonymized group email trail among faculty to explore the sequelae of an optional “essay help session” for a group of students who have failed an essay assignment.As the author ran an active learning workshop session for 8 students, a latecomer interrupted the proceedings to complain about her original mark in the form of not understanding what was wrong with the original failed essay. In our system, remarking is neither encouraged nor allowed except in extraordinary circumstances. The author, falling into the situation of wanting to teach in good faith, skimmed the essay during the class and found it on first glance to have only a series of subtle problems. The promise “to look into it after class” resulted in a series of group emails that suggested that the author ‐‐ despite extensive efforts to avoid the obvious conflict between faculty ‐‐ had undermined the original tutor while being absorbed by a student's aims that may have been in bad faith from the beginning. The student definitely took responsibility for addressing their failure, but not necessarily by learning the skills being taught. Despite the instructor's explicit recognition of the potential conflicts and acknowledgment of the important roles of other instructors, the conflicts can still arise.
Novel Anosmia‐Inducing Compounds for Environmentally Friendly Mosquito Vector Control: Structural Determinants of ORco Ligands Antagonizing Odorant Receptor Function
Authors: Iatrou Kostas , Kythreoti Georgia , Thireou Trias , Karoussiotis Christos , Georgoussi Zafiroula , Zographos Spyros E. , Liggri Panagiota , Michaelakis Antonios , Schulz Stefan 
Published: May 2022

Insect repellents are important means of personal protection against bites from mosquitoes carrying various pathogens. Odorant‐dependent behaviours are triggered by odor ligands bound to odorant receptors. Insect odorant receptors are heterotetrameric ligand‐gated cation channels composed of an obligatory subunit, ORco, and one of many variable subunits, ORx, to which odorant ligands bind. Upon expression ex vivo, ORco forms homomeric channels gated by specific ligands acting as channel agonists. In past studies, we identified ligands of natural origin that bind to the African malaria mosquito vector Anopheles gambiae ORco (AgamORco). Some of these ligands function as specific ORco channel antagonists, orthosteric or allosteric relative to a predicted ORco agonist binding site, and cause severe inhibition of the olfactory function in a variety of mosquito species. Given that ORco is evolutionarily conserved, we hypothesized that it should be feasible to develop an AgamORco‐based screening platform allowing fast identification of new ORco ligands acting as mosquito odorant receptor antagonists causing anosmia‐like deficits to mosquitoes.We are now reporting on the compilation of common structural features of previously identified orthosteric AgamORco antagonists and generation of a ligand‐based pharmacophore. In silico screening of a collection of volatile compounds of natural origin resulted in identification of several AgamORco ligand hits. Parallel cell‐based screening of the same compounds against AgamORco was also employed in order to identify ligands acting as AgamORco antagonists. The screening resulted in identification of several ligands inhibiting AgamORco channel function ex vivo by at least 40% and inducing anosmic behaviors to Aedes albopictus mosquitoes in vivo. To test the pharmacophore model for binding site specificity, binding competition assays were undertaken, which distinguished the identified antagonists into orthosteric and allosteric ones. Direct comparisons of the pharmacophore predictions with the results of the cell‐based screen revealed that the pharmacophore predicted correctly 100% of the orthosteric antagonists and none of the allosteric ones. These results confirm the pharmacophore's value for in silico prediction of AgamORco orthosteric ligands. Upon combination with the AgamORco‐specific cell‐based screening platform, the pharmacophore provides a valuable tool for fast identification of multiple, ecologically friendly vector control agents. Finally, to confirm the predicted AgamORco agonist binding site and determine the binding orientation of orthosteric antagonists in it, we are assessing the interactions of these ligands with specific amino acids in the AgamORco binding pocket by site‐specific mutagenesis.
Differential remodelling of visceral and pericardial adipose tissue in response to stress and exercise
Authors: Boateng Samuel , Ige Susan , Dallas Mark , Chantler Paul 
Published: May 2022

Obesity is driven by an imbalance between caloric intake and energy expenditure, causing excessive storage of nutrients in adipose tissue at different sites around the body. Increased visceral adipose tissue (VAT) is associated with diabetes, whilst pericardial adipose tissue (PAT) is associated with cardiac pathology. Adipose tissue can expand either through cellular hypertrophy or hyperplasia, with the former correlating with decreased metabolic health in obesity. The aim of this study was to determine how VAT and PAT remodel in response to obesity, stress and exercise.Here we have used the obese Zucker rats which develop hyperphagia with reduced energy expenditure, resulting in morbid obesity as a result of leptin resistance. At 9 weeks of age lean (LZR) and obese (OZR) Zucker male rats were treated with or without unpredictable chronic mild stress or exercise for 8 weeks. To determine the phenotype for PAT and VAT, tissue cellularity and gene expression were analyzed. Tissue cellularity was determined following haematoxylin and eosin staining, whilst qPCR was used to examine gene expression.PAT adipocytes were significantly smaller than those from VAT and had a more biege‐like appearance. In the OZR group, VAT adipocyte cell size increased significantly compared with LZR, whilst PAT showed no change. Exercise and stress resulted in a significant reduction in VAT cellularity in OZR, whilst PAT showed no change. This suggests that PAT cellularity does not remodel significantly compared with VAT. Picro sirus red staining indicated that PAT had significantly more fibrosis than VAT. However, this fibrosis was decreased following stress treatment. This data indicate that the extracellular matrix of PAT is able to remodel more readily than in VAT.Gene expression analysis showed that PAT expressed higher levels of UCP1 compared with VAT, indicating that it has a more brown‐like phenotype. In the LZR group, exercise increased insulin receptor substrate 1 (IRS1) in PAT, but was decreased in the OZR group. On the other hand, in VAT, exercise decreased IRS1 in LZR, whilst increasing it in the OZR. This suggests that in obesity, VAT is more responsive to exercise and subsequently becomes less insulin resistant compared with PAT. In VAT, stress increased PPAR‐γ expression in the OZR group but decreased it in the PAT. This suggests that in obesity, stress increases adipogenesis more significantly in the VAT compared with PAT.Taken together, our data suggest that VAT is considerably more plastic than PAT and remodels rapidly in response to obesity, exercise and psychological stress.
Breast Cancer Revisited: Stress Induced Conspiracy, Sensitivity and Specificity
Authors: Malik Samina , Waquar Sulayman , Malik Arif 
Published: May 2022

INTRODUCTIONCancer and related disorders remain as one of the most devastating ailments worldwide. It signifies the importance to devise particular techniques, which could help in attenuating the effects of breast cancer and related outcomes. Primary aim of the current study is to revisit the role of inflammatory and stress markers in the development and progression of breast cancer and to determine their sensitivity and specificity.MATERIAL AND METHODSA local sample of premenopausal Pakistani women (age 40 ± 3.6) diagnosed with breast cancer (n = 498) at Jinnah Hospital Lahore, and equal number of controls (age 36 ± 5.2) were selected for the current case control study after informed consent. Serum samples were separated and estimated for MMPs, ILs, HSPs, TNF‐α, INOS and Vitamin D on ELISA, whereas, MDA, SOD, NO, CAT, GSH, Vitamin A and D were estimated on Spectrophotometry.RESULTSLevels of MDA, ILs, MMPs, TNF‐α, NO, INOS and HSPs were significantly higher in the breast cancer patients, but the levels of SOD, CAT, GSH, Vitamins A, C and D were significantly lower, determining the relatively positive relationship of oxidants and negative relationship of antioxidants with the increased incidence of pathology among the patients. Furthermore, HSP‐27, MMP‐9 and IL‐1 levels revealed remarkable sensitivity and specificity on ROC analysis.CONCLUSIONIt concludes that HSP‐27, MMP‐9 and IL‐1 may serve as diagnostic and prognostic markers. Furthermore, it can be extrapolated how the increased levels of oxidative and nitrosative stress species along with inflammatory cytokines predispose to the incidence of cell invasion, cell migration and epithelial‐mesenchymal transition. Therefore, it infers that increase in growth factors i.e., VEGF, TGF‐β and Bcl2 under the influence of said variables play a crucial role in the metastasis of breast cancer.
Vascular and glomerular vs. proximal tubular components in calcineurin inhibitor‐related nephrotoxicity
Authors: Popovic Suncica , Demirci Hasan , Yilmaz Duygu E. , Dittmayer Carsten , Ellison David H. , Mutig Kerim , Bachmann Sebastian 
Published: May 2022

Calcineurin inhibitors (CNI) are widely in use for immunosuppression in transplant recipients, but their nephrotoxicity may cause or aggravate renal disease. CNI pathology includes vascular and tubulointerstitial alterations.We have compared the effects of cyclosporine A (CsA) and tacrolimus (Tac) upon chronic administration in a rat model. We have tested whether Tac caused less damage than CsA. To this end, functional as well as glomerular and tubulointerstitial parameters were compared.Adult Wistar rats received CsA (25 mg/kg/d), Tac (2 mg/kg/d), or vehicle via subcutaneously implanted minipumps. After four weeks, rats were sacrificed and organs removed for protein analysis or perfusion‐fixed and kidneys analyzed for histopathology. NRK cells were treated with graded concentrations of CNI for 24h. For evaluation, confocal immunohistochemistry, EM nanotomy, EM immunostaining, Western blot, and clinical chemistry methods were applied.In rats, CsA and Tac produced distinct alterations in the tubulointerstitium. With CsA, dysmorphic lysosomes with peripheral LAMP1 signal, autophagic and mitophagic vacuoles caused epithelial decay of the initial proximal tubule, while glomerular changes were less pronounced. With Tac, glomerulosclerosis and damage encroachment to proximal tubule were more prominent. Both drugs induced fibrotic upregulation of alpha‐smooth muscle actin in the interstitium. Alterations in unfolded protein response (UPR) parameters included rises in p‐eIF2α, p‐PERK, p‐IRE1, sXBP1, CHOP in CsA‐, but not in Tac‐treated rats. Epithelial TUNEL signal was stronger in the CsA than in the Tac groups. Results were verified in NRK cells using graded caspase‐3 and lysosome formation criteria.Data revealed distinct nephrotoxicity patterns in the two examined immunosuppressive medications. While CsA seems to be primarily tubulotoxic, a stronger glomerular component was detected with Tac. Results may serve to better adjust treatment combinations in transplant patients.
Evidence of Sex Differences in the Endothelin Pathway in Diabetes
Authors: Derella Cassandra C. , Thomas Jeffrey , Layman Lawrence C. , Harris Ryan A. 
Published: May 2022

BackgroundThe endothelin system has been identified as a key regulator of vascular function and is comprised of two receptors; a constricting A‐receptor (ETAR) and dilating B‐receptor (ETBR). Sex differences in the ET‐1 pathway have been established. Specifically, when compared to men, activation of the ETBR in women results in a favorable dilatory response. In the presence of diabetes; however, the endothelin system in general, is negatively altered. Whether sex differences in the endothelin pathway are observed in type 1 diabetes (T1D), is unknown. Thus, the present investigation sought to test the hypothesis that ETB receptor function is reduced in women with T1D compared to men with T1D.MethodsPremenopausal women (n=2, HbA1c=10.4±0.8%, age=29±13 years, BMI=29.9±2.8 kg/m2) and men (n=4, HbA1c=8.5±1.0%, age=22±3 years, BMI=21.5±2.8 kg/m2) with a clinical diagnosis of T1D were recruited to participate. Three microdialysis fibers were inserted into the dermal layer of the right forearm where cutaneous blood flow was measured using laser speckle contrast imaging. Microvascular function was determined by a ten dose incremental perfusion of acetylcholine (Ach; 10‐2‐2*103 M). Endothelin receptor function was determined two ways: 1) by a seven dose incremental perfusion of ET‐1 (10‐20‐10‐8 M), and 2) by a seven dose incremental perfusion of ET‐1 (10‐20‐10‐8 M) combined with the selective ETAR antagonist, BQ‐123 (750 nM). The dose response area under the curve (AUC) for cutaneous vascular conductance of each fiber was calculated for each individual.ResultsWomen with T1D had a significantly greater BMI (p=0.026) and HbA1C(p=0.089) compared to men with T1D. The Ach dose response AUC was greater (p=0.135) in women with T1D (753.5±12.7 AU) when compared to men with T1D (691.7±61.1 AU). The ET‐1 + BQ‐123 dose response AUC tended (p=0.298) to be lower in women with T1D (295.5±14.1 AU) when compared to men with T1D (357.8±98.6 AU). A similar lower response in women was observed for the ET‐1 AUC (p=0.102; men: 1411.9±508.9 AU vs women: 821.7±38.5 AU).ConclusionThese data suggest that, compared to men with T1D, microvascular function is greater in women, albeit weighing more and having a higher HbA1c. In contrast, preliminary findings indicate that ETBR function may be impaired in women with T1D compared to men with T1D.