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Background: Pain is a very important factor in patient recovery and satisfaction. Following incision and drainage of perianal abscess, wound packing has been found to be very painful. The aim of this study is to compare packing the wound and not packing the wound after incision and drainage (I&D) of perianal abscess, taking into account recurrence rate, rate of occurrence of perianal fistula as well as post-operative pain. Materials and Method: Standard medical electronic databases were searched with the help of a local librarian and relevant published randomised controlled trials (RCT) were shortlisted according to the inclusion criteria. The summated outcome of post-operative pain score, recurrence rate, and rate of occurrence of perianal fistula was evaluated using the principles of meta-analysis on RevMan 5 statistical software. Result: Three RCTs on 490 patients undergoing I&D of perianal abscess were found suitable for this meta-analysis. In the random effects model analysis, the post operative pain score was statistically lower in NPG [risk ratio 0.66, 95%, CI (0.36, 0.97), Z=4.25, P=0.0001]. There was no heterogeneity [Tau2=0.15; chi2=9.32; df=6; I2=36 %; p=0.16] between the studies, however, statistically it was not significant. In addition, there was no statistical difference between the 2 groups in terms of recurrence of perianal abscess or the occurrence of perianal fistula [risk ratio 0.64, 95%, CI (0.31, 1.31), Z=1.23, P=0.22], [risk ratio 1.41, 95%, CI (0.89, 2.23), Z=1.47, P=0.14] respectively. Conclusion: Not packing the wound post I&D of perianal abscess is associated with significantly reduced VAS pain scores, which may result in improved recovery and patient satisfaction and has no effect on recurrence rate or the occurrence of perianal fistula. However, more RCTs recruiting a greater number of patients are required to endorse these findings.

BACKGROUND: SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.METHODS: Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood-brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68 + Iba1 + cells; morphological analysis).RESULTS: Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood-brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1 + CD68 + cells, increased soma size and shortened processes, was partly reduced by amlodipine.CONCLUSION: Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation.

Aging; Arteriosclerosis; Hemodynamics Envelliment; Arteriosclerosi; Hemodinàmica Envejecimiento; Arteriosclerosis; Hemodinámica Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life. This article is based upon work from COST Action “Network for Research in Vascular Ageing” (VascAgeNet, CA18216), supported by COST (European Cooperation in Science and Technology, www.cost.eu). This work was supported by British Heart Foundation Grants PG/15/104/31913 (to J.A. and P.H.C.), FS/20/20/34626 (to P.H.C.), and AA/18/6/34223, PG/17/90/33415, SPG 2822621, and SP/F/21/150020 (to A.D.H.); Kaunas University of Technology Grant INP2022/16 (to B.P.); European Research Executive Agency, Marie-Sklodowska Curie Actions Individual Fellowship Grant 101038096 (to S.P.); Istinye University, BAP Project Grant 2019B1 (to S.P.); “la Caixa” Foundation Grant LCF/BQ/PR22/11920008 (to A.G.); and National Institute for Health and Care Research Grant AI AWARD02499 and EU Horizon 2020 Grant H2020 848109 (to A.D.H.).

Salt-inducible kinases (SIKs), which comprise a family of three homologous serine-threonine kinases, were first described for their role in sodium sensing but have since been shown to regulate multiple aspects of physiology. These kinases are activated or deactivated in response to extracellular signals that are cell surface receptor mediated and go on to phosphorylate multiple targets including the transcription cofactors CRTC1–3 and the class IIa histone deacetylases (HDACs). Thus, the SIK family conveys signals about the cellular environment to reprogram transcriptional and posttranscriptional processes in response. In this manner, SIKs have been shown to regulate metabolic responses to feeding/fasting, cell division and oncogenesis, inflammation, immune responses, and most recently, sleep and circadian rhythms. Sleep and circadian rhythms are master regulators of physiology and are exquisitely sensitive to regulation by environmental light and physiological signals such as the need for sleep. Salt-inducible kinases have been shown to be central to the molecular regulation of both these processes. Here, we summarize the molecular mechanisms by which SIKs control these different domains of physiology and highlight where there is mechanistic overlap with sleep/circadian rhythm control.

Genome-wide association studies (GWAS) aim to identify common genetic variants that are associated with traits and diseases. Since 2005, more than 5,000 GWAS have been published for almost as many traits. These studies have offered insights into the loci and genes underlying phenotypic traits, have highlighted genetic correlations across traits and diseases, and are beginning to demonstrate clinical utility by identifying individuals at increased risk for common diseases. GWAS have been widely utilized across cardiovascular diseases and associated phenotypic traits, with insights facilitated by multicenter registry studies and large biobank data sets. In this review, we describe how GWAS have informed the genetic architecture of cardiovascular diseases and the insights they have provided into disease pathophysiology, using archetypal conditions for both common and rare diseases. We also describe how biobank data sets can complement disease-specific studies, particularly for rarer cardiovascular diseases, and how findings from GWAS have the potential to impact on clinical care. Finally, we discuss the outstanding challenges facing research in this field and how they can be addressed.

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation, and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a “trial-and-error” approach, with the experience and practices of successful coaches and athletes often providing the bases for “post hoc” scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and interindividual differences in exercise capacity and performance, with special consideration given to aging athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise and how such adaptations translate from “molecules to medals.”

The intercalated disc (ID) is a highly specialized structure that connects cardiomyocytes via mechanical and electrical junctions. Although described in some detail by light microscopy in the 19th century, it was in 1966 that electron microscopy images showed that the ID represented apposing cell borders and provided detailed insight into the complex ID nanostructure. Since then, much has been learned about the ID and its molecular composition, and it has become evident that a large number of proteins, not all of them involved in direct cell-to-cell coupling via mechanical or gap junctions, reside at the ID. Furthermore, an increasing number of functional interactions between ID components are emerging, leading to the concept that the ID is not the sum of isolated molecular silos but an interacting molecular complex, an “organelle” where components work in concert to bring about electrical and mechanical synchrony. The aim of the present review is to give a short historical account of the ID’s discovery and an updated overview of its composition and organization, followed by a discussion of the physiological implications of the ID architecture and the local intermolecular interactions. The latter will focus on both the importance of normal conduction of cardiac action potentials as well as the impact on the pathophysiology of arrhythmias.

The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.

Myoglobin is essential for oxygen transport to the muscle fibers. However, measurements of myoglobin (Mb) protein concentrations within individual human muscle fibers are scarce. Recent observations have revealed surprisingly low Mb concentrations in elite cyclists, however it remains unclear whether this relates to Mb translation, transcription and/or myonuclear content. The aim was to compare Mb concentration, Mb messenger RNA (mRNA) expression levels and myonuclear content within muscle fibers of these elite cyclists with those of physically-active controls. Muscle biopsies were obtained from m. vastus lateralis in 29 cyclists and 20 physically-active subjects. Mb concentration was determined by peroxidase staining for both type I and type II fibers, Mb mRNA expression level was determined by quantitative PCR and myonuclear domain size (MDS) was obtained by immunofluorescence staining. Average Mb concentrations (mean ± SD: 0.38 ± 0.04 mM vs. 0.48 ± 0.19 mM; P = 0.014) and Mb mRNA expression levels (0.067 ± 0.019 vs. 0.088 ± 0.027; P = 0.002) were lower in cyclists compared to controls. In contrast, MDS and total RNA per mg muscle were not different between groups. Interestingly, in cyclists compared to controls, Mb concentration was only lower for type I fibers (P P > 0.05). In conclusion, the lower Mb concentration in muscle fibers of elite cyclists is partly explained by lower Mb mRNA expression levels per myonucleus and not by a lower myonuclear content. It remains to be determined whether cyclists may benefit from strategies that upregulate Mb mRNA expression levels, particularly in type I fibers, to enhance their oxygen supply.

Pregnancy is established during the periconceptional period as a continuum beginning with blastocyst attachment to the endometrial epithelial surface followed by embryo invasion and placenta formation. This period sets the foundation for the child and mother’s health during pregnancy. Emerging evidence indicates that prevention of downstream pathologies in both the embryo/newborn and pregnant mother may be possible at this stage. In this review, we discuss current advances in the periconceptional space, including the preimplantation human embryo and maternal endometrium. We also discuss the role of the maternal decidua, the periconceptional maternal-embryonic interface, the dialogue between these elements, and the importance of the endometrial microbiome in the implantation process and pregnancy. Finally, we discuss the myometrium in the periconceptional space and review its role in determining pregnancy health.

The pulmonary circulation is a low-resistance, low-pressure, and high-compliance system that allows the lungs to receive the entire cardiac output. Pulmonary arterial pressure is a function of cardiac output and pulmonary vascular resistance, and pulmonary vascular resistance is inversely proportional to the fourth power of the intraluminal radius of the pulmonary artery. Therefore, a very small decrease of the pulmonary vascular lumen diameter results in a significant increase in pulmonary vascular resistance and pulmonary arterial pressure. Pulmonary arterial hypertension is a fatal and progressive disease with poor prognosis. Regardless of the initial pathogenic triggers, sustained pulmonary vasoconstriction, concentric vascular remodeling, occlusive intimal lesions, in situ thrombosis, and vascular wall stiffening are the major and direct causes for elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension and other forms of precapillary pulmonary hypertension. In this review, we aim to discuss the basic principles and physiological mechanisms involved in the regulation of lung vascular hemodynamics and pulmonary vascular function, the changes in the pulmonary vasculature that contribute to the increased vascular resistance and arterial pressure, and the pathogenic mechanisms involved in the development and progression of pulmonary hypertension. We focus on reviewing the pathogenic roles of membrane receptors, ion channels, and intracellular Ca2+ signaling in pulmonary vascular smooth muscle cells in the development and progression of pulmonary hypertension.

Solar ultraviolet-B (UV-B) radiation has played a crucial role in the evolution of life on Earth. UV exposure presents both risks and benefits to humans. Optimal UV-B exposure behaviors, that ensure balance between the risks and benefits of exposure to UV-B depend both on environmental and physiological factors and cannot be easily determined. The present review provides the current state of knowledge relative to the effects of UV-B radiation to humans. The physical mechanisms that control the levels of solar UV-B radiation at the Earth’s surface are also discussed. A comprehensive review of the studies reporting on current trends in the levels of solar UV-B radiation at the surface and model projections of its future levels is examined and reveals the important role of man-made climatic changes in its evolution. The review provides evidence that despite the success of the Montreal Protocol, the future evolution of the levels of solar UV-B radiation at the Earth’s surface has important uncertainties caused by the expected changes in our climate. Therefore, it is recommended that the usual precautionary measures to protect from excess exposure of humans to solar UV-B radiation should continue to apply in the decades to come.

The continuous use of antibiotics is associated with the spread of antimicrobial resistances and the not yet clear link to cancer development. Many conventional antibi-otics have already shown different effects on a variety of cancer types raising questions for their rational use in cancer. However, discrepancy in the observed trend for some antibiotics reducing cancer development and be-ing associated with higher risk of cancer underscores the lack of understanding the complex link between antibiotics and cancer. Here, we briefly summarize the possible antibiotic-mediated effects on cancer and con-clude that those effects can be direct via i) specific tar-geting of tumor/cancer, ii) antimicrobial activity and iii) immunomodulatory activity whereby iv) indirectly caused effects primarily affect immune equilibrium be-tween bacteria, cancer and immune cells. Furthermore, we also conclude that there is a great need for bulk profiling, comprehensive screening programs in all countries and in-depth studies to understand the risks and benefits of antibiotic use.

We included a 3-dimensional puzzle (3Dsp) of electrical and chemical synapses in the physiology of synaptic transmission (ST) teaching. After a traditional or video lesson class, students from private and public universities were oriented to use the educational resource. More than 90% of the students affirmed that the 3Dsp improved their comprehension of ST content.

Locally derived endothelial nitric oxide (NO) contributes to the full expression of cutaneous vasodilation responses. Acute ultraviolet radiation (UVR) exposure attenuates NO-mediated vasodilation of the cutaneous microvasculature. Our findings suggest that in constitutively lightly pigmented skin, variation in skin melanin due to seasonal exposure to UVR does not alter the NO contribution to cutaneous vasodilation. Seasonal UVR exposure does not impact the NO-mediated cutaneous microvascular function.

We find that removal of gonadal hormones does not exacerbate muscle loss in males or females during exposure to either simulated microgravity or partial-gravity environments. However, simulated micro- and partial gravity did affect females’ estrous cycles, with more time spent in low-estrogen phases. Our findings provide important data on the influence of gonadal hormones on the trajectory of muscle loss during unloading and will help inform NASA for future crewed missions to space and other planets.

Interval training has been found to lower glucose concentrations and increase insulin sensitivity in males but not in females, which may be due to inherent sex-based differences in metabolism. Twenty-four (12/sex) participants completed a bout of high-intensity interval exercise (HIIE, 10 × 1 min at 90% HRmax) to evaluate whether sex influenced the physiological effects of HIIE on postexercise glycemic control during an oral glucose tolerance test (OGTT). Given that body anthropometrics influence postprandial glucose, data were also expressed as a function of the normalized glucose dose. In addition, we examined whether sex differences in postexercise glycemic control were related to sex differences in muscle metabolism and/or insulin signaling proteins. HIIE increased insulin sensitivity in both sexes as characterized by the Matsuda ( P = 0.03, ηp2= 0.20) and HOMA-IR ( P = 0.047, ηp2 = 0.17) indices. HIIE also lowered insulin concentration during the OGTT ( P = 0.04, ηp2 = 0.18) as compared with control. When normalized for glucose dose relative to lean mass, glucose area under the curve (AUC) was lower in females than in males ( P ≤ 0.001, ηp2 = 0.47). TBC1D1 Ser237 phosphorylation increased in males, but not in females, postexercise ( P = 0.03, ηp2 = 0.19). There was no difference in total insulin signaling protein content, muscle glycogen utilization, or AMPK activation during exercise between the sexes. These findings indicate that when the glucose dose is normalized for differences in body composition glycemic handling is better in females and that an acute bout of HIIE improves insulin sensitivity equally in healthy males and females.

Hot yoga significantly altered endothelial function responses to high-sodium intake in Black female adults. Blood pressure responses were unaltered by the yoga intervention in this population.

Investigating students’ alternative reasoning in neurophysiology, this research is the first to investigate how analyzing the most common incorrect answer can shed light on the concepts students struggle with when reasoning about neurophysiological problems, especially those dealing with both chemical and electrical driving forces to predict ion movement across cell membranes.

We found that forskolin-induced swelling in G550X-CFTR patient-derived intestinal organoids (PDOs) was significantly higher than in G542X-CFTR PDOs after treatment with ELX-02. Tryptophan (W) was the sole amino acid inserted in the G550X position after readthrough. Resulting G550W-CFTR protein exhibited supernormal CFTR activity, PKA sensitivity, and open probability. These results show that aminoglycoside-induced readthrough of G550X produces greater CFTR function because of the gain-of-function properties of the CFTR readthrough product.

Hypertension remains a significant global health problem. Although hypertension research and therapies are keenly focused on the heart and arterial circulation, the venous circulation has been neglected comparatively. We determined whether hypoxia, known to cause peripheral chemoreflex activation, evoked more pronounced changes in lower limb venous capacity and compliance in hypertensives (HTN) than in age-matched normotensives (NT). We found that hypoxia reduced venous capacity in the great saphenous vein in HTN and increased its compliance twofold. However, hypoxia did not affect venous function in NT. Our data indicate the venomotor response to hypoxia is enhanced in hypertension, and this may contribute to the hypertensive state.

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis. Chronic microinjuries, mainly caused by environmental factors to an aging alveolar epithelium, would lead to the aberrant differentiation and accumulation of aberrant mesenchymal cells with a contractile phenotype, known as fibrosis-associated myofibroblasts, which trigger abnormal extracellular matrix accumulation and fibrosis. The origin of those pathological myofibroblasts in pulmonary fibrosis is not fully understood to date. Lineage tracing methods using mouse models have opened new avenues for studying cell fate in a pathological context. This review aims to present a nonexhaustive list of different potential sources of those harmful myofibroblasts during lung fibrosis, based on these in vivo approaches, and considering the normal and fibrotic lung cellular atlas recently established by single-cell RNA sequencing.

Our students often focus on the grades they need to advance through academic programs. How can instructors harness this understandable interest in grades to help students gain a true understanding of core concepts? The new framework of Test Question Templates (TQTs) shows promise in linking student priorities like test scores to instructor priorities like core concepts.

The novel total left anterior descending devascularization (TLD) approach in a canine ischemic heart failure model limits collateral flow in the ischemic zone and provides excellent early survival and repeatable development of chronic ischemic heart failure in the canine heart. This work provides a consistent large animal model for investigating heart failure mechanisms and testing novel therapeutics.

Repetitive transcranial magnetic stimulation (TMS) is currently applied in various neuropsychiatric disorders. The aim of this study was to explore the effect of TMS on hypertension and its mechanism. We found TMS attenuates hypertension after T4 or L2 spinal column stimulation via reduction of catecholamines in male spontaneously hypertensive rat. Treatment with TMS may be a strategy for hypertension therapy in the future.

Objective: This study determined the effects of dietary treatments and castration on meat quality, fatty acids (FAs) profiles, and volatile compounds in Korean native black goats (KNBG, Capra hircus coreanae), including the relationship between the population of rumen microbiomes and meat FA profiles.Methods: Twenty-four KNBG (48.6±1.4 kg) were randomly allocated to one of four treatments arranged into a 2×2 factorial structure. The factors were dietary forage to concentrate ratio (high forage [HF, 80:20] and low forage [LF, 20:80]), and a castration treatment (castration [CA] vs non-castration [NCA]).Results: Among meat quality traits, the CA group exhibited a higher percentage of crude fat and water holding capacity (p

Muscle O2 saturation (%SmO2) rate can be used to not only identify sustainable from unsustainable exercise intensities but also delineate the transition from heavy to severe exercise domains. This report is the first to identify, and then validate, that the highest steady-state metabolic rate is related to a zero-slope muscle O2 saturation and is therefore dependent on muscle oxygen supply-demand balance.

Objective: Angora rabbits fed a low-protein diet exhibit decreased hair production performance. This study was set out to evaluate the effects of methionine on hair properties and nitrogen metabolism in Angora rabbits fed a low-protein diet and to investigate the gene expression related to hair follicle development to determine the possible molecular mechanism of methionine effects on hair follicle development.Methods: An experiment was conducted to investigate the effects of DL-methionine addition on a low-protein diet on hair development in Angora rabbits. Angora rabbits were divided into 5 groups: fed a normal diet (control), fed a low-protein diet (LP), or fed an LP supplemented with 0.2%, 0.4%, or 0.6% DL-methionine (Met).Results: The results showed that rabbits in the LP group had lower wool yield than the control rabbits, but the addition of 0.4% to 0.6% Met to LP attenuated these effects (pIGF1), keratin-associated protein (KAP) 3.1, and KAP 6.1 mRNA levels compared with the control, but the addition of 0.4% Met in LP attenuated these effects (pIGF1, KAP, and the versican signaling.

This study involved a teaching reform based on problem-based self-designed experiments in a physiology laboratory course. Students in the test group were required to conduct self-designed experiments based on questions for each experimental theme, in addition to completing the specified experimental items. The results showed that the teaching reform promoted the students’ self-directed learning and problem-solving ability, stimulated their enthusiasm for scientific research, and was conducive to cultivating innovative medical talents.

This study used Ripple Effects Mapping (REM) to identify undergraduate student-perceived benefits of research projects, to assess whether REM could confirm achievement of course learning objectives for a research project-based course, and to compare themes identified from the mind mapping component of REM to those identified by inductive analysis. Mind mapping confirmed achievement of course objectives and may be a better choice compared to inductive reasoning when time is limited.

The major new finding in this study is that in people who smoke tobacco cigarettes, using an electronic cigarette but not a tobacco cigarette acutely and significantly prolongs several metrics of ventricular repolarization, including Tpeak-Tend, Tpeak-Tend/QT, and Tpeak-Tend/QTc. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers.

Drug induced liver injury (DILI) or hepatotoxicity has been a hot issue to overcome on the safety and physiological function of liver, since it is known to have biochemical, cellular, immunological and molecular alterations in liver mainly induced by alcohol, chemicals, drugs, heavy metals and genetic factors. Recently efficient therapeutic and preventive strategies by some phytochemicals are of interest, targeting oxidative stress mediated hepatotoxicity alone or in combination with anticancer drugs.To assess DILI, the variety of in vitro and in vivo animal models have been developed mainly by using carbon tetrachloride (CCl4), d-Galactosamine, acetaminophen (APAP) and lipopolysaccharide (LPS). Also, the mechanisms on hepatotoxicity by several drugs and herbs have been explored in detail. Recent studies reveal that antioxidants including vitamins and some phytochemicals were reported to prevent against DILI.Antioxidant therapy with some phytochemicals is noteworthy, since oxidative stress is critically involved in DILI via production of chemically reactive oxygen species (ROS) or metabolites, impairment of mitochondrial respiratory chain, and induction of redox cycling.For efficient antioxidant therapy, DILI susceptibility, HLA genetic factors, biomarkers and pathogenesis implicated in hepatotoxicity should be further explored in association with oxidative stress mediated signaling, while more randomized preclinical and clinical trials are required with optimal safe doses of drugs and/or phytochemicals alone or in combination for efficient clinical practice along with development of advanced DILI diagnostic tools.

The COVID-19 pandemic has led to a massive temporary conversion of offline education to online education worldwide. Previous studies have noted that more students believed they had better learning experience in face-to-face learning. However, with our method of online teaching, we still showed a relatively similar performance result compared with offline education.

Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. The effect of fasting on free cortisol levels is modified by sex. Further study is needed to determine the mechanisms driving the increases in cortisol.

Objective: This study aimed to investigate the effect of dorsal cranial myopathy (DCM) on chicken meat quality.Methods: Sixty-six Ross 308 AP broilers, 47 days old, of both sexes, weighing about 3.51 kg, were slaughtered according to standard industrial practices, and evaluated for meat color, pH, chemical composition, collagen content, fatty acid profile, and histopathological parameters. Comparisons between normal and DCM-affected meat were performed using Student's t-test at the 5% significance level.Results: Histological analysis of muscle tissues affected by DCM showed myofiber degeneration, proliferation of inflammatory cells, fibroplasia, and necrosis with fibrosis. DCM samples had lower protein content and higher moisture, ash, insoluble collagen, total collagen, and pH. DCM-affected meat was redder and more yellowish. There were no differences in lipid or soluble collagen contents between groups. DCM-affected meat had higher percentages of arachidonic acid (C20:4n−6) and eicosapentaenoic acid (C20:5n−3).Conclusion: This study revealed that DCM-affected meat exhibits considerable changes in quality parameters.

NR2F2 loss in the endothelial lining of blood vessels is associated with cardiovascular disease. Here, NR2F2-silenced human endothelial cells were inflammatory, proliferative, hypermigratory, and apoptosis-resistant with increased oxidant stress and endothelial-to-mesenchymal transition. DKK1 was induced in NR2F2-silenced endothelial cells, while co-silencing NR2F2 and DKK1 prevented NR2F2-loss-associated abnormalities in endothelial signaling and phenotype. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating vascular diseases associated with endothelial dysfunction.

When stopping a closing door or catching an object, humans process the motion of inertial objects and apply reactive limb force over short period to interact with them. One way in which the visual system processes motion is through extraretinal signals associated with smooth pursuit eye movements (SPEM). We conducted three experiments to investigate how SPEM contribute to anticipatory and reactive hand force modulation when interacting with a virtual object moving in the horizontal plane. We hypothesized that SPEM signals are critical for timing motor responses, anticipatory control of hand force, and task performance. Participants held a robotic manipulandum and attempted to stop an approaching simulated object by applying a force impulse (area under force-time curve) that matched the object’s virtual momentum upon contact. We manipulated the object’s momentum by varying either its virtual mass or its speed under free gaze or constrained gaze conditions. We examined gaze variables, timing of hand motor responses, anticipatory force control, and overall task performance. Our results show that when SPEM were constrained, anticipatory modulation of hand force prior to contact decreased. However, constraining SPEM did not seem to affect the timing of the motor response or the task performance. Together, these results suggest that SPEM may be important for anticipatory control of hand force prior to contact and may also play a critical role in anticipatory stabilization of limb posture when humans interact with moving objects.New and NoteworthyWe show for the first time that smooth pursuit eye movements (SPEM) play a role in modulation of anticipatory control of hand force to stabilize posture against contact forces. SPEM are critical for tracking moving objects, facilitate processing motion of moving objects, and are impacted during aging and in many neurological disorders, such as Alzheimer’s disease and Multiple Sclerosis. These results provide a novel basis to probe how changes in SPEM could contribute to deficient limb motor control in older adults and patients with neurological disorders.

The central aortic pressure waveform, while simple in form, is complex in its physiological interpretation. Although general agreement has been reached on the contour and mechanisms responsible for pressure waveforms in the ascending aorta of healthy humans, in recent years there has been increasing interest in the contour of the pressure wave in elderly patients with aortic valve stenosis (AS). As aortic valve leaflets succumb to fibrosis and calcification, they increase opposition to forward flow. This results in a protracted pressure rise and manifests as the classical finding of pulsus parvus et tardus. Equally, changes to arterial properties (including elasticity and geometry) and pulse wave velocity (PWV) with age, heart failure, or hypertension can cause profound changes to the contour. Increased accessibility of methods to measure the central aortic pressure waveform, as well as the rapid uptake of transcatheter aortic valve implantation technologies, has created a renewed focus on better understanding of characteristic perturbations to the waveform in elderly patients with AS. In this review, we investigate the evolution of our understanding of the central aortic pressure waveform in varying AS disease states to highlight the importance of the physiological and biological basis for alterations in this waveform.

We developed a new structured teaching format, the LecturePlus, to promote deep learning. A LecturePlus session consists of a brief lecture, followed by small-group problem-solving exercises, ending with a closing discussion moderated by the teacher. During the small-group exercises, students were divided into groups of three (triads) and given case-based problems. One faculty tutor supervised the entire session. LecturePlus resulted in improved learning outcomes and was rated highly by medical students.

Although many articles and books exist describing various classroom strategies to increase student engagement, often advice to newer faculty is given as prescriptive ways to organize a class or to repeat what was given by the last person who presented the material. Yet irrespective of the structure of the class or learning environment, there are subtle hurdles that many faculty erect that hinder a student’s progress. This Personal View discusses some of the potential barriers educators put up that deter effective student learning and, importantly, offers advice on how those barriers can be dismantled.

Remote practical classes, supported by physiological monitoring smartphone applications, were assessed for their utility in facilitating learning and raising student motivation in health sciences education in this study. A comparison of remote practicals with traditional in-class practicals revealed that a remote practical is an effective method for reinforcing physiology learning objectives with the added advantage of increased student motivation. The added value of remote practicals may be attributed to more experiential learning opportunities and increased engagement levels.

Objective: This study aims to evaluate the target genes of gga-miR-20a-5p and the regulated immune responses in the chicken macrophage cell line, HD11, by the exosome-mediated delivery of miR-20a-5p.Methods: Exosomes were purified from the chicken macrophage cell line HD11. Then, mimic gga-miR-20p or negative control miRNA were internalized into HD11 exosomes. HD11 cells were transfected with gga-miR-20a-5p or negative control miRNA containing exosomes. After 44 h of transfection, cells were incubated with or without 5 μg/mL poly(I:C) for 4 h. Then, expression of target genes and cytokines was evaluated by quantitative real-time polymerase chain reaction.Results: Using a luciferase reporter assay, we identified that gga-miR-20a-5p directly targeted interferon gamma receptor 2 (IFNGR2), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase kinase kinase 5 (MAP3K5), and mitogen-activated protein kinase kinase kinase 14 (MAP3K14). Moreover, the exosome-mediated delivery of gga-miR-20a-5p successfully repressed the expression of IFNGR2, MAPK1, MAP3K5, and MAP3K14 in HD11 cells. The expressions of interferon-stimulated genes (MX dynamin like GTPase 1 [MX1], eukaryotic translation initiation factor 2A [EIF2A], and oligoadenylate synthase-like [OASL]) and proinflammatory cytokines (interferon-gamma [IFNG], interleukin-1 beta [IL1B], and tumor necrosis factor-alpha [TNFA]) were also downregulated by exosomal miR-20a-5p. In addition, the proliferation of HD11 cells was increased by exosomal miR-20a-5p.Conclusion: The exosome-mediated delivery of gga-miR-20a-5p regulated immune responses by controlling the MAPK and apoptotic signaling pathways. Furthermore, we expected that exosomal miR-20a-5p could maintain immune homeostasis against highly pathogenic avian influenza virus H5N1 infection by regulating the expression of proinflammatory cytokines and cell death.

The development of teaching methods that support integrated learning and build student confidence is a priority. An audience response system was used to engage early year medical students in large classes in preparation for teaching within a hospital setting. Results showed high levels of student engagement and a greater appreciation for the link between theory and practice. This study describes a simple, active, and integrated method of learning that improves student confidence in clinical reasoning.

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease globally, which is defined as an excess accumulation of fat caused by the imbalance of lipogenesis and lipid catabolism. Recently, increasing evidence suggests that peroxiredoxin 6 (PRDX6) is involved in the pathogenesis and progression of NAFLD. However, little is known regarding its role in liver lipid catabolism.We found that PRDX6 level was significantly increased in liver tissues after high-fat diet (HFD) treatment. PRDX6 knockout (KO) exacerbated HFD-induced hepatic steatosis. PRDX6 KO did not affect mRNA and protein levels of peroxisome proliferator-activated receptor alphaα (PPARα). However, PRDX6 KO decreased the mRNA and protein levels of carnitine palmitoyltransferase-1alpha (CPT-1α) and acyl-CoA oxidase 1 (ACOX1), the target genes of PPARα. PRDX6 KO also did not activate AMPKα/PGC-1α, the upstream signal of PPARα. However, PRDX6 KO reduces the levels of PPARα activators, the oxidized fatty acids (9 and 13-hydroxyoctadecadienoic acid) in HFD rats. More interestingly, PRDX6 promoted the production of oxidized fatty acids by hydrolyzing oxidized low-density lipoprotein (Ox-LDL), which depends on its phospholipase A2 (PLA2) activity. PRDX6 mutation on its PLA2 and its competitive phospholipase inhibitor inhibited the production of the oxidized fatty acids as well as the activation of PPARα. Furthermore, PRDX6 overexpression enhanced the transcriptional activation of PPARα.This study elucidates for the first time the role of PLA2 enzyme activity of PRDX6 in fatty acid oxidation and reveals a novel mechanism of PRDX6 involved in liver steatosis.

This article will 1) outline prelicensure nursing and exercise sciences student perspective examinations of the 2011 Michael-McFarland (M-M 2011) core principles in physiology through an anonymous online survey, and 2) model an updated approach largely based on qualitative survey responses from first-year nursing students. As a result, the author presents a “Top Ten” List of Core Principles of Human Physiology for Undergraduate Health Professions students.