Conduction of vasodilator signals plays an important role in the coordination of blood flow distribution. It is thought that endothelium-dependent vasodilation’s are conducted by electrotonic spread through gap junctions of the endothelial cell hyperpolarization generated at the stimulation site. However, nitric oxide (NO) was found to reduce the propagation of vasodilator responses, suggesting the participation of this signaling molecule in the mechanism of conduction. Mouse cremasteric arterioles were stimulated through micro-application of ACh or the NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and the responses were evaluated at the stimulation site (local) and at sites located 500, 1000 and 2000 µm upstream from the vessel segment stimulated with ACh. The response to ACh spread along the entire vessel showing a slight decay and, in contrast, the dilation evoked by SNAP was restricted to the stimulation site, independently of the magnitude of the response. Blockade of NO production with 100 µM NG-nitro-L-arginine methyl ester (L-NAME) or 100 µM NG-nitro-L-arginine (L-NA) reduced the resting diameter by 10-12% (n=4), but the combination of two NO blockers enhanced the basal vasoconstrictor tone by ~38% (n=5) and inhibited the local (~45%) and conducted (~20-35%) responses to ACh. Interestingly, the conduction of ACh-induced vasodilation increased along the vessel length in the presence of L-NAME and L-NA. In addition, endothelial cell hyperpolarization blockade exclusively at the stimulation site through microsuperfusion of tetraethylammonium inhibited the local vasodilation, but not the conduction of the response. These results indicate that ACh activates a NO-sensitive regenerative vasodilator mechanism that is coupled to the activation of NO production and endothelium-dependent hyperpolarization along the vessel length.

The ECM is composed of a considerable number of biochemically and structurally diverse con-stituents. ECM is a highly dynamic system that constantly receives and sends biological, chemical and mechanical signals. Several studies suggest that mechanical signals derived from the extra-cellular microenvironment regulate skin regeneration and wound healing. We evaluated effects of a mixture of biomolecules extracted and purified from bovine colostrum on restoring the me-chanical properties of ECM. Test measuring collagen contraction showed a significant difference in contraction activation in samples treated with the 2% colostrum derivative mixture compared to the control. The analysis of the supernatant showed an inhibition of metalloproteinase-2 ex-pression and an increase in collagen secretion by fibroblasts in treatment samples. Our hypothesis is that the molecules extracted and purified from bovine colostrum restore the ECM environment qualitative and quantitative characteristics, thus guaranteeing through a mechanical action the restoration of the wound due to the transduction of the signal activated by the integrins.

Veterinary science has benefitted from technological advancements in the past and will hopefully continue to do so, especially in the field of equine gait analysis. There is a need for rapid and easy to use technology that is accurate and portable, but at the same time is also readily interpretable. This manuscript presents two new approaches to equine gait analysis, both of which are commer-cial devices. The use of Acoustic MyoGraphy (AMG) has been proven in the field of muscle func-tion and performance as well as ligament health, but it can also provide details concerning gait when placed on the wall of the hoof of a horse. The TendibootTM system is a limb focused unit that can be easily attached, activated and used in a Veterinary clinic setting, rapidly providing gait details for equine diagnostic purposes. In conclusion this manuscript provides an insight into gait parameters from recent research trials that are novel and challenge current thinking.

The Characteristics of the cardiac muscle cell are described as a rod-shaped structure, single nu-cleus, and intercalated discs which make the heart’s action practical for enhancing contraction ef-ficiency. Mitochondria within these cells are vital for ATP synthesis, redox balance, calcium ho-meostasis, and lipid synthesis. The crucial role of Hsp60 is in protein folding and immune re-sponses; Hsp60 is a mitochondrial chaperonin, and its expression rises when the heart is under a stress condition like myocardial infarction and heart failure. This review has tried to deeply un-derstand the structural resemblance between cardiac and skeletal muscle cells, the amplitude number of mitochondria, its roles in cardiomyocytes, and the polyhedral functions of Hsp60. In this review, by investigating various articles, we brighten up Hsp60's distribution within cells, its association with apoptosis, and its action as a Damage Associated Molecular Pattern (DAMP), interacting with Toll-like receptors to modulate immune responses. Cardiac remodeling and failure are linked to cardiac-specific micro-RNAs whose expression may be affected by dysregu-lation of Hsp60. In conclusion, targeting mitochondrial function and Hsp60 expression may be of therapeutic potential for heart diseases.

The marathon sport events and those who participate in these have grown over the last years reflecting notably an augmentation of women and master runners participation. The aim of the present narrative review was to briefly present the results of studies on anthropometric, physiological and training characteristics, as well as predictors of performance, in marathon runners. It was observed that performance was better in runners with small body weight, body mass index, body fat percentage, and rate of endomorphy. With regards to physiology, an increased maximal oxygen uptake, anaerobic threshold, and improved running economy could result in faster race time. The training variables that could predict performance involved weekly training volume (distance) and intensity (running speed), as well as history of training (years). A combination of these three broad categories of characteristics may offer an approximate estimation of the race speed considering that other aspects (e.g., nutrition, biomechanic and motivation) influence race performance, too. In summary, the findings of the present study provided an overview of anthropometric, physiological and training characteristics associated with marathon race time; thus, an optimization of any of these characteristics would be expected to improve race time.

Background: The cumulative exposure of UV radiation can result in dangerous consequences such as skin burns, photoaging, and skin cancer, hence the importance of using photoprotective formulations. Currently, the formulations seek to be more efficient, innovative and reach a wider audience. Many sunscreens are vegan, and have antioxidant substances to ensure additional photochemoprotective action. To evaluate biological, functional, and mechanical characteristics of them on the skin, biometric and rheologic methods can be used. Objective: Evaluate biophysical, rheological and sensorial parameters of Face Care Facial Moisturizing Cream® (P1) and a vegan formulation (P2) by in vitro and in vivo tests. Methods: A UV scan experiment was performed covering the range of 250 to 400 nm. Sun Protection Factor (SPF) was evaluated by Mansur method. Rheological profiles were obtained using a MARS II (Haake®) controlled shear stress and gradient rheometer. Biophysical parameters were analyzed: skin sebum content, hydration level, transepidermal water loss, erythema and melanin level, skin color, and skin pH. The acceptance profile of the formulations by the volunteers was determined using a 9-point hedonic scale and a 5-point purchase intention test. Results: The formulations effectively absorbed light covering the UV radiation spectrum from UVA to UVB. The SPF of P1 was 25.21 and of P2 was 12.10 by in vitro tests. They had also pseudoplastic and thixotropic behavior, it can contribute to better spreadability and to form a protective film. Biometric tests showed an increase in hydration and skin sebum, decreased erythema, and maintenance of skin pH after application of both formulations. The products also had similarly good acceptance and purchase intention by the volunteers. Conclusion: The comparation of a commercialized product and a vegan test version showed very similar rheological and great acceptance profiles. Therefore, the vegan formulation is a good alternative to reach a different market.

The anatomy of mature vertebrate hearts is marked by a looped design, which is roughly characterized by two components: (1), s-shaped (sigmoid) routing of the cardiac flow path(s), and (2,) bilaterally asymmetric (chiral) routing of the cardiac flow path(s). The looped heart design is regarded as a phylogenetically conserved feature among vertebrates and is thought to represent a significant determinant of the cardiac pumping function. It evolves during the embryonic period of development by a morphogenetic process called “cardiac looping”. During the past decades, remarkable progress has been made in the uncovering of the genetic, molecular, and biophysical factors contributing to cardiac looping. Thereby, a special focus was directed on the evolution of a bilaterally asymmetric (chiral) heart configuration, which is said to play a central role in the determination of the alignments and separations of the pulmonary and systemic flow paths in the multi-chambered hearts of tetrapods. In contrast to the recent progress made in uncovering of the biological driver of cardiac looping, our present knowledge about the functional consequences of cardiac looping is at an immature state. This article provides an overview and discussion of the currently available information about the looped design of vertebrate hearts and its functional implications.

Acomys cahirinus is a unique Rodentia species with several distinctive physiological traits, such as precocial development and remarkable regenerative abilities. These characteristics render A. cahirinus increasingly valuable for regenerative and developmental physiology studies. Despite this, the structure and postnatal development of the central nervous system in A. cahirinus have been inadequately explored, with only sporadic data available. This study is the first in a series of papers addressing these gaps. Our first objective was to characterize the structure of the main visual thalamic region, the lateral geniculate complex, using several neuronal markers (including Ca2+-binding proteins, glutamic acid decarboxylase enzyme, and non-phosphorylated domains of heavy-chain neurofilaments) to label populations of principal neurons and interneurons in adult and newborn A. cahirinus. As typically found in other rodents, we identified three subdivisions in the geniculate complex: the dorsal and ventral geniculate nuclei (LGNd and LGNv) and the intergeniculate leaflet (IGL). Additionally, we characterized internal diversity in the LGN nuclei. The "shell" and "core" regions of the LGNd were identified using calretinin in adults and newborns. In adults, the inner and outer parts of the LGNv were identified using calbindin, calretinin, parvalbumin, GAD67, and SMI-32, whereas in newborns, calretinin and SMI-32 were employed for this purpose. Our findings revealed more pronounced developmental changes in LGNd compared to LGNv and IGL, suggesting that LGNd is less mature at birth and more influenced by visual experience.

Surfing is a growing, high participation recreational and competitive activity. It is relatively unique being performed on, in, and through water with a range of temperatures. In other sports, warm-up and heat retention have proved useful at augmenting performance and ameliorating injury risk. Little work has been done examining this in surfing. The purpose of this work was to measure thermal profiles in surfers with and without warm-up and passive heat retention, and secondarily to assess any potential influence on free surfing. A repeated measures pre- and post- design was adopted whereby participants surfed in an artificial wave pool following an active warm-up combined with passive heat retention (experimental condition), and after no warm-up (control). Core body temperature was measured both occasions. Our results showed a clear advantage to body temperature for the experimental condition versus control. Both groups showed a warm-up effect in the water itself, presumably due to further activity (e.g. paddling) and wetsuit properties. Finally, performance trended to being superior following warm-up. We conclude, body warmth in surfers may be facilitated by an active warm-up and passive heat retention. In free surfing this is associated with a trend towards better performance; it may also reduce injury risk.

Student-centered active learning (SCAL) shifts the focus from the teacher to the student. Implementing SCAL requires the development of new forms of assessment beyond memorization and comprehension. This paper aims to demonstrate the effectiveness of SCAL by analyzing student performance at different cognitive levels. In flipped classrooms, students completed tasks with varying cognitive demands. The tests measured knowledge (level 1), comprehension (level 2), application (level 3) and analysis (level 4). This approach to assessment assesses not only the acquisition of content, but also skills that are critical to a health science student's future career. The results of expository learning were compared with student-centered collaborative learning in the Anatomy and Embryology I course over three academic years. Student opinions were collected through 326 anonymous Wooclap® surveys. No differences in performance were found for low cognitive level questions. However, SCAL significantly improved performance on higher cognitive level questions that required problem solving and application of knowledge. Despite the benefits of SCAL, it requires more effort from both teachers and students. The current assessment system, which measures the quality of teaching, penalizes this effort and requires teachers to believe strongly in the effectiveness of SCAL.

Understanding pollen and ovule fertility as factors influencing fruit and seed set is important in cassava breeding. Red light (RL) and plant growth regulators (PGRs) have been used to induce or enhance flowering and fruit set in cassava without any reference to effects on pollen viability or ovule fertilizability. This study investigated effects of field-applied RL and PGR on pollen viability and ovule fertilizability. Panels of cassava genotypes, with early or moderate flowering responses were used. RL was administered from dusk to dawn. Two PGRs, a cytokinin (6-benzyl adenine, BA) and an anti‑ethylene (silver thiosulphate, STS) were applied. Pollen viability was assessed basing on pollen grain diameter, in vitro stainability, in vivo germinability, ovule fertilizability and ploidy level. Treating flowers with RL led to increased pollen diameter from 143.6 to 148.5µm, stainability from 82.9 to 93.0%, ovule fertilizability from 52.0 to 56.9% in treated female flowers and 47.7 to 64.3% on using pollen from treated male flowers. Fruit set increased from 51.5 to 71.8% in RL-treated female flowers and from 53.7 to 71.1% when pollen from RL-treated male flowers was used. Seed set followed a trend similar to that of fruit set. Ploidy level of pollen from RL-treated flowers increased slightly and positively correlated with pollen diameter (R2 = 0.09*), ovule fertilization (R2 = 0.20*), fruit (R2 = 0.59*) and seed set (R2 = 0.60*); but negatively correlated with pollen stainability. Treating flowers with PGR did not affect pollen diameter and stainability, but increased ovule fertilizability from 42.9 to 64.9% and fruit set from 23.2 to 51.9% in treated female flowers and 31.3 to 54.7% when pollen from treated male flowers was used. Application of combined BA+STS on male flowers caused the highest ovule fertilizability, fruit and seed set efficiency, though this varied among study genotypes. These results show that RL and PGR treatment of flowers increases pollen viability and ovule fertilizability. This is important for planning pollination strategies in cassava breeding programmes.

Aim: The aim of this study is to evaluate the possibility of discriminating between the two sexes through the simultaneous use of cheiloscopy and palatine rugoscopy. Materials and methods: 80 palate and lip impressions (40 male and 40 female) were analyzed. The palate impressions were acquired using both analogue and digital methods. The lip impres-sions were first acquired analogically and then scanned. The morphology of the palatine rugae in the palate impressions was analyzed, with the exclusion of segmental rugae. The lip prints were analyzed in sextants and the morphology of the lip wrinkles was evaluated. Results: Palatine rugoscopy shows that women have more curvy rugae than men and that men have more rugae on the left side than on the right. Cheiloscopy gave no statistically significant re-sults. Discussion: Palatine rugoscopy showed some differences between the sexes, however, these re-sults were not solid enough for reliable sex discrimination. Differences between the results of dif-ferent studies can be attributed to ethnic and methodological variations. Cheiloscopy, on the other hand, did not provide statistically significant results for sex discrimination. Conclusions: Given the scant results obtained from palatine rugoscopy and the lack of statisti-cally relevant results in cheiloscopy, together with a lack of concordance among the data found in literature, it is believed that it is not possible to discriminate between the two sexes by using the two methods contemporarily. Further research is needed.

It is desirable to upgrade previous evolutionary theories, which have remained incomplete and controversial for decades. Here we employ the concept of carbon-based entities (CBEs), which include methane, amino acids, proteins, organisms, and other entities containing relatively many carbon atoms. We deduce the driving force, mechanisms, steps, modes, tempos of CBE evolution, through integration of biology, physics, and chemistry using logics for complex issues. We hence establish the Carbon-Based Evolutionary Theory (CBET). The CBET suggests that evolution is the increase in hierarchy, diversity, fitness of CBEs under natural selection and driven by thermodynamics due to the chemical effect of the thermodynamic features of the Earth on CBEs. It provides better explanations for life origin, macroevolution events, natural selection, sympatric speciation, and evolution tempos than previous evolutionary theories. It reveals the evolutionary basis of multiple important social notions, including diversity, collaboration, altruism, obeying rules, and proper increase in freedom. It refutes some wrong notions in thermodynamics, including negative entropy (negentropy) and that biological order is equal to thermodynamic order, which have misled many people. The CBET is supported by its deduction and application. It could be a rare bridge linking laws of thermodynamics, evolution of life, and development of human society, and could have great significance in various sciences.

SIBO is a pathology of the small intestine and may predispose individuals to a range of nutritional deficiencies. Very little is known whether specific subtypes of SIBO, such as hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane –dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p<0.001), low serum ferritin (p=0.001) and low fiber intake (p=0.001). The M+ group was correlated with high serum folic acid (p=0.002) and low intakes of fiber (p=0.001) and lactose (p=0.002). The H+ group was associated with low lactose intake (p=0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of deficiencies in the body. Conversely, specific dietary patterns may predispose to the development of a SIBO subtype. The assessment of nutritional status and diet, along with diagnosis of SIBO substype, are believed to be key components of SIBO therapy.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between stiff AA and reduced longitudinal strain and subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). A proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in-silico utilizing Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with A) Elastic AA; B) Stiff AA; and C) Stiff AA with free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that can abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of LV longitudinal strain are common in patients HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

A single-center, randomized, double-blind, placebo-controlled clinical trial with two arms was conducted in 71 healthy subjects suffering from sleep disturbances, which were treated with a dietary supplement based on an extract of Aloysia citrodora (or Lippia citriodora, lemon verbena) (n = 33) for 90 days. Subjects in the placebo group (n = 38) received capsules of microcrystalline and maltodextrin with the same organoleptic properties. Between-group significant differences in favor of the experimental group were found in the visual analogue scale (VAS) score rating sleep quality; overall score, sleep latency and sleep efficiency of the Pittsburg Sleep Quality Index (PSQI); and sleep latency, sleep efficiency, wakefulness after sleep onset and duration of awakening assessed by actigraphy. Plasma nocturnal melatonin levels also increased significantly in the experimental group. Changes in anthropometric parameters and physical activity levels were not found. This study shows that the administration of a dietary supplement comprised lemon verbena administered for 3 months was associated with a significant improvement of sleep quality as compared with placebo in a population of healthy subjects with sleep problems. Improvements were also apparent at the mid-study visit after 45 days of supplementation.

histology, the processing and staining of cells, tissues and organs to highlight contrast, visualize and analyze their microstructure under microscopy, encompasses a vast array of techniques used to confirm, refine, or refute the macroscopic findings in forensic investigations, for example in the case of autopsies. This review presents several applications of histological protocols, staining methods and techniques to case studies, with the aim of illustrating the established, current and potential applications of histological investigations to forensic sciences. The list of disciplines include anthropology, cytology, dendrochronology, diatomology, entomology, fiber analysis, palynology,human and veterinary pathology, taphonomy and thanatology.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

Plantar flexors (PF) spasticity is known to poorly correlate with active dorsiflexion (DF) impairment throughout the swing phase of hemiparetic gait. Spastic Cocontraction, instead, stemming from descending pathways, potentially misdirect antagonist PF activity opposing DF during swing. Electromyographic (EMG) recordings, while unable to differentiate between reflex-based and descending origins, may offer valuable insights into this distinction by exploring PF EMG activity after tibial nerve neurotomy (which eliminates PF spasticity). Eleven subjects with hemiparesis walking at comfortable velocity and 11 controls walking at comfortable and slow velocity, underwent kinematic and PF/DF EMG analysis. Five of the hemiparetic subjects underwent tibial neurotomy >1 year prior. We evaluated spasticity at rest (Tardieu scale), maximal ankle dorsiflexion, tibialis anterior agonist recruitment and gastrocnemius medialis and soleus cocontraction coefficients during swing. At slow velocity, controls (0.80±0.12 m/s) moved at a similar pace as hemiparetic subjects (0.73±0.37 m/s, NS). Hemiparetic subjects showed: (i) reduced ankle DF across swing (ii) increased PF cocontraction, including before any DF (iii) higher cocontraction despite absent spasticity in tibial neurotomy subjects (iv) higher tibialis anterior recruitment. Increased PF cocontraction occurs in the absence of spasticity or ankle DF despite higher agonist recruitment. Spastic cocontraction is a major factor limiting active DF at swing, unlike spasticity.

Background: According to EWGSOP2, the diagnosis of sarcopenia is confirmed when in addition to low muscle strength, low muscle quantity or quality is present. Echo intensity (EI) determined by muscle ultrasound (US) has been proposed as an efficient method for the assessment of muscle quality. The effect of changing various US parameter settings on EI remains unclear. Therefore, the aim of this study was to assess the differences between EI values obtained by adjusting parameter settings over their entire range in a sample of middle-aged healthy subjects. Methods: Thirty-two repeated US scans of rectus femoris (RF) and rectus abdominis (RA) muscles were taken in eight men and three women with a portable Mindray M7 premium US machine, working in an Extended field-of-view, B-Mode setup, equipped with a linear 5.0-10.0 MHz transducer. The following US parameters and settings were fixed: gain 60dB, depth 6.5cm, and frequency 10 MHz. Readily adjustable parameters were dynamic range (DR), gray map (GM), line density, persistence, and IClear. A default setting DR65 was chosen as the reference setting. For each of the parameters, the settings of one single parameter of interest was changed over its entire range following a standardized protocol. The EI values were calculated using the open-source software ImageJ. Repeated measures analyses were performed to evaluate the effect of parameter settings on EI. Linear interpolation was used to determine non-significant ranges across a given parameter. Results: For the RF muscle, the EI values were significantly different across DR (p<0.001), GM (p<0.001), and IClear (p<0.001). Post hoc analysis confirmed the differences within these three settings. Echo intensity values within the range of DR55 to DR80 were not significantly different. For the RA muscle, the EI values were significantly different across DR (p=0.004) and GM (p=0.030). Post hoc pairwise comparisons revealed no significant difference with the default setting, except for DR150 (p=0.042). Conclusion: We showed that EI values differ across the DR and GM range, especially in the RF. We suggest using a DR setting within its midrange to minimize the effect of machine setting-dependent factors on EI values. These findings reconfirm the need for standardization of ultrasound echo intensity settings when applied for diagnostic purposes of muscle quality.

Brain models present a viewpoint on the fundamental structural components of the brain and their mutual organization, generally relative to a particular concept of the brain axis. A model may be based on adult brain structure or on developmental morphogenetic aspects. Brain models usually have functional implications, depending on which functional properties derive from the postulated organization. This essay examines the present scenario about brain models, emphasizing the contrast between columnar or other longitudinal models and transverse subdivisional neuromeric models. In each case, the main functional implications and apparent problems are explored and commented. Particular attention is given to the modern molecularly based ‘prosomeric model’, which postulates a set of 20 transverse prosomeres as the developmental units that serve to construct all the cerebral parts and the particular typology of many different neuronal populations within the forebrain and the hindbrain, plus a number of additional spinal cord units. These metameric developmental units (serially repeated, but with unique molecular profiles) confer to this model remarkable functional properties based mainly on its multiplicity and modularity. Many important brain functions can be decomposed into subfunctions attended to by combined sets of neuronal elements derived from different neuromeres. Each neuromere may participate in multiple functions. Most aspects related to creation of precise order in neural connections (axonal navigation and synaptogenesis) and function is due to the influence of neuromeric anteroposterior and dorsoventral positional information. Research on neuromeric functionality aspects is increasing significantly in recent times.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. Meanwhile, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems between different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: on the one hand, there is the cardiovascular, circulatory system, and on the other hand, the lymphatic vascular system, in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the “fish lymphatics” are a specialised subcompartment of the cardiovascular system, called the “secondary vascular system” (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or its entirety from an embryonic lymphatic vascular system by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish do feature more than the five VEGF genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including the phylogenetic knowledge.

Myocardial ischemia/reperfusion injury (I/R) and the resulting heart failure is one of the main causes of mortality and morbidity worldwide. Camphene has been shown to have anti-inflammatory and hypolipidemic properties, however, its role in the protection of the heart from ischemia and reperfusion has not been investigated. The cardioprotective role of camphene and the mechanism that mediates its action against I/R injury was evaluated in the present study. A single dose of camphene was administered in adult rats prior to ex vivo I/R induction. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and cardiomyocyte injury was assessed by determining the release of lactate dehydrogenase (LDH) enzyme. Camphene pretreatment provided significant protection reducing myocardial infarct size and cell death after I/R. The effect was correlated with the activation of antioxidant defense mechanisms, namely CAT, MnSOD, GPx and GR, and reduction of oxidative stress as evidenced by determination of protein carbonylation and GSH/GSSG ratio in cardiomyocytes. The results suggest that camphene can protect the heart against I/R injury by maintaining redox homeostasis and can hold therapeutic potential for mitigating the detrimental effects of I/R in the heart.

Abstract：To investigate the effects of feeding the Lincomycin and faecal bacterial on weaning stress in Tibetan piglets, we divided the weaned Tibetan piglets at 30 days of age into four groups. We measured growth performance, blood physiological indexes, and metabolomics. The results showed that the Ant, Tib, and Fec groups significantly reduced the ratio of diarrhoea to feed/weight (F/G) and increased the average daily gain (ADG) compared to the Nor group (p < 0.01). The Nor group had significantly lower leukocyte counts, hemoglobin levels, and erythrocyte counts compared to the other three groups on 21d (p < 0.05). These physiological indexes tended to stabilize on 42d. We found that there were beneficial metabolites and metabolic pathways for gastrointestinal function. Specifically, the porphyrin metabolic pathway was elevated in the Ant group, and the tryptophan metabolic pathway was significantly elevated in the Tib and Fec groups compared to the Nor group (p < 0.05). In conclusion, adding faecal bacterial supernatant and fifteen-flavour black pills of Tibetan medicine to the feed reduced the rate of diarrhoea and improved the growth performance of piglets. Moreover, it had an effect on microorganisms and their metabolites and pathways in the gastrointestinal tract of the animals, which might be the main reason for influencing the diarrhoea rate of weaned Tibetan piglets and the growth and development of the piglets. This study provides a new approach for anti-stress applications in weaned Tibetan piglets and the development of substitute anti-products.

Abstract: The septum pellucidum is a thin, translucent double-membrane structure located between the anterior horns of the lateral ventricles. This mini-review explores the gross and radiological anatomy, variations, and clinical significance of the septum pellucidum. The article elaborates on the different types of variations, including cavum septum pellucidum (CSP), cavum vergae (CV), and cavum veli interpositi (CVI). The CSP is a fluid-filled pocket located within the two leaflets of the SP. It forms during fetal development and gradually obliterates before birth. However, the fusion may be prolonged or persist into adulthood in some individuals. The CV is formed when the two commissural plates fail to fuse completely during foetal development. When associated with CSP, the CV is collectively known as the cavum septum pellucidum et vergae (CSPV). However, the isolated CV is rare. The CVI is a CSF-filled space between two tela choroidea layers and communicates with the quadrigeminal cistern, superior to the pineal gland. This article discusses the radiological features of these variations using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT). Ultrasonography is particularly useful for evaluating the SP in fetuses and infants, while MRI and CT scans provide detailed visualisation of the SP and its variations. The SP has the potential to be associated with cerebral anomalies, hydrocephalus, mental disorders, and neurological symptoms. Knowing the related anatomy and detecting variations using imaging modalities are crucial for accurately diagnosing and managing these conditions.

The purpose of the present study was to develop an experimental model for studying of the intra-articular knee movements depending on the work of the knee joint and applied muscle groups in isometric stretching conditions with different tens. The experimental procedure includes ultrasound examination of a knee joint after isometric stretching of healthy men (n=32). The changes in millimeters of the distances between the femur and tibia were measured with ultrasound sonographer at three stages. The first stage was performed on ten (n=10) healthy men at five different sitting and upright positions. In the second and third experimental model stages the lower limbs loading was on 22 participants. Our hypothesis which was confirmed, was that as a result of increasing extraloads on the participants back (2, 5, 10, 15, 17, 20 kg), a intra-articular decrease in the femur-tibia cartilage surface distance wiil be observed. The accuracy of the created experimental model was improved over its three stages from 30% to 9%. Quantitative model data can help to create a mathematical model for the mechanical effects during deformation of the knee joint bone cartilage, as well as to outlines the some future tasks: increasing loading weights; enlarge participant groups; comparison men and women; healthy and pathology comparison.

On the thirty-fifth anniversary of the first description of O2-sensitive K+ channels in the carotid body chemoreceptors [1], O2 sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K+ channel subtype(s) responsible for O2 sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O2 sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O2 levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility, and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review we will focus on the mechanisms of physiological oxygen chemotransduction by PO2-dependent K+ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field.

When the skin is afflicted by disease such as cancer, these essential functions are disrupted, putting the entire person at risk. While the American Cancer Society lists 6 major cancer types, the National Institute of Arthritis and Musculoskeletal and Skin Diseases identifies 13 significant benign skin disorders, reflecting the diversity of skin conditions in dermatology. This topical review aims to provide an overview of the pathophysiology of these major skin cancers and disorders and summarize conventional diagnostic methods and current treatment approaches.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

The purpose of the present study was to investigate the effect of post-activation performance enhancement (PAPE) induced by eccentric half-squat exercise on vertical jump performance in male jumpers. The jumping height, peak power, and work were measured and evaluated in twenty male jumpers. Participants performed five eccentric half-squats at 85% of their one-repetition maximum (1 RM), with a knee angle below 90°, followed by immediate and 2min delayed jump assessments using Squat Jump (SJ) and Countermovement Jump (CMJ) tests. Results showed that this specific PAPE protocol did not significantly improve jump performance for both SJ and CMJ tests. Factors such as stimulus specificity, rest intervals, muscle length, and the balance between potentiation and fatigue may explain these results. The study highlights the complexity of PAPE responses and suggests that a single set of eccentric squats with a short rest may not improve jump performance in male jumpers. Further research is required to optimize the interplay between conditioning stimulus and rest periods to maximize PAPE effects in athletic performance enhancement.

The carotid body is a major peripheral chemoreceptor that senses changes in arterial blood oxygen, carbon dioxide, and pH, what is important for regulation of breathing and cardiovascular function. The mechanisms by which the carotid body senses O2 and CO2 are well known; conversely, the mechanisms by which it senses pH variations are almost unknown. Here we used immunohistochemistry to investigate how the human carotid body contributes to the detection acidosis analyzing whether it expresses acid-sensing ion channels (ASIC) ion channels, and to know if these channels are in the cells chemosensory glomic cells or in the afferent nerves. ASIC1, ASIC2 and ASIC3, and to a much lesser extent ASIC4, immunoreactivity was detected in subpopulations of type I glomus cells, as well as in the nerves of the carotid body. In addition, immunoreactivity was found for all ASIC subunits in neurons of the petrosal and superior cervical sympathetic ganglia, where afferent and efferent neurons are located, respectively, innervating the carotid body. This study reports for the fist time the occurrence of ASIC proteins in the human carotid body, demonstrating that they are present in glomus chemosensory cells (ASIC1 &lt; ASIC2 &gt; ASIC3 &gt; ASIC4) and nerves, presumably both afferent an efferent supplying the organ. These results suggest that the detection of acidosis by the carotid body can be mediated by ASIC ion channels present in the type I glomus cells or directly by sensory nerve fibers.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The confluence of the maternal and fetal circulations occurs at the placenta, which is the first or-gan to develop. Placental pathology can provide an accurate diagnosis of inflammation inside the amniotic sac. The pathological alterations of preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospec-tive study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department in our institution so that grading and staging of any evident inflammatory response could be evaluated and associated with baby gender. Eighty-four full-term placentas were col-lected after delivery. Placentas that were considered normal and were not sent to the histo-pathology department were taken. Morphological examination of fresh placenta was conducted. Full thicknesses of placenta samples were taken from central and marginal regions of placental disc. Fetal and maternal inflammatory responses syndrome were assessed. Villitis of unknown etiology (VUE) and chronic deciduitis also were evaluated in the placenta. Immunohistochemis-try (IHC) was also performed to evaluate patterns of inflammation in the placenta using an-ti-CD8 and anti-CD68 antibodies. The correlation between the silent pathologies and clinical complications or involvement of developing fetal inflammatory response syndrome was meas-ured. In this study, seventeen (20%) maternal inflammatory samples and ten (12%) fetal inflam-matory samples showed inflammatory responses. The frequency of chronic deciduitis and villi-tis of unknown etiology was more remarkable among Saudi pregnant women than the previ-ously reported findings in the literature of placental pathology. The prevalence of fetal and ma-ternal inflammatory response was greater in the placentas of mothers of males than in placentas of female mothers. Grading placental inflammation usually predict the degree of maternal an-ti-fetal cellular rejection. Fetal inflammatory response syndrome usually goes unnoticed in Sau-di Arabia. There are differences in the inflammatory response in the placenta based on the sex of the newborn. Increasing the number of placental samples that must be sent for microscopic in-spection may be preferable due to their significance in identifying the causes of chronic disor-ders.

The need to carry different items, which become an extra load, is a characteristic of trail running. The aim of this study is to determine physiological-metabolic changes produced by running with extra load. Four male well-trained trail runners completed three treadmill maximal metabolic tests carrying different loads (0% (L0), 5% (L5), and 10% (L10) of their body mass) in a weighted vest. Gasses exchange was monitored to assess ventilatory thresholds 1 (VT1), and 2 (VT2), zone of maximal fat oxidation, and peak oxygen consumption (VO2peak). Heart rate (HR), power and velocity (V) were tracked for comparing their behavior. A repeated measures ANOVA showed significant differences in V (p&lt;.001; ηp2= 0.910) as a limitation for reaching peak velocity (Vpeak) with L10 respect to L0 (p=0.001), and L5 (p=0.011). Power expression showed differences (p=0.068; ηp2= 0.592). It tended to be greater with L10 than L0 (p=0.057), despite achieving lower V. VT2 tended to occur at different %VO2peak (p=0.069; ηp2= 0.591). L5 VT2 was reached at higher %VO2peak than L0 (p=0.062), and L10 (p=0.071). ANOVA also showed a tendency to signification for V at this point (p= 0.098; ηp2= 0.538). In conclusion, L10 seems to limit Vpeak while L5 may delay VT2 expression.

The phototransduction cascade allows the photoreceptor to avoid saturation and retain the ability to detect light over a very wide range of intensities. The main second messenger of the cascade is cGMP and the main regulatory mechanism is calcium feedback, however some experimental data suggest that cAMP may also be involved in the regulation of the phototransduction cascade. For this to be the case, cAMP would have to change on a time scale of seconds. Currently, there are no data on the dynamics of changes in intracellular cAMP levels on this time scale, largely due to the specificity of the sensory modality of photoreceptors, where it is practically impossible to use conventional experimental approaches based on fluorescence methods. In the present work, we used the method of rapid cryofixation of retinal samples after light stimulation and subsequent isolation of outer segment preparations. Levels of cAMP were measured using highly sensitive metabolomics approaches. PKA activity was also measured in these samples by Western blot. We show that when illuminated with near-saturating but still moderate light, cAMP levels rise transiently within approximately the first second and then return to pre-stimulus levels. The increase in cAMP activates PKA, leading to phosphorylation of PKA-specific substrates in frog retinal outer segments.

Life on Earth evolved to accommodate the biochemical and biophysical boundary conditions of the planet millions of years ago. The former includes nutrients, water, and ability to synthesize other needed chemicals. The latter include the 1 g gravity of the planet, radiation, and the geomagnetic field (GMF)of the planet. How complex life forms have accommodated the GMF is not known in detail considering that Homo sapiens evolved a neuro system and a cardiovascular system that develops electromagnetic fields as part of their functioning. In addition, many proteins and physiologic processes utilize Fe ions, an ion that exhibits magnetic properties. Thus, complex organisms such as current humans generate magnetic fields, contain significant quantities of the Fe ion, and also respond to exogenous-supplied static and electromagnetic fields. Whether humans can store information in self-generated magnetic fields remains to be determined. Given the current body of literature, it remains somewhat unclear how Homo sapiens use exogenous magnetic fields to regulate function, and what can happen if the boundary condition of the GMF of Earth is no longer exerting an effect. Proposed deep space flights to destinations such as Mars will provide some insights as space flight could not have been anticipated by evolution. The results of such space flight “experiments” will provide new insights in the role of magnetic fields on human functioning. The outcomes may also have implications for those on Earth as magnetic field influences may play a role in developmental conditions such as autism and senescence-associated conditions such as dementia when integration of the biological and biophysical aspects of humans of humans are required for effective functioning. This review will discuss the involvement of magnetic fields on various normal and disturbed processes in humans while on Earth and then further discuss potential outcomes when the GMF is no longer available to impact host systems. Thus, the GMF of the Earth has been present throughout evolution but details of its role in human functions still remain to be elucidated.

The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent regulators of muscle mass, with a decrease in mechanical loading leading to a decrease in muscle mass. This concept has been supported by a plethora of of human- and animal-based studies during the last 100 years and has resulted in the commonly used term of “disuse atrophy”. These same studies have also provided a great deal of insight into the structural adaptations that mediate disuse-induced atrophy. For instance, disuse results in radial atrophy of fascicles, and this is driven, at least in part, by radial atrophy of the muscle fibers. However, the ultrastructural adaptations that mediate these changes remain far from defined. Indeed, even the most basic questions, such as whether the radial atrophy of muscle fibers is driven by the radial atrophy of myofibrils and/or myofibril hypoplasia, have yet to be answered. In this review, we thoroughly summarize what is known about the macroscopic, microscopic, and ultrastructural adaptations that mediated disuse-induced atrophy and highlight some of the major gaps in knowledge that need to be filled.

The Atlantic puffin is a medium-sized seabird with black and white plumage and orange feet. It is distributed mainly along the northern Atlantic Ocean and due, among other reasons, to human activities, it is in a threatened situation and classified as a vulnerable species according to the International Union of Conservation of Nature (IUCN). In this study, we used a total of 20 carcasses of juvenile Atlantic puffins to perform anatomical cross sections and magnetic resonance images. Thus, an adequate description of the head was made, providing valuable information that could be helpful as a diagnostic tool for veterinary clinicians, who increasingly treat these birds in zoos, rehabilitation centers and even in the wild.

Prolonged application (&gt; 20 minutes) of LV on muscles or tendons is known to reduce maximal isometric strength. However, the effect of short vibration durations (&lt; 6 minutes) is still unknown. In fourteen participants, the changes in maximal voluntary isometric contraction (MVIC) were measured after 1, 3, and 6 minutes of rest (CONT) or local vibration (LV) over the quadricipital tendon (frequency: 100 Hz; amplitude: 0.5mm). Before and after each condition, the amplitude of the twitch induced by a 100 Hz potentiated electrical doublet (PDPOT), relative electromyographic activity of the vastus medialis and rectus femoris muscle during the MVIC (RMSMVIC.M-1), the torque developed 50 ms after the onset of contraction (T50) and the voluntary activation level (VAL) were evaluated. None of the three LV durations significantly changed MVIC compared with the control condition (p = .379). Indices of central (i.e., VAL, T50, RMSMVIC.M-1) and peripheral (PDPOT) fatigue were unaffected (p &gt; .147). In conclusion, a short duration of LV (&lt;6min) on a voluminous muscle group, does not impair maximal force production nor induce any central or peripherical fatigue.

Regulated deficit irrigation (RDI) strategies aim to improve water usage without reducing yield. Generally, irrigation strategy effectiveness is measured as fruit yield, with little consideration of fruit quality. As water deficit and increased plant cell sclerification often associated, this study explores the effect of RDI on pear fruit stone cells, a crucial factor affecting flesh texture. The presence, distribution and development of pear fruit stone cells under RDI and full irrigation are compared using Pyrus communis L. cv. Barlett trees, employing recently developed microscope image analysis technology. The Control treatment was maintained under non-stress conditions, while the RDI treatment received an average of 15% of Control water during the latter part of Stage I fruit development. Observations at the end of Stage I and at harvest showed no effect on stone cell presence under the tested RDI strategy. Relative area of stone cells within the flesh was greater at Stage I than at harvest, as stone cell expansion occurred early in development while the (unsclerified) parenchyma cells, dominant component of the fruit flesh, expanded until harvest. Stone cell cluster density was higher near the fruit core than in the cortex center and exterior. These initial results suggest that well-planned RDI strategies will generally not affect pear fruit stone cell content and thus, textural quality. Microscope image analysis supported results from previously used analytical techniques, principally chemical, while providing a tool for better understanding the process and timing of stone cell differentiation and thus testing the factors involved.

Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the sample size to detect the differences in the post-operative complications, and surgical and functional outcomes between patients who underwent laparoscopically assisted subtotal colectomy with and without SRA preservation. We conducted a retrospective single-center analysis of patients with STC who underwent laparoscopically assisted subtotal colectomy between 2016 and 2020. The diagnosis of STC was based on the colonic transit and anal functional tests, and barium enema to exclude secondary causes. Patients were divided into group A that underwent surgery with SRA preservation, and group B that underwent ligation of the SRA during surgery. Outcome assessments for both groups included the incidence of anastomotic breakdown, intraoperative complications, length of hospital stay, estimated blood loss, time to first flatus, and complications. Propensity-score matching allocated 34 patients to groups A and B each. Postoperative bowel function, including time to first flatus, stool, and oral intake, recovered better in group A than that in group B. Anastomotic leakage, a significant postoperative complication, was less frequent in patients with SRA preservation. Preservation of the SRA in patients undergoing laparoscopically assisted subtotal colectomy with ileorectal anastomosis for STC is associated with favorable postoperative bowel function recovery and lower anastomotic leakage rates.

Abstract: The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may considered as the 1st barrier of a tripartite blood-brain barrier (BBB) consisting of 1) ecGCx; 2) BECs; (3) extravascular compartment of pericytes, extracellular matrix, and perivascular astrocytes, Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally-derived leukocytes into the perivascular spaces (PVS) to result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the 5th review of a series quintet that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are progressively being regarded as a marker of cerebrovascular and neurodegenerative pathology.

Transcutaneous electrical stimulation of the spinal cord is used to restore locomotion and body weight support in patients with severe motor disorders. We studied effects of this non-invasive stimulation on postural control in healthy subjects. Stimulation at the L1-L2 vertebrae was performed to activate the extensor muscles of the lower limbs. Because postural regulation depends on the cognitive style, the effects of the stimulation were analyzed separately in field-dependent (FD) and field-independent (FI) participants. During the study young adults (N=16, half FD and half FI participants, all right dominant leg) stood on a force platform in a soundproof chamber with their eyes closed. Stimulation was applied in the midline between the L1-L2 vertebrae or over the left or right dorsal roots of the spinal cord; under control condition there was no stimulation. Stimulation destabilized posture in healthy subjects, whereas patients with movement disorders usually showed an improvement in postural control. In FD participants, left dorsal root and midline stimulation increased several postural parameters by up to 30%. Dorsal root stimulation on the side of the supporting leg reduced postural control, while stimulation on the side of the dominant leg did not. No significant changes were observed in the FI participants.

We are witnessing the revival of the CAM model, which was already used in the past by some authors studying angiogenesis and anti-cancer drugs, that now offers a refined model to fill, in the translational meaning, the gap between in vitro-in vivo studies. It can be used for a wide range of purposes, from testing cytotoxicity, pharmacokinetics, tumorigenesis, invasion, to action mechanisms of molecules, and validation of new materials from tissue engineering research. CAM model is easy to use with a fast outcome and makes experimental research more sustainable since allowing to replace, reduce and refine pre-clinical experimentation ("3Rs" rules [1]). This re-view aims to highlight some unique potentials that CAM-assay presents; in particular, the authors intend to use in the next future the CAM model to verify, in a microenvironment comparable to in vivo conditions, albeit simplified, the angiogenic ability of functionalized 3D constructs to be used in regenerative medicine strategies in the recovery of skeletal injuries of critical size (CSD) that do not repair spontaneously. For this purpose, organotypic cultures will be planned on sever-al CAMs set up in temporal sequence: a sort of organ model for assessing CSD conducted in the CAM bioreactor, rather than in vivo.

Living beings are composite thermodynamic systems in non-equilibrium conditions. Within this context, there are a number of thermodynamic potential differences (forces) between them and the surroundings, as well as internally. These forces lead to flows, which, ultimately, are essential to life itself. Living beings are under the pressures of natural selection, thus are biological flows as well. At the same time, the maintenance of homeostatic conditions, the tenet of physiology, demands regulation of these flows by control of variables. However, due to the very nature of these systems, regulation of flows and control of variables become entangled in closed loops. Therefore, the search for adaptation in flows takes a different path than the search for adaptation in morphological traits. Being at the roots of transfer processes, thermodynamic criteria turn out to be as natural physical candidates. Likewise, being at the roots of physiology, control turns out to be as a natural biological candidate in that path. Here we show how to combine entropy generation, with respect to a generalized process, and control of parameters (in such a generalized process) in order to create a criterium of optimal ways to regulate changes in generalized flows.

The aim of this study was to assess the effects of three warm-up durations on post-exercise oxidative stress biomarkers, as well as recovery from the Wingate test in 14 amateur handball players. These players completed the Wingate test three times: after 5-min, after 10-min, and then after 15-min of warm-up, spread over two weeks with an interval of one week between each session. At the end of each session of the Wingate test, blood samples were taken: at rest (PR), after warming up (PWU) and immediately at the end of the test (P0), then after 10-min (P10) and after 20-min (P20) of recovery. The measured parameters are the total antioxidant status (TAS), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA), protein-bound-carbonyls (PC) and thiobarbituric acid reactive substances (TBARS). The main findings revealed that anaerobic exercise induces oxidative stress, as evidenced by changes in antioxidant status and significant increases in concentrations of the majority of oxidative stress indicators (p < 0.05). At P20, plasma GPx, SOD, GR, TBARS, and PC contents, are lower and significantly different after a 15-min warm-up than after a 10-min or 5-min warm-up. ANOVA showed a significant ‘‘warm-up×recovery’’ effect on plasma GPx, SOD, GR, TBARS, and PC contents [F(8.104)=3.61; p<0.001; η2p=0.22, F(8.104): from 1.88 to 19.97; η2p: from 0.19 to 0.61: 0.05<p<0.001], respectively. We concluded that a 15-min warm-up was more efficient than the other duration in reducing free radical rise, emphasizing the importance of warm-up length on plasma oxidative stress biomarkers.

Body weight support (BWS) and incline running (IR) are commonly used either during rehabilitation or during training separately, with many positive effects on athletes’ performance and rehabilitation. The aim of this study is to investigate the effect of BWS and IR. In eighteen healthy men (age: 20.3 ± 1.2 yr, body weight: 70.2 ± 4.8 kg, body height: 179.6 ± 5.4 cm), the changes in electromyographic activity (EMGA) during a 10-min run with BWS (15% or 30% of body weight; in different occasions) and IR at 7%, as well as jumping performance and gait spatiotemporal parameters were evaluated. Lower Rating of Perceived Exertion and a significant decrease in VL (33,4%), SOL (17%), and GL EMGA (28.5%, p &lt; 0.05) but not in GM (10.5%, p &gt; 0.05), were observed during BWS30% at 7% slope compared to flat running. Also, low-frequency fatigue of the quadriceps was induced only after running without BWS at 7% slope (P = 0.011). No changes were found in jumping performance (p = 0.246) and gait spatiotemporal parameters (p &gt; 0.05) except for flight time (p &lt; 0.006). In conclusion, compared to normal flat running, BWS reduces electromyographic activity and fatigue during slope running.

The saphenous vein is the conduit of choice for bypass grafting. Unfortunately, the hemodynamic stress associated with the arterial environment of the bypass vein graft leads to the development of intimal hyperplasia (IH), an excessive cellular growth and collagen deposition that results in restenosis and secondary graft occlusion. Hydrogen sulfide (H2S) is a ubiquitous redox-modifying gasotransmitter that inhibits IH. H2S is produced via the reverse trans-sulfuration pathway by 3 enzymes: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). However, the expression and regulation of these enzymes in the human vasculature remains unclear. Here, we investigated the expression of CSE, CBS and 3-MST in segments of native human saphenous vein and large arteries. Furthermore, we evaluated the regulation of these enzymes in vein segments cultured under static, venous (7 mmHg pressure) or arterial (100 mmHg pressure) pressure. CSE was expressed in the media, neointima and intima of the vessels and was negatively regulated by arterial shear stress. Adenoviral-mediated CSE overexpression or RNA interference-mediated CSE knock-down revealed that CSE inhibited primary human VSMC migration but not proliferation. We propose that high shear stress in arteriovenous bypass grafts inhibits CSE expression in both the media and endothelium, which may contribute to increased VSMC migration in the context of IH.

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism's response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GR) play a role in fertility, reproduction, placental function, and fetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by supressing the hypothalamic-pituitary-gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother's exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the fetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GRα and GRβ, GRγ and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in human, guinea pig, sheep, rat and mouse indicating it is conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in GR and glucocorticoid signalling during pregnancy. This review will delve into the existing understanding of GR isoforms and explore the possible roles that these distinct isoforms may have in regulating glucocorticoid signalling, along with their impact on gonadal activity, placental function, and fetal growth.

Extraocular eye muscles (EOMs) are innervated by axons of three ocular motor nuclei, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the EOMs, pro-vide an overview of vestibular pathway inputs to ocular motor nuclei, and describe congenital disorders that alter the development of ocular motor neurons. Oculomotor neurons originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae which are contra-laterally innervated. Trochlear motor neurons originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons originate variously in the rhombomeres r4-6 and innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow yielding a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. The ocular motor neurons are innervating somites, which receive innervates vestibular nuclei that connects with the brainstem motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders.

This paper aimed to describe an atlas of the head of the crested porcupine (Hystrix cristata), applying advanced imaging techniques such as MRI. Furthermore, by combining the images acquired through these techniques with anatomical gross sections, we obtained an adequate description of the structures that form the CNS and associated structures of this species. This anatomical information could serve as a valuable diagnostic tool for the clinical evaluation of different pathological processes in porcupines such as abscesses, skull malformations, fractures, and neoplasia.

The importance of PAs for CNS functions are well known. Less clear is, however, where PAs in the brain are derived from. Principally, there are three possibilities: (i) intake by nutrition, release into the bloodstream, and subsequent uptake from CNS capillaries, (ii) products of parenchymatous organs as the liver, and again uptake from CNS capillaries, and (iii) uptake of precursors such as arginine from the blood and subsequent local biosynthesis of polyamines within the CNS.The present investigation aimed to unequivocally answer the question, whether PAs, especially the higher ones like SPD and SPM can or cannot be taken up into the brain from the bloodstream. For this purpose a biotin-labelled analogue of SPM was synthesized, characterized, and used to visualize its uptake into brain cells subsequent to application to surviving brain slices, to the intraventricular space, or to the bloodstream.In surviving slices uptake of B-X-SPM is massive into protoplasmic and absent in fibrous type astrocytes. It is also taken up by neurons but to a lesser degree. Under in-vivo conditions astrocyte uptake of biotinylated SPM also is massive from the brain interstitial fluid subsequent to intraventricular application. In contrast, following intracardial injection there is no uptake from the bloodstream, indicating that the brain is completely dependent on the local synthesis of polyamines.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

Mulberry leaves are a classic herb commonly used in traditional Chinese medicine, and experience since ancient times has shown that leaves collected after frost have better medicinal properties. However, the characteristics of the changes of critical metabolic components in mulberry leaves, especially Morus nigra L., are still unknown. To further study the influence of harvesting time on the dynamic changes of metabolites, especially DNJ compounds and flavonoids, in mulberry leaves after frost. We used metabolomics technology to select 100+ metabolites as indexes to reflect the dynamic changes of metabolites in mulberry leaves comprehensively. The results showed significant differences in the effects of defrosting on the accumulation of metabolites in the leaves of Morus nigra L. and Morus alba L. The content of DNJ in the leaves of Morus nigra L. showed a decreasing trend after the frost, while flavonoids reached the peak of the second frost. For Morus alba L, DNJ showed an increasing trend after frost, especially reaching its peak one day after the second frost. Flavonoids mainly peak in the week before the frost. In addition, by analyzing the influence of picking time on metabolite accumulation in two mulberry leaves, it was concluded that higher DNJ alkaloids and flavonoids would be obtained in mulberry leaves collected in the morning. This study also provides scientific guidance for the optimum harvesting time of mulberry leaves.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

Three-point shooting plays an important role in determining the outcome of the basketball games, and could be relevant for player selection. However, there has been little research into the relationship between basketball players' physical capacities, metabolic capacities and three-point shooting accuracy, particularly among female players. The aim of this study was to examine the relationship between physical capacities, metabolic capacities and dynamic three-point shooting accuracy in female professional basketball players. Twelve female professional basketball players from the Women’s Chinese Basketball Association (WCBA) league (age: 19.04±1.31 years, height: 181.33±4.90cm, playing experience: 7.83±1.7 years) were recruited for this study. Pearson correlations and multiple linear regression analysis were run to assess the relationship between physical capacities, metabolic capacities and dynamic three-point shooting. Results showed that coordination, balance, core strength and relative average power were positively correlated with the three-point shooting accuracy (r>0.58, P<0.05), while no other variables showed significant correlations. The current study suggests that coaching staff should consider coordination, balance, core strength and anaerobic capacities when selecting players as well as in their training periodization if three-point shooting accuracy is considered relevant.

The aim of this study was to develop and assess the reliability and validity of an innovative field test that measures lower limb explosive power in basketball players (i.e., alactic anaerobic capacity) for the dominant and non-dominant leg. The test examines the performance of vertical, horizontal, and combined movements while holding the ball – similar to penetration of the basket or layup. Such capabilities are required throughout basketball practice and games, combined with upper and lower body coordination. The study included 22 male basketball players, ages 16-18, members of an elite youth league team in Israel. To assess validity, the participants performed the test for each leg, followed by nine standardized tests that were developed for a range of ball games, including basketball. To assess reliability, the participants performed a retest of the unique test 72-hours later. Our findings indicate the validity and reliability of the proposed anaerobic alactic field test for basketball players, for the dominant and non-dominant leg. Moreover, strong correlations were seen between the novel test and the standardized tests, with a high correlation for horizontal explosive power (0.5<r<0.7), a very high correlation for vertical explosive power (0.7<r<0.9), and a nearly perfect correlation for the two combined (r>0.9). In conclusion, this unique field test for basketball players could assist coaches in developing and applying optimal training programs and game plans, for players individually, and for the team as a whole. As the test measures each leg separately, it could also offer an assessment tool following players’ injuries.

Mandarins occupy the third group among citrus produced in Brazil. Primarily aimed at the fresh fruit market, commercial orchards have suffered significant losses in production, due to the high incidence of diseases, such as alternaria brown spot (ABS) and huanglongbing (HLB). The fact that 80% of the orchards are composed of two varieties, Ponkan mandarin and Murcott tangor, are highly susceptible to both diseases, demand intensive chemical control of the diseases in the field, which has resulted in a significant increase in production costs and a negative environmental impact. A total of one hundred and seventy-three mandarin accessions, including several species and hybrids, belonging to the Collections of the Instituto Agronômico de Campinas (IAC), were evaluated in the field, in an endemic location for the diseases. Evaluations of the incidence and severity of the diseases showed that there is a range of genotypes tolerant to ABS with potential to replace the current commercial varieties, mainly within the clementina and Willow leaf mandarin groups. Although with differences in incidence and susceptibility to HLB, there are no varieties tolerant to this disease, which significantly impacts the loss of fruit quality.

This study examined the ventral process of C6 in extinct and extant Equus (sister taxa to Equus ferus caballus only) with the purpose of describing normal morphology and identifying anomalous variations relevant to recent studies describing a congenital malformation in E. ferus caballus. Overall, 83 specimens from 9 museums and 3 research/educational facilities were examined – 71 extinct specimens from 12 species and 12 extant specimens from 5 species. The lateral view revealed a large convexity existed in the ventral process between the cranial ventral tubercle (CrVT) and the caudal ventral tubercle (CVT) in the earliest ancestor Hyracotherium grangeri 55mya that receded throughout the millennia to a smaller convexity in E. ferus caballus and sister taxa. The CrVT was visibly shorter and narrower than the CVT with a constricted section directly ventral to the transverse process essentially demarcating the CrVT and CVT. No congenital malformations were evident. As the ventral process of C6 is an integral component for muscle attachment in supporting the head/neck during posture and locomotion, this would indicate the caudal module in the cervical column might be compromised when a partial or complete absence of the CVT is detected via radiographs in modern E. ferus caballus.

Coincident changes in abundance and behavior pose a challenge for interpreting abundance data from monitoring programs. In the San Francisco Estuary, long-term monitoring documented the declines of many species including the anadromous Longfin Smelt (Spirinchus thaleichthys). We identified seasonal patterns in reginal presence of Longfin Smelt through its life cycle using monitoring data and generalized additive modelling. We then investigated the year-to-year variability in the seasonal patterns of presence using functional data analysis (FDA). FDA separated the variability due to population size from variability due to differences in timing of presence. We found that Longfin Smelt have consistent seasonal distribution patterns and that two trawl types were needed to accurately describe those patterns. After accounting for variability due to year-class strength, shifts in the timing of presence were evident in three regions. The most variable period for the upstream regions Suisun Bay and West Delta was for age-0 fish in summer and for the downstream region Central Bay was for age-0 fish in late fall. This manifested as a delay in the typical fall re-occupation of upstream regions that comprise the study area for another monitoring study (Fall Midwater Trawl). Thus, a portion of the recent reductions in Fall Midwater Trawl abundance of Longfin Smelt resulted from changes in behavior rather than a decline in abundance. The presence of multiple monitoring surveys allowed analysis of distribution from one data set to aid interpretation of patterns in abundance from another monitoring survey. This study highlights how identifying portions of the life cycle with the most and least variability in distribution can help inform the types of management strategies that will be most effective. It also illustrates an analytical method that can be used to address the problem of confounded effects of abundance and behavior on patterns in monitoring data.

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and the process of aging. Analyzing these disease states is possible with GWAS and PheWAS methodology, and through our analysis, we aimed to explore the relationships between polymorphisms in the compendium of ECM genes (i.e., matrisome genes) in various disease states. A significant contribution on the part of the ECM polymorphisms is evident in many varying types of diseases, particularly those in the core matrisome genes. Our results confirm previous links to connective tissue disorders, but also unearth new and underexplored relationships with neurological, psychiatric, and age-related disease states. Upon analysis of drug indications for gene-disease relationships, we identified numerous targets that may be repurposed for age-related pathology. The identification of ECM polymorphisms and their contribution to disease plays an integral role in future therapeutic developments, drug repurposing, precision medicine, and personalized care.

The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on forebrain and sense organs development. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions.

This case study features an observation of an obese female (body mass index ≥ 30 kgm-2) who undertook a 10-day water and electrolyte fast with the aim of reducing body fat and improving physiological markers of health. A comprehensive range of physiological measures (body mass, girths, blood pressure, body fluid balance, urine osmolarity, and resting oxygen consumption), mood indicators, metabolic markers (blood ketones, blood glucose, breath ketones, urine ketones), and measurement of intake and expenditure (fluid intake, food intake, nutritional macros, steps taken, and estimated movement caloric expenditure) were measured before, during and after the fasting period to determine the effectiveness of undertaking extended therapeutic fasting for improving markers of health and weight loss. Body mass on the first day of the fast was 95.1 kg and on the tenth and final day of the fast it was 88.1 kg representing a loss of 7 kg at a rate of 0.7 kg·day1. Mean body mass in the 15 days after the fast was 88.3 ± 0.4 kg. This case study is novel in reporting key physiological and psychological markers over a 10-day fast, and in pre- and post-fast periods. A 10-day fast appears to be a safe and effective method of weight loss, mood is positively affected by fasting and weight loss from fasting can be sustained providing care is taken in the approach to post-fasting nutrition.

An iconic feature of insects is the apparent lack of legs on the abdomen, which is believed to be due to the repression of the leg-patterning gene Distalless (Dll) by abdominal Hox genes. However, in contrast to these molecular observations, it is not widely appreciated that the embryos of most insect groups do in fact form paired protrusions on most abdominal segments that appear to be homologous to the thoracic legs. However, these degenerate before hatching to form the abdominal body wall. To resolve this discordance between molecular and morphological observations, the expression patterns of pannier and araucan, genes known to distinguish proximal leg segments in all arthropods, are examined in embryos of the flour beetle Tribolium castaneum. In Tribolium embryos, all pregenital abdominal segments develop leg-like paired protrusions, and the stripes of pannier and araucan expression that delineate the proximal leg segments of the thorax are also expressed in the same configuration around these abdominal protrusions. This suggests that insect abdominal legs are homologous to only the proximal portion of the thoracic legs, which in insect adults forms the body wall (lateral tergum and pleura). These cryptic, truncated abdominal legs – likely inherited from their crustacean ancestors – appear to be an important wellspring for new functions in insects, such as caterpillar prolegs, gills, and structures for camouflage¹⁶ and aposematic warning.

Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.

Consumption of poultry meat is higher than red meat due to easy availability, good taste, low cost and palatability. Significant improvement in meat yield and growth rate of broiler chicken has been brought about with the help of genetic selection of desirable traits. The present study was conducted to comparatively evaluate the chronic effect of domestic and broiler chicken meat consumption on male hypothalamic pituitary gonadal axis, lipid profile and oxidative stress on postnatal male rats. Rats were divided into five groups: control, B1, B2, D1 and D2 groups and were fed with 0.17g and 0.34g of broiler and domestic chicken meat from postnatal day 21 to PND90.The significant elevated body weight and weight gain in B2 group (P<0.01), minor change in B1 and D40 group (P<0.05) were detected. In gonadosomatic index absolute and relative epididymis weight, weight of seminal vesical and Prostate weight was significantly augmented in B2 compared to control and D2. Kidney and liver weight in B1, B2 was markedly elevated and minor change in D2 groups. ROS level in B2 was significantly higher than other experimental groups. Serum level of FSH, LH, testosterone, estradiol and low density lipoprotein was significantly elevated in B2 compared to control and D2. In B2 rats fed with 0.34g broiler meat exhibited a marked decreased seminiferous tubule diameter, epithelial height and increased lumen diameter changes that were more prominent compared to rats fed with 0.34g domestic chicken meat. Conclusively chronic administration of broiler meat induces marked alteration in reproductive system, testicular morphology, sexual hormones and oxidative stress in postnatal Sprague Dawley male rats compared to domestic chicken meat.

The aim of this work was to study the, so far, unexplored possibility that non-genetic inheritance of animal behavioral characteristics could depend on the state of the parents at the time of conception, by studying inheritance of high and low motor and exploratory activity in the first generation of rats. In this study, we measured the levels of motor and exploratory activity in rats at the ages of 2 and 5 months. Male and female rats were mated at the age of 5 months. The following groups were used: male and female rats with high motor activity at ages of 2 and 5 months (ACT+); male and female rats with high activity at the age of 2 months, but low activity at the age of 5 months (ACT–); male and female rats with low activity at the ages of 2 and 5 months (PAS–); male and female rats with low activity at the age of 2 months, but high activity at the age of 5 months (PAS+). Significant differences in the severity of exploratory activity were found between the offspring of ACT+ and ACT– rats. Moreover, these differences were observed only in males, and not in females. Differences between the offspring of PAS+ and PAS– rats were observed in both the male and female rats. The motor activity of animals in the period from 20 minutes after the start of registration did not differ between groups. Thus, it can be considered that individual characteristics of general motor activity are due to genetically inherited factors, while differences in the level of exploratory activity, apparently, are formed due to non-genetic influences from parents during mating.

Coordination of cellular biological processes is regulated in part via metabolic enzymes acting to match cellular metabolism to current conditions. The acetate activating enzyme, acyl-coenzyme A synthetase short-chain family member 2 (Acss2) has long been considered to have a predominantly lipogenic function. More recent evidence suggests that this enzyme has regulatory functions in addition to its role in providing acetyl-CoA for lipid synthesis. We used Acss2 knockout mice (Acss2-/-) to further investigate the roles this enzyme plays in three physiologically distinct organ systems that make extensive use of lipid synthesis and storage including the liver, brain and adipose tissue. We examined the resulting transcriptomic changes resulting from Acss2 deletion and assessed these changes in relation to fatty acid constitution. We find that loss of Acss2 leads to dysregulation of numerous canonical signaling pathways, upstream transcriptional regulatory molecules, cellular processes, and biological functions, which were distinct in the liver, brain and mesenteric adipose tissues. The detected organ-specific transcriptional regulatory patterns reflect the complementary functional roles of these organ systems within the context of systemic physiology. While alterations in transcriptional states were evident, the loss of Acss2 resulted in few changes in fatty acid constitution in all three organ systems. Overall, we demonstrate Acss2 loss institutes organ-specific transcriptional regulatory patterns reflecting the complementary functional roles of these organ systems. Collectively, these findings provide further confirmation that Acss2 regulates key transcription factors and pathways under well-fed, non-stressed conditions, and acts as a transcriptional regulatory enzyme.

Background/Objectives: The purpose of the proposed study is disclosure of correlations between the dynamics of the Breathe Rate (BR) and Heart Rate (HR) when performing the intermittent physical operation at maximum power on a cycle ergometer.Methods: The stage on the study of the General functional athlete readiness (GFAR) performed using the sports standard “Red Engine” and the cycle ergometer in 16 volunteers (10 men, 6 women) whose average age was 21±1.17 years. To determine the sports potential of the volunteers in this study, we used own Coefficient of Anaerobic Capacity (CANAC Q, beats). Continuous recording of the heart rate and respiratory rate of volunteers in the maximum power sports test was carried out by the “RheoCardioMonitor” device with an athlete functional readiness module based on the method of Transthoracic electrical impedance rheography (TEIRG).Results: The degree of correlation of functional indicators (M, HR_M, GFAR) with CANAC Q for the group in full (n=80) occurred at a very high level, which confirmed the effectiveness of using the Coefficient of Anaerobic Capacity (CANAC Q) in assessing the general functional athlete readiness of the volunteers. Conclusions: CANAC Q measured in “beats” of the heart and recorded very accurately using the method of transthoracic electrical impedance rheography (TEIRG). For this reason as promising sports PSM-system, CANAC Q can replace the methods for determining the functional athlete readiness by blood lactate concentration and maximum oxygen consumption.

Antarctica is the continent with the lowest local human impact, yet it is still vulnerable to contaminants coming from external sources. Emerging pollutants, like PFAS, pose an increasing threat to this environment and therefore require more in-depth investigations to understand their environmental fate and biological impacts. The present study, part of the AntaGPS project, focuses on expression analysis at the transcriptional level of genes coding for 4 antioxidant enzymes (sod1, sod2, gpx1, gpx4) in different organs of an Antarctic fish species, Trematomus newnesi. The kidney showed a higher level of expression than the liver of wildlife specimens. The mRNA levels were also assessed in fish exposed to 1.5 μg/L of PFOA for 10 days. In the liver, the treatment induced an increase in gene expression for all the considered enzymes, while in the kidney it induced a general decrease. The obtained results constitute a starting point for using the expression of antioxidant enzymes as biomarkers, both of oxidative stress and exposure to PFAS, in future biomonitoring campaigns in the Antarctic marine environment.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

Laser patterning of implant materials for bone tissue engineering purposes has shown to be a promising technique to control cell properties such as adhesion or differentiation, resulting in an enhanced osteointegration. However, the perspective of patterning the bone tissue side interface to generate microstructure effects has never been investigated. In the present study, three different laser-generated patterns were machined on the bone surface with the aim to identify the best surface morphology compatible with osteogenic-related cells recolonization. The laser patterned bone tissue was characterized by electron scanning microscopy and confocal microscopy in order to obtain a comprehensive picture of the bone surface morphology. Cortical bone patterning impact upon cell compatibility and cytoskeleton rearrangement to the patterned surfaces was performed with Stromal Cells from Apical Papilla (SCAPs). Results indicated that laser machining had no detrimental effect upon consecutively seeded cells metabolism. Orientation assays revealed that surface patterning characterized by larger hatch distances was correlated with a higher cell cytoskeletal conformation to the laser-machined patterns. For the first time, to our knowledge, bone is considered and assessed here as a potentially engineered-improvable biological interface. Further studies shall focus on in vivo implications of this direct patterning.

The cerebellum is an encephalic region classically known for its central role in the control of movement, although recent research has revealed its involvement in other cognitive and affective tasks. Several different pathologies are known to affect this structure, causing a wide range of behavioral and gait impairments. Intriguingly, although the neurodegenerative factors affect all Purkinje cells of the cerebellum uniformly, certain neurodegeneration patterns can be distinguished, in which some Purkinje cells persist longer than other cell types. Precisely, there is a cerebellar region, lobe X, which is more resistant to different types of neurodegeneration regardless of the injury. This work will review the main models of cerebellar degeneration, with special emphasis on this region, and aims to reveal a common origin for its resistance to neuronal death.

The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially fatty acid (FA) dysfunctional metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose me-tabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expres-sion of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects was evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differ-entiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA se-quencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. Finally, we report sev-eral highly expressed GPCRs with no known role in adipose biology whose expression was sig-nificantly altered during adipogenic differentiation and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

Aging is a complex biological process, with gradual and progressive decline in structure and function in many organ systems. Our objective is to determine if structural changes produced by aging, vary with sex, in a stressful situation such as dehydration. The expression of Slc12a3 mRNA in renal cortex, α-smooth muscle actin (α-SMA) and fibronectin, was evaluated in male and female rats aged 3 and 18 months submitted or not to water deprivation (WD) for 48 hours. When comparing ages, 18-month-old males showed lower expression of Slc12a3 mRNA than 3-month-old males, and control and WD 18-moth-old male and female rats exhibited higher expression of α-SMA than respective 3-month-old rats. Fibronectin was higher in both control and WD 18-month-old males than respective 3-month-old males. In females, only control 18-month-old rats showed higher fibronectin than control 3-month-old rats. When we compared sex, control and WD 3-month-old female rats had lower expression of Slc12a3 mRNA than re-spective males. WD 18-month-old male rats presented higher expression of fibronectin and α-SMA than WD 18-month-old female rats. When we compared hydric condition, WD 18-month-old males displayed lower relative expression of Slc12a3 mRNA and higher α-SMA expression than control 18-month-old males. Aging, sex, and dehydration lead to alteration in kidney structure.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG in-duction of obesity upon systemic and muscular parameters of Wistar rats. Animals were exposed to MSG subcutaneously (4 mg.g-1 b.w.) or saline (1.25 mg.g-1 b.w.) daily from PND01 to PND05 (n = 24). After, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, and increased adiposity, induction hyperinsulinemia, and a pro-inflammatory scenario. In adulthood were found, peripheral insulin resistance, reduced muscle mass, oxidative capacity, neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty in restoring the muscle profile are related to the metabolic damages established early.

Two putative boar pheromones (Androstenone and Androstenol) were discovered in endangered mouse deer during captive breeding program. This study further examined the molecular characteristics, pheromone synthesis pathway, and the functional role of these pheromones in reproduction of mouse deer. CYP17A1 and CYB5 genes were cloned and expressed in HEK-293, COS-7 cell lines and gonads of mouse deer to investigate CYP17A1 gene’s andien-β-synthase activity towards synthesis of sex pheromones in mouse deer. An enzyme immunoassay was also developed and standardized to measure the fecal androstenone during reproductive cycles of mouse deer. Results showed that mouse deer’s CYP17A1 gene possesses andien-β-synthase activity and could transform pregnenolone into 5,16-androstadien-3β-ol. The expression of CYP17A1 gene upregulated in the testis and ovary, compared to other tissues in mouse deer. Significantly elevated pheromones and estrogens were recorded prior to delivery and postpartum estrus / mating in mouse deer. Further, there were weak correlations between fecal pheromones and estrogens/ androgens in mouse deer during breeding season. The findings suggest that the boar pheromones might play a direct role in the reproductive activities of mouse deer which might be used for breeding of mouse deer elsewhere.

We have previously discussed the pathological characteristics, clinical characteristics, detection methods, pathogenesis, and treatment of Epstein–Barr virus (EBV)-positive gastric cancer, but we have not discussed the unique immune microenvironment in EBV-positive gastric cancer. Here, we reviewed studies on the immune microenvironment in EBV-positive gastric cancer and found that CD8+ T lymphocytes and a small number of CD204+ macrophages infiltrate the immune microenvironment in EBV-positive gastric cancer. Moreover, immune checkpoints, such as IDO1 and PD-L1, are expressed at high levels in EBV-positive gastric cancer. Lastly, we also analyzed the mechanisms underlying the formation of the immune microenvironment in EBV-positive gastric cancer. Our findings and conclusions have significance in clinical guidance and provide research direction for basic experiments.

A human case of dengue virus 2 was detected from a febrile patient living in the Sare yoba, Kolda region (Southern Senegal). Phylogenetic analysis based on the partial sequence of the NS5 gene reveals that the virus belongs to the DENV2 Sylvatic genotype and is closely related to a strain (JF260983/ 98.98% identity) detected in Spain from a tourist who travelled to Guinee Bissau (bordering Kolda region) in 2009. This highlights a potential recent underreported circulation of sylvatic Dengue in the southern part of Senegal and calls for re-enforced integrated surveillance among humans, non-human primates and arboreal mosquitoes throughout a one-health approach.

Metal bioaccumulation and metallothionein (MT) expression were investigated in gills and liver of the red-blooded Antarctic teleost Trematomus hansoni with the aim to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper or cadmium concentrations in the environment. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory condi-tions. The two treatments lead to a significant accumulation of both metals and an increase of gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in speci-mens exposed to Cd, but the majority of these proteins were soon oxidized, probably because they were involved in cell protection against the risk of oxidative stress, by reactive oxygen spe-cies scavenging. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species evolved in an environment characterized by natural high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming every day more toxic.

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

French academies almost all implement reactivity drills and small-sided games (SSG) the day preceding a match (MD-1). The present study aimed to determine the physical impact of different training durations on MD-1 on the subsequent matchday performance (MD). Eleven elite U19 academy soccer players con-ducted three typical training sessions lasting 45min (TS45), 60min (TS60), and 75min (TS75) on MD-1. Dur-ing TS60, warm-up, reactivity and SSG were 10, 15, and 24min, respectively, plus coaches' feedback or wa-ter breaks. Durations decreased and increased by 25% for TS45 and TS75, respectively. Tests were con-ducted on MD-4 (CONTROL) and MD before the match (TEST). Tests consisted of a counter movement jump (CMJ), 20m sprint, Illinois agility test (IAT), and Hooper questionnaire. CONTROL values were simi-lar over the three experimental conditions. TEST on MD revealed greater CMJ for TS45 (42.7 ± 5.1cm) compared to TS60 (40.5 ± 5.5cm, p=0.032) and TS75 (40.9 ± 5.7cm, p=0.037). 20m time was lower for TS45 (3.07 ± 0.10s, p<0.001) and TS60 (3.13 ± 0.10s, p=0.017) compared to TS75 (3.20 ± 0.10s). IAT time was lower on TS45 (14.82 ± 0.49s) compared to TS60 (15.43 ± 0.29s, p<0.001) and TS75 (15.24 ± 0.33s, p=0.006). Further-more, the Hooper index was lower at TEST for TS45 (7.64 ± 1.50) compared to TS60 (11.00 ± 3.49, p=0.014) and TS75 (9.73 ± 2.41, p=0.045) indicating a better readiness level. We concluded that as training session duration increases, performance decreases on MD. A 45min training session including reactivity and SSG exercises is therefore recommended on MD-1.

The association of the APOE4 (vs APOE3) isoform with an increased risk of Alzheimer’s Disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elu-cidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking apolipoprotein isoform to disease aetiology. APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several alterations in pathways of lipid homeostasis in the brains of mice expressing the human APOE4 versus APOE3 isoform. Carriers of APOE4 had deficient cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing poly-unsaturated fatty acids and an overall eleva-tion in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related with increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of AP-OE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

The morphology and maturation process of gonads of 70 Burmeister´s porpoises, with body lengths ranging 135–183 cm (n= 34 females) and 64.5-182 cm (n= 36 males) were described. Samples were collected in six ports of central and northern Peru in 1987-1999. In the field, females were classified as immature, mature (resting, lactating, pregnant) and males as immature, pubescent and mature based on, respectively, the presence of ovarian corpora and the relative quantity of semen in cut epididymides. The ovaries of P. spinipinnis are ovoid or bean-shaped and flattened, with corpora modifying surface appearance. In the laboratory, ovaries were examined macro- and microscopically, measured, weighed and sliced in 1-3 mm sections. The number of corpora ovarica (lutea, albicantia, atretica) found in each ovary as well as their macroscopic and microscopic characteristics were documented in some detail. The follicles, their oocytes and nucleus were measured. Follicular development in P. spinipinnis is predominantly left-sided, but occurs in both ovaries in 16.3% of females, mainly in those with numerous corpora. Macroscopically, several corpora atretica with luteinization had characteristics similar to those of corpora albicantia, making microscopic determination essential. Inconclusive evidence of recent ovulation was found in January. Two of three immature females showed good follicular development in March and April. The body length at 50% sexual maturity in females was estimated at 152.7 cm. There was no evidence of reproductive senescence. The testes of P. spinipinnis are elongated and cylindrical. Of the 36 males examined macroscopically, 7 were immature, 5 pubescent and 24 mature. The histological analysis determining the presence and abundance of Sertoli cells, spermatogonia, spermatocytes, spermatids and spermatozoa, the relative amount of interstitial tissue, the elongation and mean diameter of the seminiferous tubules and the relative size of the lumen allowed to confidently determine sexual maturity status. The field evaluation of maturity based on the presence of sperm in the epididymides is a useful but, in 8.3% of cases, not exact method. For males the body length at 50% sexual maturity was estimated at 157 cm. No histological evidence of male reproductive seasonality was found. Spermatogenesis was perceptible year-round and tubule diameters had non-specific variations for each month.

The occurrence of potential spikes in a cell is a sign of life, and it is called action potential. There is a common notion that neuron signal conduction is the conduction of action potential. Hence, action potential is a typical and essential life activity. However, such potential spikes occur even in simple nonliving systems. According to the experimental observations by Pollack, structured water molecules can generate a negative potential environment. From this observation, the potential spike generation process for both living and nonliving systems caused by ion and water molecule adsorption-desorption process could be explained in this paper. So, taking into consideration the electrically neutral water molecules,the action potential generation mechanism could be explained. It is a fully inanimate model. Hence, the action potential may not be a life activity. Here, the role of water molecules in life is investigated further. It was found that the phase transition of the membrane is involved in the neuron signal conduction, but the membrane phase transition could be due to the change of state of the water molecules, which forms a large-scale structure in the cavities created by a number of lipids.

Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, and many others. Glycosides and caffeic acid conjugates are the common forms of esculetin present in medicinal plants. Esculetin acts as an antioxidant, anti-inflammatory, anti-diabetic, anti-hepatic, and anti-cancer agent by inhibiting the production of free radicals, inflammatory mediators, and genes that cause liver diseases and cancer. It also aids in the regulation of blood sugar. Scientists developing pharmaceutical formulations require some rationale and preliminary studies for drug design, but a small number of clinical studies on humans containing esculetin limit its potential for use as a safe alternative drug. Therefore, in this review article, the published studies have been reviewed to identify the pathogenesis of cancer, oxidative stress, inflammation, arthritis, diabetes and fatty liver along with the discussion on potential therapeutic strategies of esculetin. Advancements in our understanding of these diseases will aid in the development of new and innovative medications for treating many ailments. In conclusion, esculetin has immense potential to be used as a safe drug against many diseases but requires further testing and confirmation through clinical trials.

A model for cell proliferation in developmental fields is derived from information theory using a few biological postulates. The model provides an explanation for the success of the Gompertz equation in describing the growth of embryonic, neoplastic, and regenerative systems. Although this equation has been applied to many growth phenomena, its use has been entirely empirical. A theoretical justification for the use of the Gompertz equation in characterizing developmental processes is presented. The model also accounts for a reported relationship among the parameters of the Gompertz equation. A method for quantification and comparison of the determination of developmental fields at different levels of organization is suggested.

This article is a followup to an earlier review which outlined some of the interesting features of the soliton/wave-action potential (AP) model, and noted the need to test its key aspects; including the need to test if its presumed lipid phase transition is actually happening during AP firings in excitable cells. The intent here is to point out the sort of tests, and evidence from them, that might be needed if the soliton/wave-AP model is to be accepted broadly by biologists. Here, after an overview of the modern electrophysiological-AP model and of the soliton/wave-AP model, there are three areas considered. First, possible compositional influences on membrane properties relative to the soliton/wave-AP model are presented. Including questions with regard to the soliton/wave-AP model’s assumption that changes in surface potentials influence the transmembrane potential. Second, some recent work from the good folks who advocate for the soliton/wave-AP model concerning the occurrence of lipid phase transitions in neurons or in extracts from nervous tissues are examined. Here it is noted that there is a need to consider whether these lipid phase transitions happen within normal physiological conditions or not. Third, and finally, the advocates for the soliton/wave-AP model have adopted a thermodynamic/theory-based philosophical approach in their studies. It is argued that this philosophical approach is a radical departure from the philosophical approach used under the scientific method. The features of this new approach, and implications its use, are examined.

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein-1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that Gabarapl1 is primarily involved as the Atg8 family protein recruiting the Stbd1-glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

Evidence indicates that unhealthy eating habits constitute multilevel obstacles threatening our health and well-being—studies suggesting that consumer choices turn irremovably towards Western diets. Mediterranean diets (MD) have been identified as one of the most effective in preventing and treating overweight and obesity. Considering this scientific substantiation in prevention and treatment activity, the purpose of this investigation is to verify this evidence. In our prospective interventional study, we examined the effect of MD on body weight in a female cohort sample. The analyzed group consisted of (n=181) females divided into three distinct groups based on their age (tricenarian, quadragenarian, and quinquagenarian). Anthropometric (weight, BMI, FATP, VFATL, FFM, TBW, and BMR), biochemical examinations (urea, creatinine, uric acid, ALT, AST, GGT, CHOL, HDL-CH, non-HDL, LDL-CH, TAG, GLU, and CRP) and comprehensive, personalized three months MD program was completed on the examined subjects. We didn’t establish convincing evidence of MD on weight reduction and its magnitude of correlation with a positive correspondence on selected determinants in all groups combined. There is a challenge to construct more robust prospective cohort studies that will incorporate add-on critical integrands that will be appropriate to monitor, evaluate and predict weight management in experimenting.

The modification of proteins by small ubiquitin-related modifier (SUMO) molecules, SUMOylation, is a key post-translational modification involved in a variety of biological processes such as chromosomes organization, DNA replication and repair, transcription, nuclear transport, and cell signaling transduction. In recent years, emerging evidence has shown that SUMOylation regulates the development and homeostasis of the skeletal system, with its dysregulation causing skeletal diseases, suggesting that SUMOylation pathways may serve as a promising therapeutic target. In this review, we summarize the current understanding of the molecular mechanisms by which SUMOylation pathways regulate skeletal cells in the physiological and disease contexts.

Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the implant site have been shown to decrease with chronic administration of antioxidant melatonin at week 16, but its effects on the acute landscape have not been studied. To assess the effect of melatonin administration in the acute phase, specifically the first week post-implantation, we utilized histological and q-PCR methods to quantify cellular and molecular indicators of inflammation and oxidative stress as well as two-photon microscopy to track the microglial responses in real-time. Histological results indicate that melatonin effectively maintained neuron density surrounding the electrode, inhibited accumulation and activation of microglia, astrocytes, and reduced oxidative tissue damage. The expression of the pro-inflammatory cytokines, TNF-α and IL-6, were significantly reduced in melatonin-treated animals. Additionally, microglia encapsulation of the implant surface was inhibited by melatonin as compared to control animals following implantation. Our results combined with previous research suggest that melatonin is a particularly suitable drug for modulating inflammatory activity around neural electrode implants both acutely and chronically, translating to more stable and reliable interfaces.

All living cells maintain a charge distribution across their cell membrane (membrane potential) by carefully controlled ion fluxes. These bioelectric signals regulate cell behavior (such as migration, proliferation, differentiation) as well as higher-level tissue and organ patterning. Thus, voltage gradients represent an important parameter for diagnostics as well as a promising target for therapeutic interventions in birth defects, injury, and cancer. However, despite much progress in cell and molecular biology, little is known about bioelectric states in human stem cells. Here, we present simple methods to simultaneously track ion dynamics, membrane voltage, cell morphology, and cell activity (pH and ROS), using fluorescent reporter dyes in living human neurons derived from induced neural stem cells (hiNSC). We developed and tested functional protocols for manipulating ion fluxes, membrane potential, and cell activity, and tracking neural responses to wounding and re-innervation in vitro. Finally, using morphology sensor, we tested and quantified the ability of physiological actuators (neurotransmitters and pH) to manipulate nerve wound re-innervation. These methods are not specific to a particular cell type and should be broadly applicable to the study of bioelectrical controls across a wide range of combinations of models and endpoints.

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3’untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30-kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers Danlos Syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population.