The Biology of Physiological Health.

The ability to maintain health, or recover to a healthy state after disease, is an active process involving distinct adaptation mechanisms coordinating interactions between all physiological systems of an organism. Studies over the past several decades have assumed the mechanisms of health and disease are essentially inter-changeable, focusing on the elucidation of the mechanisms of disease pathogenesis to enhance health, treat disease, and increase healthspan. Here, I propose that the evolved mechanisms of health are distinct from disease pathogenesis mechanisms and suggest that we develop an understanding of the biology of physiological health. In this Perspective, I provide a definition of, a conceptual framework for, and proposed mechanisms of physiological health to complement our understanding of disease and its treatment.

Facial masculinity does not appear to be a condition-dependent male ornament and does not reflect MHC heterozygosity in humans.

Recent studies have called into question the idea that facial masculinity is a condition-dependent male ornament that indicates immunocompetence in humans. We add to this growing body of research by calculating an objective measure of facial masculinity/femininity using 3D images in a large sample (n = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females. However, facial masculinity scales with growth similarly in males and females, suggesting that facial masculinity is not exclusively a male ornament, as male ornaments are typically more sensitive to growth in males compared with females. Additionally, we measured immunocompetence via heterozygosity at the major histocompatibility complex (MHC), a widely-used genetic marker of immunity. We show that, while height is positively correlated with MHC heterozygosity, facial masculinity is not. Thus, facial masculinity does not reflect immunocompetence measured by MHC heterozygosity in humans. Overall, we find no support for the idea that facial masculinity is a condition-dependent male ornament that has evolved to indicate immunocompetence.

Age-related differences in torque in angle-specific and peak torque hamstring to quadriceps ratios in female soccer players from 11 to 18 years old: Α Cross-sectional study.

The aim of this study was to evaluate and compare the hamstring (H) and quadriceps (Q) strength, bilateral difference and balance ratios in female soccer players. Ninety-three athletes from three age groups: under 13 (U13), 15 (U15) and 18 (U18) participated in the study performing isokinetic tests to measure peak torque, total work, average power and torque at 30º of thigh muscles. Conventional strength balance ratios, angle-specific balance ratio and bilateral strength difference were evaluated. There was bilateral strength difference for extensor muscles total work (p = 0.02) in U13 and flexor muscles peak torque (p = 0.02) in U15. All variables were superior in U15 than U13 (p <.05). There was no strength difference between U15 and U18. Balance ratios did not differ between sides or age groups. The study showed that although peak torque values were higher in U15 than in U13, balance ratios were similar.

Ventilation/Perfusion Matching: Of Myths, Mice, and Men.

Despite a huge range in lung size between species, there is little measured difference in the ability of the lung to provide a well-matched air flow (ventilation) to blood flow (perfusion) at the gas exchange tissue. Here, we consider the remarkable similarities in ventilation/perfusion matching between species through a biophysical lens and consider evidence that matching in large animals is dominated by gravity but in small animals by structure.

Biosensors for real-time monitoring of physiological processes in the musculoskeletal system: A systematic review.

Biosensors are composed of (bio)receptors, transducers, and detection systems and are able to convert the biological stimulus into a measurable signal. This systematic review evaluates the current state of the art of innovation and research in this field, identifying the biosensors that in vitro monitor the musculoskeletal system cellular processes. Two databases found 20 in vitro studies, from January 1, 2008 to December 31, 2017, dealing with musculoskeletal system cells. The biosensors were divided into two groups based on the transduction mechanism: optical or electrochemical. The first group evaluated osteoblasts or mesenchymal stem cell (MSC) biocompatibility, viability, differentiation, alkaline phosphatase, enzyme, and protein detection. The second group detected cell impedance, ATP release, and superoxide concentration in tenocytes, osteoblasts, MSCs, and myoblasts. This review highlighted that the in vitro scenario is still at an early phase and limited for what concerns both the type of bioanalyte and for the type of system detector used.

Conceptually Rich, Perceptually Sparse: Object Representations in 6-Month-Old Infants' Working Memory.

Six-month-old infants can store representations of multiple objects in working memory but do not always remember the objects' features (e.g., shape). Here, we asked whether infants' object representations (a) may contain conceptual content and (b) may contain this content even if perceptual features are forgotten. We hid two conceptually distinct objects (a humanlike doll and a nonhuman ball) one at a time in two separate locations and then tested infants' memory for the first-hidden object by revealing either the original hidden object or an unexpected other object. Using looking time, we found that infants remembered the categorical identity of the hidden object but failed to remember its perceptual identity. Our results suggest that young infants may encode conceptual category in a representation of an occluded object, even when perceptual features are lost.

Issues in the determination of 'responders' and 'non-responders' in physiological research.

NEW FINDINGS: What is the topic for this review? We discuss the dichotomization of continuous-level physiological measurements into 'responders' and 'non-responders' when interventions/treatments are examined in robust parallel-group studies. What advances does it highlight? Sample responder counts are biased by pre-to-post within-subject variability. Sample differences in counts may be explained wholly by differences in mean response, even without individual response heterogeneity and even if test-retest measurement error informs the choice of response threshold. A less biased and more informative approach uses the SD of individual responses to estimate the chance a new person from the population of interest will be a responder. ABSTRACT: As a follow-up to our 2015 review, we cover more issues on the topic of 'response heterogeneity', which we define as clinically important individual differences in the physiological responses to the same treatment/intervention that cannot be attributed to random within-subject variability. We highlight various pitfalls with the common practice of counting the number of 'responders', 'non-responders' and 'adverse responders' in samples that have been given certain treatments or interventions for research purposes. We focus on the classical parallel-group randomized controlled trial and assume typical good practice in trial design. We show that sample responder counts are biased because individuals differ in terms of pre-to-post within-subject random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample. The dichotomization of individual responses in a research sample is fraught with pitfalls. Less biased approaches for estimating the proportion of responders in a population of interest are now available. Importantly, these approaches are based on the SD for true individual responses, directly incorporating information from the control group.

Harnessing formal concepts of biological mechanism to analyze human disease.

Mechanism is a widely used concept in biology. In 2017, more than 10% of PubMed abstracts used the term. Therefore, searching for and reasoning about mechanisms is fundamental to much of biomedical research, but until now there has been almost no computational infrastructure for this purpose. Recent work in the philosophy of science has explored the central role that the search for mechanistic accounts of biological phenomena plays in biomedical research, providing a conceptual basis for representing and analyzing biological mechanism. The foundational categories for components of mechanisms-entities and activities-guide the development of general, abstract types of biological mechanism parts. Building on that analysis, we have developed a formal framework for describing and representing biological mechanism, MecCog, and applied it to describing mechanisms underlying human genetic disease. Mechanisms are depicted using a graphical notation. Key features are assignment of mechanism components to stages of biological organization and classes; visual representation of uncertainty, ignorance, and ambiguity; and tight integration with literature sources. The MecCog framework facilitates analysis of many aspects of disease mechanism, including the prioritization of future experiments, probing of gene-drug and gene-environment interactions, identification of possible new drug targets, personalized drug choice, analysis of nonlinear interactions between relevant genetic loci, and classification of diseases based on mechanism.

Impact of Changes in Systemic Physiology on fNIRS/NIRS Signals: Analysis Based on Oblique Subspace Projections Decomposition.

Measurements of cerebral and muscle oxygenation (StO2) and perfusion ([tHb]) with functional near-infrared spectroscopy (fNIRS) and near infrared spectroscopy (NIRS), respectively, can be influenced by changes in systemic physiology. The aim of our study was to apply the oblique subspace projections signal decomposition (OSPSD) to find the contribution from systemic physiology, i.e. heart rate (HR), electrocardiography (ECG)-derived respiration (EDR) and partial pressure of carbon dioxide (pCO2) to StO2 and [tHb] signals measured on the prefrontal cortex (PFC) and calf muscle. OSPSD was applied to two datasets (n1 = 42, n2 = 79 measurements) from two fNIRS/NIRS speech studies. We found that (i) all StO2 and [tHb] signals contained components related to changes in systemic physiology, (ii) the contribution from systemic physiology varied strongly between subjects, and (iii) changes in systemic physiology generally influenced fNIRS signals on the left and right PFC to a similar degree.

Physiological reactions to long-term fishing in the Barents Sea.

Background: Fishing in distant waters for months may induce physiological stress. Aims: To assess the physiological stress reactions in fishermen working for 2-3 months continuously in 6-h shifts on trawlers in the Barents Sea. Methods: The crew of five trawlers fishing in the Barents Sea from January to April 2004 were invited to participate. In the week before and 5-7 days after the trip, the following measures were collected: salivary cortisol four times a day, 24-h urinary cortisol, blood pressure, heart rate, serum cholesterol, serum high-density lipoprotein (HDL-cholesterol), HbA1c (glycosylated haemoglobin) and weight. In addition, 24-h urinary cortisol, blood pressure and heart rate were measured three times. A questionnaire on health, social conditions and work environment was obtained after the trip. Results: In total, 136 men agreed to participate. Full data were obtained for 96 fishermen (70%). A significant decrease in salivary and urinary cortisol was found during the trip. Adjustment for age, body mass index, smoking, shift work schedule and time of day for sample collection did not change this finding. Systolic and diastolic blood pressure declined significantly and remained significantly lower after the trip compared to before the trip. Serum cholesterol/HDL ratio declined significantly, whereas triglycerides, HbA1c and weight were unchanged. Conclusions: Working up to 3 months on 6-h shifts, 84 h a week, with moderate physical activity, even in artificial light and cold weather on a ship, did not result in increased physiological stress.

How do students deal with difficult physiological knowledge?

Physiology courses are considered to be challenging for students to master due to the highly conceptual nature of the discipline and the substantial cognitive effort required to understand disciplinary knowledge. Students must choose appropriate learning strategies to develop their understanding, as their choices may influence both their understanding and their academic achievement. The primary aim of this study was to develop an understanding of why students experience difficulties with physiology and how they respond when facing the challenge of learning this discipline. Undergraduate allied health students ( n = 231) studying physiology were asked to identify the topics they had difficulty understanding, the strategies they used to deal with that difficult knowledge, and the reasons for their difficulties. Consenting students' responses were subjected to inductive and deductive thematic analyses, and their performance on examinations were collated. Students reported that they found physiology difficult due to their lack of familiarity with it and the level of detail required. To aid their understanding of difficult topics, students commonly reported reviewing information, seeking further information, and seeking social assistance, with more high-achieving students reporting reviewing records, and fewer reporting seeking social assistance than poor-achieving students. Most notably, a disconnect was found between students' reporting of difficult modules and their academic achievement on those modules, with students who cited difficulties performing equally well, if not better, than those who do not. Importantly, these findings suggest that students, in recognizing their difficulties and the reasons for them, can implement effective learning strategies to overcome them.

Small Molecules from Deep within the Gut.

Although the influence of the human microbiome on host functions is widely recognized, the underlying molecular mechanisms are still largely unknown. A recent study by the Fischbach group now provides an experimental workflow for characterizing and evaluating the impact of microbiome-derived small molecules on host physiology.

Kinesia paradoxa: a challenging Parkinson's phenomenon for simulation.

The present work aims to study extensively the literature on the phenomenon of "kinesia paradoxa" presented in Parkinson's disease patients, who generally cannot move but under certain circumstances exhibit a sudden, brief period of mobility (walking or even running). The objective of this study was to identify the mechanisms causing this phenomenon and relate them with respectively computational simulations aiming to draw attention to gaps and weaknesses and possible directions for future research. The study of this phenomenon with the use of modeling techniques may be a decisive factor for its interpretation.

Water and electrolyte homeostasis brings balance to physiology.

The American Physiological Society officially recognized the area of research in Water and Electrolyte Homeostasis (WEH) over 30 years ago when the Section of WEH was established. This minireview illuminates the importance of WEH research to the physiology community. By the narrowest definition, WEH research studies the regulation of body fluids; however, this research area is much broader and more relevant today than when this subdiscipline was first recognized because of the translational and systemic "point of view" of WEH research. This minireview highlights how WEH research serves as a balanced force between the full range of other more traditional organ-based physiological and pathophysiological concepts. The breadth of research in which WEH investigators engage is on full display with the publication of minireviews from the annual Data Diuresis session at Experimental Biology.

The growth hormone secretagogue receptor: its intracellular signaling and regulation.

The growth hormone secretagogue receptor (GHSR), also known as the ghrelin receptor, is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase of food intake and body weight, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. Dependent on the tissues and cells, activation of GHSR may trigger a diversity of signaling mechanisms and subsequent distinct physiological responses. Distinct regulation of GHSR occurs at levels of transcription, receptor interaction and internalization. Here we review the current understanding on the intracellular signaling pathways of GHSR and its modulation. An overview of the molecular structure of GHSR is presented first, followed by the discussion on its signaling mechanisms. Finally, potential mechanisms regulating GHSR are reviewed.

Monitoring and quantifying dynamic physiological processes in live neurons using fluorescence recovery after photobleaching.

The direct visualization of subcellular dynamic processes is often hampered by limitations in the resolving power achievable with conventional microscopy techniques. Fluorescence recovery after photobleaching has emerged as a highly informative approach to address this challenge, permitting the quantitative measurement of the movement of small organelles and proteins in living functioning cells, and offering detailed insights into fundamental cellular phenomena of physiological importance. In recent years, its implementation has benefited from the increasing availability of confocal microscopy systems and of powerful labeling techniques based on genetically encoded fluorescent proteins or other chemical markers. In this review, we present fluorescence recovery after photobleaching and related techniques in the context of contemporary neurobiological research and discuss quantitative and semi-quantitative approaches to their interpretation.

Obsolete ideas and logical confusions can be obstacles for biogerontology research.

Some misconceptions can be an obstacle for biogerontology research. These misconceptions can be classified in two categories: (1) obsolete ideas in biology, for example "aging has a universal cause" and "living beings are like machines", and (2) conceptual and logical confusions, such as "longevity is not dependent on other life-history traits", "between-groups variability allows to infer conclusions about individual variability", and "the burden of the proof lies with the opponents to the hypothesis". This opinion article describes these problems in the hope it will help to overcome them.