A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks

AbstractStress activates a complex network of hormones known as the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is dysregulated in chronic stress and psychiatric disorders, but the origin of this dysregulation is unclear and cannot be explained by current HPA models. To address this, we developed a new mathematical model for the HPA axis that incorporates changes in the total functional mass of the HPA hormone-secreting glands. The mass changes are caused by the HPA hormones which act as growth factors for the glands in the axis. We find that the HPA axis shows the property of dynamical compensation, where gland masses adjust over weeks to buffer variation in physiological parameters. These mass changes explain the experimental findings on dysregulation of cortisol and ACTH dynamics in alcoholism, anorexia and postpartum. Dysregulation occurs for a wide range of parameters, and is exacerbated by impaired glucocorticoid receptor (GR) feedback, providing an explanation for the implication of GR in mood disorders. These findings suggest that gland-mass dynamics may play an important role in the pathophysiology of stress-related disorders.Author SummaryThe HPA axis is a neuroendocrine axis that is activated in response to stressors. The classical description of this axis includes three hormones that act in a cascade, with the final hormone cortisol inhibiting the two upstream hormones, ACTH and CRH. This classical picture has timescales of hours due to hormone half-lives, and cannot explain phenomena on the scale of weeks to months associated with this axis, such as the dysregulation observed in depression, alcohol addiction, postpartum, and other conditions. Here, we use a minimal-model approach to add to the classical model two known interactions in which CRH and ACTH not only regulate downstream hormones, but also act as growth factors for the cells that secrete these hormones. This creates a physiological circuit that can maintain total cell mass and buffer parameter changes. It has a fragility in which after prolonged stress, the total cell functional masses grow and take weeks to return to baseline. This is sufficient to explain the specific dynamics of hormone dysregulation found in several contexts. It also quantifies the effect of the cortisol (glucocorticoid) receptor on resilience to prolonged stress. Our findings suggest that interactions between hormones and cell functional mass may play an important role in HPA axis regulation on the timescale of weeks to months.SynopsisThe HPA axis helps the body adapt to stress, but becomes dysregulated after prolonged activation, with clinical consequences. The origin of this dysregulation is unclear. We provide a mechanism for dysregulation based on the effect of the HPA hormones as growth factors for their downstream glands. A mathematical model that includes gland functional mass dynamics, introduces a new slow timescale of weeks to the HPA axis; previous models had only fast timescales of hours.The gland masses grow during prolonged activation, providing dynamical compensation, and recover with overshoots over weeks after withdrawal of activation.These overshoots are sufficient to explain the observed HPA dysregulation in pathological conditions, and clarify the role of glucocorticoid receptors in resilience to prolonged stress.

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Beat the heat: Culex quinquefasciatus regulates its body temperature during blood-feeding

10.1101/2020.07.07.190157 ◽

2020 ◽

Author(s):

Joanna M. Reinhold ◽

Ryan Shaw ◽

Chloé Lahondère

Keyword(s):

Heat Stress ◽

Body Temperature ◽

Culex Quinquefasciatus ◽

Evaporative Cooling ◽

Blood Feeding ◽

The Body ◽

List Type ◽

Physiological Level ◽

Wide Range ◽

Warm Blood

AbstractMosquitoes are regarded as one of the most dangerous animals on earth. As they are responsible for the spread of a wide range of both human and animal diseases, research of the underlying mechanisms of their feeding behavior and physiology is critical. Among disease vector mosquitoes, Culex quinquefasciatus, which is a known carrier of West Nile virus and Western Equine Encephalitis, remains relatively understudied. As blood sucking insects, adaptations (either at the molecular or physiological level) while feeding on warm blood is crucial to their survival, as overheating can result in death due to heat stress. Our research aims to study how Cx. quinquefasciatus copes with heat associated with the ingestion of a warm blood-meal and to possibly uncover the adaptations this species uses to avoid thermal stress. Through the use of thermographic imaging, we analyzed the body temperature of Cx. quinquefasciatus while blood feeding. Infrared thermography has allowed us to identify a cooling strategy, evaporative cooling via the production of fluid droplets, and an overall low body temperature in comparison to the blood temperature during feeding. Understanding Cx. quinquefasciatus’ adaptations and various strategies that they employ to reduce their body temperature while blood-feeding constitutes the first step towards the discovery of potential targets of opportunity for their control.HighlightsMosquitoes have evolved to cope with heat stress associated with warm blood ingestionCulex quinquefasciatus displays heterothermy while blood-feedingThe abdominal temperature decreases due to evaporative cooling using urine dropletsOverall, the mosquito body temperature is much cooler than the ingested blood

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The Interaction between Maternal and Fetal Hypothalamic – Pituitary – Adrenal Axes

10.5772/intechopen.98722 ◽

2021 ◽

Author(s):

Aml M. Erhuma

Keyword(s):

Hpa Axis ◽

Later Life ◽

Postnatal Period ◽

The Body ◽

Prenatal Period ◽

Hormonal Responses ◽

Hypothalamic Pituitary Adrenal ◽

External Threats ◽

Unique System ◽

Wide Range

The Hypothalamic – Pituitary – Adrenal (HPA) Axis is a unique system that mediates an immediate reactivity to a wide range of stimuli. It has a crucial role in synchronizing the behavioral and hormonal responses to internal and external threats, therefore, increases the chance of survival. It also enables the body systems to adapt to challenges put up by the pregnancy. Since the early stages of pregnancy and throughout delivery, HPA axis of the mother continuously navigates that of the fetus, and both have a specific cross talk even beyond the point of delivery and during postnatal period. Any disturbance in the interaction between the maternal and fetal HPA axes can adversely affect both. The HPA axis is argued to be the mechanism through which maternal stress and other suboptimal conditions during prenatal period can program the fetus for chronic disease in later life. In this chapter, the physiological and non-physiological communications between maternal and fetal HPA axes will be addressed while highlighting specific and unique aspects of this pathway.

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Advantages and Clinical Applications of Lyophilized Platelet-Rich Plasma in Various Disease Conditions: A Review

International Journal for Research in Applied Science and Engineering Technology ◽

10.22214/ijraset.2021.39092 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1885-1892

Author(s):

Pradeep Mahajan

Keyword(s):

Growth Factors ◽

Platelet Rich Plasma ◽

Autologous Blood ◽

Healing Process ◽

Coagulation Factor ◽

The Body ◽

Plasma Therapy ◽

Plasma Fraction ◽

Wide Range ◽

Platelet Concentration

Abstract: Platelet rich plasma (PRP) is a biological product defined as a portion of the plasma fraction of autologous blood with a platelet concentration above the baseline. The plasma occupies 55% of blood, which is rich in immunoglobulins and proteins that have a wide range of applications in various medical fields. Plasma therapy is applied to tackle various disorders or diseases as it induces the body to develop new healthy cells. It contains important components like antibodies, coagulation factor, enzymes, fibrinogen, proteins and albumin. PRP is a unique and advanced treatment which helps to increases the body’s natural healing process. Platelet lysate which is obtained from platelet rich plasma consist of various growth factors such as chemokines, cytokines, and antibacterial molecules and also has anti-inflammatory, immunomodulatory, anti-fibrotic and repairing effects. As PRP is rich in the proteins and several antibodies, it is used for various chronic therapies such as hemophilia and autoimmune disorders as well as in various severe health problems. Lyophilized Platelet-rich plasma (LPRP) therapy is currently used in various fields such as in tissue regeneration, wound healing, scar revision, skin rejuvenating effects, alopecia and for the coronavirus disease (COVID-19). It is also used to heal wounds and illnesses. LPRP therapy is gaining attraction by many health professionals as it is a safe, effective, efficient, and easy approach in procuring, preserving, and therapy. In this review we described the advantages and applications of using lyophilized PRP in various diseases which might found to be effective in different treatment. Keywords: Plasma, Platelet, Growth Factors, Lyophilized platelet rich plasma.

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Comparison of Deterministic and Linear Cosine Spatial Filtering of Transmission Electron Micrographs

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100096230 ◽

1972 ◽

Vol 30 ◽

pp. 596-597

Author(s):

David A. Ansley

Keyword(s):

Spherical Aberration ◽

Focal Length ◽

Chromatic Aberration ◽

Spatial Filter ◽

Operating Conditions ◽

Objective Lens ◽

List Type ◽

Spatial Filters ◽

Transmission Electron ◽

Wide Range

The coherence of the electron flux of a transmission electron microscope (TEM) limits the direct application of deconvolution techniques which have been used successfully on unmanned spacecraft programs. The theory assumes noncoherent illumination. Deconvolution of a TEM micrograph will, therefore, in general produce spurious detail rather than improved resolution.A primary goal of our research is to study the performance of several types of linear spatial filters as a function of specimen contrast, phase, and coherence. We have, therefore, developed a one-dimensional analysis and plotting program to simulate a wide 'range of operating conditions of the TEM, including adjustment of the:(1) Specimen amplitude, phase, and separation(2) Illumination wavelength, half-angle, and tilt(3) Objective lens focal length and aperture width(4) Spherical aberration, defocus, and chromatic aberration focus shift(5) Detector gamma, additive, and multiplicative noise constants(6) Type of spatial filter: linear cosine, linear sine, or deterministic

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Triply-periodic nanostructures in surfactant, block copolymer, and biomembrane systems, and simulation of TEMs

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100150253 ◽

1993 ◽

Vol 51 ◽

pp. 884-885

Author(s):

David M. Anderson ◽

Tomas Landh

Keyword(s):

Liquid Crystalline ◽

Diblock Copolymers ◽

Cubic Phase ◽

List Type ◽

Interpenetrating Networks ◽

Triply Periodic ◽

Wide Range ◽

Bicontinuous Cubic ◽

Phase Liquid ◽

Dividing Surface

First discovered in surfactant-water liquid crystalline systems, so-called ‘bicontinuous cubic phases’ have the property that hydropnilic and lipophilic microdomains form interpenetrating networks conforming to cubic lattices on the scale of nanometers. Later these same structures were found in star diblock copolymers, where the simultaneous continuity of elastomeric and glassy domains gives rise to unique physical properties. Today it is well-established that the symmetry and topology of such a morphology are accurately described by one of several triply-periodic minimal surfaces, and that the interface between hydrophilic and hydrophobic, or immiscible polymer, domains is described by a triply-periodic surface of constant, nonzero mean curvature. One example of such a dividing surface is shown in figure 5.The study of these structures has become of increasing importance in the past five years for two reasons:1)Bicontinuous cubic phase liquid crystals are now being polymerized to create microporous materials with monodispersed pores and readily functionalizable porewalls; figure 3 shows a TEM from a polymerized surfactant / methylmethacrylate / water cubic phase; and2)Compelling evidence has been found that these same morphologies describe biomembrane systems in a wide range of cells.

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Creating the Wind

Latin American and Latinx Visual Culture ◽

10.1525/lavc.2020.2.4.14 ◽

2020 ◽

Vol 2 (4) ◽

pp. 14-31

Author(s):

Élodie Dupey García

Keyword(s):

Indigenous Communities ◽

The Body ◽

Historical Sources ◽

Natural Behavior ◽

Sensory Experiences ◽

Identity And Agency ◽

Wide Range ◽

Late Postclassic ◽

Comparative Examination ◽

Meteorological Phenomenon

This article explores how the Nahua of late Postclassic Mesoamerica (1200–1521 CE) created living and material embodiments of their wind god constructed on the basis of sensory experiences that shaped their conception of this divinized meteorological phenomenon. In this process, they employed chromatic and design devices, based on a wide range of natural elements, to add several layers of meaning to the human, painted, and sculpted supports dressed in the god’s insignia. Through a comparative examination of pre-Columbian visual production—especially codices and sculptures—historical sources mainly written in Nahuatl during the viceregal period, and ethnographic data on indigenous communities in modern Mexico, my analysis targets the body paint and shell jewelry of the anthropomorphic “images” of the wind god, along with the Feathered Serpent and the monkey-inspired embodiments of the deity. This study identifies the centrality of other human senses beyond sight in the conception of the wind god and the making of its earthly manifestations. Constructing these deity “images” was tantamount to creating the wind because they were intended to be visual replicas of the wind’s natural behavior. At the same time, they referred to the identity and agency of the wind god in myths and rituals.

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Hypothetical Role of Growth Factors to Reduce Intervertebral Disc Degeneration Significantly through Trained Biological Transformations

Current Pharmaceutical Design ◽

10.2174/1381612826666201019104201 ◽

2020 ◽

Vol 26 ◽

Author(s):

Cristian Muresanu ◽

Siva G. Somasundaram ◽

Sergey V. Vissarionov ◽

Liliya V. Gavryushova ◽

Vladimir N. Nikolenko ◽

...

Keyword(s):

Growth Factors ◽

Blood Circulation ◽

Seminal Fluid ◽

Prostate Gland ◽

The Body ◽

Personal Experiences ◽

Biological Transformation ◽

The Mind

Background: From the evidence of failed injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. Objective: We seek to stimulate discussions and more research about the possibility of using the already available growth factors found in the prostate gland and endometrium by starting a novel educable physiology, known as biological transformations controlled by the mind. Methods: We summarized the stretch-gated ion channel mechanism of the cell membrane, and offer several practical methods that can be applied by anyone, in order to stimulate and enhance the blood circulation of the growth factors from the seminal fluid to sites throughout the body. This details the practical application of our earlier published studies about biological transformations. Results: A previously reported single-patient case study has been extended, adding more from his personal experiences continually improving this novel physiological training and extending the ideas from our earlier findings in detail. Conclusion: The biological transformation findings demonstrate the need additional research to establish the benefits of these natural therapies to repair and rejuvenate tissues affected by various chronic diseases or aging processes.

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GPER-Deficient Rats Exhibit Lower Serum Corticosterone Level and Increased Anxiety-Like Behavior

Neural Plasticity ◽

10.1155/2020/8866187 ◽

2020 ◽

Vol 2020 ◽

pp. 1-22 ◽

Cited By ~ 2

Author(s):

Yi Zheng ◽

Meimei Wu ◽

Ting Gao ◽

Li Meng ◽

Xiaowei Ding ◽

...

Keyword(s):

Hpa Axis ◽

Corticosterone Level ◽

Brain Structures ◽

Ample Evidence ◽

Genetic Ablation ◽

Serum Corticosterone ◽

Underlying Mechanisms ◽

G Protein Coupled ◽

Prolonged Stress

Ample evidence suggests that estrogens have strong influences on the occurrence of stress-related mood disorders, but the underlying mechanisms remain poorly understood. Through multiple approaches, we demonstrate that the G protein-coupled estrogen receptor (GPER) is widely distributed along the HPA axis and in brain structures critically involved in mood control. Genetic ablation of GPER in the rat resulted in significantly lower basal serum corticosterone level but enhanced ACTH release in response to acute restraint stress, especially in the female. GPER-/- rats of either sex displayed increased anxiety-like behaviors and deficits in learning and memory. Additionally, GPER deficiency led to aggravation of anxiety-like behaviors following single-prolonged stress (SPS). SPS caused significant decreases in serum corticosterone in WT but not in GPER-deficient rats. The results highlight an important role of GPER at multiple sites in regulation of the HPA axis and mood.

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332 The diagnostic role of shunt series radiographs (SSR) in children presenting to the children’s emergency department (CED) with suspected ventriculoperitoneal (VP) shunt failure

Emergency Medicine Journal ◽

10.1136/emj-2020-rcemabstracts.56 ◽

2020 ◽

Vol 37 (12) ◽

pp. 852.3-853

Author(s):

Angharad Griffiths ◽

Ikechukwu Okafor ◽

Thomas Beattie

Keyword(s):

Clinical Outcome ◽

Sensitivity And Specificity ◽

Clinical Information ◽

Flow Diagram ◽

List Type ◽

Shunt Failure ◽

Vp Shunt ◽

Wide Range ◽

Diagnostic Role

Aims/Objectives/BackgroundVP shunts are used to drain CSF from the cranial vault because of a wide range of pathologies and, like any piece of hardware, can fail. Traditionally investigations include SSR and CT. This project examines the role of SSR in evaluating children with suspected VP shunt failure.Primary outcome: Sensitivity and specificity of SSR in children presenting to the CED with concern for shunt failure.Methods/DesignConducted in a single centre, tertiary CED of the national Irish Neurosurgical(NS) referral centre (ED attendance:>50,000 patients/year). 100 sequential SSR requested by the CED were reviewed. Clinical information was extracted from electronic requests. Shunt failure was defined by the need for NS intervention(Revision).Abstract 332 Figure 1Abstract 332 Figure 2Results/ConclusionsSensitivity and specificity is presented in figure 1 (two by two table).100 radiographs performed in 84 children.22% shunts revised (see flow diagram).7 SSR’s were abnormal.85% (n=6) shunts revised. [5 following abnormal CT].Of the normal SSR’s; 16 had abnormal CT and revised.85/100 received CT.64 of 85 CT’s (75%) were normal.□6 of the 64 had focal shunt concern.SSR’s shouldn’t be used in isolation. NPV&PPV, Sensitivity&Specificity is low.SSR’s are beneficial where there’s concern over focal shunt problems (injury/pain/swelling) or following abnormal CT.VP shunt failure is not well investigated with SSR alone.SSR’s could be omitted where there is no focal shunt concern/after normal CT (without impacting clinical outcome) reducing radiation exposure and reduce impact on CED’s.59 SSR’s could have been avoided without adverse clinical outcome.

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Development and Validation of a New Scoring Tool to Evaluate the Clinical Evolution of Adult Patients with Nonsegmental Vitiligo

Dermatology ◽

10.1159/000511890 ◽

2021 ◽

pp. 1-9

Author(s):

María Luisa Peralta-Pedrero ◽

Denisse Herrera-Bringas ◽

Karla Samantha Torres-González ◽

Martha Alejandra Morales-Sánchez ◽

Fermín Jurado Santa-Cruz ◽

...

Keyword(s):

Body Surface ◽

Task Force ◽

Intraclass Correlation ◽

The Body ◽

Response To Treatment ◽

Similar Response ◽

Clinical Evolution ◽

Wide Range ◽

Patient Reported ◽

Extreme Groups

Background: Vitiligo has an unpredictable course and a variable response to treatment. Furthermore, the improvement of some vitiligo lesions cannot be considered a guarantee of a similar response to the other lesions. Instruments for patient-reported outcome measures (PROM) can be an alternative to measure complex constructions such as clinical evolution. Objective: The aim of this study was to validate a PROM that allows to measure the clinical evolution of patients with nonsegmental vitiligo in a simple but standardized way that serves to gather information for a better understanding of the disease. Methods: The instrument was created through expert consensus and patient participation. For the validation study, a prospective cohort design was performed. The body surface area affected was measured with the Vitiligo Extension Score (VES), the extension, the stage, and the spread by the evaluation of the Vitiligo European Task Force assessment (VETFa). Reliability was determined with test-retest, construct validity through hypothesis testing, discriminative capacity with extreme groups, and response capacity by comparing initial and final measurements. Results: Eighteen semi-structured interviews and 7 cognitive interviews were conducted, and 4 dermatologists were consulted. The instrument Clinical Evolution-Vitiligo (CV-6) was answered by 119 patients with a minimum of primary schooling. A wide range was observed in the affected body surface; incident and prevalent cases were included. The average time to answer the CV-6 was 3.08 ± 0.58 min. In the test-retest (n = 53), an intraclass correlation coefficient was obtained: 0.896 (95% CI 0.82–0.94; p < 0.001). In extreme groups, the mean score was 2 (2–3) and 5 (4–6); p < 0.001. The initial CV-6 score was different from the final one and the change was verified with VES and VETFa (p < 0.05, n = 92). Conclusions: The CV-6 instrument allows patient collaboration, it is simple and brief, and it makes it easier for the doctor to focus attention on injuries that present changes at the time of medical consultation.

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