Hygienic Assessment of Risks of Thermal Balance Disruption in Medical Laboratory Workers Using Personal Protective Equipment for Biohazards

Introduction: Specifics of activities of medical personnel in different types of laboratories can potentially create working conditions that violate occupational safety and health regulations. Objective: The study aimed to assess health risks of thermal balance disruption in PCR laboratory staff wearing personal protective equipment for biohazards in the context of the COVID-19 pandemic. Materials and methods: The study was conducted in winter 2020–2021 in PCR laboratories of the Volgograd Region. It included measurements of laboratory microclimate parameters, such as relative humidity, air temperature and velocity, used to estimate the heat load index. An observation cohort of 31 female medical laboratory workers aged 32.48 ± 1.45 years with a three to nine months experience of work in the PCR laboratory was formed to monitor the thermal state at the start and end of the work shift by measuring skin temperature at five points, sublingual temperature, and heat sensation. The results of measurements were used to estimate the mean skin temperature and heart rate while the dynamics of work ability was assessed by the results of contact tremorometry. Results: We established a significant increase in all measured values. The mean skin temperature at the end of the shift reached 33.85 ± 0.24 °C, thus exceeding the upper limit of the permissible value. The heart rate and heat sensation parameters approached the upper values of the maximum permissible thermal state of a person. Contact tremorometry results indicated a decrease in the performance by the end of the work shift. The findings gave evidence of tension of thermoregulatory reactions and the risk of thermal balance disruption posed by the use of a specific type of personal protective equipment in the PCR laboratory. Conclusion: The research results provide strong support for the conclusion that the use of PPE for biohazards poses a risk of thermal balance disruption in medical laboratory personnel. The severity of stress of thermoregulatory reactions depends on technical and design characteristics of the PPE used. The necessity of a physiological and hygienic substantiation of acceptable duration of work of medical workers wearing various types of PPE for biohazards in PCR laboratories justifies the importance of further studies.

Building Thermal Comfort Research Based on Energy-Saving Concept

Under the trend of building green and comfortable development, effective control of building energy consumption has become one of the problems that countries are actively facing to solve. People’s demand for residential buildings has changed from the past survival type to a comfortable and livable type. The high level of heating energy consumption is worthy of in-depth study. In order to reduce energy consumption, realize the mapping of energy-saving concepts in buildings, and understand the energy consumption of different building materials and the influence of external factors on human thermal comfort, this book has conducted research on building thermal comfort based on energy-saving concepts. First of all, this article introduces the concept and application mode of energy-saving concepts in buildings and the concept of thermal comfort and the SET index of standard effective temperature, including the two-node model and the algorithm involved in the Fanger heat balance equation. In the experimental part, a model based on the concept of energy saving was designed to predict and analyze the energy consumption and thermal comfort effects of the building. In the analysis part, a comprehensive analysis of the effects of temperature, humidity, wind speed, and gender on thermal comfort, methods to improve thermal comfort, cumulative load changes with the heat transfer coefficient of windows, and the effects of windows of different materials on energy consumption was performed. At the same temperature, the wind speed is different, and the degree of heat sensation is also different. When the wind speed is 0.18 m/s and the temperature is 28°C, the thermal sensation is 0.32, and the human sensation is close to neutral. When the wind speed increases to 0.72 m/s, the heat sensation drops to −0.45, and the human body feels neutral and cool. It can be seen that the increase in wind speed has a certain compensation effect on the thermal sensation of the human body. When the wind speed does not change, increase the air temperature. For example, when the wind speed is 0.72 m/s, the temperature is 28°C, and the thermal sensation is −0.45, and when the temperature is increased to 29°C, the thermal sensation is 0.08, which shows that the temperature is improving the thermal sensation of the human body which has a certain offsetting effect. By studying the thermal comfort of buildings based on energy-saving concepts, it is possible to obtain the effect of external factors on thermal comfort, thereby optimizing building materials and using building materials with lower heat transfer coefficients to reduce heating energy consumption.

Effect of Adrenomedullin on Migraine-like Attacks in Patients With Migraine: A Randomized Crossover Study

ObjectiveTo determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.MethodsTwenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline) administrated via an automated intravenous pump (20 minutes). The patients participated in two study days with washout period of minimum of seven days. The primary outcome of the study was predefined as a difference in migraine incidence (0–12 h) and the secondary outcome were the headache intensity score’s area under curve (AUC0-12 h) and the (AUC 0-90 min) for MAP, flushing and HR.ResultsEleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo (P= 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion (P= 0.035). AUC0-90 min for HR and, flushing (P < 0.05) were significant and MAP (P = 0.502) remain unchanged. Common adverse events reported were facial flushing, heat sensation and palpitation (P <0.001)ConclusionOur data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor.

Hot flashes: Why?

Hot flashes (HF), transitory episodes of erythema, heat sensation, anxiety followed by chills, are described in carcinoid syndrome, mastocytosis, medullary thyroid cancer, hyperthyroidism, pheochromocytoma, alcohol consumption, side effects of drugs, and infections. They are pivotal among menopause-related vasomotor symptoms beside genitourinary syndrome in addition to sleep disturbances (40-60% of females), and metabolic changes. HF affect 70% of women (20% of them have a severe impairment of life quality); they last for 4-7 years, starting 4-6 years before last menstruation. The main HF cause is ovarian-derivate estrogen deprivation which activates complex endocrine and neuroendocrine mechanisms involving noradrenaline, 5-hydroxytriptamine (5-HT), calcitonin gen-related peptide, orexin, kisspeptin, neurokinin B, and epigenetic elements like modulation of tachykinin receptor 3, accelerated epigenetic aging (as found in Women's Health Initiative Observational Study), expression of central serotonin transporters. Estrogen deficiency uncouples the negative feedback with preoptic area of hypothalamus, responsible for thermoregulation by inducing an exacerbated vasodilatory response to a small increase of body temperature. TRPV1 (transient receptor potential vanilloid 1) in preoptic hypothalamic area may play a role by NE-α2ADR (norepinephrine-activated α2-adrenergic receptors) activation. Higher expression of serotonin transporter SLC6A4 causes a lack of 5-HT at synapsis which is a trigger for presynaptic 5-HT receptor feedback, thus a release of serotonin amount prevents hot flashes. Kisspeptin and neurokinin B which are co-expressed in infundibular nucleus of hypothalamus are involved in central thermoregulation and gonadotropin releasing hormone anomalies. The NKR3 (neurokinin 3 receptor) antagonist receptor improves HF. Understanding the pivotal role of central neurotransmitters in hot flashes is the basis of new therapeutically researches because otherwise estrogen replacement has a long list of side effects, and it is contraindicated in breast cancer-related hypogonadism

Identification and functional characterization of the Piezo1 channel pore domain

Mechanotransduction is the process by which cells convert physical forces into electro-chemical responses. On a molecular scale these forces are detected by mechanically activated ion channels, which constitute the basis for hearing, touch, pain, cold and heat sensation amongst other physiological processes. Exciting high-resolution structural details of these channels are currently emerging that will eventually allow us to delineate the molecular determinants of gating and ion permeation. However, our structural-functional understanding across the family remains limited. Piezo1 is one of the largest and least understood of these channels, with various structurally identified features within its trimeric assembly. This study seeks to determine the modularity and function of Piezo1 channels by constructing deletion proteins guided by cryo EM structural knowledge. Our comprehensive functional study identified, for the first time, the minimal amino acid sequence of the full-length Piezo1 that can fold and function as the channel’s pore domain between E2172 and the last residue E2547. While, the addition of an anchor region has no effect on permeation properties. The Piezo1 pore domain is not pressure sensitive and the appending of Piezo Repeat-A did not restore pressure-dependent gating, hence the sensing module must exist between residues 1-1952. Our efforts delineating the permeation and gating regions within this complex ion channel have implications in identifying small molecules that exclusively regulate the activity of the channel’s pore module to influence mechanotransduction and downstream processes.

The Mysteries of Capsaicin-Sensitive Afferents

A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as “capsaicin desensitization,” during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several “mysteries” remain unsolved to date, including the molecular underpinnings of “capsaicin desensitization,” and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms.

Keratinocytes contribute to normal cold and heat sensation

Keratinocytes are the most abundant cell type in the epidermis, the most superficial layer of skin. Historically, epidermal-innervating sensory neurons were thought to be the exclusive detectors and transmitters of environmental stimuli. However, recent work from our lab (Moehring et al., 2018) and others (Baumbauer et al., 2015) has demonstrated that keratinocytes are also critical for normal mechanotransduction and mechanically-evoked behavioral responses in mice. Here, we asked whether keratinocyte activity is also required for normal cold and heat sensation. Using calcium imaging, we determined that keratinocyte cold activity is conserved across mammalian species and requires the release of intracellular calcium through one or more unknown cold-sensitive proteins. Both epidermal cell optogenetic inhibition and interruption of ATP-P2X4 signaling reduced reflexive behavioral responses to cold and heat stimuli. Based on these data and our previous findings, keratinocyte purinergic signaling is a modality-conserved amplification system that is required for normal somatosensation in vivo.